Publications Test2

Ouvrages édités à titre de seul éditeur ou en collaboration

2011

XXIIIrd congress of the International Society of Biomechanics - ISB2011 Conference book - Programme & Abstracts

ISB 2011 Conference book

2005

3D Reconstruction of the Necropolis in Itanos, Crete

Articles dans des revues avec comité de lecture

A paraître

Impact of imperfect annotations on CNN training and performance for instance segmentation and classification in digital pathology

Segmentation and classification of large numbers of instances, such as cell nuclei, are crucial tasks in digital pathology for accurate diagnosis. However, the availability of high-quality datasets for deep learning methods is often limited due to the complexity of the annotation process. In this work, we investigate the impact of noisy annotations on the training and performance of a state-of-the-art CNN model for the combined task of detecting, segmenting and classifying nuclei in histopathology images. In this context, we investigate the conditions for determining an appropriate number of training epochs to prevent overfitting to annotation noise during training. Our results indicate that the utilisation of a small, correctly annotated validation set is instrumental in avoiding overfitting and maintaining model performance to a large extent. Additionally, our findings underscore the beneficial role of pre-training.

Low-rank Constrained Super-Resolution for Mixed-Resolution Multiview Video

Multiview video allows for simultaneously presenting dynamic imaging from multiple viewpoints, enabling a broad range of immersive applications. This paper proposes a novel super-resolution (SR) approach to mixed-resolution (MR) multiview video, whereby the low-resolution (LR) videos produced by MR camera setups are up-sampled based on the neighboring HR videos. Our solution analyzes the statistical correlation of different resolutions between multiple views, and introduces a low-rank prior based SR optimization framework using local linear embedding and weighted nuclear norm minimization. The target HR patch is reconstructed by learning texture details from the neighboring HR camera views using local linear embedding. A low-rank constrained patch optimization solution is introduced to effectively restrain visual artifacts and the ADMM framework is used to solve the resulting optimization problem. Comprehensive experiments including objective and subjective test metrics demonstrate that the proposed method outperforms the state-of-the-art SR methods for MR multiview video.

2024

Data Augmentation Based on Depth Information for Neural Radiance Fields

Abstract Neural Radiance Fields (NeRF) have attracted particular attention due to their exceptional capability in virtual view generation from a sparse set of input images. However, their scope is constrained by the substantial amount of images required for training. This work introduces a data augmentation methodology to train NeRF using external depth information. The approach entails generating new virtual images at different positions through the utilization of MPEG's reference view synthesizer (RVS) to augment the training image pool for NeRF. Results demonstrate a substantial enhancement in the output quality when employing the generated views in comparison to a scenario where they are omitted.

Validation of a targeted next-generation sequencing panel for pancreatic ductal adenocarcinomas

Pancreatic ductal adenocarcinoma (PDAC) is reported to be amongst the cancers with the lowest survival rate at 5 years. In the present study we aimed to validate a targeted next-generation sequencing (tNGS) panel to use in clinical routine, investigating genes important for PDAC diagnostic, prognostic and potential theragnostic aspect. In this NGS panel we also designed target regions to inquire about loss of heterozygosity (LOH) of chromosome 18 that has been described to be possibly linked to a worse disease progression. Copy number alteration has also been explored for a subset of genes. The last two methods are not commonly used for routine diagnostic with tNGS panels and we investigated their possible contribution to better characterize PDAC. A series of 140 formalin-fixed paraffin-embedded (FFPE) PDAC samples from 140 patients was characterized using this panel. Ninety-two % of patients showed alterations in at least one of the investigated genes (most frequent KRAS, TP53, SMAD4, CDKN2A and RNF43). Regarding LOH evaluation, we were able to detect chr18 LOH starting at 20% cell tumor percentage. The presence of LOH on chr18 is associated with a worse disease- and metastasis-free survival, in uni- and multivariate analyses. The present study validates the use of a tNGS panel for PDAC characterization, also evaluating chr18 LOH status for prognostic stratification.

Schematics Retrieval Using Whole-Graph Embedding Similarity

This paper addresses the pressing environmental concern of plastic waste, particularly in the biopharmaceutical production sector, where single-use assemblies (SUAs) significantly contribute to this issue. To address and mitigate this problem, we propose a unique approach centered around the standardization and optimization of SUA drawings through digitization and structured representation. Leveraging the non-Euclidean properties of SUA drawings, we employ a graph-based representation, utilizing graph convolutional networks (GCNs) to capture complex structural relationships. Introducing a novel weakly supervised method for the similarity-based retrieval of SUA graph networks, we optimize graph embeddings in a low-dimensional Euclidean space. Our method demonstrates effectiveness in retrieving similar graphs that share the same functionality, offering a promising solution to reduce plastic waste in pharmaceutical assembly processes.

Performance analysis of multiview video compression based on MIV and VVC multilayer

Time Series Analysis of Landsat Images for Monitoring Flooded Areas in the Inner Niger Delta, Mali

This paper presents an R-based approach to mapping dynamics of the flooded areas in the Inner Niger Delta (IND), Mali, using time series analysis of Landsat 8-9 satellite images. As the largest inland wetland in West Africa, the habitats of IND offers high potential for biodiversity of the flood-dependent e c o systems. IND is one of the most productive areas in West Africa. Mapping flooded areas based on satellite images enables to provide strategies for land management and rice planting and modelling vegetation types of IND. Our approach is based on using libraries of R programming language for processing six Landsat images, and each image was taken on November from 2013 to 2022. By capturing spatial and temporal structures of the satellite images on 2013, 2015, 2018, 2020, 2021 and 2022, the remote sensing data are combined to yield estimates of landscape dynamics that is temporally coherent, while helping to analyse fluctuations of spatial extent in fluvial wetlands caused by the hydrological processes of seasonal flooding. Further, by allowing packages of R to support image processing, an approach to mapping vegetation by NDVI, SAVI and EVI indices and visualising changes in distribution of different land cover classes over time is realised. In this context, processing Earth observation data by advanced scripting tools of R language provides new insights into complex interlace of climate-hydrological processes and vegetation responses. Our study contributes to the sustainable management of natural resources and improving knowledge on the functioning of IND ecosystems in Mali, West Africa.

2023

Environmental mapping of Burkina Faso using TerraClimate data and satellite images by GMT and R scripts

In this paper, the climate and environmental datasets were processed by the scripts of Generic Mapping Tools (GMT) and R to evaluate changes in climate parameters, vegetation patters and land cover types in Burkina Faso. Located in the southern Sahel zone, Burkina Faso experiences one of the most extreme climatic hazards in sub-saharan Africa varying from the extreme floods in Volta River Basin, to desertification and recurrent droughts.. The data include the TerraClimate dataset and satellite images Landsat 8-9 Operational Land Imager (OLI) and Thermal Infrared (TIRS) C2 L1. The dynamics of target climate characteristics of Burkina Faso was visualised for 2013-2022 using remote sensing data. To evaluate the environmental dynamics the TerraClimate data were used for visualizing key climate parameter: extreme temperatures, precipitation, soil moisture, downward surface shortwave radiation, vapour pressure deficit and anomaly. The Palmer Drought Severity Index (PDSI) was modelled over the study area to estimate soil water balance related to the soil moisture conditions as a prerequisites for vegetation growth. The land cover types were mapped using the k-means clustering by R. Two vegetation indices were computed to evaluate the changes in vegetation patterns over recent decade. These included the Normalized Difference Vegetation Index (NDVI) and the Soil-Adjusted Vegetation Index (SAVI) The scripts used for cartographic workflow are presented and discussed. This study contributes to the environmental mapping of Burkina Faso with aim to highlight the links between the climate processes and vegetation dynamics in West Africa.

Usefulness of FAPα assessment in bronchoalveolar lavage as a marker of fibrogenesis: results of a preclinical study and first report in patients with idiopathic pulmonary fibrosis.

Fibroblast activation protein-α (FAPα) is a marker of activated fibroblasts that can be selectively targeted by an inhibitor (FAPI) and visualised by PET/CT imaging. We evaluated whether the measurement of FAPα in bronchoalveolar lavage fluids (BALF) and the uptake of FAPI by PET/CT could be used as biomarkers of fibrogenesis.

Pharmacological targeting of netrin-1 inhibits EMT in cancer.

Epithelial-to-mesenchymal transition (EMT) regulates tumour initiation, progression, metastasis and resistance to anti-cancer therapy1-7. Although great progress has been made in understanding the role of EMT and its regulatory mechanisms in cancer, no therapeutic strategy to pharmacologically target EMT has been identified. Here we found that netrin-1 is upregulated in a primary mouse model of skin squamous cell carcinoma (SCC) exhibiting spontaneous EMT. Pharmacological inhibition of netrin-1 by administration of NP137, a netrin-1-blocking monoclonal antibody currently used in clinical trials in human cancer (ClinicalTrials.gov identifier NCT02977195 ), decreased the proportion of EMT tumour cells in skin SCC, decreased the number of metastases and increased the sensitivity of tumour cells to chemotherapy. Single-cell RNA sequencing revealed the presence of different EMT states, including epithelial, early and late hybrid EMT, and full EMT states, in control SCC. By contrast, administration of NP137 prevented the progression of cancer cells towards a late EMT state and sustained tumour epithelial states. Short hairpin RNA knockdown of netrin-1 and its receptor UNC5B in EPCAM+ tumour cells inhibited EMT in vitro in the absence of stromal cells and regulated a common gene signature that promotes tumour epithelial state and restricts EMT. To assess the relevance of these findings to human cancers, we treated mice transplanted with the A549 human cancer cell line-which undergoes EMT following TGFβ1 administration8,9-with NP137. Netrin-1 inhibition decreased EMT in these transplanted A549 cells. Together, our results identify a pharmacological strategy for targeting EMT in cancer, opening up novel therapeutic interventions for anti-cancer therapy.

Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer.

Netrin-1 is upregulated in cancers as a protumoural mechanism1. Here we describe netrin-1 upregulation in a majority of human endometrial carcinomas (ECs) and demonstrate that netrin-1 blockade, using an anti-netrin-1 antibody (NP137), is effective in reduction of tumour progression in an EC mouse model. We next examined the efficacy of NP137, as a first-in-class single agent, in a Phase I trial comprising 14 patients with advanced EC. As best response we observed 8 stable disease (8 out of 14, 57.1%) and 1 objective response as RECIST v.1.1 (partial response, 1 out of 14 (7.1%), 51.16% reduction in target lesions at 6 weeks and up to 54.65% reduction during the following 6 months). To evaluate the NP137 mechanism of action, mouse tumour gene profiling was performed, and we observed, in addition to cell death induction, that NP137 inhibited epithelial-to-mesenchymal transition (EMT). By performing bulk RNA sequencing (RNA-seq), spatial transcriptomics and single-cell RNA-seq on paired pre- and on-treatment biopsies from patients with EC from the NP137 trial, we noted a net reduction in tumour EMT. This was associated with changes in immune infiltrate and increased interactions between cancer cells and the tumour microenvironment. Given the importance of EMT in resistance to current standards of care2, we show in the EC mouse model that a combination of NP137 with carboplatin-paclitaxel outperformed carboplatin-paclitaxel alone. Our results identify netrin-1 blockade as a clinical strategy triggering both tumour debulking and EMT inhibition, thus potentially alleviating resistance to standard treatments.

Correlations between the Topography-Induced Gravity, Terrain Structure and the Seismicity in the Gulf of Panama

This study presents new maps of the topographic and geophysical setting and seismicity in the region of the Gulf of Panama. The spatial analysis is based on the comparative analysis of the datasets on geoid, free-air gravity anomaly, topography and earthquakes. The cartographic framework is developed using the Generic Mapping Tools (GMT) scripting toolset. Seismic activity in the Central America is high due to the complex geologic setting, tectonic activity and lithosphere plate subduction. The data include the Earth Gravitational Model (EGM2008), the General Bathymetric Chart of the Oceans (GEBCO) and gravity grids. The seismicity data were collected from the Incorporated Research Institutions for Seismology (IRIS) catalogue on 1970-2021. The variations in data were compared to analyse correlations between the geophysical, seismic and topographic parameters. Free-air gravity, geoid and topographic data derived from the high-resolution datasets were used to investigate their effects on the main seismic sources in the region. The comparison of the maps showed that the distribution of the shallow earthquakes in the Pacific segment of Panama coincides with negative free-air anomalies and lower geoid values. The results revealed high values of geoid in the high mountainous regions of Panama (Cordilliera de Talamanca, southern coast of Peninsula de Azuero and eastern Panama, 77.5-78.5°W), which correspond to the topographic roughness in the highlands. Negative values of geoid are found over the Caribbean Sea basin (−4 to 0 m). The analyses of seismicity showed 1740 earthquake events varying by magnitudes from 2.9 to 7.8 at the depths up to 225 m (near the west coast of Colombia). A high concentration of the earthquakes is in the western region of the Panama's shelf waters (~82-83.5°W), and on the border with Colombia (~77-78.5°W). High gravity anomalies (over 220 mGal) are found in the mountainous regions which match the geodynamic processes associated with the Earth structure and geodetic and geophysical effects. The regions of the high seismicity were defined in the Gulf of Chiriqui and eastern part of the Gulf of Panama.

SMAD4 Positive Pancreatic Ductal Adenocarcinomas Are Associated with Better Outcomes in Patients Receiving FOLFIRINOX-Based Neoadjuvant Therapy.

SMAD4 is inactivated in 50-55% of pancreatic ductal adenocarcinomas (PDACs). SMAD4 loss of expression has been described as a negative prognostic factor in PDAC associated with an increased rate of metastasis and resistance to therapy. However, the impact of SMAD4 inactivation in patients receiving neoadjuvant therapy (NAT) is not well characterized. The aim of our study was to investigate whether SMAD4 status is a prognostic and predictive factor in patients receiving NAT.

Multispectral Satellite Image Analysis for Computing Vegetation Indices by R in the Khartoum Region of Sudan, Northeast Africa

Desertification is one of the most destructive climate-related issues in the Sudan-Sahel region of Africa. As the assessment of desertification is possible by satellite image analysis using vegetation indices (VIs), this study reports on the technical advantages and capabilities of scripting the ‘raster' and ‘terra' R-language packages for computing the VIs. The test area which was considered includes the region of the confluence between the Blue and White Niles in Khartoum, southern Sudan, northeast Africa and the Landsat 8-9 OLI/TIRS images taken for the years 2013, 2018 and 2022, which were chosen as test datasets. The VIs used here are robust indicators of plant greenness, and combined with vegetation coverage, are essential parameters for environmental analytics. Five VIs were calculated to compare both the status and dynamics of vegetation through the differences between the images collected within the nine-year span. Using scripts for computing and visualising the VIs over Sudan demonstrates previously unreported patterns of vegetation to reveal climate-vegetation relationships. The ability of the R packages ‘raster' and ‘terra' to process spatial data was enhanced through scripting to automate image analysis and mapping, and choosing Sudan for the case study enables us to present new perspectives for image processing.

SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature

Abstract Introduction COVID-19-infected patients harbour neurological symptoms such as stroke and anosmia, leading to the hypothesis that there is direct invasion of the central nervous system (CNS) by SARS-CoV-2. Several studies have reported the neuropathological examination of brain samples from patients who died from COVID-19. However, there is still sparse evidence of virus replication in the human brain, suggesting that neurologic symptoms could be related to mechanisms other than CNS infection by the virus. Our objective was to provide an extensive review of the literature on the neuropathological findings of postmortem brain samples from patients who died from COVID-19 and to report our own experience with 18 postmortem brain samples. Material and methods We used microscopic examination, immunohistochemistry (using two different antibodies) and PCR-based techniques to describe the neuropathological findings and the presence of SARS-CoV-2 virus in postmortem brain samples. For comparison, similar techniques (IHC and PCR) were applied to the lung tissue samples for each patient from our cohort. The systematic literature review was conducted from the beginning of the pandemic in 2019 until June 1st, 2022. Results In our cohort, the most common neuropathological findings were perivascular haemosiderin-laden macrophages and hypoxic-ischaemic changes in neurons, which were found in all cases (n = 18). Only one brain tissue sample harboured SARS-CoV-2 viral spike and nucleocapsid protein expression, while all brain cases harboured SARS-CoV-2 RNA positivity by PCR. A colocalization immunohistochemistry study revealed that SARS-CoV-2 antigens could be located in brain perivascular macrophages. The literature review highlighted that the most frequent neuropathological findings were ischaemic and haemorrhagic lesions, including hypoxic/ischaemic alterations. However, few studies have confirmed the presence of SARS-CoV-2 antigens in brain tissue samples. Conclusion This study highlighted the lack of specific neuropathological alterations in COVID-19-infected patients. There is still no evidence of neurotropism for SARS-CoV-2 in our cohort or in the literature.

Panoptic quality should be avoided as a metric for assessing cell nuclei segmentation and classification in digital pathology.

Panoptic Quality (PQ), designed for the task of "Panoptic Segmentation" (PS), has been used in several digital pathology challenges and publications on cell nucleus instance segmentation and classification (ISC) since its introduction in 2019. Its purpose is to encompass the detection and the segmentation aspects of the task in a single measure, so that algorithms can be ranked according to their overall performance. A careful analysis of the properties of the metric, its application to ISC and the characteristics of nucleus ISC datasets, shows that is not suitable for this purpose and should be avoided. Through a theoretical analysis we demonstrate that PS and ISC, despite their similarities, have some fundamental differences that make PQ unsuitable. We also show that the use of the Intersection over Union as a matching rule and as a segmentation quality measure within PQ is not adapted for such small objects as nuclei. We illustrate these findings with examples taken from the NuCLS and MoNuSAC datasets. The code for replicating our results is available on GitHub ( https://github.com/adfoucart/panoptic-quality-suppl ).

Coherence of Bangui Magnetic Anomaly with Topographic and Gravity Contrasts across Central African Republic

The interactions between the geophysical processes and geodynamics of the lithosphere play a crucial role in the geologic structure of the Earth's crust. The Bangui magnetic anomaly is a notable feature in the lithospheric structure of the Central African Republic (CAR) resulting from a complex tectonic evolution. This study reports on the coherence in the geophysical data and magnetic anomaly field analysed from a series of maps. The data used here include raster grids on free-air altimetric gravity, magnetic EMAG2 maps, geoid EGM2008 model and topographic SRTM/ETOPO1 relief. The data were processed to analyse the correspondence between the geophysical and geologic setting in the CAR region. Histogram equalization of the topographic grids was implemented by partition of the raster grids into equal-area patches of data ranged by the segments with relative highs and lows of the relief. The original data were compared with the equalized, normalized and quadratic models. The scripts used for cartographic data processing are presented and commented. The consistency and equalization of topography, gravity and geoid data were based using GMT modules ‘grdfft' and ‘grdhisteq' modules. Using GMT scripts for mapping the geophysical and gravity data over CAR shows an advanced approach to multi-source data visualization to reveal the relationships in the geophysical and topographic processes in central Africa. The results highlighted the correlation between the distribution of rocks with high magnetism in the central part of the Bangui anomaly, and distribution of granites, greenstone belts, and metamorphosed basalts as rock exposure. The correspondence between the negative Bouguer anomaly (<−80 mGal), low geoid values (<−12 m) and the extent of the magnetic anomaly with extreme negative values ranging from −1000 to −200 nT is identified. The integration of the multi-source data provides new insights into the analysis of crustal thicknesses and the average density of the Earth in CAR, as well as the magnitude of the magnetic fields with notable deviations caused by the magnetic flux density in the Bangui area related to the distribution of mineral resources in CAR.

Recognizing the Wadi Fluvial Structure and Stream Network in the Qena Bend of the Nile River, Egypt, on Landsat 8-9 OLI Images

With methods for processing remote sensing data becoming widely available, the ability to quantify changes in spatial data and to evaluate the distribution of diverse landforms across target areas in datasets becomes increasingly important. One way to approach this problem is through satellite image processing. In this paper, we primarily focus on the methods of the unsupervised classification of the Landsat OLI/TIRS images covering the region of the Qena governorate in Upper Egypt. The Qena Bend of the Nile River presents a remarkable morphological feature in Upper Egypt, including a dense drainage network of wadi aquifer systems and plateaus largely dissected by numerous valleys of dry rivers. To identify the fluvial structure and stream network of the Wadi Qena region, this study addresses the problem of interpreting the relevant space-borne data using R, with an aim to visualize the land surface structures corresponding to various land cover types. To this effect, high-resolution 2D and 3D topographic and geologic maps were used for the analysis of the geomorphological setting of the Qena region. The information was extracted from the space-borne data for the comparative analysis of the distribution of wadi streams in the Qena Bend area over several years: 2013, 2015, 2016, 2019, 2022, and 2023. Six images were processed using computer vision methods made available by R libraries. The results of the k-means clustering of each scene retrieved from the multi-temporal images covering the Qena Bend of the Nile River were thus compared to visualize changes in landforms caused by the cumulative effects of geomorphological disasters and climate-environmental processes. The proposed method, tied together through the use of R scripts, runs effectively and performs favorably in computer vision tasks aimed at geospatial image processing and the analysis of remote sensing data.

Computing Vegetation Indices from the Satellite Images Using GRASS GIS Scripts for Monitoring Mangrove Forests in the Coastal Landscapes of Niger Delta, Nigeria

This paper addresses the issue of the satellite image processing using GRASS GIS in the mangrove forests of the Niger River Delta, southern Nigeria. The estuary of the Niger River Delta in the Gulf of Guinea is an essential hotspot of biodiversity on the western coast of Africa. At the same time, climate issues and anthropogenic factors affect vulnerable coastal ecosystems and result in the rapid decline of mangrove habitats. This motivates monitoring of the vegetation patterns using advanced cartographic methods and data analysis. As a response to this need, this study aimed to calculate and map several vegetation indices (VI) using scripts as advanced programming methods integrated in geospatial studies. The data include four Landsat 8-9 OLI/TIRS images covering the western segment of the Niger River Delta in the Bight of Benin for 2013, 2015, 2021, and 2022. The techniques included the 'i.vi', 'i.landsat.toar' and other modules of the GRASS GIS. Based on the GRASS GIS 'i.vi' module, ten VI were computed and mapped for the western segment of the Niger River Delta estuary: Atmospherically Resistant Vegetation Index (ARVI), Green Atmospherically Resistant Vegetation Index (GARI), Green Vegetation Index (GVI), Difference Vegetation Index (DVI), Perpendicular Vegetation Index (PVI), Global Environmental Monitoring Index (GEMI), Normalized Difference Water Index (NDWI), Second Modified Soil Adjusted Vegetation Index (MSAVI2), Infrared Percentage Vegetation Index (IPVI), and Enhanced Vegetation Index (EVI). The results showed variations in the vegetation patterns in mangrove habitats situated in the Niger River Delta over the last decade as well as the increase in urban areas (Onitsha, Sapele, Warri and Benin City) and settlements in the Delta State due to urbanization. The advanced techniques of the GRASS GIS of satellite image processing and analysis enabled us to identify and visualize changes in vegetation patterns. The technical excellence of the GRASS GIS in image processing and analysis was demonstrated in the scripts used in this study.

Evaluating participating methods in image analysis challenges: lessons from MoNuSAC 2020

Biomedical image analysis competitions often rank the participants based on a single metric that combines assessments of different aspects of the task at hand. While this is useful for declaring a single winner for a competition, it makes it difficult to assess the strengths and weaknesses of participating algorithms. By involving multiple capabilities (detection, segmentation and classification) and releasing the prediction masks provided by several teams, the MoNuSAC 2020 challenge provides an interesting opportunity to look at what information may be lost by using entangled metrics. We analyse the challenge results based on the “Panoptic Quality” (PQ) used by the organizers, as well as on disentangled metrics that assess the detection, classification and segmentation abilities of the algorithms separately. We show that the PQ hides interesting aspects of the results, and that its sensitivity to small changes in the prediction masks makes it hard to interpret these results and to draw useful insights from them. Our results also demonstrate the necessity to have access, as much as possible, to the raw predictions provided by the participating teams so that challenge results can be more easily analysed and thus more useful to the research community.

GDAL and PROJ Libraries Integrated with GRASS GIS for Terrain Modelling of the Georeferenced Raster Image

Libraries with pre-written codes optimize the workflow in cartography and reduce labour intensive data processing by iteratively applying scripts to implementing mapping tasks. Most existing Geographic Information System (GIS) approaches are based on traditional software with a graphical user's interface which significantly limits their performance. Although plugins are proposed to improve the functionality of many GIS programs, they are usually ad hoc in finding specific mapping solutions, e.g., cartographic projections and data conversion. We address this limitation by applying the principled approach of Geospatial Data Abstraction Library (GDAL), library for conversions between cartographic projections (PROJ) and Geographic Resources Analysis Support System (GRASS) GIS for geospatial data processing and morphometric analysis. This research presents topographic analysis of the dataset using scripting methods which include several tools: (1) GDAL, a translator library for raster and vector geospatial data formats used for converting Earth Global Relief Model (ETOPO1) GeoTIFF in XY Cartesian coordinates into World Geodetic System 1984 (WGS84) by the 'gdalwarp' utility; (2) PROJ projection transformation library used for converting ETOPO1 WGS84 grid to cartographic projections (Cassini-Soldner equirectangular, Equal Area Cylindrical, Two-Point Equidistant Azimuthal, and Oblique Mercator); and (3) GRASS GIS by sequential use of the following modules: r.info, d.mon, d.rast, r.colors, d.rast.leg, d.legend, d.northarrow, d.grid, d.text, g.region, and r.contour. The depth frequency was analysed by the module 'd.histogram'. The proposed approach provided a systematic way for morphometric measuring of topographic data and combine the advantages of the GDAL, PROJ, and GRASS GIS tools that include the informativeness, effectiveness, and representativeness in spatial data processing. The morphometric analysis included the computed slope, aspect, profile, and tangential curvature of the study area. The data analysis revealed the distribution pattern in topographic data: 24% of data with elevations below 400 m, 13% of data with depths −5000 to −6000 m, 4% of depths have values −3000 to −4000 m, the least frequent data (−6000 to 7000 m) <1%, 2% of depths have values −2000 to 3000 m in the basin, while other values are distributed proportionally. Further, by incorporating the generic coordinate transformation software library PROJ, the raster grid was transformed into various cartographic projections to demonstrate distortions in shape and area. Scripting techniques of GRASS GIS are demonstrated for applications in topographic modelling and raster data processing. The GRASS GIS shows the effectiveness for mapping and visualization, compatibility with libraries (GDAL, PROJ), technical flexibility in combining Graphical User Interface (GUI), and command-line data processing. The research contributes to the technical cartographic development.

Quantitative Morphometric 3D Terrain Analysis of Japan Using Scripts of GMT and R

In this paper, we describe two related scripting methods of cartographic data processing and visualization that provide 2D and 3D mapping of Japan with different algorithm complexity. The first algorithm utilizes Generic Mapping Toolset (GMT), which is known as an advanced console-based program for spatial data processing. The modules of GMT combine the functionality of scripting with the aspects of geoinformatics, which is especially effective for the rapid analysis of large geospatial datasets, multi-format data processing, and mapping in 2D and 3D modes. The second algorithm presents the use of the R programming language for cartographic visualization and spatial analysis. This R method utilizes the packages ‘tmap', ‘raster', ‘maps', and ‘mapdata' to model the morphometric elements of the Japanese archipelago, such as slope, aspect, hillshade and elevation. The general purpose graphical package ‘ggplot2' of R was used for mapping the prefectures of Japan. The two scripting approaches demonstrated an established correspondence between the programming languages and cartography determined with the use of scripts for data processing. They outperform several well-known and state-of-the-art GIS methods for mapping due to their high automation of data processing. Cartography has largely reflected recent advances in data science, the rapid development of scripting languages, and transfer in the approaches of data processing. This extends to the shift from the traditional GIS to programming languages. As a response to these new challenges, we demonstrated in this paper the advantages of using scripts in mapping, which consist of repeatability and the flexible applicability of scripts in similar works.

Comparison Between Manual and Automated Assessment of Ki-67 in Breast Carcinoma: Test of a Simple Method in Daily Practice.

In the era of "precision medicine," the availability of high-quality tumor biomarker tests is critical and tumor proliferation evaluated by Ki-67 antibody is one of the most important prognostic factors in breast cancer. But the evaluation of Ki-67 index has been shown to suffer from some interobserver variability. The goal of the study is to develop an easy, automated, and reliable Ki-67 assessment approach for invasive breast carcinoma in routine practice.

The use of time‐of‐flight camera to assess respiratory rates and thoracoabdominal depths in patients with chronic respiratory disease

Introduction: Over the last 5 years, the analysis of respiratory patterns presents a growing usage in clinical and research purposes, but there is still currently a lack of easy-to-use and affordable devices to perform such kind of evaluation. Objectives: The aim of this study is to validate a new specifically developed method, based on Kinect sensor, to assess respiratory patterns against spirometry under various conditions. Methods: One hundred and one participants took parts in one of the three validations studies. Twenty-five chronic respiratory disease patients (14 with chronic obstructive pulmonary disease (COPD) [65 ± 10 years old, FEV1 = 37 (15% predicted value), VC = 62 (20% predicted value)], and 11 with lung fibrosis (LF) [64 ± 14 years old, FEV1 = 55 (19% predicted value), VC = 62 (20% predicted value)]) and 76 healthy controls (HC) were recruited. The correlations between the signal of the Kinect (depth and respiratory rate) and the spirometer (tidal volume and respiratory rate) were computed in part 1. We then included 66 HC to test the ability of the system to detect modifications of respiratory patterns induced by various conditions known to modify respiratory pattern (cognitive load, inspiratory load and combination) in parts 2 and 3. Results: There is a strong correlation between the depth recorded by the Kinect and the tidal volume recorded by the spirometer: r = 0.973 for COPD patients, r = 0.989 for LF patients and r = 0.984 for HC. The Kinect is able to detect changes in breathing patterns induced by different respiratory disturbance conditions, gender and oral task. Conclusions: Measurements performed with the Kinect sensors are highly correlated with the spirometer in HC and patients with COPD and LF. Kinect is also able to assess respiratory patterns under various loads and disturbances. This method is affordable, easy to use, fully automated and could be used in the current clinical context. Respiratory patterns are important to assess in daily clinics. However, there is currently no affordable and easy-to-use tool to evaluate these parameters in clinics. We validated a new system to assess respiratory patterns using the Kinect sensor in patients with chronic respiratory diseases.

2022

Computer Vision Algorithms of DigitSeis for Building a Vectorised Dataset of Historical Seismograms from the Archive of Royal Observatory of Belgium

Archived seismograms recorded in the 20th century present a valuable source of information for monitoring earthquake activity. However, old data, which are only available as scanned paper-based images should be digitised and converted from raster to vector format prior to reuse for geophysical modelling. Seismograms have special characteristics and specific features recorded by a seismometer and encrypted in the images: signal trace lines, minute time gaps, timing and wave amplitudes. This information should be recognised and interpreted automatically when processing archives of seismograms containing large collections of data. The objective was to automatically digitise historical seismograms obtained from the archives of the Royal Observatory of Belgium (ROB). The images were originally recorded by the Galitzine seismometer in 1954 in Uccle seismic station, Belgium. A dataset included 145 TIFF images which required automatic approach of data processing. Software for digitising seismograms are limited and many have disadvantages. We applied the DigitSeis for machine-based vectorisation and reported here a full workflow of data processing. This included pattern recognition, classification, digitising, corrections and converting TIFFs to the digital vector format. The generated contours of signals were presented as time series and converted into digital format (mat files) which indicated information on ground motion signals contained in analog seismograms. We performed the quality control of the digitised traces in Python to evaluate the discriminating functionality of seismic signals by DigitSeis. We shown a robust approach of DigitSeis as a powerful toolset for processing analog seismic signals. The graphical visualisation of signal traces and analysis of the performed vectorisation results shown that the algorithms of data processing performed accurately and can be recommended in similar applications of seismic signal processing in future related works in geophysical research.

Satellite Altimetry and Gravimetry Data for Mapping Marine Geodetic and Geophysical Setting of the Seychelles and the Somali Sea, Indian Ocean

Evaluation of the representative cartographic techniques demonstrated that there are still considerable challenges facing the methods of marine geodetic, geophysical and bathymetric data visualisation. In an oceanic seafloor formation, the interaction between the geological structural elements and topographical relief can be analysed by advanced mapping. In present study, a correlation between geodesy, geophysics and topography has been examined including the following variables: geological structure, coastal topography and bathymetry, geophysical fields, free-air gravity anomalies and geoid undulation, sediment thickness, bathymetric patterns, and extension of the transform faults. The variables were visualised on the high-resolution raster grids using Generic Mapping Tools (GMT) scripting toolset. The study area is located in the Seychelles and the Somali Sea segment of the Indian Ocean. The data incorporates satellite-derived gravity grid, EGM-2008, geological structures, topography from GEBCO grid and GlobSed sediment thickness, processed by GMT scripts. The results demonstrated that western continental slope of Somalia is wide, gently declining to the seafloor at depths exceeding -5000 m. Kenya and Tanzania present a wide continental foot with depths ranging from -3500 to - 5000 m. The Somali Sea basin shows low sedimentation lower than 500 m, while ridges and island chains have higher sediment influx (1,000-2,000 m). The Mozambique Channel has dominating values at 2,500-3,500 m. Higher values are noted near the Reunion and Mauritius islands until the Seychelles via the Mascarene Plateau (500 -1,000 m) against the <500 m in the areas of the Mid-Indian Ridge, Carlsberg Ridge and open water.

Shortcomings and areas for improvement in digital pathology image segmentation challenges

Digital pathology image analysis challenges have been organised regularly since 2010, often with events hosted at major conferences and results published in high-impact journals. These challenges mobilise a lot of energy from organisers, participants, and expert annotators (especially for image segmentation challenges). This study reviews image segmentation challenges in digital pathology and the top-ranked methods, with a particular focus on how reference annotations are generated and how the methods' predictions are evaluated. We found important shortcomings in the handling of inter-expert disagreement and the relevance of the evaluation process chosen. We also noted key problems with the quality control of various challenge elements that can lead to uncertainties in the published results. Our findings show the importance of greatly increasing transparency in the reporting of challenge results, and the need to make publicly available the evaluation codes, test set annotations and participants' predictions. The aim is to properly ensure the reproducibility and interpretation of the results and to increase the potential for exploitation of the substantial work done in these challenges.

R Libraries for Remote Sensing Data Classification by k-means Clustering and NDVI Computation in Congo River Basin, DRC

In this paper, an image analysis framework is formulated for Landsat-8 Operational Land Imager and Thermal Infrared Sensor (OLI/TIRS) scenes using the R programming language. The libraries of R are shown to be effective in remote sensing data processing tasks, such as classification using k-means clustering and computing the Normalized Difference Vegetation Index (NDVI). The data are processed using an integration of the RStoolbox, terra, raster, rgdal and auxiliary packages of R. The proposed approach to image processing using R is designed to exploit the parameters of image bands as cues to detect land cover types and vegetation parameters corresponding to the spectral reflectance of the objects represented on the Earth's surface. Our method is effective at processing the time series of the images taken at various periods to monitor the landscape dynamics in the middle part of the Congo River basin, Democratic Republic of the Congo (DRC). Whereas previous approaches primarily used Geographic Information System (GIS) software, we proposed to explicitly use the scripting methods for satellite image analysis by applying the extended functionality of R. The application of scripts for geospatial data is an effective and robust method compared with the traditional approaches due to its high automation and machine-based graphical processing. The algorithms of the R libraries are adjusted to spatial operations, such as projections and transformations, object topology, classification and map algebra. The data include Landsat-8 OLI-TIRS covering the three regions along the Congo river, Bumba, Basoko and Kisangani, for the years 2013, 2015 and 2022. We also validate the performance of graphical data handling for cartographic visualization using R libraries for visualising changes in land cover types by k-means clustering and calculation of the NDVI for vegetation analysis.

Investigating Cardiorespiratory Interaction Using Ballistocardiography and Seismocardiography—A Narrative Review

Ballistocardiography (BCG) and seismocardiography (SCG) are non-invasive techniques used to record the micromovements induced by cardiovascular activity at the body's center of mass and on the chest, respectively. Since their inception, their potential for evaluating cardiovascular health has been studied. However, both BCG and SCG are impacted by respiration, leading to a periodic modulation of these signals. As a result, data processing algorithms have been developed to exclude the respiratory signals, or recording protocols have been designed to limit the respiratory bias. Reviewing the present status of the literature reveals an increasing interest in applying these techniques to extract respiratory information, as well as cardiac information. The possibility of simultaneous monitoring of respiratory and cardiovascular signals via BCG or SCG enables the monitoring of vital signs during activities that require considerable mental concentration, in extreme environments, or during sleep, where data acquisition must occur without introducing recording bias due to irritating monitoring equipment. This work aims to provide a theoretical and practical overview of cardiopulmonary interaction based on BCG and SCG signals. It covers the recent improvements in extracting respiratory signals, computing markers of the cardiorespiratory interaction with practical applications, and investigating sleep breathing disorders, as well as a comparison of different sensors used for these applications. According to the results of this review, recent studies have mainly concentrated on a few domains, especially sleep studies and heart rate variability computation. Even in those instances, the study population is not always large or diversified. Furthermore, BCG and SCG are prone to movement artifacts and are relatively subject dependent. However, the growing tendency toward artificial intelligence may help achieve a more accurate and efficient diagnosis. These encouraging results bring hope that, in the near future, such compact, lightweight BCG and SCG devices will offer a good proxy for the gold standard methods for assessing cardiorespiratory function, with the added benefit of being able to perform measurements in real-world situations, outside of the clinic, and thus decrease costs and time.

Seismotectonics of Shallow-Focus Earthquakes in Venezuela with Links to Gravity Anomalies and Geologic Heterogeneity Mapped by a GMT Scripting Language

This paper presents a cartographic framework based on algorithms of GMT codes for mapping seismically active areas in Venezuela. The data included raster grids from GEBCO, EGM- 2008, and vector geological layers from the USGS. The data were iteratively processed in the console of GMT, converted by GDAL, formatted, and mapped for geophysical data visualisation; the QGIS was applied for geological mapping. We analyzed 2000 samples of the earthquake events obtained from the IRIS seismic database with a 25-year time span (1997-2021) in order to map the seismicity. The approach to linking geological, topographic, and geophysical data using GMT scripts aimed to map correlations among the geophysical phenomena, tectonic processes, geological setting, seismicity, and earthquakes. The practical application of the GMT scripts consists in automated mapping for the visualization of geological risks and hazards in the mountainous region of the Venezuelan Andes. The proposed method integrates the approach of GMT scripts with state-of-the-art GIS techniques, which demonstrated its effectiveness as a tool for mapping spatial datasets and rapid data processing in an iterative regime. In this context, using GMT and GIS to find similarities between the regional earthquake distribution and the geological and topographic setting is essential for hazard risk assessment. This study can serve as a basis for predictive seismic analysis in geologically vulnerable regions of Venezuela. In addition to a technical demonstration of GMT algorithms, this study also contributes to geological and geophysical mapping and seismic hazard assessments in South America. We present the full scripts used for mapping in a GitHub repository.

Satellite Image Processing by Python and R Using Landsat 9 OLI/TIRS and SRTM DEM Data on Côte d'Ivoire, West Africa

In this paper, we propose an advanced scripting approach using Python and R for satellite image processing and modelling terrain in Côte d'Ivoire, West Africa. Data include Landsat 9 OLI/TIRS C2 L1 and the SRTM digital elevation model (DEM). The EarthPy library of Python and ‘raster' and ‘terra' packages of R are used as tools for data processing. The methodology includes computing vegetation indices to derive information on vegetation coverage and terrain modelling. Four vegetation indices were computed and visualised using R: the Normalized Difference Vegetation Index (NDVI), Enhanced Vegetation Index 2 (EVI2), Soil-Adjusted Vegetation Index (SAVI) and Atmospherically Resistant Vegetation Index 2 (ARVI2). The SAVI index is demonstrated to be more suitable and better adjusted to the vegetation analysis, which is beneficial for agricultural monitoring in Côte d'Ivoire. The terrain analysis is performed using Python and includes slope, aspect, hillshade and relief modelling with changed parameters for the sun azimuth and angle. The vegetation pattern in Côte d'Ivoire is heterogeneous, which reflects the complexity of the terrain structure. Therefore, the terrain and vegetation data modelling is aimed at the analysis of the relationship between the regional topography and environmental setting in the study area. The upscaled mapping is performed as regional environmental analysis of the Yamoussoukro surroundings and local topographic modelling of the Kossou Lake. The algorithms of the data processing include image resampling, band composition, statistical analysis and map algebra used for calculation of the vegetation indices in Côte d'Ivoire. This study demonstrates the effective application of the advanced programming algorithms in Python and R for satellite image processing.

Chemerin plasma levels are increased in COVID-19 patients and are an independent risk factor of mortality.

Chemerin is an extracellular protein with chemotactic activities and its expression is increased in various diseases such as metabolic syndrome and inflammatory conditions. Its role in lung pathology has not yet been extensively studied but both known pro- and anti-inflammatory properties have been observed. The aim of our study was to evaluate the involvement of the chemerin/ChemR23 system in the physiopathology of COVID-19 with a particular focus on its prognostic value.

The MPEG Immersive Video Standard - Current Status and Future Outlook

Deep Learning for Reaction-Diffusion Glioma Growth Modeling: Towards a Fully Personalized Model?

Reaction-diffusion models have been proposed for decades to capture the growth of gliomas, the most common primary brain tumors. However, ill-posedness of the initialization at diagnosis time and parameter estimation of such models have restrained their clinical use as a personalized predictive tool. In this work, we investigate the ability of deep convolutional neural networks (DCNNs) to address commonly encountered pitfalls in the field. Based on 1200 synthetic tumors grown over real brain geometries derived from magnetic resonance (MR) data of six healthy subjects, we demonstrate the ability of DCNNs to reconstruct a whole tumor cell-density distribution from only two imaging contours at a single time point. With an additional imaging contour extracted at a prior time point, we also demonstrate the ability of DCNNs to accurately estimate the individual diffusivity and proliferation parameters of the model. From this knowledge, the spatio-temporal evolution of the tumor cell-density distribution at later time points can ultimately be precisely captured using the model. We finally show the applicability of our approach to MR data of a real glioblastoma patient. This approach may open the perspective of a clinical application of reaction-diffusion growth models for tumor prognosis and treatment planning.

Comments on “MoNuSAC2020: A Multi-Organ Nuclei Segmentation and Classification Challenge”

The MoNuSAC 2020 challenge was hosted at the ISBI 2020 conference, where the winners were announced. Challenge organizers, in addition to the leaderboard, released the evaluation code and visualisations of the prediction masks of the “top 5” teams. This shows a very high level of transparency, and provides a unique opportunity to better understand the challenge results. Our analysis of the code and all released data, however, shows three different problems in the computation of the metric used for the official ranking: a coding mistake resulting in erroneous false positives; another resulting in missed false positives; and a problem with the metric's aggregation method. We demonstrate the errors, and confirm that the mistaken version of the code was indeed used to rank the algorithms in the challenge. Our results can be fully replicated with the code provided on GitHub.

The Role of SMAD4 Inactivation in Epithelial-Mesenchymal Plasticity of Pancreatic Ductal Adenocarcinoma: The Missing Link?

Pancreatic ductal adenocarcinoma (PDAC) presents a five-year survival rate of 10% and its incidence increases over the years. It is, therefore, essential to improve our understanding of the molecular mechanisms that promote metastasis and chemoresistance in PDAC, which are the main causes of death in these patients. SMAD4 is inactivated in 50% of PDACs and its loss has been associated with worse overall survival and metastasis, although some controversy still exists. SMAD4 is the central signal transducer of the transforming growth factor-beta (TGF-beta) pathway, which is notably known to play a role in epithelial-mesenchymal transition (EMT). EMT is a biological process where epithelial cells lose their characteristics to acquire a spindle-cell phenotype and increased motility. EMT has been increasingly studied due to its potential implication in metastasis and therapy resistance. Recently, it has been suggested that cells undergo EMT transition through intermediary states, which is referred to as epithelial-mesenchymal plasticity (EMP). The intermediary states are characterized by enhanced aggressiveness and more efficient metastasis. Therefore, this review aims to summarize and analyze the current knowledge on SMAD4 loss in patients with PDAC and to investigate its potential role in EMP in order to better understand its function in PDAC carcinogenesis.

2021

Immunohistochemistry as an accurate tool for the assessment of BRAF V600E and TP53 mutations in primary and metastatic melanoma.

Metastatic melanoma is a fatal disease with poor prognosis. Ever since targeted therapy against oncogenic BRAF was approved, molecular profiling has become an integral part of the management of such patients. While molecular testing is not available in all pathology laboratories, immunohistochemistry (IHC) is a reliable screening option. The major objective of the present study was to evaluate whether IHC detection of BRAF and the tumor (suppressor) protein 53 gene (TP53) are reliable surrogates for mutation detection. Formalin-fixed paraffin-embedded samples of melanomas for which molecular data were previously obtained by targeted next-generation sequencing (NGS) between January 2014 and February 2019 were immunostained with BRAF V600E and p53 antibodies. A blinded evaluation of the IHC slides was performed by two pathologists in order to evaluate inter-observer concordance (discordant cases were reviewed by a third observer). The associations between the results of IHC and molecular profiling were evaluated. The study included a series of 37 cases of which 15 harbored a BRAF mutation and five a TP53 mutation. IHC had an overall diagnostic accuracy of 93.9% for BRAF V600E and 68.8% for TP53 compared to NGS. A statistically significant association between the two diagnostic methods was obtained for BRAF V600E (P=0.0004) but not for p53 (P=0.3098) IHC. The κ coefficient for IHC assessment of p53 was 0.55 and that for BRAF V600E was 0.72. In conclusion, the present results evidenced that IHC staining is a reliable surrogate for NGS in identifying the BRAF V600E mutation, which may become an efficient screening tool. Aberrant expression of p53 on IHC is at times associated with TP53 mutations but it was not possible to establish a direct link.

Initial Condition Assessment for Reaction-Diffusion Glioma Growth Models: A Translational MRI-Histology (In)Validation Study

Reaction-diffusion models have been proposed for decades to capture the growth of gliomas. Nevertheless, these models require an initial condition: the tumor cell density distribution over the whole brain at diagnosis time. Several works have proposed to relate this distribution to abnormalities visible on magnetic resonance imaging (MRI). In this work, we verify these hypotheses by stereotactic histological analysis of a non-operated brain with glioblastoma using a 3D-printed slicer. Cell density maps are computed from histological slides using a deep learning approach. The density maps are then registered to a postmortem MR image and related to an MR-derived geodesic distance map to the tumor core. The relation between the edema outlines visible on T2-FLAIR MRI and the distance to the core is also investigated. Our results suggest that (i) the previously proposed exponential decrease of the tumor cell density with the distance to the core is reasonable but (ii) the edema outlines would not correspond to a cell density iso-contour and (iii) the suggested tumor cell density at these outlines is likely overestimated. These findings highlight the limitations of conventional MRI to derive glioma cell density maps and the need for other initialization methods for reaction-diffusion models to be used in clinical practice.

Analyses of DNA Methylation Profiling in the Diagnosis of Intramedullary Astrocytomas.

Intramedullary astrocytomas (IMAs) consist of a heterogeneous group of rare central nervous system (CNS) tumors associated with variable outcomes. A DNA methylation-based classification approach has recently emerged as a powerful tool to further classify CNS tumors. However, no DNA methylation-related studies specifically addressing to IMAs have been performed yet. In the present study, we analyzed 16 IMA samples subjected to morphological and molecular analyses, including DNA methylation profiling. Among the 16 samples, only 3 cases were classified in a reference methylation class (MC) with the recommended calibrated score (≥0.9). The remaining cases were either considered "no-match" cases (calibrated score <0.3, n = 7) or were classified with low calibrated scores (ranging from 0.32 to 0.53, n = 6), including inconsistent classification. To obtain a more comprehensive tool for pathologists, we used different unsupervised analyses of DNA methylation profiles, including our data and those from the Heidelberg reference cohort. Even though our cohort included only 16 cases, hypotheses regarding IMA-specific classification were underlined; a potential specific MC of PA_SPINE was identified and high-grade IMAs, probably consisting of H3K27M wild-type IMAs, were mainly associated with ANA_PA MC. These hypotheses strongly suggest that a specific classification for IMAs has to be investigated.

Light field rendering for non-lambertian objects

In this paper we propose a solution for view synthesis of scenes presenting highly non-Lambertian objects. While Image-Based Rendering methods can easily render diffuse materials given only their depth, non-Lambertian objects present non-linear displacements of their features, characterized by curved lines in epipolar plane images. Hence, we propose to replace the depth maps used for rendering new viewpoints by a more complex "non-Lambertian map"describing the light field's behavior. In a 4D light field, diffuse features are linearly displaced following their disparity, but non-Lambertian feature can follow any trajectory and need to be approximated by non-Lambertian maps. We compute those maps from nine input images using Bezier or polynomial interpolation. After the map computation, a classical Image-Based Rendering method is applied to warp the input images to novel viewpoints.

Voxelwise principal component analysis of dynamic [s-methyl-11 c]methionine pet data in glioma patients

Recent works have demonstrated the added value of dynamic amino acid positron emission tomography (PET) for glioma grading and genotyping, biopsy targeting, and recurrence diagnosis. However, most of these studies are based on hand-crafted qualitative or semi-quantitative features extracted from the mean time activity curve within predefined volumes. Voxelwise dynamic PET data analysis could instead provide a better insight into intra-tumor heterogeneity of gliomas. In this work, we investigate the ability of principal component analysis (PCA) to extract relevant quantitative features from a large number of motion-corrected [S-methyl-11 C]methionine ([11 C]MET) PET frames. We first demonstrate the robustness of our methodology to noise by means of numerical simulations. We then build a PCA model from dynamic [11 C]MET acquisitions of 20 glioma patients. In a distinct cohort of 13 glioma patients, we compare the parametric maps derived from our PCA model to these provided by the classical one-compartment pharmacokinetic model (1TCM). We show that our PCA model outperforms the 1TCM to distinguish characteristic dynamic uptake behaviors within the tumor while being less computationally expensive and not requiring arterial sampling. Such methodology could be valuable to assess the tumor aggressiveness locally with applications for treatment planning and response evaluation. This work further supports the added value of dynamic over static [11 C]MET PET in gliomas.

XCycles Backprojection Acoustic Super-Resolution

The computer vision community has paid much attention to the development of visible image super-resolution (SR) using deep neural networks (DNNs) and has achieved impressive results. The advancement of non-visible light sensors, such as acoustic imaging sensors, has attracted much attention, as they allow people to visualize the intensity of sound waves beyond the visible spectrum. However, because of the limitations imposed on acquiring acoustic data, new methods for improving the resolution of the acoustic images are necessary. At this time, there is no acoustic imaging dataset designed for the SR problem. This work proposed a novel backprojection model architecture for the acoustic image super-resolution problem, together with Acoustic Map Imaging VUB-ULB Dataset (AMIVU). The dataset provides large simulated and real captured images at different resolutions. The proposed XCycles BackProjection model (XCBP), in contrast to the feedforward model approach, fully uses the iterative correction procedure in each cycle to reconstruct the residual error correction for the encoded features in both low- and high-resolution space. The proposed approach was evaluated on the dataset and showed high outperformance compared to the classical interpolation operators and to the recent feedforward state-of-the-art models. It also contributed to a drastically reduced sub-sampling error produced during the data acquisition.

High-quality holographic stereogram generation using four RGBD images

To computer-generate high-quality holographic stereograms, a huge number of images must be provided: several hundred for a horizontal parallax and the square of this number for a full parallax. In this paper, we propose to drastically reduce this number to four input images with depth maps (or equivalently, four groups of neighboring images used to compute a depth map) in any pose, in order to create the missing images with depth image-based rendering. We evaluate the view synthesis method objectively before providing visual results of the corresponding holographic stereograms. We believe this method outperforms shearlet-based approaches in objective view synthesis quality metrics and in the number of required input images (7 × 7).

Assessing partially ordered clustering in a multicriteria comparative context

This study considers the task of clustering for data characterized by peculiar quantitative features in that they express performance according to different indicators or criteria. Performance is supposed to be optimized in one way or the other, i.e. maximized or minimized. This peculiar type of data introduces a comparative context that is not generally taken into account in the field of pattern recognition, in general, and clustering, in particular. In the present study, we introduce different concepts and develop tools that facilitate the evaluation of data partitions in this comparative context leading to the consideration of asymmetric preference relationships between objects and between clusters. We show their usefulness on the basis of artificial data and also by analyzing the results produced on real data by means of clustering methods.

A Lightweight Depth Estimation Network for Wide-baseline Light Fields

Existing traditional and ConvNet-based methods for light field depth estimation mainly work on the narrow-baseline scenario. This paper explores the feasibility and capability of ConvNets to estimate depth in another promising scenario: wide-baseline light fields. Due to the deficiency of training samples, a large-scale and diverse synthetic wide-baseline dataset with labelled data is introduced for depth prediction tasks. Considering the practical goal for real-world applications, we design an end-to-end trained lightweight convolutional network to infer depths from light fields, called LLF-Net. The proposed LLF-Net is built by incorporating a cost volume which allows variable angular light field inputs and an attention module that enables to recover details at occlusion areas. Evaluations are made on the synthetic and real-world wide-baseline light fields, and experimental results show that the proposed network achieves the best performance when compared to recent state-of-the-art methods. We also evaluate our LLF-Net on narrow-baseline datasets, and it consequently improves the performance of previous methods.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Genome Sequencing from Post-Mortem Formalin-Fixed, Paraffin-Embedded Lung Tissues.

Implementation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing in the daily practice of pathology laboratories requires procedure adaptation to formalin-fixed, paraffin-embedded (FFPE) samples. So far, one study reported the feasibility of SARS-CoV-2 genome sequencing on FFPE tissues with only one contributory case of two. This study optimized SARS-CoV-2 genome sequencing using the Ion AmpliSeq SARS-CoV-2 Panel on 22 FFPE lung tissues from 16 deceased coronavirus disease 2019 (COVID-19) patients. SARS-CoV-2 was detected in all FFPE blocks using a real-time RT-qPCR targeting the E gene with crossing point (Cp) values ranging from 16.02 to 34.16. Sequencing was considered as contributory (i.e. with a uniformity >55%) for 17 FFPE blocks. Adapting the number of target amplification PCR cycles according to the RT-qPCR Cp values allowed optimization of the sequencing quality for the contributory blocks (i.e. 20 PCR cycles for blocks with a Cp value <28 and 25 PCR cycles for blocks with a Cp value between 28 and 30). Most blocks with a Cp value >30 were non-contributory. Comparison of matched frozen and FFPE tissues revealed discordance for only three FFPE blocks, all with a Cp value >28. Variant identification and clade classification was possible for 13 patients. This study validates SARS-CoV-2 genome sequencing on FFPE blocks and opens the possibility to explore correlation between virus genotype and histopathologic lesions.

Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis

FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers1-5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype. We also found this hybrid EMT state in FAT1-mutated human squamous cell carcinomas. Skin squamous cell carcinomas in which Fat1 was deleted presented increased tumour stemness and spontaneous metastasis. We performed transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies, which revealed that loss of function of FAT1 activates a CAMK2-CD44-SRC axis that promotes YAP1 nuclear translocation and ZEB1 expression that stimulates the mesenchymal state. This loss of function also inactivates EZH2, promoting SOX2 expression, which sustains the epithelial state. Our comprehensive analysis identified drug resistance and vulnerabilities in FAT1-deficient tumours, which have important implications for cancer therapy. Our studies reveal that, in mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state.

Repeatability and reproducibility of ADC measurements: a prospective multicenter whole-body-MRI study

Multicenter oncology trials increasingly include MRI examinations with apparent diffusion coefficient (ADC) quantification for lesion characterization and follow-up. However, the repeatability and reproducibility (R&R) limits above which a true change in ADC can be considered relevant are poorly defined. This study assessed these limits in a standardized whole-body (WB)-MRI protocol.

Real-Time Depth Video-Based Rendering for 6-DoF HMD Navigation and Light Field Displays

This paper presents a novel approach to provide immersive free navigation with 6 Degrees of Freedom in real-time for natural and virtual scenery, for both static and dynamic content. Stemming from the state-of-the-art in Depth Image-Based Rendering and the OpenGL pipeline, this new View Synthesis method achieves free navigation at up to 90 FPS and can take any number of input views with their corresponding depth maps as priors. Video content can be played thanks to GPU decompression, supporting free navigation with full parallax in real-time. To render a novel viewpoint, each selected input view is warped using the camera pose and associated depth map, using an implicit 3D representation. The warped views are then blended all together to generate the chosen virtual view. Various view blending approaches specifically designed to avoid visual artifacts are compared. Using as few as four input views appears to be an optimal trade-off between computation time and quality, allowing to synthesize high-quality stereoscopic views in real-time, offering a genuine immersive virtual reality experience. Additionally, the proposed approach provides high-quality rendering of a 3D scenery on holographic light field displays. Our results are comparable - objectively and subjectively - to the state of the art view synthesis tools NeRF and LLFF, while maintaining an overall lower complexity and real-time rendering.

2020

Holographic Micromirror Array with Diffuse Areas for Accurate Calibration of 3D Light-Field Display

AIM 2020 Challenge on Real Image Super-Resolution: Methods and Results

Clinical, radiological and molecular characterization of intramedullary astrocytomas

Intramedullary astrocytomas (IMAs) are rare tumors, and few studies specific to the molecular alterations of IMAs have been performed. Recently, KIAA1549-BRAF fusions and the H3F3A p.K27M mutation have been described in low-grade (LG) and high-grade (HG) IMAs, respectively. In the present study, we collected clinico-radiological data and performed targeted next-generation sequencing for 61 IMAs (26 grade I pilocytic, 17 grade II diffuse, 3 LG, 3 grade III and 12 grade IV) to identify KIAA1549-BRAF fusions and mutations in 33 genes commonly implicated in gliomas and the 1p/19q regions. One hundred seventeen brain astrocytomas were analyzed for comparison. While we did not observe a difference in clinico-radiological features between LG and HG IMAs, we observed significantly different overall survival (OS) and event-free survival (EFS). Multivariate analysis showed that the tumor grade was associated with better OS while EFS was strongly impacted by tumor grade and surgery, with higher rates of disease progression in cases in which only biopsy could be performed. For LG IMAs, EFS was only impacted by surgery and not by grade. The most common mutations found in IMAs involved TP53, H3F3A p.K27M and ATRX. As in the brain, grade I pilocytic IMAs frequently harbored KIAA1549-BRAF fusions but with different fusion types. Non-canonical IDH mutations were observed in only 2 grade II diffuse IMAs. No EGFR or TERT promoter alterations were found in IDH wild-type grade II diffuse IMAs. These latter tumors seem to have a good prognosis, and only 2 cases underwent anaplastic evolution. All of the HG IMAs presented at least one molecular alteration, with the most frequent one being the H3F3A p.K27M mutation. The H3F3A p.K27M mutation showed significant associations with OS and EFS after multivariate analysis. This study emphasizes that IMAs have distinct clinico-radiological, natural evolution and molecular landscapes from brain astrocytomas.

Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients.

Post-mortem studies can provide important information for understanding new diseases and small autopsy case series have already reported different findings in COVID-19 patients.

A Novel Approach for Quantifying Cancer Cells Showing Hybrid Epithelial/Mesenchymal States in Large Series of Tissue Samples: Towards a New Prognostic Marker

In cancer biology, epithelial-to-mesenchymal transition (EMT) is associated with tumorigenesis, stemness, invasion, metastasis, and resistance to therapy. Evidence of co-expression of epithelial and mesenchymal markers suggests that EMT should be a stepwise process with distinct intermediate states rather than a binary switch. In the present study, we propose a morphological approach that enables the detection and quantification of cancer cells with hybrid E/M states, i.e., which combine partially epithelial (E) and partially mesenchymal (M) states. This approach is based on a sequential immunohistochemistry technique performed on the same tissue section, the digitization of whole slides, and image processing. The aim is to extract quantitative indicators able to quantify the presence of hybrid E/M states in large series of human cancer samples and to analyze their relationship with cancer aggressiveness. As a proof of concept, we applied our methodology to a series of about a hundred urothelial carcinomas and demonstrated that the presence of cancer cells with hybrid E/M phenotypes at the time of diagnosis is strongly associated with a poor prognostic value, independently of standard clinicopathological features. Although validation on a larger case series and other cancer types is required, our data support the hybrid E/M score as a promising prognostic biomarker for carcinoma patients.

The daily practice reality of PD-L1 (CD274) evaluation in non-small cell lung cancer: A retrospective study.

Treatment with pembrolizumab, an anti-programmed cell death-1 (PDCD-1) monoclonal antibody for the treatment of non-small cell lung cancers (NSCLCs) requires prior immunohistochemical (IHC) analysis of the expression of the programmed death-ligand 1 (PD-L1) (also known as CD274 molecule) which is a heterogeneous and complex marker. The present study aimed to investigate how pathological and technical factors (such as tumor location and sampling type, respectively) may affect the PD-L1 evaluation in patients with NSCLC in the daily practice of pathology laboratories. The current study was retrospective, and included 454 patients with NSCLC, for whom PD-L1 expression analysis by IHC was prospectively performed between November 2016 and January 2018. The association between PD-L1 expression and the clinicopathological characteristics of patients was statistically investigated using either the χ2 and Fisher exact tests or the Mann-Whitney and Kruskal-Wallis tests, depending on whether PD-L1 expression was assessed in three large categories (<1, 1-49, ≥50%) or in more precise percentages. Furthermore, the same statistical methodology was used to analyze the heterogeneity of PD-L1 expression according to its sampling type (cytology, biopsy or surgical specimen) and its location (primary tumor, lymph node or distant metastasis). Intra- and inter-observer discrepancies were also studied using double-blind evaluation and concordance analyses based on the weighted κ coefficient. The results demonstrated a significant association between PD-L1 expression and sample location (P=0.005), histological type (P=0.026), total number of mutations (P=0.004) and KRAS proto-oncogene, GTPase mutations (P=0.024). In addition, sampling type did not influence PD-L1 expression. The inter- and intra-observer discrepancies were 15% and between 16 and 17.5%, respectively. The present study confirmed that evaluation of PD-L1 expression by IHC can be performed on all types of samples. In addition, the results from the current study highlighted the heterogeneity of PD-L1 expression among the different types of sample location. In complex cases, a second evaluation of PD-L1 expression by IHC would be performed due to intra- and inter-observer discrepancies.

The potential of tumour microenvironment markers to stratify the risk of recurrence in prostate cancer patients.

The tumour micro-environment (TME) plays a crucial role in the onset and progression of prostate cancer (PCa). Here we studied the potential of a selected panel of TME-markers to predict clinical recurrence (CLR) in PCa. Patient cohorts were matched for the presence or absence of CLR 5 years post-prostatectomy. Tissue micro-arrays (TMA) were composed with both prostate non-tumour (PNT) and PCa tissue and subsequently processed for immunohistochemistry (IHC). The IHC panel included markers for cancer activated fibroblasts (CAFs), blood vessels and steroid hormone receptors ((SHR): androgen receptor (AR), progesterone receptor (PR) and estrogen receptor (ER)). Stained slides were digitalised, selectively annotated and analysed for percentage of marker expression with standardized and validated image analysis algorithms. A univariable analysis identified several TME markers with significant impact on CR: expression of CD31 (vascular marker) in PNT stroma, expression of alpha smooth muscle actin (αSMA) in PCa stroma, and PR expression ratio between PCa stroma and PNT stroma. A multivariable model, which included CD31 expression (vascular marker) in PNT stroma and PR expression ratio between PCa stroma and PNT stroma, could significantly stratify patients for CLR, with the identification of a low risk and high-risk subgroup. If validated and confirmed in an independent prospective series, this subgroup might have clinical potential for PCa patient stratification.

2019

Understanding MPEG-I Coding Standardization in Immersive VR/AR Applications

After decennia of developing leading-edge 2D video compression technologies, the Moving Picture Expert Group (MPEG) is currently working on the new era of coding for immersive applications, referred to as MPEG-I, where “I” refers to the “Immersive” aspects. It ranges from 360° video with head-mounted displays to free navigation in 3D space with head-mounted and 3D light field displays. Two families of coding approaches, covering typical industrial workflows, are currently considered for standardization-MultiView + Depth (MVD) Video Coding and Point Cloud Coding-both supporting high-quality rendering at bitrates of up to a couple of hundreds of megabits per second. This paper provides a technical/historical overview of the acquisition, coding, and rendering technologies considered in the MPEG-I standardization activities.

Wood anatomy variability under contrasted environmental conditions of common deciduous and evergreen species from central African forests

Key message: Wood density profiles revealed significant differences in wood formation along a precipitation gradient in the Congo Basin. The response of trees to climate change varies depending on leaf phenology properties. Abstract: Tropical forests face increasing pressures due to climate change and yet, the response of trees to varying climate conditions remains poorly understood. In the present study, we aim to fill some gaps by comparing the leaf phenology and the pith-to-bark wood anatomical variability of 13 common tree species of the Democratic Republic of Congo among three sites presenting contrasted rainfall regimes. We measured pith-to-bark density profiles on which we applied wavelet analyses to extract three descriptors, which we further used as proxies to describe and compare wood anatomical variability. They describe the growth periodicity, regularity and the amplitude of variations of the anatomical patterns. Our results show that evergreen species tend to have significantly higher anatomical variability where rainfall seasonality is more pronounced. Deciduous species, in spite of shedding leaves for longer periods in drier sites, did not show significant differences in their anatomical variability. The analyses of density profiles and phenology records suggest that the seasonality of precipitation influences both leaf phenology and cambial activity. The high intra-site variability in phenology and anatomy suggests that site-related micro-climate conditions also influence cambial activity.

Strategies to Reduce the Expert Supervision Required for Deep Learning-Based Segmentation of Histopathological Images

The emergence of computational pathology comes with a demand to extract more and more information from each tissue sample. Such information extraction often requires the segmentation of numerous histological objects (e.g., cell nuclei, glands, etc.) in histological slide images, a task for which deep learning algorithms have demonstrated their effectiveness. However, these algorithms require many training examples to be efficient and robust. For this purpose, pathologists must manually segment hundreds or even thousands of objects in histological images, i.e., a long, tedious and potentially biased task. The present paper aims to review strategies that could help provide the very large number of annotated images needed to automate the segmentation of histological images using deep learning. This review identifies and describes four different approaches: the use of immunohistochemical markers as labels, realistic data augmentation, Generative Adversarial Networks (GAN), and transfer learning. In addition, we describe alternative learning strategies that can use imperfect annotations. Adding real data with high-quality annotations to the training set is a safe way to improve the performance of a well configured deep neural network. However, the present review provides new perspectives through the use of artificially generated data and/or imperfect annotations, in addition to transfer learning opportunities.

Volumetric-Based Analysis of In-Vivo and Ex-Vivo Quantitative MR Diffusion Parameters in Pancreatic Adenocarcinoma: Correlation with Pathologic Findings.

Homography based identification for automatic and robust calibration of projection integral imaging displays

Recent advances in the creation of microlens arrays as holographic optical elements allow the creation of projector-based see-through light field displays suitable for augmented reality. These systems require an accurate calibration of the projector with relation to the microlens array, as any small misalignment causes the 3D reconstruction to fail. The methods reported so far require precise placement of the calibration camera w.r.t. the lens array screen, which affects the display configuration. We propose a calibration approach which is more robust, and which allows free camera placement. Hence, it does not limit the capabilities of the system. Both a homography-based technique and structured light play a central role in realizing such a method. The method was tested on a projection-based integral imaging display system consisting of a consumer-grade projector and a digitally designed holographic optical element based micromirror array screen. The calibration method compensates for the lens distortion, intrinsics, and positioning of the projector with relation to the screen. The method uses a single camera and does not require the use of obtrusive markers as reference. We give an in-depth explanation of the different steps of the algorithm, and verify the calibration using both a simulated and a real-world setup.

基于最优路径的多视场全天自主星图识别

Based on optimal path features and multiple fields of view (FOVs), a star recognition algorithm is developed to improve the recognition rate of star sensors with low cost and small FOV under all-sky autonomous recognition pattern. First, observed star images in multiple FOVs are fused through identification between images. Second, randomly distributed ant colonies are set at the positions of all the stars in the neighborhood of the main star. Then an optimal traversal path combining all these stars is acquired by iteration. The geometrical features of the path are applied for matching with guide star catalogue. Compared with several existing methods, the proposed algorithm provides high recognition rate and robustness against position and magnitude noise.

Robust and Automatic Calibration of a Projection See-Through Integral Imaging Display using Homography Based Mirror Identification

2018

Wood density profiles and their corresponding tissue fractions in tropical angiosperm trees

Wood density profiles reveal a tree's life strategy and growth. Density profiles are, however, rarely defined in terms of tissue fractions for wood of tropical angiosperm trees. Here, we aim at linking these fractions to corresponding density profiles of tropical trees from the Congo Basin. Cores of 8 tree species were scanned with X-ray Computed Tomography to calculate density profiles. Then, cores were sanded and the outermost 3 cm were used to semi-automatically measure vessel lumen, parenchyma and fibre fractions using theWeka segmentation tool in ImageJ. Fibre wall and lumen widths were measured using a newly developed semi-automated method. An assessment of density variation in function of growth ring boundary detection is done. A mixed regression model estimated the relative contribution of each trait to the density, with a species effect on slope and intercept of the regression. Position-dependent correlations were made between the fractions and the corresponding wood density profile. On average, density profile variation mostly reflects variations in fibre lumen and wall fractions, but these are species- and position-dependent: on some positions, parenchyma and vessels have a more pronounced effect on density. The model linking density to traits explains 92% of the variation, with 65% of the density profile variation attributed to the three measured traits. The remaining 27% is explained by species as a random effect. There is a clear variation between trees and within trees that have implications for interpreting density profiles in angiosperm trees: the exact driving anatomical fraction behind every density value will depend on the position within the core. The underlying function of density will thus vary accordingly.

Multispectral Compressive Imaging Strategies using Fabry-Pérot Filtered Sensors

UCA1 overexpression is associated with less aggressive subtypes of bladder cancer.

Non‑coding RNAs (ncRNAs) have been shown to serve important roles in carcinogenesis via complex mechanisms, including transcriptional and post‑transcriptional regulation, and chromatin interactions. Urothelial carcinoma‑associated 1 (UCA1), a long ncRNA, was recently shown to have tumorigenic properties in urothelial bladder cancer (UBC), as demonstrated by enhanced proliferation, migration, invasion and therapy resistance of UBC cell lines in vitro. These in vitro findings suggested that UCA1 is associated with aggressive tumor behavior and could have prognostic implications in UBC. The aims of the present study were to therefore to investigate the statistical associations between UCA1 RNA expression and UBC pathological features, patient prognosis and p53 and Ki‑67 expression. Chromogenic in situ hybridization and immunohistochemistry were performed on UBC tissue microarrays to characterize UCA1 RNA, and p53 and Ki‑67 expression in 208 UBC cases, including 145 non‑muscle‑invasive and 63 muscle‑invasive cases. UCA1 was observed in the tumor cells of 166/208 (80%) UBC cases tested. No expression was noted in normal stromal and endothelium cells. Patients with UBC that overexpressed UCA1 (35%) had a significantly higher survival rate (P=0.006) compared with that in patients with UBC that did not overexpress UCA1. This prognostic factor was independent of tumor morphology, concomitant carcinoma in situ, tumor grade and tumor stage. In addition, the absence of UCA1 overexpression was significantly associated with a high Ki‑67 proliferative index (P=0.008) and a p53 'mutated' immunoprofile (strong nuclear expression or complete absence of staining; P=0.003). In conclusion, the present results identified UCA1 as potentially being a novel independent prognostic marker in UBC that was associated with a better patient prognosis and that could serve a pivotal role in bladder cancer carcinogenesis.

The Prognostic Value of the Combination of Low VEGFR-1 and High VEGFR-2 Expression in Endothelial Cells of Colorectal Cancer.

Research on tumor angiogenesis has mainly focused on the vascular endothelial growth factor (VEGF) family and on methods to block its actions. However, reports on VEGF receptor (VEGFR) expression in tumor-associated endothelial cells (ECs) are limited. Thus, we evaluated VEGF, VEGFR-1 and VEGFR-2 expression in ECs of colorectal cancer (CRC) using immunohistochemistry. VEGF, VEGFR-1 and -2 expression in ECs was quantitatively evaluated by digital image analysis in a retrospective series of 204 tumor tissue samples and related to clinical variables. The data show that the VEGF, VEGFR-1 and VEGFR-2 expression in ECs is heterogeneous. Multivariate analysis including a set of clinicopathological variables reveals that high EC VEGFR-1 expression is an independent prognostic factor for overall survival (OS). The combination of low VEGFR-1 and high VEGFR-2 expression in ECs outperforms models integrating VEGFR-1 and VEGFR-2 as separate markers. Indeed, this VEGFR-1_VEGFR-2 combination is an independent negative prognostic factor for OS (p = 0.012) and metastasis-free survival (p = 0.007). In conclusion, this work illustrates the importance of studying the distribution of VEGF members in ECs of CRC. Interestingly, our preliminary data suggest that high VEGFR-1 and low VEGFR-2 expression in ECs appear to be involved in the progression of CRC, suggesting that targeting EC VEGFR-1 could offer novel opportunities for CRC treatment. However, a prospective validation study is needed.

Assessment of cardiac-driven liver movements with filtered harmonic phase image representation, optical flow quantification, and motion amplification.

To characterize cardiac-driven liver movements using a harmonic phase image representation (HARP) with an optical flow quantification and motion amplification method. The method was applied to define the cardiac trigger delay providing minimal signal losses in liver DWI images.

Segmentation of glandular epithelium in colorectal tumours to automatically compartmentalise IHC biomarker quantification: a deep learning approach

In this paper, we propose a method for automatically annotating slide images from colorectal tissue samples. Our objective is to segment glandular epithelium in histological images from tissue slides submitted to different staining techniques, including usual haematoxylin-eosin (H&E) as well as immunohistochemistry (IHC). The proposed method makes use of Deep Learning and is based on a new convolutional network architecture. Our method achieves better performances than the state of the art on the H&E images of the GlaS challenge contest, whereas it uses only the haematoxylin colour channel extracted by colour deconvolution from the RGB images in order to extend its applicability to IHC. The network only needs to be fine-tuned on a small number of additional examples to be accurate on a new IHC dataset. Our approach also includes a new method of data augmentation to achieve good generalisation when working with different experimental conditions and different IHC markers. We show that our methodology enables to automate the compartmentalisation of the IHC biomarker analysis, results concurring highly with manual annotations.

Implementing and Evaluation of SECOND-MVD Method to Multiview Video Transmission System REI

Comparing the expression profiles of steroid hormone receptors and stromal cell markers in prostate cancer at different Gleason scores.

The recent developments in anti-angiogenic and immunomodulatory drugs show that the tumour micro-environment (TME) becomes increasingly important in cancer research. Here we investigated the correlation between the Gleason score (GS) and the TME by comparing tissue expression profiles of steroid hormone receptors, cancer activated fibroblast (CAF) markers and vessel densities between different GS groups. Therefore, matched patient cohorts were composed for different GS (6-7-8). Tissue micro-arrays with 6 samples/patient were processed for immunohistochemistry. Stained slides were digitised, stroma and epithelium were selectively annotated, and all selected areas were quantitatively analysed for marker expression. The most striking findings were decreased stromal expression levels of several steroid hormone receptors, increased CAF-phenotypes and increased vessel densities in high GS prostate cancer compared to low GS prostate cancer and paired prostate non-tumour tissue. The present data reveal a complex correlation between prostate cancer differentiation and TME components and suggest that different GS can be associated with different possible actionable targets in the TME. The use of standardised digital image analysis tools generated robust and reproducible quantitative data, which is novel and more informative compared to the classic semi-quantitative and observer-dependent visual scoring of immunohistochemistry.

Scalable light field disparity estimation with occlusion detection

An occlusion-aware framework is proposed to robustly estimate the disparities of light field images. It is mainly realized by leveraging multiple edge cues to occlusion detection and then integrate it with local costs into an energy function. To check the performance, the quantitative and/or qualitative evaluations are performed on both synthetic and natural light field datasets. It demonstrates that the proposed framework is robust to the density and disparity range of the light field, advancing the state-of-the-art light field disparity estimation frameworks on aspect of accuracies.

Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial.

Recent retrospective data suggest that neoadjuvant androgen deprivation therapy can improve the prognosis of high-risk prostate cancer (PCa) patients. Novel androgen receptor pathway inhibitors are nowadays available for treatment of metastatic PCa and these compounds are promising for early stage disease. Apalutamide is a pure androgen antagonist with a very high affinity with the androgen receptor. The combination of apalutamide with degarelix, an LHRH antagonist, could increase the efficacy compared to degarelix alone.

View synthesis from sparse camera array for pop-out rendering on hologram displays

A hologram of a scene can be digitally created by using a large set of images of that scene. Since capturing such a large amount is infeasible to accomplish, one may use view synthesis approaches to reduce the number of cameras and generate the missing views. We propose a view interpolation algorithm that creates views inside the scene, based on a sparse set of camera images. This allows the objects to pop out of the holographic display. We show that our approach outperforms existing view synthesis approaches and show the applicability on holographic stereograms.

A prospective clinical study of the implications of IL-8 in the diagnosis, aggressiveness and prognosis of prostate cancer.

We evaluated the relationship between IL-8 and prostate cancer (PCa) with emphasis on diagnosis, aggressiveness and prognosis.

Robust disparity estimation on sparse sampled light field images

The paper presents a robust approach to compute disparities on sparse sampled light field images based on Epipolar-Plane Image (EPI) analysis. The Relative Gradient is leveraged as a kernel density function to cope with radiometric changes in non-Lambertian scenes. To account for the sparse light field, a window-based filtering is introduced to handle the noisy and homogenous regions, decomposing the scene images into edge and non-edge regions. Separate score-volume filtering over these regions avoids boundary fattening effects common to stereo matching. Finally, a consistency measure detects unreliable pixels with false disparities, to which a disparity refinement is applied. Evaluation analysis is performed on the Disney light field dataset and the proposed method shows superior results over state-of-the-art.

Robust Multiview Synthesis For Wide-Baseline Camera Arrays

Regulatory T cells constrain the TCR repertoire of antigen-stimulated conventional CD4 T cells.

To analyze the potential role of Tregs in controlling the TCR repertoire breadth to a non-self-antigen, a TCRβ transgenic mouse model (EF4.1) expressing a limited, yet polyclonal naïve T-cell repertoire was used. The response of EF4.1 mice to an I-Ab-associated epitope of the F-MuLV envelope protein is dominated by clones expressing a Vα2 gene segment, thus allowing a comprehensive analysis of the TCRα repertoire in a relatively large cohort of mice. Control and Treg-depleted EF4.1 mice were immunized, and the extent of the Vα2-bearing, antigen-specific TCR repertoire was characterized by high-throughput sequencing and spectratyping analysis. In addition to increased clonal expansion and acquisition of effector functions, Treg depletion led to the expression of a more diverse TCR repertoire comprising several private clonotypes rarely observed in control mice or in the pre-immune repertoire. Injection of anti-CD86 antibodies in vivo led to a strong reduction in TCR diversity, suggesting that Tregs may influence TCR repertoire diversity by modulating costimulatory molecule availability. Collectively, these studies illustrate an additional mechanism whereby Tregs control the immune response to non-self-antigens.

Star Recognition Based on Path Optimization in Star Sensor with Multiple Fields of View

Star sensors make use of astronomical information in stars to determine attitude for spacecrafts by star image recognition. For low-cost star sensors with small field of view, fusion of observed images from multiple fields of view is performed and a novel recognition algorithm based on path optimization by randomly distributed ant colony is proposed. According to pheromone intensity, the ant colony can autonomously figure out a close optimal path without starting or ending point, rather than certifying a starting point first. Feature patterns extracted from the optimal path in guiding template and observed image after fusion are compared to perform star recognition. By the proposed algorithm, starting point for path optimization has no influence on the extracted feature pattern. Thus the star recognition rate is improved due to the higher stability of the extracted pattern. Simulations indicate that the algorithm improves recognition accuracy and robustness against noise for sensors with multiple fields of view.

Star image recognition based on mutual star distribution

A novel method is designed to divide the star image into polygons, in order to solve the problem of setting the grid size in the grid algorithm. Via the method, each star is located in a corresponding polygon. The geometric features of these polygons are extracted and applied for matching the feature patterns of the guidance star database and the observed star image. Simulations indicate that the novel method removes the possible phenomenon in the grid algorithm where more than one star are located in the same grid. The grid algorithm's disadvantage of recognition failure resulting from identifying incorrect close neighbor star for reference star can be overcome and the accuracy of star image recognition is greatly improved.

2017

Reliability of tumor-infiltrating lymphocyte and tertiary lymphoid structure assessment in human breast cancer.

The presence of tumor-infiltrating lymphocytes (TIL), reflecting host immune activity, is frequently correlated with better clinical outcomes, particularly in HER2-positive and triple-negative breast cancer. Recent findings suggest that organization of immune infiltrates in tertiary lymphoid structures also has a beneficial effect on survival. This study investigated inter- and intra-observer variation in TIL assessment using conventional hematoxylin-eosin versus immunohistochemical staining to identify immune cells. Global, intratumoral, and stromal TIL, as well as tertiary lymphoid structures were scored independently by experienced pathologists on full-face tumor sections (n=124). The fidelity of scoring infiltrates in core biopsies compared to surgical specimens, and pathological assessment compared to quantitative digital analysis was also evaluated. The inter-observer concordance correlation coefficient was 0.80 for global, 0.72 for intratumoral, and 0.71 for stromal TIL, while the intra-observer concordance correlation coefficient was 0.90 for global, 0.77 for intratumoral, and 0.89 for stromal TIL using immunohistochemical stains. Correlations were lower with hematoxylin-eosin stains, particularly for intratumoral TIL, while global scores had the highest concordance correlation coefficients. Our study concluded that tertiary lymphoid structures are accurately and consistently scored using immunohistochemical but not hematoxylin-eosin stains. A strong association was observed between TIL in core biopsies and surgical samples (R(2)=0.74) but this did not extend to tertiary lymphoid structures (R(2)=0.26). TIL scored by pathologists and digital analysis were correlated but our analysis reveals a constant bias between these methods. These data challenge current criteria for TIL and tertiary lymphoid structure assessment in breast cancer and recommend that how pathologists evaluate immune infiltrates be reexamined for future studies.Modern Pathology advance online publication, 16 June 2017; doi:10.1038/modpathol.2017.43.

Galectin-1 is a diagnostic marker involved in thyroid cancer progression

Fine-needle aspiration (FNA) is the most commonly used pre-operative technique for diagnosis of malignant thyroid tumor. However, many benign lesions, with indeterminate diagnosis following FNA, are referred to surgery. Based on multifunctionality of the endogenous galectin-1, we aimed to assess its status for early diagnosis of thyroid cancer. Immunohistochemistry for galectin-1 and -3 was performed on a clinical series of 69 cases of thyroid lesions. Galectin-1 expression was further examined in two additional tissue microarrays (TMA) composed of 66 follicular adenomas and 66 papillary carcinomas in comparison to galectin-3 and cytokeratin-19 (CK19). In addition, a knockdown of galectin-1 in papillary (TPC-1) and anaplastic (8505C) thyroid cancer cell lines was achieved by lentiviral transduction for in vitro experiments. A murine orthotopic thyroid cancer model was used to investigate tumor growth and metastatic ability. Immunohistochemical analyses of galectin-1 and -3 in the series of 69 cases of thyroid lesions revealed that galectin-1 was completely absent in the epithelial compartment of all benign thyroid lesions. Levels of both galectins significantly increased in the cytoplasmic compartment of malignant thyroid cells. Galectin-1 expression in the TMA yielded an excellent specificity (97%), while galectin-3 and CK19 presented a higher sensitivity (>97%) in discriminating benign from malignant thyroid lesions. In vitro experiments revealed that migration was negatively affected in TPC-1 galectin-1 knockdown (KD) cells, and that proliferation and invasion capacity of 8505C cells decreased after galectin-1 KD. Moreover, an orthotopic mouse model displayed a lower rate of tumor development with galectin-1 KD thyroid anaplastic cancer cells than in the control. Our findings support the introduction of galectin-1 as a reliable diagnostic marker for thyroid carcinomas. Its involvement in cell proliferation, migration, invasion and tumor growth also intimate functional involvement of galectin-1 in the progression of thyroid carcinoma, suggesting its potential as a therapeutic target.

Estimation of Dense Displacement by Scale Invariant Polynomial Expansion of Heterogeneous Multi-View Images

Star pattern recognition based on features invariant under rotation

A star pattern recognition algorithm is proposed on the basis of features invariant under rotation. Guidance star identification via the algorithm is performed on star images captured by star sensor and simulated images. The results indicate that the proposed method presents better robustness against position and magnitude noise than conventional ones and eliminates rotation procedure and avoids the influence caused by grid size choice. The database feature storage for each pattern consists of simply four floating point numbers.

Free-viewpoint image synthesis using superpixel segmentation

A free-viewpoint image can be synthesized using color and depth maps of reference viewpoints, via depth-image-based rendering (DIBR). In this process, three-dimensional (3D) warping is generally used. A 3D warped image consists of disocclusion holes with missing pixels that correspond to occluded regions in the reference images, and non-disocclusion holes due to limited sampling density of the reference images. The non-disocclusion holes are those among scattered pixels of a same region or object. These holes are larger when the reference viewpoints and the free viewpoint images have a larger physical distance. Filling these holes has a crucial impact on the quality of free-viewpoint image. In this paper, we focus on free-viewpoint image synthesis that is precisely capable of filling the non-disocclusion holes caused by limited sampling density, using superpixel segmentation. In this approach, we proposed two criteria for segmenting depth and color data of each reference viewpoint. By these criteria, we can detect which neighboring pixels should be connected or kept isolated in each references image, before being warped. Polygons enclosed by the connected pixels, i.e. superpixel, are inpainted by k-means interpolation. Our superpixel approach has a high accuracy since we use both color and depth data to detect superpixels at the location of the reference viewpoint. Therefore, once a reference image that consists of superpixels is 3D warped to a virtual viewpoint, the non-disocclusion holes are significantly reduced. Experimental results verify the advantage of our approach and demonstrate high quality of synthesized image when the virtual viewpoint is physically far from the reference viewpoints.

ADAM-17/FHL2 Colocalisation Suggests Interaction and Role of These Proteins in Colorectal Cancer

FHL2 is a multifunctional scaffolding protein; its expression is associated with poor prognosis in colorectal cancer. ADAM-17 is a metalloprotease implicated in ectodomain shedding. FHL2 regulates ADAM-17 plasma membrane localisation, and FHL2 deficiency leads to decreased activity of ADAM-17 in mouse macrophages. Presence and relationship of the ADAM-17/FHL2 complex with colorectal cancer progression is unknown. We studied FHL2 and ADAM-17 expression in several colon cancer cell lines by immunocytochemistry and western blot. To highlight the interaction between both molecules, we used the Duolink® kit for proximity ligation assay on SW480 cells. We also performed proximity ligation assay on biopsies and surgical specimens of colorectal adenocarcinoma and on matched normal mucosa. Furthermore, biopsies of colorectal adenoma with matched normal mucosa were selected. For quantification, pictures of the malignant, adenomatous and normal tissues were taken. Proximity ligation assay signals were quantified. Mean numbers of proximity ligation assay signals and of proximity ligation assay signals/nucleus were calculated. All cell lines showed FHL2 immunoreactivity; strongest positivity was observed in SW480 cells. ADAM-17 was expressed in all cell lines. Proximity ligation assay signals were present in SW480 cells. Quantitative analysis revealed that the interaction between FHL2 and ADAM-17 is more frequent in malignant than in normal tissue (p = 0.005). The mean number of ADAM-17/FHL2 proximity ligation assay signals was higher in colorectal adenocarcinoma than in adenoma with low-grade dysplasia (p = 0.0004). FHL2 interacts with ADAM-17 in normal, dysplastic and malignant colon epithelial cells. Colocalisation of these proteins is more frequent in malignant than in normal and dysplastic cells, suggesting a role for ADAM-17/FHL2 complex in the development of colorectal cancer.

Image processing in digital pathology: an opportunity to solve inter-batch variability of immunohistochemical staining

Immunohistochemistry (IHC) is a widely used technique in pathology to evidence protein expression in tissue samples. However, this staining technique is known for presenting inter-batch variations. Whole slide imaging in digital pathology offers a possibility to overcome this problem by means of image normalisation techniques. In the present paper we propose a methodology to objectively evaluate the need of image normalisation and to identify the best way to perform it. This methodology uses tissue microarray (TMA) materials and statistical analyses to evidence the possible variations occurring at colour and intensity levels as well as to evaluate the efficiency of image normalisation methods in correcting them. We applied our methodology to test different methods of image normalisation based on blind colour deconvolution that we adapted for IHC staining. These tests were carried out for different IHC experiments on different tissue types and targeting different proteins with different subcellular localisations. Our methodology enabled us to establish and to validate inter-batch normalization transforms which correct the non-relevant IHC staining variations. The normalised image series were then processed to extract coherent quantitative features characterising the IHC staining patterns.

3D augmented reality mirror visual feedback therapy applied to the treatment of persistent, unilateral upper extremity neuropathic pain: a preliminary study.

Objective: We assessed whether or not pain relief could be achieved with a new system that combines 3D augmented reality system (3DARS) and the principles of mirror visual feedback. Methods: Twenty-two patients between 18 and 75 years of age who suffered of chronic neuropathic pain. Each patient performed five 3DARS sessions treatment of 20 mins spread over a period of one week. The following pain parameters were assessed: (1) visual analogic scale after each treatment session (2) McGill pain scale and DN4 questionnaire were completed before the first session and 24 h after the last session. Results: The mean improvement of VAS per session was 29% (p < 0.001). There was an immediate session effect demonstrating a systematic improvement in pain between the beginning and the end of each session. We noted that this pain reduction was partially preserved until the next session. If we compare the pain level at baseline and 24 h after the last session, there was a significant decrease (p < 0.001) of pain of 37%. There was a significant decrease (p < 0.001) on the McGill Pain Questionnaire and DN4 questionnaire (p < 0.01). Conclusion: Our results indicate that 3DARS induced a significant pain decrease for patients who presented chronic neuropathic pain in a unilateral upper extremity. While further research is necessary before definitive conclusions can be drawn, clinicians could implement the approach as a preparatory adjunct for providing temporary pain relief aimed at enhancing chronic pain patients' tolerance of manual therapy and exercise intervention. Level of Evidence: 4.

Radiofrequence des cornets inferieurs versus turbinectomie partielle : Une evaluation des symptomes post-operatoires

Introduction: The aim of this study is to compare the degree of patient's satisfaction after partial turbinectomy versus radiofrequency turbinate reduction in a context of nasal obstruction due to inferior turbinate hypertrophy with or without nasal septum deviation. Material and methods: A retrospective cohort study was conducted at the department of Otolaryngology and Head and Neck surgery of the Saint-Pierre Hospital, from January 1, 2007 to December 31, 2010. A total of 177 patients composed 2 groups: The patients of the first group were treated by partial turbinectomy (N= 120), and the patients of the second group underwent an inferior turbinate radiofrequency (N= 57). A phone questionnaire was used to assess patients' satisfaction after at least 6 months after, the treatment. Results: Patients of the both groups have a high score of satisfaction. No statistically significant difference was found between both groups regarding the improvement of symptoms and the level of global satisfaction. Conclusions: Radiofrequency seems to be an efficient alternative approach in the treatment of nasal congestion due to inferior turbinate hypertrophy. Long-term studies with larger samples and control group are necessary to corroborate our results.

2016

Efficient MRF-based disocclusion inpainting in multiview video

View synthesis using depth image-based rendering generates virtual viewpoints of a 3D scene based on texture and depth information from a set of available cameras. One of the core components in view synthesis is image inpainting which performs the reconstruction of areas that were occluded in the available cameras but are visible from the virtual viewpoint. Inpainting methods based on Markov random fields (MRFs) have been shown to be very effective in inpainting large areas in images. In this paper, we propose a novel MRF-based in-painting method for multiview video. The proposed method steers the MRF optimization towards completion from background to foreground and exploits the available depth information in order to avoid bleeding artifacts. The proposed approach allows for efficiently filling-in large disocclusion areas and greatly accelerates execution compared to traditional MRF-based inpainting techniques. The experimental results show that view synthesis based on the proposed inpainting method systematically improves performance over the state-of-the-art in multiview view synthesis. Average PSNR gains up to 1.88 dB compared to the MPEG View Synthesis Reference software were observed.

Multi-view wide baseline depth estimation robust to sparse input sampling

In this paper, we propose a depth map estimation algorithm, based on Epipolar Plane Image (EPI) line extraction, that is able to correctly handle partially occluded objects in wide baseline camera setups. Furthermore, we introduce a descriptor matching technique to reduce the negative influence of inaccurate color correction and similarly textured objects on the depth maps. A visual comparison between an existing EPI-line extraction algorithm and our method is provided, showing that our method provides more accurate and consistent depth maps in most cases.

New visual coding exploration in MPEG: Super-multiview and free navigation in free viewpoint TV

ISO/IEC MPEG and ITU-T VCEG have recently jointly issued a new multiview video compression standard, called 3D-HEVC, which reaches unpreceded compression performances for linear, dense camera arrangements. In view of supporting future high-quality, auto-stereoscopic 3D displays and Free Navigation virtual/augmented reality applications with sparse, arbitrarily arranged camera setups, innovative depth estimation and virtual view synthesis techniques with global optimizations over all camera views should be developed. Preliminary studies in response to the MPEG-FTV (Free viewpoint TV) Call for Evidence suggest these targets are within reach, with at least 6% bitrate gains over 3D-HEVC technology.

Classical risk factors, but not HPV status, predict survival after chemoradiotherapy in advanced head and neck cancer patients

Purpose: Despite the advent of concomitant chemoradiotherapy (CCRT), the prognosis of advanced head and neck squamous cell carcinoma (HNSCC) patients remains particularly poor. Classically, HNSCC, especially oropharyngeal carcinomas, associated with human papillomavirus (HPV) exhibits better treatment outcomes than HNSCCs in non-infected patients, eliciting a call for the de-escalation of current therapies. To improve the management of HNSCC patients, we aimed to determine the impact of active HPV infection on patient response, recurrence and survival after CCRT in a population of heavy tobacco and alcohol consumers. Methods: Paraffin-embedded samples from 218 advanced HNSCC patients, mostly smokers and/or drinkers treated by CCRT, were tested for the presence of HPV DNA by surrogate type-specific E6/E7 qPCR and p16 immunohistochemistry. Associations between the response to CCRT and patient outcomes according to HPV status and clinical data were evaluated by Kaplan-Meier analysis and both univariate and multivariate Cox regression. Results: Type-specific E6/E7 PCR demonstrated HPV positivity in 20 % of HNSCC. Regarding HPV status, we did not find any significant relation with response to therapy in terms of progression-free survival or overall survival. However, we observed a significantly worse prognosis for consumers of alcohol and tobacco compared to nondrinkers (p = 0.003) and non-smokers (p = 0.03). Survival analyses also revealed that the outcome is compromised in stage IV patients (p = 0.007) and, in particular, for oral cavity, hypopharynx and oropharynx carcinoma patients (p = 0.001). Conclusion: The risk of death from HNSCC significantly increases when patients are exposed to tobacco and alcohol during their therapy, regardless of HPV status.

2015

Generalized inpainting method for hyperspectral image acquisition

A recently designed hyperspectral imaging device enables multiplexed acquisition of an entire data volume in a single snapshot thanks to monolithically-integrated spectral filters. Such an agile imaging technique comes at the cost of a reduced spatial resolution and the need for a demosaicing procedure on its interleaved data. In this work, we address both issues and propose an approach inspired by recent developments in compressed sensing and analysis sparse models. We formulate our superresolution and demosaicing task as a 3-D generalized inpainting problem. Interestingly, the target spatial resolution can be adjusted for mitigating the compression level of our sensing. The reconstruction procedure uses a fast greedy method called Pseudo-inverse IHT. We also show on simulations that a random arrangement of the spectral filters on the sensor is preferable to regular mosaic layout as it improves the quality of the reconstruction. The efficiency of our technique is demonstrated through numerical experiments on both synthetic and real data as acquired by the snapshot imager.

Color retargeting: Interactive time-varying color image composition from time-lapse sequences

In this paper, we present an interactive static image composition approach, namely color retargeting, to flexibly represent time-varying color editing effect based on time-lapse video sequences. Instead of performing precise image matting or blending techniques, our approach treats the color composition as a pixel-level resampling problem. In order to both satisfy the user's editing requirements and avoid visual artifacts, we construct a globally optimized interpolation field. This field defines from which input video frames the output pixels should be resampled. Our proposed resampling solution ensures that (i) the global color transition in the output image is as smooth as possible, (ii) the desired colors/objects specified by the user from different video frames are well preserved, and (iii) additional local color transition directions in the image space assigned by the user are also satisfied. Various examples have been shown to demonstrate that our efficient solution enables the user to easily create time-varying color image composition results.

Impact of neoadjuvant therapy on cancer-associated fibroblasts in rectal cancer.

Cancer-associated fibroblasts (CAFs) are increasingly recognised as promoters of tumour progression. It is poorly investigated whether cancer management protocols, such as neoadjuvant radio(chemo)therapy, have an impact on CAFs and, by consequence, on tumour progression. This prompted us to study the impact of neoadjuvant radio(chemo)therapy on the α-SMA/epithelial area ratio in rectal cancer, and the impact of this ratio on recurrence-free survival.

IGF-IR: a new prognostic biomarker for human glioblastoma.

Glioblastomas (GBMs) are the most common malignant primary brain tumours in adults and are refractory to conventional therapy, including surgical resection, radiotherapy and chemotherapy. The insulin-like growth factor (IGF) system is a complex network that includes ligands (IGFI and IGFII), receptors (IGF-IR and IGF-IIR) and high-affinity binding proteins (IGFBP-1 to IGFBP-6). Many studies have reported a role for the IGF system in the regulation of tumour cell biology. However, the role of this system remains unclear in GBMs.

Light Field Reconstruction Using Weighted L1 Norm Minimization from Compressed Samples Captured by a Coded Aperture Camera

Microsatellite instable vs stable colon carcinomas: analysis of tumour heterogeneity, inflammation and angiogenesis.

Microsatellite instability (MSI) accounts for 15% of all colorectal tumours. Several specific clinicopathologicals (e.g., preference for the proximal colon over the distal colon, improved prognosis and altered response to chemotherapeutics) are described for this subset of tumours. This study aimed to analyse morphological, inflammatory and angiogenic features of MSI vs microsatellite stable (MSS) tumours.

Associating Approximate Paths and Temporal Sequences of Noisy Detections: Application to the Recovery of Spatio-temporal Cancer Cell Trajectories

In this paper we address the problem of recovering spatio-temporal trajectories of cancer cells in phase contrast video-microscopy where the user provides the paths on which the cells are moving. The paths are purely spatial, without temporal information. To recover the temporal information associated to a given path we propose an approach based on automatic cell detection and on a graph-based shortest path search. The nodes in the graph consist of the projections of the cell detections onto the geometrical cell path. The edges relate nodes which correspond to different frames of the sequence and potentially to the same cell and trajectory. In this directed graph we search for the shortest path and use it to define a temporal parametrization of the corresponding geometrical cell path. An evaluation based on 286 paths of 7 phase contrast microscopy videos shows that our algorithm allows to recover 92% of trajectory points with respect to the associated ground truth. We compare our method with a state-of-the-art algorithm for semi-automated cell tracking in phase contrast microscopy which requires interactively placed starting points for the cells to track. The comparison shows that supporting geometrical paths in combination with our algorithm allow us to obtain more reliable cell trajectories.

Identification of OLIG2 as the most specific glioblastoma stem cell marker starting from comparative analysis of data from similar DNA chip microarray platforms.

Despite advances in surgical and adjuvant treatments, overall survival of glioblastoma (GBM) patients remains poor. The cancer stem cell concept suggests that a rare stem cell population, called glioma stem cells (GSCs), has high ability to self-renewal leading to recurrence in GBM. The identification of specific markers of GSCs would provide a powerful tool to detect and to characterise them in order to develop targeted therapies. We carried out a comparative analysis based on the identification of inter-study concordances to identify the genes that exhibit at best differential levels of expression between GSC-enriched cell cultures and differentiated tumour cell cultures from independent studies using DNA chip microarray technologies. We finally studied the protein expression of the marker we considered the most specific by immunohistochemistry and semi-quantitative analysis on a retrospective series of 18 GBMs. Of the selected studies, 32 genes were retained. Among them, eight genes were identified to be overexpressed in GSC-enriched cultures compared to differentiated tumour cell cultures. Finally, among the eight genes, oligodendrocyte lineage transcription factor 2 (OLIG2) was characterised by the most different expression level in the "GSC model" compared to the "differentiated tumour cells model". Our approach suggests that OLIG2 is the most specific GSC marker; additional investigations with careful considerations about methodology and strategies of validation are, however, mandatory.

An open data ecosystem for cell migration research.

Cell migration research has recently become both a high content and a high throughput field thanks to technological, computational, and methodological advances. Simultaneously, however, urgent bioinformatics needs regarding data management, standardization, and dissemination have emerged. To address these concerns, we propose to establish an open data ecosystem for cell migration research.

Registration of whole immunohistochemical slide images: an efficient way to characterize biomarker colocalization.

Extracting accurate information from complex biological processes involved in diseases, such as cancers, requires the simultaneous targeting of multiple proteins and locating their respective expression in tissue samples. This information can be collected by imaging and registering adjacent sections from the same tissue sample and stained by immunohistochemistry (IHC). Registration accuracy should be on the scale of a few cells to enable protein colocalization to be assessed.

Morphometric and quantitative immunohistochemical analysis of disease-related changes in the upper (suburothelial) lamina propria of the human bladder dome.

The upper (suburothelial) lamina propria (ULP) is a distinct region in the human bladder with dense populations of interstitial cells (IC), fine vascular networks and variable development of muscularis mucosae (MM). It is more and more obvious that the ULP plays an important role in bladder physiology and bladder disease, and in the present study we have quantified changes in the cellular key players of the ULP in bladders from patients with carcinoma in situ (CIS), multiple sclerosis (MS) and bladder pain syndrome (BPS). Tissue samples for the different patient groups were obtained from radical cystectomy-specimens. Standardized immunohistochemistry with a panel of specific cell markers was used to characterise the ULP cellular structures, followed by digitalised morphometry and quantitative staining analysis. Alterations in the ULP area were most pronounced in MS bladders, but also present in BPS and CIS bladders. We observed an increased thickness and increased variability in thickness of the ULP IC area in MS and BPS bladders; a significantly increased development of MM in MS bladders; a changed organization of vascular plexuses in the lamina propria in most pathologic bladders and a changed phenotype of ULP IC: a significantly decreased expression of progesterone receptor in MS bladders and a trend towards decreased expression of alpha-smooth muscle actin in BPS bladders. We show here for the first time the presence of disease-specific changes in organisation and/or phenotype of the different key players of the ULP area in human bladder. The present findings further support the hypothesis that the ULP area is involved and altered in different bladder diseases.

Diagnostic value of the UCA1 test for bladder cancer detection: a clinical study.

To evaluate the efficiency of the UCA1 test as a diagnostic tool for the detection of bladder cancer.

An approach for combining multiple descriptors for image classification

Recently, efficient image descriptors have shown promise for image classification tasks. Moreover, methods based on the combination of multiple image features provide better performance compared to methods based on a single feature. This work presents a simple and efficient approach for combining multiple image descriptors. We first employ a Naive-Bayes Nearest-Neighbor scheme to evaluate four widely used descriptors. For all features, a Image-to-Classa distances are directly computed without descriptor quantization. Since distances measured by different metrics can be of different nature and they may not be on the same numerical scale, a normalization step is essential to transform these distances into a common domain prior to combining them. Our experiments conducted on a challenging database indicate that z-score normalization followed by a simple sum of distances fusion technique can significantly improve the performance compared to applications in which individual features are used. It was also observed that our experimental results on the Caltech 101 dataset outperform other previous results.

Real-time edge-sensitive local stereo matching with iterative disparity refinement

First, we present a novel cost aggregation method for stereo matching that uses two edge-sensitive shape-adaptive support windows per pixel region; one following the horizontal edges in the image, the other the vertical edges. Their combination defines the final aggregation window shape that closely follows all object edges and thereby achieves increased hypothesis confidence. Second, we present a novel iterative disparity refinement process and apply it to the initially estimated disparity map. The process consists of four rigorously defined and lightweight modules that can be iterated multiple times: a disparity cross check, bitwise fast voting, invalid disparity handling, and median filtering. We demonstrate that our iterative refinement has a large effect on the overall quality, resulting in smooth disparity maps with sharp object edges, especially around occluded areas. It can be applied to any stereo matching algorithm and tends to converge to a final solution. Finally, we perform a quantitative evaluation on various Middlebury datasets, showing an increase in quality of over several dB PSNR compared with their ground truth. Our whole disparity estimation algorithm supports efficient GPU implementation to facilitate scalability and real-time performance.

Outdoor Road-to-Vehicle Visible Light Communication Using On-Vehicle High-Speed Camera

2014

Galectins and neovascularization in central nervous system tumors.

Despite advances in diagnosis and treatment, the overall outcomes for patients with brain tumors remain unpredictable. New prognostic markers are still needed to identify high-risk patients for whom the standard treatment has poor outcomes and would thus be well suited for more aggressive therapies. Neovascularization has long been implicated as a salient feature of glioma progression. In fact, high-grade gliomas are among the most vascular of all solid tumors, and vascular proliferation is a pathological hallmark of glioblastomas. Galectins are known to play important roles in cancer biology, including cancer cell migration, tumor immune escape or tumor angiogenesis. Moreover, galectins were reported to be involved in glioma progression. Given the key role of angiogenesis in brain tumors, the expression of galectins in tumor-associated endothelial cells (EC) and the implication of galectins in angiogenesis, the present review will focus on the expression of galectins in ECs of normal brain and brain tumors.

Involvement of macrophage migration inhibitory factor and its receptor (CD74) in human breast cancer.

Macrophage migration inhibitory factor (MIF) and its receptor CD74 appear to be involved in tumorigenesis. We evaluated, by immunohistochemical staining, the tissue expression and distribution of MIF and CD74 in serial sections of human invasive breast cancer tumor specimens. The serum MIF level was also determined in breast cancer patients. We showed a significant increase in serum MIF average levels in breast cancer patients compared to healthy individuals. MIF tissue expression, quantified by a modified Allred score, was strongly increased in carcinoma compared to tumor-free specimens, in the cancer cells and in the peritumoral stroma, with fibroblasts the most intensely stained. We did not find any significant correlation with histoprognostic factors, except for a significant inverse correlation between tumor size and MIF stromal positivity. CD74 staining was heterogeneous and significantly decreased in cancer cells but increased in the surrounding stroma, namely in lymphocytes, macrophages and vessel endothelium. There was no significant variation according to classical histoprognostic factors, except that CD74 stromal expression was significantly correlated with triple-negative receptor (TRN) status and the absence of estrogen receptors. In conclusion, our data support the concept of a functional role of MIF in human breast cancer. In addition to auto- and paracrine effects on cancer cells, MIF could contribute to shape the tumor microenvironment leading to immunomodulation and angiogenesis. Interfering with MIF effects in breast tumors in a therapeutic perspective remains an attractive but complex challenge. Level of co-expression of MIF and CD74 could be a surrogate marker for efficacy of anti-angiogenic drugs, particularly in TRN breast cancer tumor.

Galectin fingerprinting in naso-sinusal diseases.

Galectins, a family of endogenous lectins, are multifunctional effectors that act at various sites and can be used in immunohistochemical localization studies of diseased states. Since they form a potentially cooperative and antagonistic network, we tested the hypothesis that histopathological fingerprinting of galectins could refine the molecular understanding of naso-sinusal pathologies. Using non-cross-reactive antibodies against galectin-1, -3, -4, -7, -8 and -9, we characterized the galectin profiles in chronic rhinosinusitis, nasal polyposis, inverted papillomas and squamous cell carcinomas. The expression, signal location and quantitative parameters describing the percentage of positive cells and labeling intensity were assessed for various cases. We discovered that inverted papillomas showed a distinct galectin immunohistochemical profile. Indeed, epithelial overexpression of galectin-3 (p=0.0002), galectin-4 (p<10-6), galectin-7 (p<10-6) and galectin-9 (p<10-6) was observed in inverted papillomas compared to non-malignant diseases. Regarding carcinomas, we observed increased expression of galectin-9 (p<10-6) in epithelial cells compared to non-tumor pathologies. Our results suggest that galectin-3, -4, -7 and -9 could be involved in the biology of inverted papillomas. In addition, we observed that the expression of galectin in naso-sinusal diseases seems to be affected by tumor progression and not inflammatory or allergic phenomena.

Immunohistochemical toolkit for tracking and quantifying xenotransplanted human stem cells.

Biomarker-based tracking of human stem cells xenotransplanted into animal models is crucial for studying their fate in the field of cell therapy or tumor xenografting.

3D augmented reality mirror visual feedback applied to the treatment of persistent neuropathic pain in the upper extremity.

Helicase-like transcription factor: a new marker of well-differentiated thyroid cancers.

The preoperative characterization of thyroid nodules is a challenge for the clinicians. Fine-needle aspiration (FNA) is the commonly used pre-operative technique for diagnosis of malignant thyroid tumor. However, many benign lesions, with indeterminate diagnosis following FNA, are referred to surgery. There is an urgent need to identify biomarkers that could be used with the FNA to distinguish benign thyroid nodules from malignant tumors. The purpose of the study is to examine the level of expression of the helicase-like transcription factor (HLTF) in relation to neoplastic progression of thyroid carcinomas.

Polymerase chain reaction for Enterococcus faecalis in drain fluid: the first screening test for symptomatic colorectal anastomotic leakage. The Appeal-study: analysis of parameters predictive for evident anastomotic leakage.

With current diagnostic methods, the majority of patients with symptomatic colorectal anastomotic leakage(CAL) is identified approximately 1 week after operation.The aim of this study is to determine whether real-time polymerase chain reaction (RT-PCR) for detection of Escherichia coli and Enterococcus faecalis on drain fluid can serve as a screening test for CAL in the early postoperative phase.

D-SIFER: Derivative-based Scale Invariant Image Feature Detector with Error Resilience

2013

An Automated Blur Detection Method for Histological Whole Slide Imaging

Whole slide scanners are novel devices that enable high-resolution imaging of an entire histological slide. Furthermore, the imaging is achieved in only a few minutes, which enables image rendering of large-scale studies involving multiple immunohistochemistry biomarkers. Although whole slide imaging has improved considerably, locally poor focusing causes blurred regions of the image. These artifacts may strongly affect the quality of subsequent analyses, making a slide review process mandatory. This tedious and time-consuming task requires the scanner operator to carefully assess the virtual slide and to manually select new focus points. We propose a statistical learning method that provides early image quality feedback and automatically identifies regions of the image that require additional focus points.

Automated Cell Tracking and Analysis in Phase-Contrast Videos (iTrack4U): Development of Java Software Based on Combined Mean-Shift Processes

Cell migration is a key biological process with a role in both physiological and pathological conditions. Locomotion of cells during embryonic development is essential for their correct positioning in the organism; immune cells have to migrate and circulate in response to injury. Failure of cells to migrate or an inappropriate acquisition of migratory capacities can result in severe defects such as altered pigmentation, skull and limb abnormalities during development, and defective wound repair, immunosuppression or tumor dissemination. The ability to accurately analyze and quantify cell migration is important for our understanding of development, homeostasis and disease. In vitro cell tracking experiments, using primary or established cell cultures, are often used to study migration as cells can quickly and easily be genetically or chemically manipulated. Images of the cells are acquired at regular time intervals over several hours using microscopes equipped with CCD camera. The locations (x,y,t) of each cell on the recorded sequence of frames then need to be tracked. Manual computer-assisted tracking is the traditional method for analyzing the migratory behavior of cells. However, this processing is extremely tedious and time-consuming. Most existing tracking algorithms require experience in programming languages that are unfamiliar to most biologists. We therefore developed an automated cell tracking program, written in Java, which uses a mean-shift algorithm and ImageJ as a library. iTrack4U is a user-friendly software. Compared to manual tracking, it saves considerable amount of time to generate and analyze the variables characterizing cell migration, since they are automatically computed with iTrack4U. Another major interest of iTrack4U is the standardization and the lack of inter-experimenter differences. Finally, iTrack4U is adapted for phase contrast and fluorescent cells. © 2013 CORDELIERES et al.

Epithelial expression of FHL2 is negatively associated with metastasis-free and overall survival in colorectal cancer

Background:Four-and-a-half LIM domains protein 2 (FHL2) is a component of the focal adhesion structures and has been suggested to have a role in cancer progression. It has been shown to be overexpressed in the colorectal cancer (CRC).Methods:Here, we examined a possible prognostic value of FHL2 in CRC. Immunohistochemistry for FHL2 was performed on 296 CRCs without distant metastases at the time of surgery. Staining in the epithelial compartment was quantitatively evaluated using image analysis, and results were related to clinical variables. Antibody specificity was tested using small-interfering RNA transfection in hTERT-immortalised myofibroblasts.Results:Varying degrees of cytoplasmic FHL2 expression by neoplastic epithelial cells were detectable in all cases. Higher FHL2 expression in the epithelial compartment was an independent adverse prognostic factor. Multivariate Cox analysis shows that expression in the tumour invasion front (P<0.001) as well as in the centre of the tumour (P<0.001) was associated with metachronous metastases independently of the clinicopathological variables; expression in the tumour invasion front was also associated with overall survival independently of the clinicopathological variables (P<0.01).Conclusion:Higher FHL2 expression is involved in CRC progression and correlates with the development of metachronous metastases and overall survival, suggesting that FHL2 is an independent adverse prognostic indicator for CRC. © 2013 Cancer Research UK. All rights reserved.

Human papillomavirus predicts the outcome following concomitant chemoradiotherapy in patients with head and neck squamous cell carcinomas.

We investigated the prevalence of human papillomavirus (HPV) in a clinical series of 72 patients with head and neck squamous cell carcinoma (HNSCC) using a retrospective and prospective study design. The majority of patients were smokers and/or drinkers and were treated with concomitant chemoradiotherapy (CCR). Furthermore, we assessed the impact of HPV positivity on the response to CCR. Paraffin-embedded samples from HNSCC patients (n=72) were evaluated for the presence of HPV DNA using both GP5+/GP6+ consensus PCR and type-specific E6/E7 PCR to detect HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67 and 68. The type-specific E6/E7 PCR demonstrated that 20 out of 69 HNSCC patients (29%) presented with high-risk (HR) HPV types and that 5 of the 69 HNSCC patients (7%) presented with low-risk (LR) HPV types. Using the GP5+/GP6+ PCR, we observed that the rate of response was statistically lower in the HPV+ group (P=0.02). Concerning patient outcomes in terms of recurrence and survival, we observed that the prognosis was poorer for HPV+ patients. We showed for the first time that patients with HPV+ HNSCC present with a worse prognosis after CCR. This observation highlights the need for prospective studies with large numbers of patients and a detailed history of tobacco and alcohol consumption before validating HPV as a marker of prognosis following CCR.

VEGFR1 and VEGFR2 Involvement in Extracellular Galectin-1- and Galectin-3-Induced Angiogenesis

Aim:Accumulating evidence suggests that extracellular galectin-1 and galectin-3 promote angiogenesis. Increased expression of galectin-1 and/or galectin-3 has been reported to be associated with tumour progression. Thus, it is critical to identify their influence on angiogenesis.Methods:We examined the individual and combined effects of galectin-1 and galectin-3 on endothelial cell (EC) growth and tube formation using two EC lines, EA.hy926 and HUVEC. The activation of vascular endothelial growth factor receptors (VEGFR1 and VEGFR2) was determined by ELISA and Western blots. We evaluated the VEGFR1 and VEGFR2 levels in endosomes by proximity ligation assay.Results:We observed different responses to exogenous galectins depending on the EC line. An enhanced effect on EA.hy926 cell growth and tube formation was observed when both galectins were added together. Focusing on this enhanced effect, we observed that together galectins induced the phosphorylation of both VEGFR1 and VEGFR2, whereas galectin-1 and -3 alone induced VEGFR2 phosphorylation only. In the same way, the addition of a blocking VEGFR1 antibody completely abolished the increase in tube formation induced by the combined addition of both galectins. In contrast, the addition of a blocking VEGFR2 antibody only partially inhibited this effect. Finally, the addition of both galectins induced a decrease in the VEGFR1 and VEGFR2 endocytic pools, with a significantly enhanced effect on the VEGFR1 endocytic pool. These results suggest that the combined action of galectin-1 and galectin-3 has an enhanced effect on angiogenesis via VEGFR1 activation, which could be related to a decrease in receptor endocytosis. © 2013 D'Haene et al.

Robust Structured Light Pattern for Use with a Spatial Light Modulator in 3-D Endoscopy

This article introduces a novel structured light pattern designed to be compatible with the spatial light modulator (SLM) projection. The proposed pattern is a De Bruijn-based sequence applied to a combination of continuous and dashed lines for the pattern. The sequence is coded in the period and duty cycles of the dashed lines. It provides 16 different lines which limits to two the required number of dashed lines needed for identification. The segmentation has been made easier by alternating continuous and dashed lines. As required by the use of SLMs, the sequence has been adapted by making it symmetric. It has been improved by guaranteeing a hamming distance equal to two for two successive dashed lines. The implementation on a virtual model has shown that a subpixel accuracy has been achieved. This pattern has been developped for 3-D endoscopy. © 2013 Copyright Taylor and Francis Group, LLC.

Macrophage migration inhibitory factor in head and neck squamous cell carcinoma: clinical and experimental studies.

The present in vivo/in vitro study was undertaken in order to evaluate the importance of macrophage migration inhibitory factor (MIF) in the progression of head and neck squamous cell carcinoma (HNSCC).

Sleep spindle detection through amplitude-frequency normal modelling.

A Masked PY-NLS in Drosophila TIS11 and Its Mammalian Homolog Tristetraprolin.

Many RNA-binding proteins (RBPs) dynamically shuttle between the nucleus and the cytoplasm, often exerting different functions in each compartment. Therefore, the nucleo-cytoplasmic distribution of RBPs has a strong impact on their activity. Here we describe the localization and the shuttling properties of the tandem zinc finger RBP dTIS11, which is the Drosophila homolog of mammalian TIS11 proteins. Drosophila and mammalian TIS11 proteins act as destabilizing factors in ARE-mediated decay. At equilibrium, dTIS11 is concentrated mainly in the cytoplasm. We show that dTIS11 is a nucleo-cytoplasmic shuttling protein whose nuclear export is mediated by the exportin CRM1 through the recognition of a nuclear export signal (NES) located in a different region comparatively to its mammalian homologs. We also identify a cryptic Transportin-dependent PY nuclear localization signal (PY-NLS) in the tandem zinc finger region of dTIS11 and show that it is conserved across the TIS11 protein family. This NLS partially overlaps the second zinc finger ZnF2. Importantly, mutations disrupting the capacity of the ZnF2 to coordinate a Zinc ion unmask dTIS11 and TTP NLS and promote nuclear import. All together, our results indicate that the nuclear export of TIS11 proteins is mediated by CRM1 through diverging NESs, while their nuclear import mechanism may rely on a highly conserved PY-NLS whose activity is negatively regulated by ZnF2 folding.

Fast and accurate cell tracking by a novel optical-digital hybrid method

An innovative methodology to detect and track cells using microscope images enhanced by optical cross-correlation techniques is proposed in this paper. In order to increase the tracking sensibility, image pre-processing has been implemented as a morphological operator on the microscope image. Results show that the pre-processing process allows for additional frames of cell tracking, therefore increasing its robustness. The proposed methodology can be used in analyzing different problems such as mitosis, cell collisions, and cell overlapping, ultimately designed to identify and treat illnesses and malignancies. © Springer Science+Business Media New York 2013.

SIFER: Scale-Invariant Feature Detector with Error Resilience

2012

Expression of macrophage migration-inhibitory factor is correlated with progression in oral cavity carcinomas.

We have previously reported that macrophage migration-inhibitory factor (MIF) is associated with an unfavorable prognosis in hypopharyngeal carcinoma. Here, we quantified MIF expression in oral cavity carcinomas and looked for possible correlations with clinical outcome.

A simplified approach for the molecular classification of glioblastomas.

Glioblastoma (GBM) is the most common malignant primary brain tumors in adults and exhibit striking aggressiveness. Although GBM constitute a single histological entity, they exhibit considerable variability in biological behavior, resulting in significant differences in terms of prognosis and response to treatment. In an attempt to better understand the biology of GBM, many groups have performed high-scale profiling studies based on gene or protein expression. These studies have revealed the existence of several GBM subtypes. Although there remains to be a clear consensus, two to four major subtypes have been identified. Interestingly, these different subtypes are associated with both differential prognoses and responses to therapy. In the present study, we investigated an alternative immunohistochemistry (IHC)-based approach to achieve a molecular classification for GBM. For this purpose, a cohort of 100 surgical GBM samples was retrospectively evaluated by immunohistochemical analysis of EGFR, PDGFRA and p53. The quantitative analysis of these immunostainings allowed us to identify the following two GBM subtypes: the "Classical-like" (CL) subtype, characterized by EGFR-positive and p53- and PDGFRA-negative staining and the "Proneural-like" (PNL) subtype, characterized by p53- and/or PDGFRA-positive staining. This classification represents an independent prognostic factor in terms of overall survival compared to age, extent of resection and adjuvant treatment, with a significantly longer survival associated with the PNL subtype. Moreover, these two GBM subtypes exhibited different responses to chemotherapy. The addition of temozolomide to conventional radiotherapy significantly improved the survival of patients belonging to the CL subtype, but it did not affect the survival of patients belonging to the PNL subtype. We have thus shown that it is possible to differentiate between different clinically relevant subtypes of GBM by using IHC-based profiling, a method that is advantageous in its ease of daily implementation and in large-scale clinical application.

Clustering methods applied in the detection of Ki67 hot-spots in whole tumor slide images: An efficient way to characterize heterogeneous tissue-based biomarkers.

Whole-slide scanners allow the digitization of an entire histological slide at very high resolution. This new acquisition technique opens a wide range of possibilities for addressing challenging image analysis problems, including the identification of tissue-based biomarkers. In this study, we use whole-slide scanner technology for imaging the proliferating activity patterns in tumor slides based on Ki67 immunohistochemistry. Faced with large images, pathologists require tools that can help them identify tumor regions that exhibit high proliferating activity, called "hot-spots" (HSs). Pathologists need tools that can quantitatively characterize these HS patterns. To respond to this clinical need, the present study investigates various clustering methods with the aim of identifying Ki67 HSs in whole tumor slide images. This task requires a method capable of identifying an unknown number of clusters, which may be highly variable in terms of shape, size, and density. We developed a hybrid clustering method, referred to as Seedlink. Compared to manual HS selections by three pathologists, we show that Seedlink provides an efficient way of detecting Ki67 HSs and improves the agreement among pathologists when identifying HSs. © 2012 International Society for Advancement of Cytometry.

Cells lacking β-actin are genetically reprogrammed and maintain conditional migratory capacity

Vertebrate nonmuscle cells express two actin isoforms: cytoplasmic β- and γ-actin. Because of the presence and localized translation of β-actin at the leading edge, this isoform is generally accepted to specifically generate protrusive forces for cell migration. Recent evidence also implicates β-actin in gene regulation. Cell migration without β-actin has remained unstudied until recently and it is unclear whether other actin isoforms can compensate for this cytoplasmic function and/or for its nuclear role. Primary mouse embryonic fibroblasts lacking β-actin display compensatory expression of other actin isoforms. Consistent with this preservation of polymerization capacity, β-actin knockout cells have unchanged lamellipodial protrusion rates despite a severe migration defect. To solve this paradox we applied quantitative proteomics revealing a broad genetic reprogramming of β-actin knockout cells. This also explains why reintroducing β-actin in knockout cells does not restore the affected cell migration. Pathway analysis suggested increased Rho-ROCK signaling, consistent with observed phenotypic changes. We therefore developed and tested a model explaining the phenotypes in β-actin knockout cells based on increased Rho-ROCK signaling and increased TGFβ production resulting in increased adhesion and contractility in the knockout cells. Inhibiting ROCK or myosin restores migration of β-actin knockout cells indicating that other actins compensate for β-actin in this process. Consequently, isoactins act redundantly in providing propulsive forces for cell migration, but β-actin has a unique nuclear function, regulating expression on transcriptional and post-translational levels, thereby preventing myogenic differentiation. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

An easy, cheap computerized method to assess two-dimensional trajectory parameters

Human papillomavirus DNA strongly correlates with a poorer prognosis in oral cavity carcinoma.

The prevalence of human papillomavirus (HPV) in a clinical series of 162 patients with oral squamous cell carcinoma (OSCC) was studied. Furthermore, we analyzed the correlation between the immunohistochemical expression of p16, p53, epidermal growth factor receptor (EGFR), and HPV status to predict survival in OSCC patients.

Traffic Sign Recognition with Invariance to Lighting in Dual-Focal Active Camera System

FTV for 3-D Spatial Communication

Sigma receptors and their ligands in cancer biology: overview and new perspectives for cancer therapy.

A large number of drugs are known to bind with high affinity to sigma receptors (sigma-Rs) and have been used in the clinic to treat mental disorders for many years. However, recent publications highlighting sigma-R overexpression in many cancer tissues suggest potential applications for sigma-R ligands in cancer diagnosis and therapy. The present review focuses on the involvement of sigma-Rs in cancer biology and the potential therapeutic contributions of their pharmacologic ligands in oncology. After summarizing the current and general knowledge regarding sigma-Rs, we detail data reported in the particular context of oncology. We then investigate the potential and specific signal transduction pathways and mechanisms involved in the actions of sigma-R ligands in cancer biology. These processes include modulations of (1) the plasma membrane and lipid raft components, (2) intracellular calcium levels, (3) cytoskeletal protein functions, and (4) endoplasmic reticulum stress. Finally, we conclude by speculating on the roles of sigma-R overexpression and sigma-R ligands in cancer biology and offer perspectives on cancer therapy. (c) 2010 Wiley Periodicals, Inc. Med Res Rev.

Clinicopathological significance of indoleamine 2,3-dioxygenase 1 expression in colorectal cancer.

Background:Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan-catabolising enzyme that induces immune tolerance by modulating T-cell responses. Carcinomas may create an immunosuppressive state via IDO1 expression. Here we examined a possible contribution of IDO1 on this phenomenon and investigated whether IDO1 has prognostic value in colorectal cancer (CRC).Methods:IDO1 expression was investigated by quantitative PCR and western blotting in three colon cancer cell lines, in basal state and after interferon (IFN)-γ stimulation. Semi-quantitative immunohistochemistry was used to evaluate IDO1 expression in 265 pT1-4N0-2Mx-staged CRCs. Results were related to clinical variables and correlated with amounts of CD3(+) and CD8(+) T lymphocytes, which were quantitatively evaluated using image analysis.Results:In vitro expression of IDO1 depended on IFN-γ stimulation. Higher IDO1 expression at the tumour invasion front was an independent adverse prognostic factor in pT1-4N1Mx-staged CRC. It was associated with overall survival (P=0.001) and with metachronous metastases (P=0.018). IDO1 expression was not associated with the presence of CD3(+) or CD8(+) T lymphocytes.Conclusion:Higher IDO1 expression at the tumour invasion front is involved in CRC progression and correlates with impaired clinical outcome, suggesting that IDO1 is an independent prognostic indicator for CRC.British Journal of Cancer advance online publication, 22 November 2011; doi:10.1038/bjc.2011.513 www.bjcancer.com.

Constant time joint bilateral filtering using joint integral histograms

2011

Spatio-Temporal Free-Viewpoint Image Generation Using Moving Camera Array

Multi-View Ray Acquisition System Using Camera and Mirror

Close-up View Synthesis for Free-Viewpoint Image Generation

High-quality virtual view synthesis in 3DTV and FTV

A New Method to Address Unmet Needs for Extracting Individual Cell Migration Features from a Large Number of Cells Embedded in 3D Volumes

Background: In vitro cell observation has been widely used by biologists and pharmacologists for screening molecule-induced effects on cancer cells. Computer-assisted time-lapse microscopy enables automated live cell imaging in vitro, enabling cell behavior characterization through image analysis, in particular regarding cell migration. In this context, 3D cell assays in transparent matrix gels have been developed to provide more realistic in vitro 3D environments for monitoring cell migration (fundamentally different from cell motility behavior observed in 2D), which is related to the spread of cancer and metastases. Methodology/Principal Findings: In this paper we propose an improved automated tracking method that is designed to robustly and individually follow a large number of unlabeled cells observed under phase-contrast microscopy in 3D gels. The method automatically detects and tracks individual cells across a sequence of acquired volumes, using a template matching filtering method that in turn allows for robust detection and mean-shift tracking. The robustness of the method results from detecting and managing the cases where two cell (mean-shift) trackers converge to the same point. The resulting trajectories quantify cell migration through statistical analysis of 3D trajectory descriptors. We manually validated the method and observed efficient cell detection and a low tracking error rate (6%). We also applied the method in a real biological experiment where the pro-migratory effects of hyaluronic acid (HA) were analyzed on brain cancer cells. Using collagen gels with increased HA proportions, we were able to evidence a dose-response effect on cell migration abilities. Conclusions/Significance: The developed method enables biomedical researchers to automatically and robustly quantify the pro- or anti-migratory effects of different experimental conditions on unlabeled cell cultures in a 3D environment. © 2011 Adanja et al.

High incidence of high-risk HPV in benign and malignant lesions of the larynx.

The aim of this study was to determine the prevalence of human papillomavirus (HPV) in patients with laryngeal benign lesions (LBLs) and laryngeal squamous cell carcinomas (LSCCs) using a sensitive E6/E7 type-specific PCR. Paraffin-embedded samples from LBL (n=39) and LSCC patients (n=67) were evaluated for the presence of HPV DNA by GP5+/GP6+ consensus PCR and E6/E7 type-specific PCR for HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68. In LSCCs, immunohistochemical staining of p16, p53 and EGFR was also assessed. The E6/E7 type-specific PCR showed that 44 out of 59 LSCC patients (i.e., 75%) had high-risk (hr) HPV types and that 27 out of 35 LBL patients (i.e., 77%) had hrHPV types. HPV-16 viral load was significantly higher in LSCC than in LBL patients (p<10-6). The presence of hrHPV DNA did not correlate with the proportion of disease-free patients. Comparable levels of p16, p53 and EGFR expression were observed in the hrHPV+ tumor group (100% p16+, 56% p53+ and 97% EGFR+) and in the HPV- or low-risk (lr) HPV+ tumor group (92% p16+, 66% p53+ and 100% EGFR+). A very high prevalence of oncogenic HPV-16 was found in a series of benign and malignant laryngeal lesions. LSCC appears to be characterized by an active hrHPV infection. In LSCCs, the hrHPV+ subgroup had a similar prognosis (in terms of risk of recurrence) as the HPV- subgroup.

Traffic Sign Recognition Using Hybrid Camera System

Depth Coding using Downsampling and View based Upsampling

Quantitative immunohistochemical fingerprinting of adhesion/growth-regulatory galectins in salivary gland tumours: divergent profiles with diagnostic potential.

This study tests the hypothesis that histopathological fingerprinting of galectins, which are emerging multifunctional effectors in cell sociology, could refine the differential diagnosis of salivary tumours.

Changes in Paramecium caudatum (Protozoa) near a switched-on GSM telephone

The protozoan Paramecium caudatum was examined under normal conditions versus aside a switched-on GSM telephone (900 MHz; 2 Watts). Exposed individuals moved more slowly and more sinuously than usual. Their physiology was affected: they became broader, their cytopharynx appeared broader, their pulse vesicles had difficult in expelling their content outside the cell, their cilia less efficiently moved, and trichocysts became more visible. All these effects might result from some bad functioning or damage of the cellular membrane. The first target of communication electromagnetic waves might thus be the cellular membrane. © Informa Healthcare USA, Inc.

LED Traffic Light Detection Using High-speed-camera Image Processing for Visible Light Communication

Développements originaux des techniques de navigation en traumatologie.

This article presents an original method for long objects modeling and two navigation applications in trauma surgery. Both concern long bone fracture treatment. Our modeling method requires only two x-ray views. The projection cones of the object are determined and their intersection is computed, providing an approached 30 model, which can be improved by adding a priori knowledge or other information. The first application concerns the control of diaphyseal fracture reduction treated by external fixation. Reference frames are fixed to the bone fragments and tracked by a 3D optical localizer, allowing the computation of their relative position. Approached 3D models of the fragments are displayed in real time according to the manipulation effected by the surgeon. The principal axes of the fragments, very useful for the fracture reduction, are also displayed. The alignment of the bone fragments is quantified by parameters provided in real time during the reduction. The second application concerns the distal locking of intra-medullary nails. A 3D model of the nail and its locking holes is built from two calibrated fluoroscopic views. The nail and the surgical tool are tracked thanks to reference frames fixed to each of them. A 3D view of these two elements is displayed in real time, guiding the surgeon in the difficult task of distal targeting. Experiments and results are presented for both applications. These techniques provide real 3D models to the surgeon during the operation, allowing precise guidance of the surgical gesture and considerable reduction of the irradiation to the patient and the surgical team.

Combined analysis of HPV DNA, p16, p21 and p53 to predict prognosis in patients with stage IV hypopharyngeal carcinoma.

We examined p16, p21 and p53 expression in combination with the presence of human papillomavirus (HPV) DNA as molecular markers to predict survival in patients with stage IV hypopharyngeal squamous cell carcinoma (HSCC).

Robust low complexity corner detector

Real-Time and Accurate Stereo: A Scalable Approach with Bitwise Fast Voting on CUDA

Free-Viewpoint TV

2010

Automatic grading of Bi-colored apples by multispectral machine vision

In this paper we present a novel application work for grading of apple fruits by machine vision. Following precise segmentation of defects by minimal confusion with stem/calyx areas on multispectral images, statistical, textural and geometric features are extracted from the segmented area. Using these features, statistical and syntactical classifiers are trained for two- and multi-category grading of the fruits. Results showed that feature selection provided improved performance by retaining only the important features, and statistical classifiers outperformed their syntactical counterparts. Compared to the state-of-the-art, our two-category grading solution achieved better recognition rates (93.5% overall accuracy). In this work we further provided a more realistic multi-category grading solution, where different classification architectures are evaluated. Our observations showed that the single-classifier architecture is computationally less demanding, while the cascaded one is more accurate. © 2010 Elsevier B.V.

A Semi-Automatic Depth Estimation Method for FTV

View Synthesis Using Probabilistic Reliability Reasoning for FTV

TIMP-4 and CD63: new prognostic biomarkers in human astrocytomas.

Based on the molecular profiling of astrocytomas, we previously identified a series of genes involved in astrocytoma invasion. Of these, tissue inhibitor of metalloproteinase-4 (TIMP-4) was found to be overexpressed in pilocytic astrocytomas relative to diffuse astrocytomas of any histological grade. Although some data suggest that TIMP-4 may be an anti-tumoral actor in astrocytomas, recent findings challenge this concept. The present study aims to investigate the diagnostic and prognostic values of TIMP-4 and its putative partner CD63 in human astrocytomas. Tissue microarray and image analysis were first carried out to quantitatively analyze the immunohistochemical expression of these proteins in 471 gliomas including 354 astrocytomas. Pathological semi-quantitative scores of both markers' expression were then established and correlated to astrocytoma diagnosis and patient prognosis. TIMP-4 and CD63 expressions were both overexpressed in astrocytomas compared with oligodendrogliomas (P<0.001) and in pilocytic astrocytomas compared with grade II diffuse astrocytomas (P<0.001). In glioblastomas, high TIMP-4/CD63 co-expression scores were identified as independent prognostic factors associated with progression and shorter survival. In conclusion, this work provides the first evidence of a TIMP-4/CD63 association in astrocytoma tumor cells. It identifies TIMP-4 and CD63 as markers of the astrocytic phenotype in patients with gliomas. In addition, this work highlights the contribution of high TIMP-4/CD63 co-expression to the adverse outcomes of patients with glioblastomas.

Increased expression of macrophage migration inhibitory factor during progression to hypopharyngeal squamous cell carcinoma.

BACKGROUND/AIM: To examine the presence of macrophage migration inhibitory factor (MIF) quantitatively in relation to neoplastic progression of hypopharyngeal squamous cell carcinoma (HSCC). MATERIALS AND METHODS: The presence of MIF was analysed by quantitative immunohistochemistry in sections of 81 HSCCs, and compared to 15 specimens of tumour-free epithelia (TF_E), 29 low-grade dysplasias (Low_D) and 25 high-grade dysplasias (High_D). In parallel, MIF expression was studied using Western blotting on a series of 19 fresh biopsies. RESULTS: A significant increase in MIF staining intensity (mean optical density) was observed in carcinoma samples compared to TF_E (p<10(-6)), Low_D (p=0.0006) or High_D (p=0.0006). Immunohistochemical MIF positivity was significantly higher in HSCCs than in TF_E (p=0.00001) or Low_D (p=0.001). The percentage of MIF-immunopositive cells (labelling index) significantly decreased in parallel with an apparent loss of histological differentiation (p=0.003). CONCLUSION: This study identified the presence of MIF as a parameter that positively correlates with neoplastic progression of HSCC and cell differentiation status.

Long-term in vitro treatment of human glioblastoma cells with temozolomide increases resistance in vivo through up-regulation of GLUT transporter and aldo-keto reductase enzyme AKR1C expression.

Glioblastoma (GBM) is the most frequent malignant glioma. Treatment of GBM patients is multimodal with maximum surgical resection, followed by concurrent radiation and chemotherapy with the alkylating drug temozolomide (TMZ). The present study aims to identify genes implicated in the acquired resistance of two human GBM cells of astrocytic origin, T98G and U373, to TMZ. Resistance to TMZ was induced by culturing these cells in vitro for months with incremental TMZ concentrations up to 1 mM. Only partial resistance to TMZ has been achieved and was demonstrated in vivo in immunocompromised mice bearing orthotopic U373 and T98G xenografts. Our data show that long-term treatment of human astroglioma cells with TMZ induces increased expression of facilitative glucose transporter/solute carrier GLUT/SLC2A family members, mainly GLUT-3, and of the AKR1C family of proteins. The latter proteins are phase 1 drug-metabolizing enzymes involved in the maintenance of steroid homeostasis, prostaglandin metabolism, and metabolic activation of polycyclic aromatic hydrocarbons. GLUT-3 has been previously suggested to exert roles in GBM neovascularization processes, and TMZ was found to exert antiangiogenic effects in experimental gliomas. AKR1C1 was previously shown to be associated with oncogenic potential, with proproliferative effects similar to AKR1C3 in the latter case. Both AKR1C1 and AKR1C2 proteins are involved in cancer pro-proliferative cell chemoresistance. Selective targeting of GLUT-3 in GBM and/or AKR1C proteins (by means of jasmonates, for example) could thus delay the acquisition of resistance to TMZ of astroglioma cells in the context of prolonged treatment with this drug.

In vitro antiprotozoal, antimicrobial and antitumor activity of Pavetta crassipes K. Schum leaf extracts.

AIM OF THE STUDY: To study the potential benefit of the traditional medicinal plant Pavetta crassipes K. Schum (Rubiaceae), which is widely distributed throughout West Africa, the methanol and dichloromethane extracts were isolated from the plant leaves to determine if they exhibited antiprotozoal, antibacterial, antifungal or antitumor activity in vitro. MATERIALS AND METHODS: The methanol and dichloromethane extracts and their specific fractions were obtained using bioassay-guided fractionation and investigated for antiproliferative activity in vitro in microorganisms (Staphylococcus aureus, Escherichia coli and Candida albicans), protozoans (Trypanosoma cruzi, Trypanosoma brucei, Leishmania infantum and Plasmodium falciparum), and cancer (U373, PC3, MXT and A549) and normal cell lines (NHDF and MRC-5). RESULTS: Most of the alkaloid fractions investigated exhibited antiproliferative activity in all the cancer cell lines, microorganisms and protozoans studied. CONCLUSIONS: The benefit of Pavetta crassipes as a traditional medicinal remedy was confirmed using antiprotozoal and cytotoxicity assays in vitro. These analyses revealed that the components present in the alkaloid extract of Pavetta crassipes are responsible for its antiprotozoal and cytotoxic efficacy.

The Seelinder: Cylindrical 3D display viewable from 360 degrees

Artifact reduction using reliability reasoning for image generation of FTV

Iterative colour correction of multicamera systems using corresponding feature points

Ultrasound-guided fine-needle aspiration of thyroid nodules: stratification of malignancy risk using follicular proliferation grading, clinical and ultrasonographic features.

OBJECTIVE: To evaluate the diagnostic value of fine-needle aspiration (FNA) cytology and the additive contribution brought by clinical and ultrasound (US) features. METHOD: Cytological and histological diagnoses were compared in a series of 924 patients who underwent US-guided FNA before surgery. We additionally developed a grading system for follicular proliferation (FP) FNA diagnosis, and investigated its impact on the malignancy risk as well as the additive contribution of clinical and US features by means of decision tree analysis. RESULTS: Excluding FP cases (n=395), our data demonstrated that strictly benign or malignant FNA diagnoses exhibit great concordance with benign or malignant histological diagnoses (97.8% accuracy). Our grading system that was applied to the 395 FP cases revealed that grades 1, 2 and 3 were associated with a 7.7, 17.7 and 45.7% incidence of malignancy respectively. Decision tree analysis resulted in a classification model which involved FP grade, patient's age, serum thyroglobulin level, nodule size and nodule uniqueness. This model identified a subgroup of patients with grade 1 FP nodules who were older than 50 years, and who had a higher risk of malignancy (17.9%). In addition, high serum thyroglobulin levels were associated with a very high malignancy risk (75.0%) for patients with grade 3 FP nodules. Finally, among grade 2 FP patients, unique and large nodules were associated with a high malignancy risk of 36.1%. CONCLUSIONS: The integration of FP grade, clinical and US features allows the stratification of patients with FP cytology according to their risk of malignancy.

Galectin fingerprinting in Warthin's tumors: lectin-based approach to trace its origin?

Warthin's tumor of the parotid gland is assumed to originate from the proliferation of epithelial inclusions within parotid lymph nodes. In that case, these cells are supposed to retain characteristics similar to common salivary gland ductal cells. Using immunohistochemical fingerprinting with four members of the family of adhesion/growth-regulatory galectins and comparison to intra- and interlobular ducts, marked similarities were noted for presence of galectins-3, -7 and -8. Notably, profiles of lectin binding, determined by applying human lectins as probes, were also similar when testing biotinylated galectins-3 and -8. Besides defining the galectin histochemical parameters in Warthin's tumors this study adds support to the hypothesis of heterotopia.

La surdité moyenne: Étiologie, évaluation linguistique et scolaire

Precise Extraction of Moving Objects in Video Stream

Aristolochic acid nephropathy revisited: a place for innate and adaptive immunity?

Pozdzik A A, Berton A, Schmeiser H H, Missoum W, Decaestecker C, Salmon I J, Vanherweghem J-L & Nortier J L(2010) Histopathology56, 449-463Aristolochic acid nephropathy revisited: a place for innate and adaptive immunity?Aims:  The histological features of aristolochic acid nephropathy (AAN) consist of paucicellular interstitial fibrosis, severe tubular atrophy, and almost intact glomeruli with media lesions of interlobular arteries. As an early phase of interstitial inflammation preceded peritubular fibrosis in the rat model of AAN, the aim was to investigate the presence of inflammatory cells in human AAN.Methods and results:  Reports of confirmed cases and case series of AAN were reviewed in terms of interstitial inflammation and found to have very conflicting results. This prompted us to search for and characterize inflammatory cells within the native kidneys provided from four end-stage AAN patients. Prior aristolochic acid exposure was attested by the intrarenal presence of the typical aristolactam I-derived DNA adduct. Besides the tubulointerstitial lesions usually seen in the cortex, a massive infiltration of macrophages, T and B lymphocytes was detected by immunohistochemistry in the medullary rays and in the outer medullae with some extension to the upper cortical labyrinth.Conclusions:  In parallel with histological findings reported in the rat model, inflammatory cells are present preferentially in the interstitium of the medullary rays and of the outer medulllae in renal interstitium from human AAN cases, even in the terminal stages. Further studies must be undertaken to determine the respective roles of innate and adaptive immunity in the progression of AAN.

Quantitative Analysis of Melanocyte Migration in vitro Based on Automated Cell Tracking under Phase Contrast Microscopy Considering the Combined Influence of Cell Division and Cell-Matrix Interactions

The aim of this study was to describe and analyze the regulation and spatio-temporal dynamics of melanocyte migration in vitro and its coupling to cell division and interaction with the matrix. The melanocyte lineage is particularly interesting because it is involved in both embryonic development and oncogenesis/metastasis (melanoma). Biological experiments were performed on two melanocyte cell lines established from wild-type and β-catenin- transgenic mice (bcat*). The multi-functional β-catenin molecule is known to be able to regulate the transcription of various genes involved in cell proliferation and migration, particularly in the melanocyte lineage. We also investigated fibronectin, an extra-cellular matrix protein that binds integrins, thereby providing adhesion points for cells and encouraging migration. As the migration of individual cells were followed, automated methods were required for processing the large amount of data generated by the time-lapse video-microscopy. A model-based approach for automated cell tracking was evaluated on a sample by comparison with manual tracking. This method was found reliable in studying overall cell behaviour. Its application to all the observed sequences provided insight into the factors affecting melanocyte migration in vitro: melanocytes of mutated form of β-catenin showed higher division rates and no contact inhibition of growth was induced by the resulting increase in cell density. However, cell density limited the amplitude of cell displacements, although their motility was less affected. The high fibronectin concentration bound to substratum promoted cell migration and motility, the effect being more intense for wild-type cells than for cells with β-catenin over-expression. During the division process, cell migration speed increased rapidly then decreased slowly. Analyses of such data is expected to lead both to biological answers and to a framework for a better modeling processes in the future. © EDP Sciences, 2010.

Automated tracking of unmarked cells migrating in three-dimensional matrices applied to anti-cancer drug screening.

In oncology, combating the spread of tumor cells is a clinical need which currently remains unsatisfied. Identifying anti-migratory compounds usually requires in vitro screening of a large number of molecules. Efficient and realistic (i.e., preferably 3D) in vitro tests are thus required in order to quantify the anti-migratory effects of anti-cancer drugs. To remain compatible with high-throughput screening, we focus on assays where unlabeled cells are migrating in 3D transparent gels and are observed under time-lapse 3D phase-contrast microscopy. In this context, we present a method for automatically tracking cells that combines a template matching preprocessing step with a mean-shift process. The preprocessing step consists in performing a correlation of a cell template with each observed volume in order to provide a phase-contrast artifact-free volume where the cells appear as correlation peaks surrounded by smooth gradients. This transformation enables the cells to be efficiently tracked by a mean-shift process. Robustness and efficiency of this approach are qualitatively and quantitatively shown in various experiments. Finally, we successfully applied our method to the quantitative characterization of the anti-migratory impact of cytochalasin-D on cancer cells. In conclusion, our method can efficiently be used for drug screening aiming to evidence drug-induced effects on cell migration in 3D transparent environments, such as matrix gels.

Factors influencing the spatial precision of electromagnetic tracking systems used for MEG/EEG source imaging

OBJECTIVES: The purpose of this study is to determine the factors influencing the spatial precision and the replicability of electromagnetic trackers (EMT) for the localization of electrodes and natural landmarks on the patient's head. MATERIALS AND METHODS: The effects of seven conditions on the measurement of the EMT were investigated with a Polhemus Fastrack: distance, contact between two components of the EMT, presence of magnetic object, localization of landmarks and electrodes on a phantom and a human subject without and with movements. RESULTS: The EMT has a precision of 0.15mm+/-0.36mm for the measurements made on still objects in a non-magnetic environment. On a human subject, the mean variation of the nasion position is 1.6mm+/-1.46mm and 2.7mm+/-1.40mm for the tragus. The increase of the electrode measurement dispersions is significant between the phantom and the human subject with a mean variation of 2.39mm+/-1.26mm. In certain conditions, up to 15% of the measurements may be considered as outliers. CONCLUSION: The precision significantly decreases for this application in the following cases: (1) physical contacts between the stylus/transmitter/receiver cables, (2) presence of magnetic objects in the surrounding of the EMT system, (3) skin and hair softness and (4) subject's head movements.

Detecting man-made structure changes to assist geographic data producers in planning their update strategy

Topographical data producers are currently confronted with the need for a faster updating method. Indeed, this need was assessed at the first stage of the ARMURS(∗) project by surveying several Belgian and international mapping agencies. The aim of the project is to build a demonstrator to assist data producers in planning the update of their topographic database more efficiently relying on remote sensing images, together with socio-economic and demographic data. At a regional scale, the man-made structure changes extracted by the ETATS module on a SPOT5 panchromatic image will be fused with a change analysis on socio-demographic data. At a local scale, as regards areas of predicted changes, the older databases are compared with recent very high-resolution satellite or aerial images in order to detect changes in man-made structures. Changes are detected by comparing an object-oriented classified VHR image to a simplified version of the old database. This object-oriented approach consists in a segmentation followed by a classification. Three segmentation methods (Watershed Assembly, Graph Cut, Mean Shift) were implemented and compared to the one of a commercial software (Definiens); indices were proposed to assess the quality of these segmentations. Features are selected either according to a visual interpretation formalised into an interpretation key, or by quantitative methods such as the forward Jeffries-Matusita distance or mutual information criteria (mRMR); selections are compared. By using a common framework (images, training set and validation set), existing classification methods available in Definiens and in R are compared. A final step of change detection gives us preliminary results.

Long-term temozolomide treatment induces marked amino metabolism modifications and an increase in TMZ sensitivity in Hs683 oligodendroglioma cells.

Gliomas account for more than 50% of all primary brain tumors. The worst prognosis is associated with gliomas of astrocytic origin, whereas gliomas with an oligodendroglial origin offer higher sensitivity to chemotherapy, especially when oligodendroglioma cells display 1p19q deletions. Temozolomide (TMZ) provides therapeutic benefits and is commonly used with radiotherapy in highly malignant astrocytic tumors, including glioblastomas. The actual benefits of TMZ during long-term treatment in oligodendroglioma patients have not yet been clearly defined. In this study, we have investigated the effects of such a long-term TMZ treatment in the unique Hs683 oligodendroglioma model. We have observed increased TMZ sensitivity of Hs683 orthotopic tumors that were previously treated in vitro with months of progressive exposure to increasing TMZ concentrations before being xenografted into the brains of immunocompromised mice. Whole-genome and proteomic analyses have revealed that this increased TMZ sensitivity of Hs683 oligodendroglioma cells previously treated for long periods with TMZ can be explained, at least partly, by a TMZ-induced p38-dependant dormancy state, which in turn resulted in changes in amino acid metabolism balance, in growth delay, and in a decrease in Hs683 oligodendroglioma cell-invasive properties. Thus, long-term TMZ treatment seems beneficial in this Hs683 oligodendroglioma model, which revealed itself unable to develop resistance against TMZ.

In vivo assessment of temozolomide local delivery for lung cancer inhalation therapy.

The aim of this study was to compare the efficacy of local drug delivery by inhalation to intravenous delivery in a B16F10 melanoma metastatic lung model. Temozolomide was formulated as a suspension, which was elaborated and evaluated in terms of particle size, shape and agglomeration. An endotracheal administration device was used to aerosolise the suspension. This mode of delivery was evaluated at different temozolomide concentrations and was optimized for the uniformity of delivered dose, the droplet size distribution and the distribution of droplets in vivo. Of the particles in the stabilised suspension, 79% were compatible with the human respirable size range, and this formulation retained 100% in vitro anticancer activity as compared to temozolomide alone in three distinct cancer cell lines. The pulmonary delivery device provided good reproducibility in terms of both the dose delivered and the droplet size distribution. Most of the lung tissues that were exposed to aerosol droplets contained the particles, as revealed by fluorescent microscopy techniques. The global in vivo antitumour activity of the inhaled temozolomide provided a median survival period similar to that for intravenous temozolomide delivery, and three out of 27 mice (11%) survived with almost complete eradication of the lung tumours. The present study thus shows that inhalation of a simple liquid formulation is well tolerated and active against a very biologically aggressive mouse melanoma pulmonary pseudo-metastatic model. This inhalation delivery could be used to deliver other types of anticancer drugs.

Lycorine and its derivatives for anticancer drug design.

Amaryllidaceae alkaloids are extensively studied for their biological activities in several pharmaceutical areas, including, for example, Alzheimer's disease for which galanthamine has already reached the market. Among this chemical family, lycorine displays very promising anti-tumor properties. This review first focuses on the chemical diversity of natural and synthetic analogues of lycorine and their metabolites, and then on mechanisms of action and biological targets through which lycorine and its derivatives display their anti-tumor activity. Our analysis of the structure-activity relationships of this family of compounds highlights the existence of various potential leads for the development of novel anticancer agents.

Modeling and exploiting spatial locality trade-offs in wavelet-based applications under varying resource requirements

2009

Computer-assisted needle positioning for liver tumour radiofrequency ablation (RFA)

Galectin-8 up-regulation during hypopharyngeal and laryngeal tumor progression and comparison with galectin-1, -3 and -7.

To define specific staining patterns for the adhesion/growth-regulatory lectin tandem-repeat-type galectin-8 in hypopharyngeal and laryngeal tumor progression and relate these parameters to galectins 1, 3 and 7 in the quest to explore the galectin network.

Unbalancing the phosphatidylinositol-4,5-bisphosphate-cofilin interaction impairs cell steering.

Cofilin is a key player in actin dynamics during cell migration. Its activity is regulated by (de)phosphorylation, pH, and binding to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P(2)]. Here, we here use a human cofilin-1 (D122K) mutant with increased binding affinity for PI(4,5)P(2) and slower release from the plasma membrane to study the role of the PI(4,5)P(2)-cofilin interaction in migrating cells. In fibroblasts in a background of endogenous cofilin, D122K cofilin expression negatively affects cell turning frequency. In carcinoma cells with down-regulated endogenous cofilin, D122K cofilin neither rescues the drastic morphological defects nor restores the effects in cell turning capacity, unlike what has been reported for wild-type cofilin. In cofilin knockdown cells, D122K cofilin expression promotes outgrowth of an existing lamellipod in response to epidermal growth factor (EGF) but does not result in initiation of new lamellipodia. This indicates that, next to phospho- and pH regulation, the normal release kinetics of cofilin from PI(4,5)P(2) is crucial as a local activation switch for lamellipodia initiation and as a signal for migrating cells to change direction in response to external stimuli. Our results demonstrate that the PI(4,5)P(2) regulatory mechanism, that is governed by EGF-dependent phospholipase C activation, is a determinant for the spatial and temporal control of cofilin activation required for lamellipodia initiation.

Screening of anti-glioma effects induced by sigma-1 receptor ligands: potential new use for old anti-psychiatric medicines.

The prognosis of glioblastoma (GBM) remains poor. Diffuse invasion of distant brain tissue by migrating cells from the primary tumour mass has already occurred at time of diagnosis. Anti-cancer effects of a selective sigma-1 agonist, 4-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP), in glioblastoma were shown previously, leading to the present work where the effects on glioblastoma cells of 17 agonists or antagonists of sigma-1 receptors were studied, including currently marketed drugs fluvoxamine, dextromethorphan, donepezil, memantine and haloperidol. We first showed that established GBM cell lines, primary cultures and surgical specimens express sigma-1 receptors. In vitro analyses then focused on anti-proliferation and anti-migratory effects on human glioblastoma cell lines using quantitative videomicroscopy analyses. These cell monitoring assays revealed specific impacts on the mitotic cell process. Using an aggressive glioma model orthotopically grafted into the brains of immunocompromised mice, we showed that combining donepezil and temozolomide gave additive benefit in terms of long survivors as compared to temozolomide or donepezil alone. Clinical study is planned if further rodent dose-ranging studies of donepezil with temozolomide continue to show evidence of benefit in this model.

Requirements for the valid quantification of immunostains on tissue microarray materials using image analysis.

Antibody-based proteomics applied to tissue microarray (TMA) technology provides a very efficient means of visualizing and locating antigen expression in large collections of normal and pathological tissue samples. To characterize antigen expression on TMAs, the use of image analysis methods avoids the effects of human subjectivity evidenced in manual microscopical analysis. Thus, these methods have the potential to significantly enhance both precision and reproducibility. Although some commercial systems include tools for the quantitative evaluation of immunohistochemistry-stained images, there exists no clear agreement on best practices to allow for correct and reproducible quantification results. Our study focuses on practical aspects regarding (i) image acquisition (ii) segmentation of staining and counterstaining areas and (iii) extraction of quantitative features. We illustrate our findings using a commercial system to quantify different immunohistochemistry markers targeting proteins with different expression patterns (cytoplasmic, nuclear or membranous) in colon cancer or brain tumor TMAs. Our investigations led us to identify several steps that we consider essential for standardizing computer-assisted immunostaining quantification experiments. In addition, we propose a data normalization process based on reference materials to be able to compare measurements between studies involving different TMAs. In conclusion, we recommend certain critical prerequisites that commercial or in-house systems should satisfy in order to permit valid immunostaining quantification.

Comparison of four antibodies for immunohistochemical evaluation of epidermal growth factor receptor expression in non-small cell lung cancer.

Agents acting on signalling molecules of growth pathways have emerged as therapeutics for non-small cell lung cancer (NSCLC). Among them are inhibitors of the epidermal growth factor receptor (EGFR). To meet Belgian reimbursement criteria for erlotinib, patients must have an EGFR-positive tumour, defined as at least 10% of cells showing membranous staining on immunohistochemistry. This study compares results obtained with the Dako pharmDx kit versus other anti-EGFR antibodies in 634 NSCLC. More than 80% of patients qualify for erlotinib therapy using the Dako pharmDx kit or antibodies from Zymed or Novocastra; when NeoMarkers antibodies are used, less than 70% will do. Although immunohistochemical stainings for EGFR can be performed on biopsies, surgical and cytological samples from primary and metastatic NSCLC, highest positivity rates were obtained in biopsies from primary tumours. In conclusion, immunohistochemistry for patient selection for erlotinib therapy needs standardization in order to avoid results influenced by technical issues.

Narciclasine, a plant growth modulator, activates Rho and stress fibers in glioblastoma cells.

Cell motility and resistance to apoptosis characterize glioblastoma multiforme growth and malignancy. Narciclasine, a plant growth modulator, could represent a powerful new weapon targeting the Achilles' heel of glioblastoma multiforme and may offer the potential to better combat these devastating malignancies. The in vitro effects of narciclasine on cell proliferation, morphology, actin cytoskeleton organization, and the Rho/Rho kinase/LIM kinase/cofilin pathway and its antitumor activity in vivo have been determined in models of human glioblastoma multiforme. Narciclasine impairs glioblastoma multiforme growth by markedly decreasing mitotic rates without inducing apoptosis. The compound also modulates the Rho/Rho kinase/LIM kinase/cofilin signaling pathway, greatly increasing GTPase RhoA activity as well as inducing actin stress fiber formation in a RhoA-dependent manner. Lastly, the treatment of human glioblastoma multiforme orthotopic xenograft- bearing mice with nontoxic doses of narciclasine significantly increased their survival. Narciclasine antitumor effects were of the same magnitude as those of temozolomide, the drug associated with the highest therapeutic benefits in treating glioblastoma multiforme patients. Our results show for the first time that narciclasine, a plant growth modulator, activates Rho and stress fibers in glioblastoma multiforme cells and significantly increases the survival of human glioblastoma multiforme preclinical models. This statement is made despite the recognition that to date, irrespective of treatment, no single glioblastoma multiforme patient has been cured.

The helicase-like transcription factor is a strong predictor of recurrence in hypopharyngeal but not in laryngeal squamous cell carcinomas.

To examine the immunohistochemical expression of helicase-like transcription factor (HLTF) in relation to the prognosis of hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinomas, and to characterize the HLTF protein variants expressed in biopsy specimens of head and neck squamous cell carcinoma (HNSCC) as well as the HeLa cell line.

Edge-Based Tracking of an LED Traffic Light for a Road-to-Vehicle Visible Light Communication System

Synchronization of surgical data in a distributed computer system

Free Viewpoint Video Generating Method for Walk-Through Experience

High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma.

Chemokines and their receptors are involved in tumourigenicity and clinicopathological significance of chemokines receptor expression in pancreatic adenocarcinoma (PA) is not fully understood. This study was conducted to determine patients' outcome according to the expressions of CXCR4, CXCR7 and HIF-1alpha after resection of PA. Immunohistochemistry for CXCR4, CXCR7 and HIF-1alpha expressions as well as cell proliferative index (Ki-67) was conducted in 71 resected (R0) PA and their 48 related lymph nodes (LN) using tissue microarray. CXCR4 and CXCR7 expressions were positively correlated to HIF-1alpha suggesting a potential role of HIF-1alpha in CXCR4 and CXCR7 transcription activation. Patients with CXCR4(high) tumour expression had shorter OS than those with low expression (median survival: 9.7 vs 43.2 months, P=0.0006), a higher risk of LN metastases and liver recurrence. In multivariate analysis, high CXCR4 expression, LN metastases and poorly differentiated tumour are independent negative prognosis factors. In a combining analysis, patients with CXCR4(low)/CXCR7(low) tumour had a significantly shorter DFS and OS than patients with a CXCR7(high)/CXCR4(high) tumour. CXCR4 in resected PA may represent a valuable prognostic factor as well as an attractive target for therapeutic purpose.

Galectin 1 proangiogenic and promigratory effects in the Hs683 oligodendroglioma model are partly mediated through the control of BEX2 expression.

We have previously reported that galectin 1 (Gal-1) plays important biological roles in astroglial as well as in oligodendroglial cancer cells. As an oligodendroglioma model, we make use of the Hs683 cell line that has been previously extensively characterized at cell biology, molecular biology, and genetic levels. Galectin 1 has been shown to be involved in Hs683 oligodendroglioma chemoresistance, neoangiogenesis, and migration. Down-regulating Gal-1 expression in Hs683 cells through targeted small interfering RNA provokes a marked decrease in the expression of the brain-expressed X-linked gene: BEX2. Accordingly, the potential role of BEX2 in Hs683 oligodendroglioma cell biology has been investigated. The data presented here reveal that decreasing BEX2 expression in Hs683 cells increases the survival of Hs683 orthotopic xenograft-bearing mice. Furthermore, this decrease in BEX2 expression impairs vasculogenic mimicry channel formation in vitro and angiogenesis in vivo, and modulates glioma cell adhesion and invasive features through the modification of several genes previously reported to play a role in cancer cell migration, including MAP2, plexin C1, SWAP70, and integrin beta(6). We thus conclude that BEX2 is implicated in oligodendroglioma biology.

Conception of a navigation system controlling diaphyseal fracture reduction treated with external fixation

Background. The reduction of long bone fractures treated with external fixation is usually performed with fluoroscopic images, which include several disadvantages: 2D information, distortions, and irradiation to the patient and the surgical team. This article presents a new navigation technique to control the reduction of such fractures while minimizing the irradiation.Methods. Optically tracked markers are fixed to pins inserted into the bone fragments. These last are modelled using two initial calibrated radiographs. The models can be improved with several types of anatomical data and are displayed in real time.Results. This navigation system was tested on dry bones and an anatomical specimen leg.Conclusions. This new technique allows the visualization of the fracture in real time and from any viewpoint during the reduction. Irradiation is minimized using only two X-ray images. Copyright © 2009 John Wiley & Sons, Ltd.

Identification of matrix metalloproteinase-9 as an independent prognostic marker in laryngeal and hypopharyngeal cancer with opposite correlations to adhesion/growth-regulatory galectins-1 and -7.

The enzymatic activity of matrix metalloproteinase-9 (MMP-9) suggests that its presence in hypopharyngeal and laryngeal squamous cell carcinomas (HSCCs, LSCCs) could have prognostic value. We tested this hypothesis by quantitative morphometric analysis of immunohistochemical staining in histological sections of 73 stage IV HSCCs and 45 LSCCs (30 cases of stage I/II, 15 cases of stage IV). As compared to tumour-free epithelium an increase for the labelling index in LSCCs reached statistical significance (p=0.04). Specimens of Reinke's edema were strongly higher in this parameter compared to tumour-free tissue area (p=0.000001), underscoring an association between the level of MMP-9 expression and inflammation. Focusing on patients' recurrence status we identified thresholds for the labelling index of 10% for HSCCs and 18% for LSCCs, both indicating rapid recurrence and dismal prognosis unless surpassed. When relating data for MMP-9 to those for three adhesion/growth-regulatory galectins, a positive correlation with galectin-7 expression was detected in LSCCs. This finding suggests a possible potential role of this endogenous lectin as inducer of MMP-9 gene expression in situ. Of note, galectin-1 expression was negatively correlated with MMP-9 and that of galectin-3, a substrate of MMP-9, not related. In conclusion our study delineated a prognostic role of MMP-9 immunodetection in high-stage HSCCs and in LSCCs when separating patients by a distinct threshold for the labelling index. Moreover, it indicated associations between MMP-9 and multifunctional galectins-1 and -7 in situ.

Feature-based stereo vision using smart cameras for traffic surveillance

Adhesion/growth-regulatory tissue lectin galectin-1 in relation to angiogenesis/lymphocyte infiltration and prognostic relevance of stromal up-regulation in laryngeal carcinomas

Graph nodes clustering with the sigmoid commute-time kernel: a comparative study

2D cell tracking by FPGA-optical correlation method

Our work uses 1080 images sequence obtained from "in vitro" samples taken every 4 min from a microscope under phase contrast technique. These images are in JPEG format and are 500×700 pixels size with a compression rate of 3:1. We developed an algorithm and characterize it over several image operations against the tracking effectiveness and its robustness respect mitosis and cell shape change. Image equalization, dilation and erosion were the image processing procedures founded to provide best tracking results. Equalization procedure, for example, required a time delay of 5 sec for a size target of 60x90 pixels and 9 sec for size target of 89x100 pixels. This algorithm was implemented into a FPGA which controlled our optical correlator in order to performance all Fourier operations by optical method. Our results showed that the use of the optical correlator can reduce the time consuming in the image process until for 90% which able us to track cells in vascular structure. © 2009 SPIE.

Spatial locality exploitation for runtime reordering of JPEG2000 wavelet data layouts

Cross-based local stereo matching using orthogonal integral images

Stream-centric stereo matching and view synthesis: a high-speed approach on GPUs

Exploiting varying resource requirements in wavelet-based applications in dynamic execution environments

Scheduling and resource allocation for SVC streaming over OFDM downlink systems

Real-time stereo-based view synthesis algorithms: a unified framework and evaluation on commodity GPUs

2008

Expression of galectins-1, -3 and -4 varies with strain and type of experimental colitis in mice.

Galectins are increasingly the focus of biomedical research. Although they are involved at different stages in inflammation, data on galectins in colitis remain scarce. The aim of this study was to determine and compare the expression of galectins in acute and chronic experimental colitis in mice. Immunohistochemistry for galectins-1, -3 and -4 was performed on colon tissue from C57BL/6 and BALB/c mice with acute dextran sodium sulphate colitis and from 129 Sv/Ev IL-10 knock-out (IL-10(-/-)) mice. From these three mouse strains, we first detected major differences in galectin expression related to the genetic background in the control animals. With regard to inflammation, chronic colitis in IL-10(-/-) mice was associated with increased galectin-4 expression; in contrast with the two other models, no galectin-1 and -3 alterations were observed in IL-10(-/-) mice. Acute colitis in C57BL/6 and BALB/c mice showed increased galectin-3 expression in the lamina propria and the crypt epithelium, together with a decreased nuclear expression. These results suggest an involvement of galectins in the development and perpetuation of colonic inflammation and illustrate that the choice of the mouse strain for studying galectins might influence the outcome of the experiments.

Matrix metalloproteinase-9 interplays with the IGFBP2-IGFII complex to promote cell growth and motility in astrocytomas.

Insulin-like growth factor II (IGFII) acts as a potent mitogen for several tumor types and has been reported to positively influence astrocytoma cell growth and motility. In the central nervous system, IGFII bioavailability is mainly modulated by insulin-like growth factor binding protein 2 (IGFBP2), which sequestrates IGFII and therefore prevents its interaction with the type-1 IGF receptor (IGF-IR). Proteolysis of IGFBP2 is the predominant mechanism recognized to reduce the binding affinity of IGFBP2 for IGFII, thus favoring dissociation of IGFII from the IGFBP2-IGFII complex. It is known that certain proteases involved in astrocytoma malignancy, such as matrix metalloproteinase-7 (MMP-7), plasmin, and cathepsin D, are able to proteolyze IGFBP2 in vitro. The present study aims to investigate whether other proteases expressed by astrocytomas, specifically MMP-2, MMP-9, and membrane-type 1 matrix metalloprotease (MT1-MMP), are able to proteolyze the IGFBP2-IGFII complex. Our results show the following: (i) MMP-9 proteolyzes the IGFBP2-IGFII complex in vitro, while MMP-2 and MT1-MMP do not; (ii) this MMP-9-induced IGFBP2-IGFII complex proteolysis releases free IGFII, which contributes to enhance the motility and the growth of LN229 astrocytoma cells. Furthermore, this study also highlights that the formation of the IGFBP2-IGFII complex inhibits IGFBP2's cell motility promoting effect by reducing the pool of free IGFBP2. In conclusion, MMP-9-induced IGFBP2 proteolysis may be regarded as an important post-translational event involved in astrocytoma aggressiveness. These new findings support drug targeting of MMP-9 as an interesting approach in the treatment of astrocytoma.

Helicase-like transcription factor exhibits increased expression and altered intracellular distribution during tumor progression in hypopharyngeal and laryngeal squamous cell carcinomas.

The helicase-like transcription factor (HLTF) belongs to the SWI/SNF family of proteins that use the energy from adenosine triphosphate hydrolysis to remodel chromatin during a variety of cellular processes. HLTF is also involved in DNA repair. Using computer-assisted microscopy, the immunohistochemical expression of HLTF was determined using a series of 100 hypopharyngeal and 56 laryngeal squamous cell carcinomas (SCCs) compared to tumor-free epithelia (60 cases) and dysplasias (92 cases). In hypopharyngeal SCC tumor progression, increased HLTF expression was associated with the percentage of immunopositive epithelial tissue areas (p = 0.02) and the staining intensity of the positive area (p = 0.0005). In the cases of laryngeal lesions, the immunolabeling intensity of HLTF significantly decreased with malignancy (p = 0.01). We also observed a significant shift of HLTF expression from the cytoplasm toward the nuclear compartment (p = 0.0007). Our data reveal an association between the presence of HLTF and neoplastic progression of hypopharyngeal and laryngeal SCCs.

Videomicroscopic extraction of specific information on cell proliferation and migration in vitro.

In vitro cell imaging is a useful exploratory tool for cell behavior monitoring with a wide range of applications in cell biology and pharmacology. Combined with appropriate image analysis techniques, this approach has been shown to provide useful information on the detection and dynamic analysis of cell events. In this context, numerous efforts have been focused on cell migration analysis. In contrast, the cell division process has been the subject of fewer investigations. The present work focuses on this latter aspect and shows that, in complement to cell migration data, interesting information related to cell division can be extracted from phase-contrast time-lapse image series, in particular cell division duration, which is not provided by standard cell assays using endpoint analyses. We illustrate our approach by analyzing the effects induced by two sigma-1 receptor ligands (haloperidol and 4-IBP) on the behavior of two glioma cell lines using two in vitro cell models, i.e., the low-density individual cell model and the high-density scratch wound model. This illustration also shows that the data provided by our approach are suggestive as to the mechanism of action of compounds, and are thus capable of informing the appropriate selection of further time-consuming and more expensive biological evaluations required to elucidate a mechanism.

Development of a computer assisted system aimed at RFA liver surgery

Radio frequency ablation (RFA) is a minimally invasive treatment for either hepatocellular carcinoma or metastasis liver carcinoma. In order to resect large lesions, the surgeon has to perform multiple time-consuming destruction cycles and reposition the RFA needle for each of them. The critical step in handling a successful ablation and preventing local recurrence is the correct positioning of the needle. For small tumors, the surgeon places the middle of the active needle tip in the center of the tumor under intra-operative ultrasound guidance. When one application is not enough to cover the entire tumor, the surgeon needs to repeat the treatment after repositioning of the needle, but US guidance is obstructed by the opacity stemming from the first RFA application. In this case the surgeon can only rely on anatomical knowledge and the repositioning of the RFA needle becomes a subjective task limiting the treatment accuracy. We have developed a computer assisted surgery guidance application for this repositioning procedure. Our software application handles the complete process from preoperative image analysis to tool tracking in the operating room. Our framework is mostly used for this RFA procedure, but is also suitable for any other medical or surgery application. © 2008 Elsevier Ltd. All rights reserved.

A novel technique for distal locking of intramedullary nail based on two non-constrained fluoroscopic images and navigation.

Galectin-3 upregulation during tumor progression in head and neck cancer.

To examine the level of expression of galectin-3 in relation to neoplastic progression of hypopharyngeal squamous cell carcinomas (HSCCs) and laryngeal squamous cell carcinomas (LSCCs).

Patterns of interstitial inflammation during the evolution of renal injury in experimental aristolochic acid nephropathy.

BACKGROUND: Interstitial inflammation is a prominent feature associated with the severity of renal injury and progressive kidney failure. We utilized an animal model of aristolochic acid (AA)-induced nephropathy (AAN) to assess patterns of infiltration and inflammation during the evolution of tubulointerstitial damage and to relate them to the development of fibrosis. METHODS: Male Wistar rats receiving sc daily AA or vehicle were sacrificed between Days 1 and 35. Infiltrating mononuclear cells were characterized by immunohistochemistry. The kidney infiltrating T lymphocytes were phenotyped by flow cytometry. Urinary levels of Th-1/ Th-2 cytokines, of monocyte chemoattractant protein-1 and of active transforming growth factor-beta (TGF-beta) were measured. Tissue expression of phosphorylated smad 2/3 protein was used to examine the TGF-beta signalling pathway. RESULTS: In AA rats, monocytes/macrophages and T lymphocytes predominantly infiltrated areas of necrotic proximal tubular cells. The coexpressions of ED1 and/or Ki-67/MHCII by infiltrating cells reflected monocyte/macrophage proliferation and their activation, respectively. The accumulation of cytotoxic T lymphocytes was attested by severe signs of CD8+ cell tubulitis. The CD8/E-cadherin costaining confirmed intrarenal homing of CD8+CD103+ cells. Urinary levels of proinflammatory cytokines and of active TGF-beta significantly increased at Days 10 and 35. An early and persistent nuclear overexpression of phosphorylated smad 2/3 protein was detected in tubular and interstitial compartments. CONCLUSION: An early and massive interstitial inflammation characterized by activated monocytes/macrophages and cytotoxic CD8+CD103+ T lymphocytes is demonstrated for the first time during the progression of experimental AAN. The involvement in an interstitial fibrosis onset of active TGF-beta is highly suggested, at least via the psmad 2/3 intracellular signalling pathway.

Expression of galectin-3 in the tumor immune response in colon cancer.

The role of tumor-associated macrophages (TAMs) is controversial. Although most studies on different cancer types associate them with a poorer prognosis, interestingly in colon cancer, most articles indicate that TAMs prevent tumor development; patients with high TAMs have better prognosis and survival rate. M1-polarized macrophages produce high level of tumor necrosis factor-alpha, interleukin-1 beta or reactive oxygen species, which can effectively kill susceptible tumor cells. In contrast, M2-polarized macrophages can secrete different factors that promote tumor cell growth and survival or favor angiogenesis and tissue invasion. Considering the beneficial role of TAMs in colon cancer, we speculated that they may not display the M2 polarization commonly observed in tumor microenvironment, but rather develop M1 properties. Therefore, we used an in vitro model to analyze the effects of supernatants from M1-polarized macrophages on DLD-1 colon cancer cells. Our data indicate that the conditioned medium from LPS-activated macrophages (CM-LAM) contains a high level of granulocyte-macrophage colony-stimulating factor, interleukins-1 beta, -6, -8 and tumor necrosis factor-alpha, and that it exerts a marked growth inhibitory activity on DLD-1 cells. Prolonged exposure to CM-LAM results in cell death by apoptosis. Such exposure to CM-LAM leads to the modulation of gal-3 expression: we observed a marked downregulation of gal-3 mRNA and protein expression following CM-LAM treatment. We also describe that the knockdown of gal-3 sensitizes DLD-1 cells to CM-LAM. These data suggest an involvement of gal-3 in the response of colon cancer cells to proinflammatory stimuli, such as the conditioned medium from activated macrophages.

Centralized control for surgical informatics systems in an integrated digital operating theater

Tenascin-C expression relates to clinicopathological features in pilocytic and diffuse astrocytomas.

AIMS: Tenascin-C (TN-C) is an extracellular matrix brain glycoprotein for which conflicting in vitro and in vivo results are reported in the literature dealing with its involvement in astrocytoma aggressiveness, in particular astrocytoma invasion. In view of these conflicting results and the lack of data available on low-grade astrocytomas, the present study focuses on pilocytic World Health Organization (WHO) grade I, and diffuse WHO grade II astrocytomas, that is, two histological entities associated with very different invasive abilities. METHODS: Using real-time reverse transcription polymerase chain reaction and immunohistochemistry, we analysed the TN-C expression in normal brain tissue as well as in a series of 54 pilocytic and 53 grade II astrocytomas. CONCLUSIONS: Our data on normal brain showed that while TN-C is largely expressed in supratentorial white matter, it was largely absent in infratentorial white matter. Paralleling these observations, we showed that TN-C expression in low-grade astrocytomas similarly varies according to tumour site. Cox regression analysis evidenced that TN-C provided an independent prognostic value which is enhanced in the case of grade II astrocytomas for which positive TN-C expression is associated with a higher risk of recurrence. We also analysed TN-C expression specifically in vascular areas of low-grade astrocytomas without demonstrating any prognostic value for this additional feature. RESULTS: Similarly to normal brain, low-grade astrocytomas exhibit variations in TN-C expression with site, and this expression is associated with an independent prognostic value in terms of recurrence.

UNBS5162, a novel naphthalimide that decreases CXCL chemokine expression in experimental prostate cancers.

Several naphthalimides have been evaluated clinically as potential anticancer agents. UNBS3157, a naphthalimide that belongs to the same class as amonafide, was designed to avoid the specific activating metabolism that induces amonafide's hematotoxicity. The current study shows that UNBS3157 rapidly and irreversibly hydrolyzes to UNBS5162 without generating amonafide. In vivo UNBS5162 after repeat administration significantly increased survival in orthotopic human prostate cancer models. Results obtained by the National Cancer Institute (NCI) using UNBS3157 and UNBS5162 against the NCI 60 cell line panel did not show a correlation with any other compound present in the NCI database, including amonafide, thereby suggesting a unique mechanism of action for these two novel naphthalimides. Affymetrix genome-wide microarray analysis and enzyme-linked immunosorbent assay revealed that in vitro exposure of PC-3 cells to UNBS5162 (1 microM for 5 successive days) dramatically decreased the expression of the proangiogenic CXCL chemokines. Histopathology additionally revealed antiangiogenic properties in vivo for UNBS5162 in the orthotopic PC-3 model. In conclusion, the present study reveals UNBS5162 to be a pan-antagonist of CXCL chemokine expression, with the compound displaying antitumor effects in experimental models of human refractory prostate cancer when administered alone and found to enhance the activity of taxol when coadministered with the taxoid.

Evidence of galectin-1 involvement in glioma chemoresistance.

Glioblastomas (GBMs) are resistant to apoptosis but less so to autophagy; a fact that may at least partly explain the therapeutic benefits of the pro-autophagic drug temozolomide in the treatment of GBM patients. Galectin-1 (Gal1) whose expression is stimulated by hypoxia is a potent modulator of GBM cell migration and a pro-angiogenic molecule. Hypoxia is also known to confer cancer cells with resistance to chemotherapy and radiotherapy and to modulate the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. The present study investigates whether decreasing Gal1 expression (by means of a siRNA approach) in human Hs683 GBM cells increases their sensitivity to pro-autophagic or pro-apoptotic drugs. The data reveal that temozolomide, the standard treatment for glioma patients, increases Gal1 expression in Hs683 cells both in vitro and in vivo. However, reducing Gal1 expression in these cells by siRNA increases the anti-tumor effects of various chemotherapeutic agents, in particular temozolomide both in vitro and in vivo. This decrease in Gal1 expression in Hs683 cells does not induce apoptotic or autophagic features, but is found to modulate p53 transcriptional activity and decrease p53-targeted gene expression including DDIT3/GADD153/CHOP, DUSP5 ATF3 and GADD45A. The decrease in Gal1 expression also impairs the expression levels of seven other genes implicated in chemoresistance: ORP150, HERP, GRP78/Bip, TRA1, BNIP3L, GADD45B and CYR61, some of which are located in the ER and whose expression is also known to be modified by hypoxia. This novel facet of Gal1 involvement in glioblastoma biology may be amenable to therapeutic manipulation.

The galectin family and digestive disease.

The soluble-type lectins or galectins constitute a family of proteins defined by shared consensus amino acid sequence and affinity for beta-galactose-containing oligosaccharides. These molecules are widely distributed in the animal kingdom; to date, 15 mammalian galectins have been described but more are likely to be discovered. These proteins are involved in many biological processes including cell-cell and cell-matrix adhesion, growth regulation, signaling, and cytokine secretion. Over the last decade, a vast amount of reports has shown the importance of several galectins in the development and progression of malignancies in the digestive tract, mainly colorectal cancers. More recent data indicate that some of these molecules are also involved in inflammatory bowel diseases. This review focuses on the current knowledge of galectin expression and putative functions in the oesophagus, stomach, small intestine, and colon. It also highlights that the rapid accumulation of research data promises future scenarios in which individual members of the galectin family and/or their ligands will be used as diagnostic and therapeutic modalities for neoplastic as well as inflammatory disorders. However, the concretization of these potential modalities requires substantial improvements in terms of standardization of galectin expression evaluation together with prospective validation of the present data.

Nucleolus and c-Myc: potential targets of cardenolide-mediated antitumor activity.

The use of cardenolides like ouabain, digitoxin, or oleandrin has been reported previously many times as a means of potentially combating human refractory prostate cancer by inducing apoptosis through an increase in intracellular calcium concentrations. The aims of the current study were to investigate if part of the antitumor effects mediated by cardenolides concerned disorganization of nucleolar structure and whether this was further associated with a marked decrease in c-Myc expression. Accordingly, the antitumor activity of a novel hemisynthetic cardenolide [1R,3aS,3bR,5aS,6aR,7aS,9R,12aR,13aR,15aR]-3a,11a-dihydroxy-13a-(hydroxymethyl)-9,15a-dimethyl-1-(5-oxo-2,5-dihydrofuran-3-yl)icosahydro-1H,4'H-spiro[cyclopenta [7,8]phenanthro[2,3-b]pyrano[3,2-e][1,4]dioxine-11,2'-[1,3]thiazolidin]-4'-one (UNBS1450)] was compared with that of classic cardenolides and reference anticancer agents in prostate cancer cell lines in vitro and in vivo following s.c. and orthotopic prostate cancer cell grafting into mice. The present study indicates that UNBS1450 markedly decreases the in vitro viability/proliferation of human prostate cancer cell lines but not of normal cells. The induced effects are not linked to an increase in intracellular calcium concentrations and subsequent induction of apoptosis. Rather, they appear to relate to the compound's capacity to disorganize nucleolar structure and function (through an impairment of cyclin-dependent kinase and c-Myc expression and related signaling pathways; paralleled by the disorganization of cancer cell-specific perinucleolar bodies as revealed by disruption of Sam68). This nonapoptotic cancer cell death mediated by severe nucleolar targeting and down-regulation of c-Myc expression is a completely new cardenolide-induced mechanism of antitumor action.

Knocking down galectin 1 in human hs683 glioblastoma cells impairs both angiogenesis and endoplasmic reticulum stress responses.

Galectin (Gal) 1 is a hypoxia-regulated proangiogenic factor that also directly participates in glioblastoma cell migration. To determine how Gal-1 exerts its proangiogenic effects, we investigated Gal-1 signaling in the human Hs683 glioblastoma cell line. Galectin 1 signals through the endoplasmic reticulum transmembrane kinase/ribonuclease inositol-requiring 1alpha, which regulates the expression of oxygen-regulated protein 150. Oxygen-regulated protein 150 controls vascular endothelial growth factor maturation. Galectin 1 also modulates the expression of 7 other hypoxia-related genes (i.e. CTGF, ATF3, PPP1R15A, HSPA5, TRA1, and CYR61) that are implicated in angiogenesis. Decreasing Gal-1 expression in Hs683 orthotopic xenografts in mouse brains by siRNA administration impaired endoplasmic reticulum stress and enhanced the therapeutic benefits of the proautophagic drug temozolomide. These results suggest that decreasing Gal-1 expression (e.g. through brain delivery of nonviral infusions of anti-Gal-1 siRNA in patients) can represent an additional therapeutic strategy for glioblastoma.

Aristolochic acid induces proximal tubule apoptosis and epithelial to mesenchymal transformation.

Aristolochic acid contamination in herbal remedies leads to interstitial fibrosis, tubular atrophy, and renal failure in humans. To study the cellular mechanisms contributing to the pathophysiology of this renal disease, we studied Wistar rats treated with aristolochic acid and measured tubular and interstitial cell proliferation, epithelial/mesenchymal cell marker expression, tubular membrane integrity, myofibroblast accumulation, oxidative stress, mitochondrial damage, tubular apoptosis, and fibrosis. Oxidative stress, a loss of cadherin concomitant with vimentin expression, basement membrane denudation with active caspase-3 expression, and mitochondrial injury within tubular cells were evident within 5 days of administration of the toxin. During the chronic phase, interstitial mesenchymal cells accumulated in areas of collagen deposits. Impaired regeneration and apoptosis of proximal tubular cells resulted in tubule atrophy with a near absence of dedifferentiated cell transmembrane migration. We suggest that resident fibroblast activation plays a critical role in the process of renal fibrosis during aristolochic acid toxicity.

Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy: a case series with 15-year follow-up.

BACKGROUND: Aristolochic acids are nephrotoxins and predispose to upper-tract urothelial carcinoma. The risk of bladder urothelial carcinoma after kidney transplantation and its relationship to upper-tract urothelial carcinoma is not well defined. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Single-center cohort of 38 women given kidney transplants for end-stage aristolochic acid nephropathy. OUTCOMES & MEASUREMENTS: The prevalence of upper urinary tract urothelial carcinoma was determined by collecting pathological results of specimens obtained by means of bilateral ureteronephrectomy. We also established the cumulative incidence of bladder urothelial carcinoma in biopsies performed during prospective screening cystoscopies during a 15-year follow-up. RESULTS: Upper-tract urothelial carcinoma was found in 17 patients with aristolochic acid nephropathy (44.7%). During follow-up, bladder urothelial carcinoma was diagnosed in 15 patients 68 to 169 months after cessation of aristolochic acid exposure (39.5%): 8 urothelial carcinoma in situ, 4 noninvasive low-grade papillary urothelial carcinoma, and 3 infiltrating urothelial carcinoma. 12 of 17 patients (71%) with a history of upper-tract urothelial carcinoma developed bladder urothelial carcinoma during follow-up, whereas this occurred in only 3 of 21 patients (14%) without upper-tract urothelial carcinoma (P < 0.01). Despite local and/or systemic chemotherapy, 3 patients died and 2 radical cystectomies were performed. LIMITATIONS: Small sample size of this case series. CONCLUSIONS: Upper-tract and bladder urothelial carcinoma are dramatic complications in kidney transplant recipients with aristolochic acid nephropathy, confirming the carcinogenic properties of aristolochic acids. We identified upper-tract urothelial carcinoma as a potent risk factor for the subsequent development of bladder urothelial carcinoma after kidney transplantation for aristolochic acid nephropathy. Because this complication may occur years after aristolochic acid discontinuation, we suggest regular cystoscopies in addition to the bilateral ureteronephrectomy in kidney transplant recipients with aristolochic acid nephropathy.

Apparent diffusion coefficient and cerebral blood volume in brain gliomas: relation to tumor cell density and tumor microvessel density based on stereotactic biopsies.

BACKGROUND AND PURPOSE: MR imaging-based apparent diffusion coefficient (ADC) and regional cerebral blood volume (rCBV) measurements have been related respectively to both cell and microvessel density in brain tumors. However, because of the high degree of heterogeneity in gliomas, a direct correlation between these MR imaging-based measurements and histopathologic features is required. The purpose of this study was to correlate regionally ADC and rCBV values with both cell and microvessel density in gliomas, by using coregistered MR imaging and stereotactic biopsies. MATERIALS AND METHODS: Eighteen patients (9 men, 9 women; age range, 19-78 years) with gliomas underwent diffusion-weighted and dynamic susceptibility contrast-enhanced MR imaging before biopsy. Eighty-one biopsy samples were obtained and categorized as peritumoral, infiltrated tissue, or bulk tumor, with quantification of cell and microvessel density. ADC and rCBV values were measured at biopsy sites and were normalized to contralateral white matter on corresponding maps coregistered with a 3D MR imaging dataset. ADC and rCBV ratios were compared with quantitative histologic features by using the Spearman correlation test. RESULTS: The highest correlations were found within bulk tumor samples between rCBV and cell density (r=0.57, P < .001) and rCBV and microvessel density (r=0.46, P < .01). An inverse correlation was found between ADC and microvessel density within bulk tumor (r=-0.36, P < .05), whereas no significant correlation was found between ADC and cell density. CONCLUSION: rCBV regionally correlates with both cell and microvessel density within gliomas, whereas no regional correlation was found between ADC and cell density.

Increased expression and altered intracellular distribution of adhesion/growth-regulatory lectins galectins-1 and -7 during tumour progression in hypopharyngeal and laryngeal squamous cell carcinomas.

To examine the level of expression of the pleiotropic regulators galectins-1 and -7 in relation to neoplastic progression of hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinomas.

Endothelial hyperplasia and endothelial galectin-3 expression are prognostic factors in primary central nervous system lymphomas.

Recently, considerable attention has been focused on the identification of clinically relevant prognostic markers for primary central nervous system lymphomas (PCNSL). The present study investigated whether three morphological features, i.e. necrosis, reactive perivascular T-cell infiltrate and endothelial hyperplasia, and galectin-1 and galectin-3 immunohistochemical expression have prognostic roles in a series of 58 PCNSL samples from 44 immunocompetent and 14 immunocompromised patients. The presence of endothelial hyperplasia (identified in 21% of the assessable cases) was identified as a bad prognostic factor for immunocompetent PCNSL patients, whereas the other morphological features were not associated with any prognostic value. Lymphomatous cells of eight PCNSL cases expressed galectin-3 without any prognostic value, and lymphomatous cells did not express galectin-1. In contrast, endothelial expression of galectin-3 was identified (by means of uni- and multi-variate analyses) as a bad prognostic factor for immunocompetent PCNSL patients. In addition, a combination of endothelial hyperplasia and/or endothelial galectin-3 expression was shown to be an independent prognostic factor for immunocompetent PCNSL patients treated with methotrexate-based chemotherapy. In summary, this study suggests that endothelial-related markers can identify risk groups of PCNSL patients and indicates that galectin-3 could be involved in PCNSL angiogenesis.

The determination of the levels of circulating galectin-1 and -3 in HNSCC patients could be used to monitor tumor progression and/or responses to therapy.

To evaluate galectin-1, -3 and -7 serum levels as diagnostic and/or prognostic markers for head and neck squamous cell carcinomas (HNSCCs). ELISA was employed to test sera from 102 patients with HNSCCs and from 38 healthy control volunteers for galectin-1, -3 and -7 serum levels. Serum galectin levels were assayed by ELISA and the levels of galectin expression in HNSCCs were determined by means of immunohistochemistry. HNSCCs display significant immunohistochemical amounts of galectin-7, but this galectin cannot be detected in the blood of HNSCC patients. Galectin-3 levels differ significantly (p=0.03) in healthy volunteers and HNSCC patients. Using a threshold value of 4.3 ng/ml, galectin-3 serum level enabled a significant level of discrimination (p=0.03) to be established between the cancer patients and the healthy volunteers, with 90% level of specificity and 36% level of sensitivity. The discrimination was even better when using a threshold value of 13.5 ng/ml for galectin-1 (p=0.001), with 100% level of specificity and 22% level of sensitivity. A subgroup of stage IV HNSCC patients displayed significantly reduced levels of circulating galectin-1 (p=0.003) and galectin-3 (p=0.001) after treatment as opposed to before. Galectin-3 concentrations in sera from the patients with a metastatic disease were significantly (p=0.01) higher than in sera from the patients with localized tumors. The determination of circulating levels of galectin-1 and -3 could be used to monitor the progression of their disease or their response to therapy.

Morphometric study of the eye of three species of Myrmica (Formicidae)

Méthode d'étude de la forme d'une structure microscopique, opaque et solide, appliquée à l'oeil d'une fourmi

Targeting the alpha 1 subunit of the sodium pump to combat glioblastoma cells.

OBJECTIVE: Ion transporters play pivotal roles in cancer cell migration in general and in glioblastomas (GBMs) in particular. However, the specific role of Na/K-ATPase (the sodium pump) and, in particular, its alpha1 subunit, has remained unexplored in GBMs. MATERIALS AND METHODS: The expression of Na+/K+ -ATPase alpha1 in GBM clinical samples, normal brain tissue, and a human GBM cell line has been investigated. Using the novel cardenolide UNBS1450 (Unibioscreen, Brussels, Belgium), which is a ligand of the sodium pump, we have characterized the effects of inhibiting Na+/K+ -ATPase alpha1 in human GBM cells with respect to cell proliferation; morphology; impact on intracellular Na+, Ca2+, and adenosine triphosphate; and changes in the actin cytoskeleton. We have investigated the mechanism by which UNBS1450 overcomes the apoptosis resistance of GBMs and determined its anti-tumor effects in comparative studies in vitro in GBM cell viability assays and in vivo using an orthotopic human GBM xenograft model. RESULTS: Overall, the alpha1 subunit of Na+/K+ -ATPase is highly expressed in a majority of glioblastomas compared with normal brain tissues, and by binding to this subunit in human U373-MG GBM cells, UNBS1450 impairs cell proliferation and migration via an intracellular adenosine triphosphate decrease-mediated disorganization of the actin cytoskeleton and cytotoxic proautophagic effects. UNBS1450 also significantly increases the in vivo survival of mice orthotopically grafted with U373-MG GBM cells. CONCLUSION: Inhibition of the Na+/K+ -ATPase alpha1 subunit in human GBM cells impairs both cell migration and cell proliferation.

Energy-efficient bandwidth allocation for multiuser scalable video streaming over WLAN

2007

Lymph node and organs at risk segmentation on 3D CT images for head and neck radiotherapy

Design of an articulated mini-fixation device for proximal interphalangeal joint finger fractures

High resolution 3D acquisition of the Olivier Strebelle's sculpture 'Athletes' Alley in Beijing 2008'

Cardiotonic steroids on the road to anti-cancer therapy.

The sodium pump, Na(+)/K(+)-ATPase, could be an important target for the development of anti-cancer drugs as it serves as a versatile signal transducer, it is a key player in cell adhesion and its aberrant expression and activity are implicated in the development and progression of different cancers. Cardiotonic steroids, known ligands of the sodium pump have been widely used for the treatment of heart failure. However, early epidemiological evaluations and subsequent demonstration of anti-cancer activity in vitro and in vivo have indicated the possibility of developing this class of compound as chemotherapeutic agents in oncology. Their development to date as anti-cancer agents has however been impaired by a narrow therapeutic margin resulting from their potential to induce cardiovascular side-effects. The review will thus discuss (i) sodium pump structure, function, expression in diverse cancers and its chemical targeting and that of its sub-units, (ii) reported in vitro and in vivo anti-cancer activity of cardiotonic steroids, (iii) managing the toxicity of these compounds and the limitations of existing preclinical models to adequately predict the cardiotoxic potential of new molecules in man and (iv) the potential of chemical modification to reduce the cardiovascular side-effects and improve the anti-cancer activity of new molecules.

High level of galectin-1 expression is a negative prognostic predictor of recurrence in laryngeal squamous cell carcinomas.

Monitoring of gene-expression profiles is assumed to refine tumor characterization of laryngeal squamous cell carcinomas (LSCCs) with a therapeutic perspective. This is especially expected for adhesion/growth-regulatory effectors such as galectins, a class of endogenous lectins. Using computer-assisted microscopy, we investigated the prognostic value contributed by the quantitative determination of the immunohistochemical levels of expression of galectin-1, -3 and -7 in a series of 62 LSCCs including 42 low- and 20 high-stage LSCCs. As galectin-1 may have a key role leading to a tumor escape from immune surveillance, we also investigated whether or not the level of galectin-1 expression correlated with lymphocyte infiltration in LSCCs. The immunohistochemical determination of expression of galectin-1 is of prognostic value in human squamous laryngeal cancers. LSCCs that display high levels of galectin-1 have worse prognoses than laryngeal cancers with low levels of galectin-1 expression. Elevation of galectin-1 levels in laryngeal cancers can contribute to the process of tumor immune escape by killing the activated T-cells and other protumoral activities such as promoting motility or activity of oncogenic H-Ras proteins. The quantitative determination of galectin-1 in LSCCs is an independent prognostic marker when opposed to TNM staging. It has the potential to identify patients unlikely to benefit from T-cell-mediated immunotherapy, although the definitive effector function from its pro- and antitumoral activity profile has not been delineated.

4-IBP, a sigma1 receptor agonist, decreases the migration of human cancer cells, including glioblastoma cells, in vitro and sensitizes them in vitro and in vivo to cytotoxic insults of proapoptotic and proautophagic drugs.

Although the molecular function of sigma receptors has not been fully defined and the natural ligand(s) is still not known, there is increasing evidence that these receptors and their ligands might play a significant role in cancer biology. 4-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP), a selective sigma1 agonist, has been used to investigate whether this compound is able to modify: 1) in vitro the migration and proliferation of human cancer cells; 2) in vitro the sensitivity of human glioblastoma cells to cytotoxic drugs; and 3) in vivo in orthotopic glioblastoma and non-small cell lung carcinoma (NSCLC) models the survival of mice co-administered cytotoxic agents. 4-IBP has revealed weak antiproliferative effects on human U373-MG glioblastoma and C32 melanoma cells but induced marked concentration-dependent decreases in the growth of human A549 NSCLC and PC3 prostate cancer cells. The compound was also significantly antimigratory in all four cancer cell lines. This may result, at least in U373-MG cells, from modifications to the actin cytoskeleton. 4-IBP modified the sensitivity of U373-MG cells in vitro to proapoptotic lomustin and proautophagic temozolomide, and markedly decreased the expression of two proteins involved in drug resistance: glucosylceramide synthase and Rho guanine nucleotide dissociation inhibitor. In vivo, 4-IBP increased the antitumor effects of temozolomide and irinotecan in immunodeficient mice that were orthotopically grafted with invasive cancer cells.

Can anti-migratory drugs be screened in vitro? A review of 2D and 3D assays for the quantitative analysis of cell migration.

The aim of the present review is to detail and analyze the pros and cons of in vitro tests available to quantify the anti-migratory effects of anti-cancer drugs for their eventual use in combating the dispersal of tumor cells, a clinical need which currently remains unsatisfied. We therefore briefly sum up why anti-migratory drugs constitute a promising approach in oncology while at the same time emphasizing that migrating cancer cells are resistant to apoptosis. To analyze the pros and cons of the various in vitro tests under review we also briefly sum up the molecular and cellular stages of cancer cell migration, an approach that enables us to argue both that no single in vitro test is sufficient to characterize the anti-migratory potential of a drug and that standardization is needed for the efficient quantitative analysis of cell locomotion in a 3D environment. Before concluding our review we devote the final two parts (i) to the description of new prototypes which, in the near future, could enter the screening process with a view to identifying novel anti-migratory compounds, and (ii) to the anti-migratory compounds currently developed against cancer, with particular emphasis on how these compounds were selected before entering the clinical trial phase.

Stereotactic comparison among cerebral blood volume, methionine uptake, and histopathology in brain glioma.

BACKGROUND AND PURPOSE: Vascularity, metabolism, and histologic grade are related in gliomas but the exact determinants of these relationships are not fully defined. We used image coregistration and stereotactic biopsies to regionally compare cerebral blood volume (CBV) and (11)C-methionine (MET) uptake measurements in brain gliomas and to assess their relationship by histopathologic examination. MATERIALS AND METHODS: Fourteen patients with brain gliomas underwent MR imaging, including dynamic susceptibility contrast-enhanced MR and positron-emission tomography (PET) using MET acquired in identical stereotactic conditions before biopsy. MR-based CBV maps were calculated and both CBV maps and PET images were coregistered to anatomic images. Sixty-five biopsy samples were obtained on trajectories targeted toward high MET uptake area. The following histopathologic features were semiquantified in each sample: mitotic activity, endothelial proliferation, cellular pleomorphism, and tumor necrosis. CBV and MET uptake values were measured in the biopsy area and normalized to contralateral white matter. CBV ratios were compared with MET uptake ratios, and both measurements were compared with histologic features of each sample. RESULTS: CBV ratios ranged from 0.08 to 10.24 (median = 1.73), and MET uptake ratios ranged from 0.30 to 4.91 (median = 1.67). There was a positive correlation between CBV ratios and MET uptake ratios (r = 0.65, P < .001). Both CBV and MET uptake ratios were found to be significantly related to endothelial proliferation and mitotic activity (P < .01). CONCLUSION: Within glial tumors, there is a local relationship between CBV and MET uptake measurements. Both provide indices of focal malignant activity.

Neurotensin is a versatile modulator of in vitro human pancreatic ductal adenocarcinoma cell (PDAC) migration.

BACKGROUND: While the neurotensin (NT) roles in pancreatic cancer growth are well documented, its effects on pancreatic cancer cell migration have not been described. METHODS: The NT-induced effects on the migration process of human pancreatic ductal adenocarcinoma cells (PDACs) were characterized by means of various assays including computer-assisted video-microscopy, fluorescence microscopy, ELISA-based, small GTPase pull-down and phosphorylation assays. RESULTS: The NT-induced modifications on in vitro PDACs migration largely depended on the extra-cellular matrix environment and cell propensity to migrate collectively or individually. While NT significantly reduced the level of migration of collectively migrating PDACs on vitronectin, it significantly increased the level of individually migrating PDACs. These effects were mainly mediated through the sortilin/NTR3 receptor. Neurotensin both induced altered expression of alphaV and beta5 integrin subunits in PDACs cultured on vitronectin resulting in modified adhesion abilities, and caused modifications to the organization of the actin cytoskeleton through the NT-mediated activation of small Rho GTPases. While the NT effects on individually migrating PDACs were mediated at least through the EGFR/ERK signaling pathways, those on collectively migrating PDACs appeared highly dependent on the PI 3-kinase pathway. CONCLUSION: This study strongly suggests the involvement of neurotensin in the modulation of human PDAC migration.

Cell tracking by border-optical hybrid model

We propose an hybrid (image processing-correlation) method to obtain cells detection and cells migration tracking in order to analyze cells behaviors under different conditions. © 2007 OSA.

3D game content distributed adaptation in heterogeneous environments

2006

The in vitro influences of neurotensin on the motility characteristics of human U373 glioblastoma cells.

Astrocytic tumours are associated with dismal prognoses due to their pronounced ability to diffusely invade the brain parenchyma. Various neuropeptides, including gastrin, are able to modulate tumour astrocyte migration. While neurotensin has been shown to influence the proliferation of glioma cells and the migratory ability of a large set of other cell types, its role in glioma cell migration has never been investigated. Neurotensin-induced modifications to the motility features of human U373 glioblastoma cells therefore constitute the topic of the present study. We evidenced that three subtypes of neurotensin receptors (NTR1, NTR2 and NTR3) are expressed in U373 glioblastoma cells, at least as far as their mRNAs are concerned. Treating U373 tumour cells with 10 nM neurotensin markedly modified the morphological patterns of these cells and also profoundly altered the organization of their actin cytoskeletons. Pull-down assays revealed that neurotensin induced the activation in U373 cells of both Rac1 and Cdc42 but not RhoA. Scratch wound assays evidenced that neurotensin (0.1 and 10 nM) very significantly inhibited wound colonization by U373 cells cultured in the absence of serum. In addition, quantitative phase-contrast videomicroscopy analyses showed that neurotensin decreases the motility levels of U373 glioblastoma cells when these cells are cultured on plastic. In sharp contrast, neurotensin stimulates the motility of U373 cells when they are cultured on laminin, which is a pro-adhesive extracellular matrix component ubiquitously secreted by glioma cells. Our data thus strongly suggest that, in addition to gastrin, neurotensin is a neuropeptide capable of modulating tumour astrocyte migration into the brain parenchyma.

Free listening‐point synthesizing method in a large microphone array using acoustic transfer function

Exploring the distinctive biological characteristics of pilocytic and low-grade diffuse astrocytomas using microarray gene expression profiles.

Although World Health Organization (WHO) grade I pilocytic astrocytomas and grade II diffuse astrocytomas have been classified for decades as different clinicopathologic entities, few, if any, data are available on the biologic features explaining these differences. Although more than 50 microarray-related studies have been carried out to characterize the molecular profiles of astrocytic tumors, we have identified only 11 that provide sound data on low-grade astrocytomas. We have incorporated these data into a comparative analysis for the purpose of identifying the most relevant molecular markers characterizing grade I pilocytic and grade II diffuse astrocytomas. Our analysis has identified various interesting genes that are differentially expressed in either grade I or grade II astrocytomas when compared with normal tissue and/or high-grade (WHO grade III and IV) astrocytomas. A large majority of these genes encode adhesion, extracellular matrix, and invasion-related proteins. Interestingly, a group of 6 genes (TIMP4, C1NH, CHAD, THBS4, IGFBP2, and TLE2) constitute an expression profile characteristic of grade I astrocytomas as compared with all other categories of tissue (normal brain, grade II, and high-grade astrocytomas). The end products (proteins) of these genes act as antimigratory compounds, a fact that could explain why pilocytic astrocytomas behave as compact (well-circumscribed) tumors as opposed to all the other astrocytic tumor types that diffusely invade the brain parenchyma. Having validated these molecular markers by means of real-time reverse transcriptase-polymerase chain reaction, an integrated model was proposed illustrating how and why pilocytic astrocytomas constitute a distinct biologic and pathologic entity when compared with diffuse astrocytomas.

Galectin 7 (p53-induced gene 1): a new prognostic predictor of recurrence and survival in stage IV hypopharyngeal cancer.

BACKGROUND: Eighty percent of hypopharyngeal squamous cell carcinoma patients have advanced stages (III and IV) of the disease, and biological markers are required to predict high-risk head and neck squamous cell carcinoma patients in need of highly aggressive treatments after surgery to improve the survival rate. We analyzed the potential prognostic value of galectin 7 in a series of 81 stage IV hypopharyngeal SCCs because galectin 7 is an emerging marker involved in the epidermal development of pluristratified epithelia and in epidermal cell migration. METHODS: The immunohistochemical expression of galectin 7 was determined on a series of 81 stage IV hypopharyngeal SCCs and was compared with that of galectins 1 and 3. RESULTS: High levels of galectin 7 expression were associated with rapid recurrence rates and dismal prognoses in these 81 stage IV hypopharyngeal SCCs, a feature not observed with galectin 3 and one observed weakly, if at all, with galectin 1. CONCLUSIONS: These data suggest that the immunohistochemical determination of galectin 7 expression in the case of high-risk hypopharyngeal cancers is a meaningful tool to identify patients who should benefit from aggressive postsurgical adjuvant therapy after surgery, including not only radiotherapy, but also chemotherapy.

Characterization of patterns of expression of protein kinase C-alpha, -delta, -eta, -gamma and -zeta and their correlations to p53, galectin-3, the retinoic acid receptor-beta and the macrophage migration inhibitory factor (MIF) in human cholesteatomas.

Cholesteatoma is a benign disease characterized by the presence of an unrestrained growth and the accumulation of keratin in the middle ear cavity. Due to roles in cell proliferation, apoptosis and differentiation members of the protein kinase C (PKC) family could be involved in disease progression. This study focuses on the expression of protein kinase C-alpha, -delta, -eta, -gamma and -zeta in the epithelial tissues of 56 human cholesteatomas and their correlations with those of previously characterized distributions of p53, galectin-3, retinoic acid receptor-beta (RARbeta) and macrophage migration inhibitory factor (MIF). We have previously reported this marker set to be correlated with keratinocyte differentiation in human cholesteatomas. Our present data clearly show that the percentage of PKC-alpha (but not PKC-delta, -gamma, -eta and -zeta)-immunopositive cells in epithelial tissue fro recurrent cholesteatomas was significantly higher than in non-recurrent cases. Correlations between the PKC isoenzymes and the biological markers were non-uniform. PKC-alpha (but not PKC-delta, -gamma, -eta and -zeta) expression in epithelial cholesteatoma cells correlated significantly and positively with the percentages of p53-immunopositive cells. The patterns of PKC-alpha and -delta expression, but not of PKC-gamma, -eta and -zeta, correlated significantly and positively with galectin-3 expression. In addition, the correlation levels between the expression of PKC-alpha and -delta and that of galectin-3 varied depending on the infection and recurrence status. Presence of RARbeta correlated significantly (and positively) with the expression of PKC-gamma and -zeta and also in relation to the infection and recurrence status. MIF correlated presence significantly (and positively) with that of the five PKCs under study, depending on whether the cholesteatomas were non-infected or infected as well as non-recurrent or recurrent. In conclusion, the present study suggests that modifications occurring at the level of keratinocyte differentiation in human cholesteatomas involve distinct effectors, to which the activation of PKC-alpha, -delta, -eta, -gamma and -zeta can be added.

Characterization of the activities of actin-affecting drugs on tumor cell migration.

Metastases kill 90% of cancer patients. It is thus a major challenge in cancer therapy to inhibit the spreading of tumor cells from primary tumor sites to those particular organs where metastases are likely to occur. Whereas the actin cytoskeleton is a key component involved in cell migration, agents targeting actin dynamics have been relatively poorly investigated. Consequently, valuable in vitro pharmacological tools are needed to selectively identify this type of agent. In response to the absence of any standardized process, the present work aims to develop a multi-assay strategy for screening actin-affecting drugs with anti-migratory potentials. To validate our approach, we used two cancer cell lines (MCF7 and A549) and three actin-affecting drugs (cytochalasin D, latrunculin A, and jasplakinolide). We quantified the effects of these drugs on the kinetics of actin polymerization in tubes (by means of spectrofluorimetry) and on the dynamics of actin cytoskeletons within whole cells (by means of fluorescence microscopy). Using quantitative videomicroscopy, we investigated the actual effects of the drugs on cell motility. Finally, the combined drug effects on cell motility and cell growth were evaluated by means of a scratch-wound assay. While our results showed concordant drug-induced effects on actin polymerization occurring in vitro in test tubes and within whole cells, the whole cell assay appeared more sensitive than the tube assay. The inhibition of actin polymerization induced by cytochalasin D was paralleled by a decrease in cell motility for both cell types. In the case of jasplakinolide, which induces actin polymerization, while it significantly enhanced the locomotion of the A549 cells, it significantly inhibited that of the MCF-7 ones. All these effects were confirmed by means of the scratch-wound assay except of the jasplakinolide-induced effects on MCF-7 cell motility. These later seemed compensated by an additional effect occurring during wound recolonization (possibly acting on the cell growth features). In conclusion, the use of multi-assays with different levels of sophistication and biological relevance is recommended in the screening of new actin-affecting drugs with potentially anti-migratory effects.

Digital holographic microscopy for the three-dimensional dynamic analysis of in vitro cancer cell migration.

Cancer cell motility and invasion are critical targets for anticancer therapeutics. Whereas in vitro models could be designed for rapid screening with a view to investigate these targets, careful consideration must be given to the construction of appropriate model systems. Most investigations focus on two-dimensional (2-D) assays despite the fact that increasing evidence suggests that migration across rigid and planar substrates fails to recapitulate in vivo behavior. In contrast, few systems enable three-dimensional (3-D) cell migration to be quantitatively analyzed. We previously developed a digital holographic microscope (DHM) working in transmission with a partially spatial coherence source. This configuration avoids the noise artifacts of laser illumination and makes possible the direct recording of information on the 3-D structure of samples consisting of multiple objects embedded in scattering media, such as cell cultures in matrix gels. The software driving our DHM system is equipped with a time-lapse ability that enables the 3-D trajectories of living cells to be reconstituted and quantitatively analyzed.

New digital method for quantitative assessment of nasal morphology.

Our aim was to develop and validate a new method to assess objectively and quantitatively the morphology of the nostrils after nasal or nasolabial surgery. We used digital analysis using specific mathematical algorithms to assess several geometric measurements, particularly of facial asymmetry, expressed in adimensional units. Forty-five patients with no facial anomalies (control group) were used initially to evaluate the method and to obtain variables for statistical reference. Thirty-five patients operated on for unilateral cleft lip and palate (cleft group) were then analysed and compared with the control group. Individual scores were obtained for each patient, computed, and correlated with those established by a lay panel. Statistical analysis showed good sensitivity and reliability (R>0.8).

Multi-user motion JPEG2000 over wireless LAN: run-time performance-energy optimization with application-aware cross-layer scheduling

Channel adaptive rate control for energy optimization

Platform independent optimization of multi-resolution 3D content to enable universal media access

Optimized memory requirements for wavelet-based scalable multimedia codecs

Eliminating CPU overhead for on-the-fly content adaptation with MPEG-4 wavelet subdivision surfaces

2005

Co-expression/co-location of S100 proteins (S100B, S100A1 and S100A2) and protein kinase C (PKC-beta, -eta and -zeta) in a rat model of cerebral basilar artery vasospasm.

OBJECT: The cellular events leading to cerebral vasospasm after subarachnoid haemorrhages (SAH) involve a number of members of the protein kinase C (PKC) family. However, whereas calcium is thought to play a number of major roles in the pathophysiology of SAH, a number of PKCs function independently of calcium. We recently emphasized the potential role of the calcium-binding S100 proteins in a 'double haemorrhage' rat model of SAH-induced vasospasm. A number of S100 proteins are known to interfere directly with PKC, or indirectly with PKC substrates. We therefore investigated whether specific S100 proteins and PKCs are co-expressed/co-located in a rat model of SAH-induced vasospasm. METHODS AND RESULTS: SAH-induced vasospasm in rats (by means of a double cisternal injection of autologous blood from a rat femoral artery) distinctly modified the expression levels of calcium-dependent PKC-alpha and PKC-beta and calcium-independent PKC-eta and PKC-zeta in endothelial and smooth-muscle cells. The RNA levels of these four PKC isotypes were determined by quantitative RT-PCR. The present study reveals that, in endothelial cells, the S100B expression/location correlate well with those of PKC-eta, and those of S100A1 with PKC-beta. In smooth-muscle cells S100A2 expression/location correlate with those of PKC-eta, and those of S100B with PKC-zeta. CONCLUSION: The present data argue in favour of a joint action of the S100 protein network and the PKC signalling pathway during cerebral vasospasm.

Assessment of Very High Spatial Resolution Satellite Image Segmentations

Human galectin-2: expression profiling by RT-PCR/immunohistochemistry and its introduction as a histochemical tool for ligand localization.

Sugar-encoded information of glyco-conjugates is translated into cellular responses by endogenous lectins. Galectins stand out against other lectin families due to their wide range of functions including cell adhesion, tissue invasion or growth regulation exerted at extracellular, membrane, cytoplasmic and nuclear sites. This remarkable versatility warrants close scrutiny of their emerging network, in this study with focus on homodimeric human galectin-2. We first detected presence of specific mRNA in various tissue types by processing post mortem and surgical specimens by RT-PCR protocols. Overlap of gene expression was noted with proto-type galectins-1 and -7 and also family members from the other two subgroups. To monitor expression on the level of protein a polyclonal anti-galectin-2 antibody was raised. Immunopositivity was semi-quantitatively assessed in sections of 209 human samples establishing an array both of normal tissues and samples with inflammation or benign/malignant growth. In general, positivity was predominantly epithelial without restriction of staining to certain tissue types, as fittingly indicated by our RT-PCR analysis. Staining was not limited to the cytoplasm but also included nuclear sites. To examine the suitability of the labeled lectin as a histochemical probe we biotinylated galectin-2 under activity-preserving conditions and introduced it to tissue profiling. Specific cytoplasmic staining proved the validity of the concept. Our results encourage systematic histopathologic studies by immuno- and lectin histochemistry, especially by adding galectin-2 as study object to galectin fingerprinting which has already yielded prognostic information on galectins-1, -3, -4 and -8 and hereby contributed to define functional overlap/divergence in this lectin family.

The Adaptive Distributed Source Coding of Multi-View Images in Camera Sensor Networks

Nuclear galectin-3 expression is an independent predictive factor of recurrence for adenocarcinoma and squamous cell carcinoma of the lung.

The tumor stage is the most powerful prognostic tool for predicting the survival rates of lung carcinoma patients. However, prognosis of individual patients is difficult in part because of the marked clinical heterogeneity among such patients. Galectins are involved in cell growth, apoptosis and cell migration features, and their diagnostic and prognostic values have already been demonstrated in various types of cancers. In the present paper we analyze the potential prognostic value of immunohistochemical galectin-3 expression in lung adenocarcinomas and squamous cell carcinomas. In all, 165 squamous cell carcinomas and 121 adenocarcinomas were immunostained for galectin-3. In each case the immunohistochemical analyses consisted of an evaluation of the percentage of tumor cells stained and the intensity of staining. An IP score (ie Intensity x Percentage) was thus determined for each lung carcinoma. A large majority of cases displayed galectin-3 expression. While the cytoplasmic staining in the squamous cell carcinomas was focal and moderately intense, the staining in the adenocarcinomas was diffuse and intense. The IP scores were significantly (P=0.0001) higher in the adenocarcinomas than in the squamous cell carcinomas. The difference in nuclear expression profiles between the two cancer types was statistically significant (P=0.0005). Cox multivariate analysis carried out on the patients' genders, the TNM classification and the galectin-3-related variables showed that of the galectin-3-related variables, only the nuclear location of galectin-3 was identified as a prognostic indicator of recurrence independent of the clinicopathological features characterizing the patients (P=0.02). The prognostic contribution of this latter variable was enhanced when the patients with relapse-free follow-ups longer than 8 months were considered (P=0.005). Galectin-3 immunohistochemical expression differs between squamous cell carcinomas and adenocarcinomas, but the nuclear expression of galectin-3 behaves as a significant prognostic predictor for all the cases as a group.

Galectin-1 knocking down in human U87 glioblastoma cells alters their gene expression pattern.

We have previously reported that (i) progression of malignancy in patients bearing astrocytic tumors correlates with increased tumor levels of galectin-1; (ii) in vitro addition of purified galectin-1 to U87 human glioblastoma cells enhances tumor cell motility; and (iii) conversely, knocking down galectin-1 expression in this cell line by stable transfection with antisense galectin-1 mRNA impairs motility and delays mortality after their intracranial grafting to nude mice. We here used cDNA microarray analysis to compare the effect on gene expression of stable transfection with antisense galectin-1 vector to mock-transfected and wild-type cells. Among the 631 spots probing genes potentially involved in cancer that were valid for analysis on all the arrays the expression of 86 genes was increased at least 2-fold. Confirmation of increased protein levels was provided by immunocytochemistry for p21waf/cip1, cullin-2, p53, ADAM-15, and MAP-2. Major differences in the expression patterns of ADAM-15 and the actin stress fiber organization were also observed. U87 cells stably deficient for galectin-1 expression were significantly less motile than control. We conclude that the stable inhibition of galectin-1 expression alters the expression of a number of genes that either directly or indirectly influence adhesion, motility and invasion of human glioblastoma cells.

Are syngeneic mouse tumor models still valuable experimental models in the field of anti-cancer drug discovery?

To establish the pharmacological profile of a molecule with anti-cancer potential, it seems essential to add an in vivo approach to the first pharmacological experiments carried out in vitro. The present study aims to characterize the degree of sensitivity of seven syngeneic models (two leukemias and five solid tumors) to eleven molecules which have proven to be clinically reliable. We also used some of these models to investigate whether the molecular effects on the extent of growth in a subcutaneously grafted experimental model correlate with the effects of the same drug on the survival of the animals so grafted. Our data show that all the molecules demonstrated significant anti-tumor activities in two mouse leukemia models (with some discrepancies between the two). Two lymphoma models displayed weaker chemosensitivity profiles than the two leukemia models from which they were developed. Two other models, namely the MXT-HS mammary carcinoma and the B16 melanoma, appeared to be rather chemoresistant. However, a direct relationship was evident between the drug-induced decrease in the tumor growth rate and the increase observed in the survival periods of the MXT tumor-bearing mice. This relationship was also observed in the L1210_LYM lymphoma, though to a lesser extent, and was completely absent from the B16 melanoma model. Finally, our data indicated that we had developed a pair of metastasizing, as opposed to non-metastasizing, lymphoma and mammary carcinoma models. In conclusion, the present study shows that syngeneic mouse tumor models can be used as valuable in vivo experimental models for the screening of potential anti-cancer agents.

Realtime System of Free Viewpoint Television

Tracking of migrating cells under phase-contrast video microscopy with combined mean-shift processes.

In this paper, we propose a combination of mean-shift-based tracking processes to establish migrating cell trajectories through in vitro phase-contrast video microscopy. After a recapitulation on how the mean-shift algorithm permits efficient object tracking we describe the proposed extension and apply it to the in vitro cell tracking problem. In this application, the cells are unmarked (i.e., no fluorescent probe is used) and are observed under classical phase-contrast microscopy. By introducing an adaptive combination of several kernels, we address several problems such as variations in size and shape of the tracked objects (e.g., those occurring in the case of cell membrane extensions), the presence of incomplete (or noncontrasted) object boundaries, partially overlapping objects and object splitting (in the case of cell divisions or mitoses). Comparing the tracking results automatically obtained to those generated manually by a human expert, we tested the stability of the different algorithm parameters and their effects on the tracking results. We also show how the method is resistant to a decrease in image resolution and accidental defocusing (which may occur during long experiments, e.g., dozens of hours). Finally, we applied our methodology on cancer cell tracking and showed that cytochalasin-D significantly inhibits cell motility.

Monitoring the expression profiles of integrins and adhesion/growth-regulatory galectins in adamantinomatous craniopharyngiomas: their ability to regulate tumor adhesiveness to surrounding tissue and their contribution to prognosis.

OBJECTIVE: The purpose of this study was to identify biological markers that may be involved in the adhesiveness of craniopharyngiomas to optical chiasms and/or pituitary stalks. METHODS: We determined the complete pattern of integrin expression in three craniopharyngiomas by means of a complementary deoxyribonucleic acid microarray. We quantitatively determined the levels of immunohistochemical expression of the different integrins in a series of 37 cases and the pattern of immunohistochemical expression of 10 extracellular matrix components (acting as integrin ligands) in 7 optical chiasms and 11 pituitary stalks. We also quantitatively (computer-assisted microscopy) determined the levels of immunohistochemical expression of galectin-1, -3, -4, -7, and -8 in 50 adamantinomatous craniopharyngiomas. RESULTS: The present study shows that at both the ribonucleic acid and protein levels, adamantinomatous craniopharyngiomas express the alpha2, alpha6, alpha(v), beta1, beta5, and beta8 integrin subunits, whereas optical chiasms and pituitary stalks express vitronectin, thrombospondin, and various forms of collagens. CONCLUSION: Our data suggest that at least part of the adhesiveness of craniopharyngiomas to the surrounding tissue, such as optical chiasms and pituitary stalks, could be explained by the interactions between alpha(2beta1) integrin expressed by craniopharyngiomas and collagens on the one hand, and vitronectin expressed by the surrounding tissue on the other hand. In addition, a Cox regression analysis has revealed that the levels of galectin-4 contribute significant information toward the delay in recurrence independently of surgical status.

Identification of a novel cardenolide (2''-oxovoruscharin) from Calotropis procera and the hemisynthesis of novel derivatives displaying potent in vitro antitumor activities and high in vivo tolerance: structure-activity relationship analyses.

Analysis of the methanolic extract of Calotropis procera root barks enabled the identification of a novel cardenolide (2''-oxovoruscharin) to be made. Of the 27 compounds that we hemisynthesized, one (23) exhibited a very interesting profile with respect to its hemisynthetic chemical yield, its in vitro antitumor activity, its in vitro inhibitory influence on the Na+/K+-ATPase activity, and its in vivo tolerance. Compound 23 displayed in vitro antitumor activity on a panel of 57 human cancer cell lines similar to taxol, and higher than SN-38 (the active metabolite of irinotecan), two of the most potent drugs used in hospitals to combat cancer.

Identification by means of cDNA microarray analyses of gene expression modifications in squamous non-small cell lung cancers as compared to normal bronchial epithelial tissue.

The present work analyzed the gene pattern profiles in 6 squamous non-small cell lung cancers (NSCLCs) versus 4 normal lung epithelial tissues by means of cDNA microarrays. In addition to cDNA microarray analyses, quantitative RT-PCR and immunohisto-chemical analyses were used to validate some of the results obtained. Our data enabled 7 genes to be selected by looking at the genes which were detected as being expressed in all the tumors and not expressed in all the normal samples, or inversely. Additionally, 19 genes were detected as being overexpressed in the tumors when compared to the normal tissue specimens. Of these 26 genes, 16 are not yet suspected of influencing NSCLC biology. These genes are involved in cell proliferation (G2 cyclin), signal transduction (SMARCC2, TM4SF3), apoptosis (CFLAR/FLIP), cell cytoskeleton (cytokeratins-14 and 16, alpha-tubulin isoform 1 and S100A10), cell adhesion (JUP), invasion (cathepsins H and O) and other biological processes (OAZ1, IGHG3, SCYA5/RANTES, beta-sarcoglycan and transcobalamin I). In conclusion, we identified a number of genes as being differentially expressed in squamous NSCLCs as compared to normal lung epithelial tissue. Some of these genes (such as those involved in invasion) could be used as new prognostic markers and others, like CFLAR/FLIP, could even constitute new therapeutic targets.

The differential expression of Galectin-1 and Galectin-3 in normal lymphoid tissue and non-Hodgkin's and Hodgkin's lymphomas.

The WHO classification of lymphomas was established on the basis of clinical, morphological, immunohistochemical and genetic criteria. However, each entity displays its own spectrum of clinical aggressiveness. Treatment success varies widely and is not predictable. Since galectins are involved in oncogenesis and the physiology of immune cells, we investigated whether galectin-1 and galectin-3 immunohistochemical expression could differ in 25 normal lymphoid tissues, 42 non-Hodgkins and 14 Hodgkins lymphomas. Immunohistochemical galectin expression was submitted to semi-quantitative and quantitative (computer-assisted microscopy) evaluations. This study is completed by an analysis (by means of quantitative RT-PCR) of galectin-3 mRNA expression in 3 normal lymph nodes, 3 follicular lymphomas (FLs) and 3 diffuse large B-cell lymphomas (DLBCLs). The data show that in normal lymphoid tissue, lymphocytes do not express galectin-1 and rarely express galectin-3. In contrast, galectin-3 was expressed in 8 of the 16 DLBCL cases and in 1 of the 8 FL cases. Furthermore, galectin-3 mRNA was expressed 3 times more in the DLBCLs than in the FLs. While the blood vessel walls of the lymphomas expressed galectin-1, the vessel walls of normal lymphoid tissues did not. This expression of galectin-1 in blood vessel walls was correlated with vascular density. The present study thus shows that DLBCL can be distinguished from normal lymphoid tissue and other lymphomas on the basis of galectin-3 expression.

Memory centric design of an MPEG-4 video encoder

2004

Characterization of gastrin-induced proangiogenic effects in vivo in orthotopic U373 experimental human glioblastomas and in vitro in human umbilical vein endothelial cells.

PURPOSE: This study aims to investigate the role of gastrin-17 (G17) on angiogenesis features in gliomas both in vitro and in vivo. EXPERIMENTAL DESIGN: The influences of G17 and G17 receptor antagonists were characterized in vitro in terms of angiogenesis on human umbilical vein endothelial cell (HUVEC) tubulogenesis processes on Matrigel and in vivo with respect to U373 orthotopic glioma xenografts. The influence of phosphatidylinositol 3'-kinase, protein kinase C, and nuclear factor-kappaB inhibitors was characterized in vitro on G17-mediated HUVEC tubulogenesis. G17-mediated release of interleukin (IL)-8 from HUVECs and G17-induced modifications in nuclear factor-kappaB DNA binding activity were characterized by means of specific enzyme-linked immunosorbent assays. The influence of G17 on E- and P-selectin expression was determined by means of computer-assisted microscopy, whereas the influence of E- and P-selectin on HUVEC migration was approached by means of antisense oligonucleotides. The chemotactic influence of G17 and IL-8 on HUVEC migration was characterized by means of computer-assisted videomicroscopy with Dunn chambers. RESULTS: Messenger RNAs for cholecystokinin (CCK)A, CCKB, and CCKC receptors were present in HUVECs and microvessels dissected from a human glioblastoma. Whereas G17 significantly increased the levels of angiogenesis in vivo in the U373 experimental glioma model and in vitro in the HUVECs, the CCKB receptor antagonist L365,260 significantly counteracted the G17-mediated proangiogenic effects. G17 chemoattracted HUVECs, whereas IL-8 failed to do so. IL-8 receptor alpha (CXCR1) and IL-8 receptor beta (CXCR2) mRNAs were not detected in these endothelial cells. Gastrin significantly (but only transiently) decreased the level of expression of E-selectin, but not P-selectin, whereas IL-8 increased the expression of E-selectin. Specific antisense oligonucleotides against E- and P-selectin significantly decreased HUVEC tubulogenesis processes in vitro on Matrigel. CONCLUSIONS: The present study shows that gastrin has marked proangiogenic effects in vivo on experimental gliomas and in vitro on HUVECs. This effect depends in part on the level of E-selectin activation, but not on IL-8 expression/release by HUVECs.

Detection of S100B, S100A6 and galectin-3 ligands in meningiomas as markers of aggressiveness

The biological factors responsible for the increased aggressiveness in atypical meningiomas are not well known. The aim of this study is to evaluate the discriminatory value of a number of biological markers (S100 proteins and galectin-3 and its ligand profile) with respect to benign and atypical meningiomas. Using 63 meningiomas (39 benign and 24 atypical), we performed a semi-quantitative histochemical analysis of both the expression of galectin-3 and its ligand profile and the Ca2+-binding proteins S100A5, S100A6 and S100B. Three features were considered for each marker, namely the labeling index (LI), the staining intensity (SI) and the global score (LI + SI). A low S100A6 labeling index was observed in 51% of the benign and 25% of the atypical meningiomas (P=0.035). Furthermore, high S100B scores were observed in 46% of the benign and in only 8% of the atypical meningiomas (P=0.001). Seventy-one percent of the atypical meningiomas exhibited a low level of staining intensity for the galectin-3-binding sites as compared to only 36% of the benign meningiomas (P=0.007). The combination of these three markers (by means of a decision tree) enabled an improved discriminatory criterion to be established between the benign and the atypical meningiomas. Our results thus suggest that the galectin-3-binding sites and S100B (and S100A6 to a lesser extent) could play a role in the aggressiveness characterizing atypical meningiomas.

Distributed Source Coding Architectures for Multi-view Images

Prognostic stratification of Dukes B colon cancer by a neoglycoprotein

Disease progression of tumors is accompanied by structural changes of the glycan chains of cellular glycoconjugates. Within the concept of the sugar code the presence of complementary receptors such as lectins translates changes in ligand presentation into biological effects, for example in growth regulation and adhesion. By introducing neoglycoproteins to histopathological colon cancer analysis the questions are addressed as to whether specific binding sites for main N- and O-glycan components are present and whether they harbor potential for prognostic predictions. Synthetic conjugation of fucose, lactose, and mannose derivatives to a carrier protein yielded neoglycoproteins for glycohistochemical analysis. The tumor panel included routinely fixed tissue sections from 67 cancer cases (15 Dukes A, 20 Dukes B, 15 Dukes C, and 17 metastatic tumors) and 6 hepatic metastases as well as 20 normal biopsy specimens as control. Quantitative image analysis determined the labeling index and the mean optical density in each case, separating tumor and peritumoral connective tissue. Specific carbohydrate-dependent binding with inter-individual heterogeneity was observed. The distinct staining profiles were not associated with disease stage or metastasis formation. Strong expression of lactose-binding sites in the peritumoral connective tissue especially in terms of the labeling index was significantly correlated with reduced survival in Dukes B patients (p=0.02). A similar tendency was observed in the Dukes C group. In conclusion, the application of the synthetic markers aimed at lectin detection defines lactose binding as new prognostic marker. It has potential relevance for improving the benefit from adjuvant therapy in Dukes B colorectal cancer patients. Technically, chemical ligand immobilization to an inert carrier can find useful application beyond glycosciences in the quest to extend the panel of tumor markers.

The Optimization of Distributed Processing for Arbitrary View Generation in Camera Sensor Networks

A model-based approach for automated in vitro cell tracking and chemotaxis analyses

BACKGROUND: Chemotaxis may be studied in two main ways: 1) counting cells passing through an insert (e.g., using Boyden chambers), and 2) directly observing cell cultures (e.g., using Dunn chambers), both in response to stationary concentration gradients. This article promotes the use of Dunn chambers and in vitro cell-tracking, achieved by video microscopy coupled with automatic image analysis software, in order to extract quantitative and qualitative measurements characterizing the response of cells to a diffusible chemical agent. METHODS: Previously, we set up a videomicroscopy system coupled with image analysis software that was able to compute cell trajectories from in vitro cell cultures. In the present study, we are introducing a new software increasing the application field of this system to chemotaxis studies. This software is based on an adapted version of the active contour methodology, enabling each cell to be efficiently tracked for hours and resulting in detailed descriptions of individual cell trajectories. The major advantages of this method come from an improved robustness with respect to variability in cell morphologies between different cell lines and dynamical changes in cell shape during cell migration. Moreover, the software includes a very small number of parameters which do not require overly sensitive tuning. Finally, the running time of the software is very short, allowing improved possibilities in acquisition frequency and, consequently, improved descriptions of complex cell trajectories, i.e. trajectories including cell division and cell crossing. RESULTS: We validated this software on several artificial and real cell culture experiments in Dunn chambers also including comparisons with manual (human-controlled) analyses. CONCLUSIONS: We developed new software and data analysis tools for automated cell tracking which enable cell chemotaxis to be efficiently analyzed.

The infrared spectrum of human glioma cells is related to their in vitro and in vivo behavior

The present research investigates whether infrared spectra can be related to the biological characteristics of glioma cell lines. We used nine human glioma cell lines for which a series of in vitro and in vivo biological features had already been established [Glia 36 (2001) 375] and were able to show that their characteristic infrared spectra reflect their in vitro migration (i.e., motility and invasiveness) properties and their in vivo aggressiveness. More particularly, the infrared data evidenced correlations at the level of the lipid/protein ratio. These relationships were found to be tissue-dependent when controlled on seven pancreatic carcinoma cell lines. We also showed that oligodendroglial and astrocytic tumor cells, whose identification remains difficult, can easily be identified by their infrared spectra in the lipid acyl chain region as well as in the nucleic acid region. We concluded that infrared spectroscopy could usefully complement information provided by more conventional diagnostic and prognostic (e.g., morphological and molecular) approaches.

S100A5

Some WHO grade I intracranial meningiomas resected from the same sites and with the same quality of resection (Simpson's grading scale) recur, while others do not. The reasons for this variability in occurrence of recurrence have not yet been determined. We therefore investigated the prognostic recurrence value of seven biological markers on a series of completely resected WHO grade I meningiomas. For this purpose, we analysed a series of 33 WHO grade I meningiomas totally resected between 1980 and 1990 (a follow-up of 10 years), including 14 cases of recurrence. The fixed tumour material from each meningioma was submitted to histochemical analyses targeting galectin-3 and its binding sites, the S100A5, S100A6 and S100B proteins, and cathepsin-B and -D. The levels of expression were assessed semi-quantitatively (in terms of the staining intensity and the labelling index) and submitted to uni- and multivariate analyses. Of all the markers investigated, only S100A5 expression can be associated with any significant prognostic value in the matter of recurrence. More particularly, the meningiomas with high levels of S100A5 staining intensity either did not recur, or recurred later than those with a low immunopositive S100A5 intensity (P = 0.004). Cox regression analyses demonstrated that this latter marker was associated with significant prognostic values independent of the patients' ages. Furthermore, the combination of the patients' ages and S100A5 staining intensity permitted the identification of a group with a particularly high risk of recurrence, that is, the patients younger than 55 and with meningiomas exhibiting low S100A5 intensities (P = 0.001). In conclusion, the S100A5 protein could play a role in the recurrence of totally resected WHO grade I meningiomas.

Offset-Block Matching of Multi-view Images for Ray-Space Interpolation

Performance and complexity co-evaluation of the advanced video coding standard for cost-effective multimedia communications

Meshgrid - A compact, multi-scalable and animation-friendly surface representation

View-dependent, scalable texture streaming in 3-D QoS with MPEG-4 visual texture coding

2003

Volumetric cell-and-portal generation

We present an algorithm to generate a cell-and-portal decomposition of general indoor scenes. The method is an adaptation of the 3D watershed transform, computed on a distance-to-geometry sampled field. The watershed is processed using a flooding analogy in the distance field space. Flooding originates from local minima, each minimum producing a region. Portals are built as needed to avoid the merging of regions during their growth. As a result, the cell-and-portal decomposition is closely linked to the structure of the models. In a building, the algorithm finds all the rooms, doors and windows. To restrict the memory load, a hierarchical implementation of the algorithm is presented. We also explain how to handle possible model degeneracies -such as cracks, holes and interpenetrating geometries- using a pre-voxelisation step. The hierarchical algorithm, preceded when necessary by the pre-voxelisation, was tested on a large range of models. We show that it is able to deal with classical architectural models, as well as cave-like environments and large mixed indoor/outdoor scenes. Thanks to the intermediate distance field representation, the algorithm can be used regardless of the way the model is represented: it deals with parametric curves, implicit surfaces, volumetric data and polygon soups in a unified way.

Effect of hydrophilic components of the extracellular matrix on quantifiable diffusion-weighted imaging of human gliomas: preliminary results of correlating apparent diffusion coefficient values and hyaluronan expression level.

OBJECTIVE: The purpose of this study was to evaluate the relationship between apparent diffusion coefficient (ADC) measured by MR imaging and the level of immunohistochemical expression of hyaluronan or hyaluronic acid as one of the main hydrophilic components of the extracellular matrix in brain glial tumors. MATERIALS AND METHODS: Nineteen patients with primary glial brain tumors were included in the study. Mean ADC values were calculated in all tumors and were normalized with the ADC values of the contralateral normal-appearing brain ratios. All tumors underwent surgical resection, and the histologic diagnosis was based on the analysis of the surgical specimen. Mean values of the labeling index of hyaluronan (LI-HA) were calculated to determine quantifiably the histochemical expression of hyaluronan in the tumor. The mean ADC values and the mean ADC ratios (ADC(ratio)) of the tumors were then correlated to the mean values of the LI-HA. RESULTS: The mean ADC (93 x 10(-5) mm(2)/sec) and the mean ADC(ratio) (1.25) of the high-grade glial tumors were significantly lower than the mean ADC (123 x 10(-5) mm/sec) and the mean ADC(ratio) (1.64) of the low-grade glial tumors (p < 0.01). The mean LI-HA (72.8%) was also significantly lower in the high-grade gliomas than the mean LI-HA (93.4%) in the low-grade gliomas (p < 0.001). A positive correlation was found between mean ADC values and the mean LI-HA (tau = 0.35, p < 0.05) and also between the mean ADC(ratio) and the mean LI-HA (tau = 0.33, p < 0.05). CONCLUSION: Hyaluronan as one of the main hydrophilic components of the extracellular matrix in gliomas likely contributes to differences in the ADC values between high- and low-grade glial tumors.

A prospective comparative study of push and wireless-capsule enteroscopy in patients with obscure digestive bleeding

Expression patterns of galectin-1 and galectin-3 in nasal polyps and middle and inferior turbinates in relation to growth regulation and immunosuppression.

BACKGROUND: The term nasal polyposis describes benign growth processes in the nasal and sinus mucosa, which are mainly located in the middle meatus and never in the inferior meatus. As a step to define the biochemical determinants relevant for growth regulation, we focused on endogenous lectins known for anti-apoptotic (galectin-3) and immunomodulatory (galectin-1) activities. DESIGN: Using computer-assisted microscopy, we performed an immunohistochemical investigation defining the quantitative parameters of expression of galectin-1 and galectin-3 in 10 nasal polyps, 10 middle turbinates, and 10 inferior turbinates, all of which were obtained from surgical resection. RESULTS: Our data show that galectin-3 expression is markedly (P<.001) higher in nasal polyps than in turbinates. No relation to the allergic status was discovered. Galectin-1 expression is higher in nasal polyps than in middle turbinates (P<.001) in nonallergic patients compared with allergic ones (in glandular epithelium, P =.009; in connective tissue, P =.006). The lowest galectin-1 expression was observed in the middle turbinate. CONCLUSIONS: These data are in line with a positive influence of galectin-3 on growth and an immunoregulatory role of galectin-1, mimicking an increased expression dependent on glucocorticoid.

Binding sites for Lewis antigens are expressed by human colon cancer cells and negatively affect their migration.

In colon cancer, endothelial cell selectins can promote tumor cell attachment via interactions with sialylated Lewis antigens present at the surface of tumor cells, thereby facilitating tumor cell arrest and transmigration into the extravascular space. However, it is not known whether Lewis antigens interact with colon tumor cells and modify their migration. Our aim was to detect the presence of binding sites on human tumor cells for Lewis(a/x) antigens and their sialylated derivatives in vitro and in vivo and to analyze their influence on migration of colon cancer cells. The immunocytochemical and histochemical levels of expression of the four Lewis antigens were quantitatively determined in four human colon cancer cell lines and in in vivo nude mice xenografts. The levels of expression of specific binding sites for these sugar epitopes were determined by synthetic neoglycoconjugates. The influence of binding of these carbohydrate ligands on cancer cell migration was quantitatively evaluated by computer-assisted phase-contrast videomicroscopy performed on Matrigel culture supports either left uncoated or coated with neoglycoconjugate presenting synthetic Lewis(a), sialyl Lewis(a), Lewis(x), or sialyl Lewis(x) antigens. The influence of the calcium concentration in the culture medium on the Lewis antigen-mediated effects was checked. Human colon cancer cells expressed significant amounts of specific binding sites detected by the synthetic probes in addition to the oligosaccharide epitopes. The expression levels differed considerably between the four cell lines and between in vitro and in vivo specimens. Cell migration analysis revealed that the four Lewis antigens markedly decreased the levels of migration of the HCT-15 and LoVo cancer cells. This effect depends on the calcium concentration in the culture medium. Binding sites for Lewis epitopes are present on colon cancer cells. The functional relevance of these sites is indicated by the negative influence on cell migration of a matrix containing the oligosaccharides as ligand parts.

Prognostic values of galectin-3 and the macrophage migration inhibitory factor (MIF) in human colorectal cancers.

This study aims to investigate whether the immunohistochemical levels of expression of galectin-3 and the macrophage migration inhibitory factor (MIF) are associated with prognostic values in human colorectal tumors. This was performed on 99 specimens including 69 colorectal tumors (17 Dukes A, 19 Dukes B, 15 Dukes C and 18 metastatic tumors that we labeled as D), 10 hepatic metastases from colorectal cancers and 20 normal specimens (biopsies). The immunohistochemical levels of expression of MIF and galectin-3 were quantified on routine histological slides by means of computer-assisted microscopy. Separate analyses were performed on epithelial and connective tissue. The levels of expression of both MIF and galectin-3 were very significantly higher in epithelial tumor tissue when compared with normal epithelial specimens. A positive and significant correlation between MIF and galectin-3 expression was evidenced in connective tumor tissue, and in particular in the cases associated with short survival periods (less than 5 years). In the case of the Dukes A or B tumors, we established two new prognostic groups (labeled I and II) on the basis of the levels of galectin-3 expression measured in the tumor epithelium. In the case of the Dukes C or D tumors, we established two other prognostic groups (labeled III and IV) on the basis of the levels of MIF expression measured in the connective tissue. Kaplan-Meyer analyses confirmed the additional prognostic values (as compared with conventional clinical staging) given by this new classification (groups I to IV). They show that the Dukes A or B tumors characterized by low levels of galectin-3 expression in the tumor epithelium are associated with significantly better prognoses than those characterized by high levels. In addition, the Dukes C or D tumors characterized by high levels of MIF expression in the connective tumor tissue are associated with significantly better prognoses than those characterized by low levels. In conclusions, MIF and galectin-3 expression levels in colorectal tumors are related to their levels of biological aggressiveness. These markers could be used to identify patients at risk, for whom more aggressive adjuvant therapy seems to be indicated.

Refined prognostic evaluation in colon carcinoma using immunohistochemical galectin fingerprinting.

BACKGROUND: Knowledge of the expression of the galectins in human colon carcinomas is mainly restricted to galectin-3 and, to a lesser extent, galectin-1. The current study analyzed the prognostic values contributed by galectin-1, galectin-3, galectin-4, and galectin-8 in cases of colon carcinoma. METHODS: The authors selected 55 colon carcinomas (including 10 Dukes A, 16 Dukes B, 15 Dukes C, and 14 metastatic tumors that the authors labeled "Stage D"). The immunohistochemical levels of expression of the four galectins were determined quantitatively by means of computer-assisted microscopy. RESULTS: The data from the current study indicate that the four galectins under study are associated with significant and separate prognostic values that depend on the Dukes stage of the colon tumor. In particular, the authors observed a significant prognostic value associated with galectins-1, -3, and -4 in Dukes A and B colon tumors. In addition, significant prognostic value also was associated with galectin-8 in Dukes C and D colon tumors. The prognostic values associated with the levels of expression of galectin-1 and galectin-4 in Dukes A and B tumors appear to be independent of the Dukes stage. The same feature was observed when galectin-4 and galectin-8 were analyzed in the complete series. CONCLUSIONS: The data from the current study strongly suggest that galectins-1, -3, and -4 may be involved in the early stages of human colon carcinoma development and that galectin-8 is involved in the later stages.

Differential expression of S100 calcium-binding proteins in epidermoid cysts, branchial cysts, craniopharyngiomas and cholesteatomas.

AIMS: To investigate whether epidermoid cysts, branchial cysts, craniopharyngiomas and cholesteatomas express S100 proteins differentially by immunohistochemical assaying the presence of S100A1, S100A2, S100A3, S100A4, S100A5, S100A6 and S100B. METHODS AND RESULTS: Immunopositivity/negativity was recorded for each S100 protein in a series of 52 cases consisting of 12 epidermoid cysts, 12 branchial cysts, 15 adamantinomatous craniopharyngiomas and 13 acquired cholesteatomas. Except in the case of the craniopharyngiomas, immunoreactivity was assessed independently in the basal membrane and the basal, the internal and the keratin layers. Our data show that in contrast to S100B, which was rarely expressed, S100A1, S100A2, S100A4 and S100A5 were often present in these four types of epithelial lesions. S100A3 and S100A6 and, to a lesser extent, S100A5 were the most differentially expressed proteins across the different histopathological groups analysed. These three proteins are expressed more often in craniopharyngiomas and cholesteatomas, the two more aggressive types of lesions. CONCLUSIONS: This is the first study to report data on the expression of seven S100 proteins in different histopathological groups of epithelial head and neck lesions, whose precise embryological origins are still a matter of debate. S100 proteins could possibly be used as markers to target this embryonic origin, since our results show that S100A3 and S100A6 (and, to a lesser extent, S100A5) are expressed differentially across these different groups of epithelial lesions.

A scalable MPEG-4 Wavelet Based Visual Texture Compression System with Optimized Memory Organization

Terminal QoS for real-time 3D visualization using scalable MPEG-4 coding

High-level cache modeling for 2-D discrete wavelet transform implementations

2002

Changes in galectin-7 and cytokeratin-19 expression during the progression of malignancy in thyroid tumors: diagnostic and biological implications.

Galectin-7 is associated with p53-dependent onset of apoptosis and proliferation control/differentiation in keratinocyte development. It is also up-regulated in chemically induced rat mammary carcinogenesis. Because the levels of expression of galectin-7 have never been investigated in thyroid tumors (in contrast to those of galectin-1 and -3 associated with malignancy), we initiated analysis of the expression of galectin-7 in benign and malignant thyroid lesions together with that of cytokeratin-19 (CK19), a marker already demonstrated to be useful in diagnosing this kind of lesion. The immunohistochemical expression levels were quantitatively determined by means of computer-assisted microscopy on a series of 84 thyroid lesions including 10 multinodular goiters, 32 adenomas, and 42 carcinomas. Our data clearly indicate a marked down-regulation of galectin-7 expression in a large proportion of adenomas (including the normomacrofollicular, microfollicular, and trabecular variants) if compared with carcinomas. In accordance with results of previous studies, a marked up-regulation of CK19 expression was observed in the thyroid carcinomas, and this contrasted in particular with the low CK19 expression observed in the microfollicular adenomas. Of importance for diagnostic implications, the combination of these two markers enabled our series of microfollicular adenomas (characterized by low galectin-7 and CK19 expression) to be efficiently distinguished from the encapsulated follicular variant of papillary thyroid carcinomas (high galectin-7 and CK19 expression).

Extracellular S100A4 stimulates the migration rate of astrocytic tumor cells by modifying the organization of their actin cytoskeleton.

In previous studies, we have shown that numbers of S100 calcium-binding proteins (including S100A4) are expressed differentially in astrocytic tumors according to their levels of malignancy. S100A4 is involved in tumor progression, cell migration and metastasis. This protein is able to play extracellular roles such as neuritogenic and angiogenic activities. The present study aims to investigate the possible role played by extracellular S100A4 in the in vitro migration of astrocytic tumor cells. The speed and rate of migration of living cells were measured using computer-assisted videomicroscopy. In parallel, we also analyzed the effects of extracellular S100A4 on the organization of the actin cytoskeleton and the expression of a number of its molecular regulators. These included small Rho-GTPases (RhoA, Rac1 and Cdc42) and some of their direct effectors (mDia and N-WASP), and also actin-binding proteins such as profilin and alpha-actinin. Our data demonstrate the influence of S100A4 on astrocytic tumor cells with respect to these different aspects. Indeed, we show that extracellular S100A4 treatments decrease both the amount of polymerized F-actin and the levels of expression of RhoA, mDia and profilin. While a decrease in the Cdc42 and N-WASP expression was also observed, the Rac1 expression remained unchanged. All these activities, which result in the stimulation of cell motility, contribute to the understanding of the extracellular role of S100A4.

Expression of members of the calcium-binding S-100 protein family in a rat model of cerebral basilar artery vasospasm

OBJECT: The aim of this study was to investigate the role of S-100 proteins in the onset of vasospasm induced by subarachnoid hemorrhage (SAH), which leads to severe neurological morbidity and death. It has recently been argued that modifications in the levels of expression of some intracellular signaling elements controlling the organization of the actin cytoskeleton (including the rho A small guanosine triphosphatase and its related kinases) play significant roles in the induction of smooth-muscle cell contraction, a calcium-dependent process that is pathognomonic of SAH-induced vasospasm at the molecular level. Several members of the calcium-binding S-100 protein family are known to exercise significant control over the organization of the actin cytoskeleton. METHODS: The levels of expression of S-100 proteins in SAH-induced vasospasm have never been investigated. The authors therefore used a double-hemorrhage rat model of SAH-induced vasospasm to determine whether the levels of expression of S-100B, S-100A1, S-100A2, S-100A4, and S-100A6 proteins on immunohistochemical studies were significantly modified in this pathological condition. Quantitative determination of immunohistochemically confirmed expression of S-100 proteins (accomplished with the aid of computer-assisted microscopy) revealed that SAH-induced vasospasm is accompanied by a very significant increase in S-100B, S-100A2, and, to a lesser extent, in S-100A4 and S-100A6 expression, whereas this condition is not accompanied by significant modifications to S-100A1 expression. CONCLUSIONS: Such significant modifications in the levels of expression of different members of the S-100 protein family in SAH-induced vasospasm could relate to the various roles played by this specific class of calcium-binding proteins at the level of actin cytoskeleton organization. These modifications in S-100 protein expression seem relatively specific to SAH-induced vasospasm, because heparin-induced epilepsy-like symptoms were accompanied by dramatically distinct profiles of S-100 protein expression.

In vitro pharmacological characterizations of the anti-angiogenic and anti-tumor cell migration properties mediated by microtubule-affecting drugs, with special emphasis on the organization of the actin cytoskeleton

The aim of the present work is to investigate whether microtubule-affecting drugs including vincristine, vinblastine, vindesine and vinorelbine are able to produce an anti-angiogenic effect at non-cytotoxic doses in the same way of taxol. The cytotoxic effects were determined by means of the colorimetric MTT assay, and the anti-angiogenic effects on HUVEC cells growing on Matrigel and forming capillary networks. Sixteen additional drugs (camptothecin, SN38, topothecan, adriamycin, daunomycin, etoposide, bleomycin, melphalan, mitomycin C, TNP-470, cisplatin, carboplatin, 5-fluorouracil, methotrexate, suramin and batimastat) were used as control in order to test the specificity of the microtubule-affecting drug effects. We also investigated by means of videomicroscopy whether microtubule-affecting drugs could produce anti-migratory effects at non-cytotoxic doses on tumor cells. Finally, we used computer-assisted fluorescence microscopy to characterize the influence of microtubule-affecting drugs on the polymerization/depolymerization dynamics of the actin cytoskeleton in tumor cells. Our results show that taxol, vincristine and vindesine behave similarly in their ability to reduce the capillary network formation by HUVEC cells cultured on Matrigel. These anti-angiogenic effects appear at non-cytotoxic concentrations. In contrast, vinblastine and vinorelbine produce apparent anti-angiogenic effects by direct cytotoxicity. Microtubule-affecting agents are also able to significantly reduce the level of migration of tumor cells at non-cytotoxic concentrations, some of these effects may occur via modifications to the actin cytoskeleton organization. Several types of microtubule-affecting agents could be used as anti-angiogenic agents by administering them at non-cytotoxic concentrations, and some microtubule-affecting agents abandoned in pharmacological assays could turn out to be potent anti-migratory drugs acting on tumor cells, though without being too cytotoxic.

Calbindin-D28k

BACKGROUND: The expression of the Ca(2+)-binding protein calbindin-D(28k) was analyzed in medulloblastomas in relation to clinical features and other biologic markers related to cell proliferation, differentiation, p53, and cerebellar developmental regulated gene expression. METHODS: Immunohistochemistry was carried out on histologic slides from a first retrospective series of 29 nonmetastatic and 10 metastatic medulloblastoma formalin-fixed, paraffin-embedded tissues, using specific antibodies against calbindin-D(28k), calretinin, alpha-parvalbumin and beta-parvalbumin, and S100 proteins. Informed consent was obtained from the subjects and/or guardians. Other biologic markers for differentiation, cell proliferation, the expression of the p53 tumor suppressor gene protein, and cerebellar developmental regulated genes were similarly investigated. A second series of 16 medulloblastomas from young patients (younger than 15 years) was added in order to validate the results obtained in the first series. RESULTS: Of all the markers investigated, only calbindin-D(28k) was significantly associated with prognosis. Survival and remission (i.e. recurrence free) time analysis performed on all the cases (n = 55) confirmed a high risk of death (P = 0.004) and recurrence (P = 0.003) associated with calbindin-positivity. As calbindin-positivity was predominantly observed in tumors from young patients, the authors confirmed its prognostic value in the subgroup of patients younger than 15 years (n = 37). Cox regression analysis showed a significant and independent prognostic value for calbindin expression and, to a lesser extent, the type of surgery (total or subtotal). Three risk groups were thus identified, distinguishing among the cases characterized by a total resection and calbindin-negativity (good prognosis), by a subtotal resection and calbindin-negativity (intermediary), and by calbindin-positivity (bad prognosis). CONCLUSIONS: The current study suggests that calbindin-positive medulloblastomas represent a subclass of aggressive tumors more frequently seen in younger patients.

UPPP for snoring

UPPP for snoring: long-term results and patient satisfaction. We retrospectively survey 57 patients who underwent uvulopalatopharyngoplasty (UPPP) because of habitual snoring over a five-year period. A total of 100 patients were sent questionnaires concerning persistent snoring, excessive daytime sleepiness (EDS), body mass index (BMI) and postoperative complications. After 5 years the success rate was 53%. The mean snoring score was 16.7 preoperatively and decreased to 10.6 postoperatively. There was a relationship between the body mass index (BMI) preoperatively and the efficiency of the surgery. The mean EDS score was 11.1 before and 9.4 after surgery. UPPP in patients complaining of snoring is quite successful but the results decline significantly with time and patients should be warned of the possibility of snoring remaining or returning.

Combining Different Methods and Numbers of Weak Decision Trees

3-Aryl-2-quinolone derivatives: synthesis and characterization of in vitro and in vivo antitumor effects with emphasis on a new therapeutical target connected with cell migration

Among 25 3-aryl-2-quinolone derivatives synthesized, the antitumor activity of some of them was characterized both in vitro and in vivo. In this series, no compound appeared to be cytotoxic in vitro, as was known by the colorimetric MTT assay carried out on 12 distinct human cancer cell lines obtained from the American Type Culture Collection. Indeed, the concentration values decreasing the growth of the 12 cell lines by at least 50% (IC(50) index) were always higher than 10(-5) M. We then made use of a computer-assisted phase-contrast videomicroscopy system to quantitatively determine in vitro the level of migration of living MCF-7 human breast cancer cells. For example, at 10(-7) M, compounds 7, 13, 16, and 28 markedly decreased the migration level of these MCF-7 human breast cancer cells. The in vivo determination of the maximum tolerated dose showed that all compounds tested were definitively nontoxic. When the nontoxic, antimigratory compound 16 was combined with either doxorubicin or etoposide, two cytotoxic compounds routinely used in the clinic, this led to additive in vivo benefits from this treatment (as compared to individual administrations of the drugs) when the MXT mouse mammary adenocarcinoma was used. Thus, nontoxic antimigratory compounds, including the 2-quinolone derivatives synthesized here, can actually improve the efficiency of antitumor treatment when combined with conventional cytotoxic agents.

Textural and contextual land-cover classification using single and multiple classifier systems

Ploidy and chromatin pattern analysis as an aid for cervical smear diagnosis

In the present study we used computer-assisted microscopy to analyze the morphology of Feulgen-stained cell nuclei in cell populations obtained at the same time as routinely performed cervical smears and in the same way. We investigated in a series of 110 cases whether the quantitative morphonuclear description of cytological cervical samples is able to aid pathologists to distinguish between benign and more suspect premalignant lesions. For this task nuclear DNA content, nuclear morphometry (size and anisonucleosis level) and chromatin pattern-related parameters were compiled for each specimen enrolled in the database. A set of 32 normal and 17 high-grade squamous intraepithelial lesion (HSIL) specimens (with diagnostic confirmations) were selected as references and used to establish a discriminant model on the basis of cytometry-generated variables. This model was then used to score the remaining 61 cases in our series (including cases exhibiting benign cellular changes, squamous cells of undetermined significance, low-grade SIL and cancers). The results show that a model discriminating efficiently between normal and HSIL groups can be obtained by combining 5 quantitative features (1 DNA ploidy-related, 2 morphometrical and 2 chromatin texture features). A 97% specificity and an 88% sensitivity characterized the boundary so established. When applied to new cases, the model was in fact able to correct diagnoses for cases which had been down- or up-graded on the basis of the Bethesda system, and provided scores in accordance with histological control.

Galectin-1 is overexpressed in nasal polyps under budesonide and inhibits eosinophil migration

Because of the importance of galectins for various cellular activities, the influence of the glucocorticoid budesonide on the level of expression of galectins-1 and -3 was investigated in human nasal polyposis. Ten nasal polyps obtained from surgical resection were maintained for 24 hours in the presence of various concentrations of budesonide. As quantitatively demonstrated by means of computer-assisted microscopy, 250 ng/ml (the highest dose tested) induced a pronounced increase of galectin-1 expression. This feature was observed in nasal polyps from allergic patients but not in those from nonallergic patients. Since eosinophils represent the main inflammatory cell population in nasal polyps, we investigated the effect of galectin-1 on their migration levels by means of quantitative phase-contrast computer-assisted videomicroscopy. Our results show that galectin-1 (coated on plastic supports) markedly reduced the migration levels of eosinophils in comparison to P-selectin. On the cellular level, marked modifications in the polymerization/depolymerization dynamics of the actin cytoskeleton (as revealed by means of computer-assisted fluorescence microscopy) and, to a much lesser extent, an increase in the adhesiveness of eosinophils to tested substrata were detectable. The present study therefore reveals a new galectin-1-mediated mechanism of action for glucocorticoid-mediated anti-inflammatory effects.

Complete Polygonal Scene Voxelization

The Ca2+-binding S100A2 protein is differentially expressed in epithelial tissue of glandular or squamous origin

It has been previously shown that S100A2 is downregulated in tumor cells. The level of immunohistochemical S100A2 expression was therefore characterized in 424 normal and tumoral (benign and malignant) tissues of various origins, but mostly epithelial (with either glandular, squamous, respiratory or urothelial differentiation). We also investigated whether S100A2 could be co-localized with cytokeratin K14, an intermediate filament protein expressed in basal proliferative keratinocytes. Our data show that S100A2 has a low level of expression in non-epithelial tissue. In epithelial tissue S100A2 expression decreases remarkably in the tumors when compared to the normal specimens, and was correlated with the level of keratin K14. This decrease in S100A2 staining from normal to cancer cases is more pronounced in glandular than in squamous epithelial tissue. In addition, the patterns of S100A2 staining also differ between glandular and squamous tissue. These data suggest distinct functional roles for S100A2 in epithelial tissue of squamous or glandular origins.

characterization of the level of expression of S100B, S100A1, S100A2, S100A4 and S100A6 calcium-binding proteins in a rat model of cerebral basilar artery vasospasm

Adjusting the outputs of a classifier to new a priori probabilities: a simple procedure

It sometimes happens (for instance in case control studies) that a classifier is trained on a data set that does not reflect the true a priori probabilities of the target classes on real-world data. This may have a negative effect on the classification accuracy obtained on the real-world data set, especially when the classifier's decisions are based on the a posteriori probabilities of class membership. Indeed, in this case, the trained classifier provides estimates of the a posteriori probabilities that are not valid for this real-world data set (they rely on the a priori probabilities of the training set). Applying the classifier as is (without correcting its outputs with respect to these new conditions) on this new data set may thus be suboptimal. In this note, we present a simple iterative procedure for adjusting the outputs of the trained classifier with respect to these new a priori probabilities without having to refit the model, even when these probabilities are not known in advance. As a by-product, estimates of the new a priori probabilities are also obtained. This iterative algorithm is a straightforward instance of the expectation-maximization (EM) algorithm and is shown to maximize the likelihood of the new data. Thereafter, we discuss a statistical test that can be applied to decide if the a priori class probabilities have changed from the training set to the real-world data. The procedure is illustrated on different classification problems involving a multilayer neural network, and comparisons with a standard procedure for a priori probability estimation are provided. Our original method, based on the EM algorithm, is shown to be superior to the standard one for a priori probability estimation. Experimental results also indicate that the classifier with adjusted outputs always performs better than the original one in terms of classification accuracy, when the a priori probability conditions differ from the training set to the real-world data. The gain in classification accuracy can be significant.

Any reasonable cost function can be used for a posteriori probability approximation.

In this paper, we provide a straightforward proof of an important, but nevertheless little known, result obtained by Lindley in the framework of subjective probability theory. This result, once interpreted in the machine learning/pattern recognition context, puts new light on the probabilistic interpretation of the output of a trained classifier. A learning machine, or more generally a model, is usually trained by minimizing a criterion-the expectation of the cost function-measuring the discrepancy between the model output and the desired output. In this letter, we first show that, for the binary classification case, training the model with any "reasonable cost function" can lead to Bayesian a posteriori probability estimation. Indeed, after having trained the model by minimizing the criterion, there always exists a computable transformation that maps the output of the model to the Bayesian a posteriori probability of the class membership given the input. Then, necessary conditions allowing the computation of the transformation mapping the outputs of the model to the a posteriori probabilities are derived for the multioutput case. Finally, these theoretical results are illustrated through some simulation examples involving various cost functions.

Enabling multimedia QoS control with black-box modeling

2001

Molecular characterization of cell substratum attachments in human glial tumors relates to prognostic features

Glioma cell attachments to substratum play crucial roles in the invasion by glioma cells of normal brain tissue. These attachments are mediated through interactions between extracellular matrix (ECM) components, integrins, focal adhesion-linked molecules, and the actin cytoskeleton. In the present study, we investigate the molecular elements involved in cell substratum attachments in human glial tumors and their potential relationships to prognostic features. We used 10 human glioma cell lines, for which we characterized glial differentiation by means of quantitative RT-PCR for nestin, vimentin, and GFAP mRNA. We quantitatively determined the amounts of laminin, fibronectin, vitronectin, and thrombospondin secreted by these glioma cell lines in vitro, as well as the amount of each of the eight beta integrin subunits and the adhesion complex-related molecules, including talin, vinculin, profilin, zyxin, alpha-actinin, paxillin, and VASP. After quantification of the levels of migration and invasion of these 10 cell lines in vitro and, through grafts into the brains of nude mice, of their biological aggressiveness in vivo, it appeared that the levels of the beta 5 integrin subunit and alpha-actinin were directly related to biological aggressiveness. These experimental data were clinically confirmed because increasing immunohistochemical amounts of the beta 5 integrin subunit and alpha-actinin were directly related to dismal prognoses in the case of astrocytic tumors. In addition, we show that the beta 4 integrin subunit are expressed significantly more in oligodendrogliomas than in astrocytic tumors. A potential role for the beta 8 integrin subunit in glioma cell substratum attachments is also emphasized.

Gastrin induces over-expression of genes involved in human U373 glioblastoma cell migration

Astrocytic tumors are the most common and the most malignant primary tumors of the central nervous system. We had previously observed that gastrin could significantly modulate both cell proliferation and migration of astrocytoma cells. We have investigated in the present study which genes could be targeted by gastrin in tumor astrocyte migration. Using a subtractive hybridization PCR technique we have cloned genes differentially over-expressed in human astrocytoma U373 cells treated or not with gastrin. We found about 70 genes over-expressed by gastrin. Among the genes overexpressed by gastrin, we paid particular attention to tenascin-C, S100A6 and MLCK genes because their direct involvement in cell migration features. Their gastrin-induced overexpression was quantitatively determined by competitive RT-PCR technique. We also showed by means of a reporter gene system that S100A6 and tenascin-C respective promoters were upregulated after gastrin treatment. These data show that gastrin-mediated effects in glioblastoma cells occur through activation of a number of genes involved in cell migration and suggest that gastrin could be a target in new therapeutic strategies against malignant gliomas.

Detection of macrophage migration inhibitory factor (MIF) in human cholesteatomas and functional implications of correlations to recurrence status and to expression of matrix metalloproteinases-3/9, retinoic acid receptor-beta, and anti-apoptotic galectin-3.

OBJECTIVES: To investigate whether the expression of the macrophage migration inhibitory factor (MIF) 1) is detectable, 2) changes in relation to recurrence and infection status, and 3) relates to the levels of expression of growth regulators/differentiation markers, including galectin-1, -3, and -8, retinoid acid receptors (RAR)]-alpha, -beta, and -gamma, binding sites for sarcolectin, and invasion markers (cathepsins -B and -D, and matrix metalloproteinases [MMP]-2, -3, and -9) in human cholesteatomas. STUDY DESIGN: An analysis of 56 cholesteatomas resected by the same surgeon using canal wall up and canal wall down surgical procedures. METHODS: The immunohistochemical levels of expression of MIF and the proteases were quantitatively determined (using computer-assisted microscopy) on routine histologic slides by specific antibodies, and statistically correlated to parameters of the other markers determined previously in conjunction with data on apoptosis/proliferation. RESULTS: MIF expression was detected. It was significantly higher in the epithelium (P =.002) and vessels (P =.04) of the connective tissues (but not in the connective tissue itself) of recurrent as opposed to non-recurrent cholesteatomas. The MIF expression is significantly correlated (P =.006) to the RAR beta expression in non-infected cholesteatomas, and to MMP-3 (P <.01) and anti-apoptotic galectin-3 (P =.01) in infected cholesteatomas. The level of MIF expression was also correlated significantly to MMP-9 (P = 0.003), RAR beta (P <.001), and galectin-8 (P =.003) expression in the cholesteatomas regardless of their infection status. CONCLUSIONS: MIF expression in human cholesteatomas is related to the levels of biologic aggressiveness reflected in their recurrence status and MMP expression, and to the differentiation status reflected in their galactin and RAR beta expressions. Together with galectin-3, it could cooperate to form an anti-apoptotic feedback loop.

Synthesis and characterization of the antitumor activities of analogues of meridine, a marine pyridoacridine alkaloid.

Marine compounds with pyridoacridine skeletons are known to exhibit interesting antitumor activities. Among these compounds, meridine has already been reported as having significant antitumor activities in vitro. We synthesized 24 analogues of meridine substituted on ring A with the aim of obtaining compounds that display significantly higher in vitro antitumor activities than meridine. The 24 compounds and meridine used as a control compound were tested at 6 different concentrations on 12 different human cancer cell lines including various histopathological types (glioblastomas and breast, colon, lung, prostate, and bladder cancers). The IC(50) value (i.e., the drug concentration inhibiting the mean growth value of the 12 cell lines by 50%) of these 25 compounds ranged over 5 log concentrations, i.e., between 10 and 0.0001 microM, with four of the compounds exhibiting a significantly higher in vitro antitumor activity than meridine. These compounds will now be subjected to further pharmacological investigation including in vivo testing on both conventional murine tumors and human tumors grafted onto nude mice.

Development and progression of malignancy in human colon tissues are correlated with expression of specific Ca(2+)-binding S100 proteins.

The expression levels of seven different S100 proteins (S100A1, S100A2, S100A3, S100A4, S100A5, S100A6, and S100B) were characterized by immunohistochemistry in the epithelial versus connective tissues of a series of 35 colon specimens, including 6 normal samples, 5 adenomas with low-grade dysplasia, 5 adenomas with high-grade dysplasia, and 19 cancers. The results showed that S100A2, S100A3, and S100B proteins could not (or only marginally) be detected in colon tissues. On the other hand, the expression of S100A6 increased in epithelial tissues directly proportional to the increase of malignancy. The percentage of epithelial (or connective tissue) cells expressing S100A4 significantly decreased as the malignancy grade increased. The expression level of S100A1 proteins was somewhat higher in the connective tissues of normal cases and adenomas with low-grade dysplasia than in adenomas with high-grade dysplasia and cancers. This pattern of expression was not observed in epithelial tissues. While the node-positive cancers did not express S100A1, about half of the node-negative specimens did. The expression levels of S100A5 were similar in different epithelial tissues. However, in the connective tissues the expression levels decreased inversely proportional to the increase in pathological grading of the specimens. Therefore, the present study implicates several S100 proteins as useful tools for histochemical typing of colon cancer malignancy development.

Immunohistochemical profile of galectin-8 expression in benign and malignant tumors of epithelial, mesenchymatous and adipous origins, and of the nervous system.

This study aims to investigate whether the immunohistochemical expression of galectin-8 could be used as a diagnostic marker in tumor tissues of various histogenetic origins including specimens from epithelial (n=145), mesenchymatous (n=16), adipous (n=10) and central and peripheral nervous system (n=25) tissue, and 4 mesotheliomas. Immunohistochemical reactions were carried out with a polyclonal anti-galectin-8 antibody and histological slides from tissues derived from the files of the Laboratory of Anatomopathology of University Erasmus Hospital, Brussels. Formalin-fixed paraffin-embedded tissues of 45 normal cases as well as 41 benign and 114 malignant tumors were studied. Marked decreases in immunohistochemical galectin-8 expression were observed in colon (p=0.001), pancreas (p=0.007), liver (p=0.0008), skin (p=0.002) and larynx (p=0.02) tissue when comparing malignant tissue to normal tissue and/or benign tumors. The reverse relationship was observed for breast tissue (p=0.007). No statistically significant differences (p>0.05) were detected when comparing normal tissue and/or benign to malignant tumors in lung, bladder, kidney, prostate and stomach tissue. Significant galectin-8 expression was also measured in non-epithelial tissue including tumors of the central and peripheral nervous system as well as in skeletal muscle and mesotheliomas. Immunohistochemical monitoring of galectin-8 thus reveals an organ-type-dependent regulation of expression upon malignant transformation of various tissue types of epithelial origin. This observation will prompt further studies to delineate any relationship with prognosis.

The contribution of image cytometry to the characterization of clinical subgroups of lipomas.

The aim of the present study was to investigate whether biological features determined through image cytometry are able to characterize clinical subpopulations of lipomas. Forty lipomas excised from 36 patients were studied. On the one hand, the tumors were clinically characterized by means of patient-related and pre- and post-operative features. On the other, the tumors were analyzed by means of the computer-assisted microscopy analysis of Feulgen-stained nuclei. This analysis generated 3 groups of biological quantitative variables describing morphonuclear aspects (i.e. the chromatin pattern of the cell nuclei), the nuclear DNA content (DNA ploidy level), and architectural features (such as the cell density and the topographical cell nuclei organization). Possible relations between the clinical and the biological features of the lipomas were investigated by means of univariate and multivariate statistical analyses. The results show the existence of such relations, in particular between the morphonuclear and architectural features of lipomas, on the one hand, and their consistency, volume and weight, on the other. Furthermore, multivariate analysis made it possible to distinguish two subpopulations of lipomas exhibiting different biological characteristics in terms of morphonuclear patterns.

The levels of expression of galectin-3, but not of galectin-1 and galectin-8, correlate with apoptosis in human cholesteatomas.

OBJECTIVES: To investigate whether galectins 1, 3, and 8 are expressed in human cholesteatomas and whether any such expression does correlate with the level of apoptosis, which is, as we have previously shown, predictive of recurrence.7 STUDY DESIGN: The analysis of 52 cholesteatomas resected by the same surgeon by means of canal wall up and canal wall down procedures. METHODS: The immunohistochemical levels of expression of galectins 1, 3, and 8 were quantitatively determined (using computer-assisted microscopy) on conventional histological slides by means of specific anti-galectin-1, anti-galectin-3, and anti-galectin-8 antibodies. The level of apoptosis in each cholesteatoma under study had already been determined 7 by means of the in situ labeling of nuclear DNA fragmentation (Tolt-mediated dUTP nick end labeling [TUNEL] staining). RESULTS: Galectin-1 was expressed markedly in both the epithelial and the connective tissue areas of all the cholesteatomas under study. The levels of expression of galectin-3 and galectin-8 were considerably lower than that of galectin-1. The level of expression of galectin-3 correlated both highly and positively with the level of apoptosis. CONCLUSIONS: An upregulation of galectin-3 (known to have an antiapoptotic and antianoikis effect in certain model systems) expression, which is associated with pronounced apoptotic activity, could have a physiologically protective effect against the characteristically substantial apoptotic features occurring in recurrent cholesteatomas.

The levels of retinoid RARβ receptors correlate with galectin-1, -3 and -8 expression in human cholesteatomas

Cholesteatoma is a benign disease characterized by the presence of an unrestrained growth and the accumulation of keratin debris in the middle ear cavity. This often recurs, even when surgical resection is thought to be complete. In a previous study we showed that cholesteatomas with the highest apoptotic indices recurred more rapidly and also exhibited a high level of p53 immunopositive cells. In view of their relevance to the characterization of the cell differentiation status, the present study focuses on the expression of retinoid acid receptors (RARs) and galectins in human cholesteatomas. Retinoids control the differentiation processes in keratinocytes while galectins play strikingly modulatory roles at apoptosis and cell adhesion levels in a wide variety of tissue (embryonic, normal and neoplastic). To clarify the expression of these two protein families in human cholesteatomas we examined and quantified the levels of immunohistochemical expression of RARalpha, beta and gamma, and also galectin-1, -3 and -8 in a series of 70 human cholesteatomas. Our data show clearly that predominantly RARbeta and galectin-1 were expressed. The RARgamma concentration was significantly lower than that of the RARalpha; this was also observed for the galectin-8 concentration in comparison with the galectin-3 one. Furthermore, the level of RARbeta expression correlated highly (P=0.00001) with the level of galectin-8 expression, which also correlated significantly with the level of RARalpha and RARgamma expression. In addition, this parameter also correlated with the level of galectin-1 and galectin-3 expression. These data suggest that cholesteatomas may originate in an undifferentiated population of keratinocytes, and that a relation may exist between retinoid activity and galectins.

S100A2, a putative tumor suppressor gene, regulates in vitro squamous cell carcinoma migration.

It has been previously shown that S100A2 is down-regulated in tumor cells and can be considered a tumor suppressor. We have recently shown that this down-regulation can be observed particularly in epithelial tissue, where S100A2 expression decreases remarkably in tumors as compared with normal specimens. In the present paper we investigate whether S100A2 could play a tumor-suppressor role in certain epithelial tissues by acting at the cell migration level. To this end, we made use of five in vitro human head and neck squamous cell carcinoma lines in which we characterized S100A2 expression at both RNA and protein level. To characterize the influence of S100A2 on cell kinetic and cell motility features, we used two complementary approaches involving specific antisense oligonucleotides and the addition of S100A2 to the culture media. The different expression analyses gave a coherent demonstration of the fact that the FADU and the RPMI-2650 cell lines exhibit high and low levels of S100A2 expression, respectively. Antisense oligonucleotides (in FADU) and extracellular treatments (in RPMI) showed that, for these two models, S100A2 had a clear inhibitory influence on cell motility while modifying the cell kinetic parameters only slightly. These effects seem to be related, at least in part, to a modification in the polymerization/depolymerization dynamics of the actin microfilamentary cytoskeleton. Furthermore, we found evidence of the presence of the receptor for advanced glycation end-products (RAGE) in RPMI cells, which may act as a receptor for extracellular S100A2. The present study therefore presents experimentally based evidence showing that S100A2 could play a tumor-suppressor role in certain epithelial tissues by restraining cell migration features, at least in the case of head and neck squamous cell carcinomas.

Galectin-1 is highly expressed in human gliomas with relevance for modulation of invasion of tumor astrocytes into the brain parenchyma.

Protein (lectin)-carbohydrate interaction is supposed to be relevant for tumor cell behavior. The aims of the present work are to investigate whether galectin-1 modulates migration/invasion features in human gliomas in vitro, whether it can be detected in human gliomas immunohistochemically, and whether its expression is attributable to certain glioma subgroups with respect to invasion and prognosis. For this purpose, we quantitatively determined (by computer-assisted microscopy) the immunohistochemical expression of galectin-1 in 220 gliomas, including 151 astrocytic, 38 oligodendroglial, and 31 ependymal tumors obtained from surgical resection. We also xenografted three human glioblastoma cell lines (the H4, U87, and U373 models) into the brains of nude mice in order to characterize the in vivo galectin-1 expression pattern in relation to tumor invasion of the normal brain parenchyma. In addition, we characterized the role in vitro of galectin-1 in U373 tumor astrocyte migration and kinetics. Our data reveal expression of galectin-1 in all human glioma types with no striking differences between astrocytic, oligodendroglial, and ependymal tumors. The level of galectin-1 expression correlated with the grade in the group of astrocytic tumors only. Furthermore, immunopositivity of high-grade astrocytic tumors from patients with short-term survival periods was stronger than that of tumors from patients with long-term survivals. In human glioblastoma xenografts, galectin-1 was preferentially expressed in the more invasive parts of these xenografts. In vitro experiments revealed that galectin-1 stimulates migration of U373 astrocytes.

Reduced epithelial expression of secretory component in small airways correlates with airflow obstruction in chronic obstructive pulmonary disease.

The epithelial polymeric immunoglobulin receptor/transmembrane secretory component (pIgR/SC) transports into secretions polymeric immunoglobulin A (pIgA), which is considered the first line of defense of the respiratory tract. The present study, done with quantitative immunohistochemistry, evaluated epithelial expression of secretory component (SC) and Clara cell protein (CC16) and neutrophil infiltration into the airways of eight patients with severe chronic obstructive pulmonary disease (COPD) who were undergoing lung transplantation, as compared with these processes in six nonsmoking patients with pulmonary hypertension who were used as controls and in lung specimens from five smokers without chronic bronchitis. Staining for SC was significantly decreased in the COPD patients as compared with the controls, both in large (mean optical density [MOD]: 23.4 [range: 21.1 to 27.8] versus 42.2 [range: 28.2 to 49.3], p = 0.003) and in small airways (MOD: 30.8 [range: 20.3 to 39.4] versus 41.5 [range: 39.2 to 46.2], p = 0.003). SC expression in small airways correlated strongly with functional parameters such as FEV1 (Kendall's tau (K) = 0.76, p = 0.008), FVC (K = 0.64, p = 0.03), and midexpiratory flow at 50% of VC (MEF50) (K = 0.74, p = 0.01). The reduced expression of SC in large airways correlated with neutrophil infiltration in submucosal glands (K = -0.47, p = 0.03). Expression of CC16 in the bronchial epithelium of COPD patients was also significantly decreased as compared with that of controls, especially in small airways (MOD: 28.3 [range: 26.8 to 32.4] versus 45.8 [range: 40.7 to 56.0], p = 0.002), but no correlation was observed with lung function tests. In conclusion, this study shows that reduced expression of SC in airway epithelium is associated with airflow obstruction and neutrophil infiltration in severe COPD.

Distinct differences in binding capacity to saccharide epitopes in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas, and glioblastornas

We monitored the expression of glycan-binding sites on a panel of 10 biotinylated neoglycoconjugates by means of quantitative computer-assisted microscopy to further study the molecular mechanisms in the extensive infiltration of the surrounding brain parenchyma by most astrocytic tumors. Three distinct histological compartments were analyzed for each of the 108 astrocytic tumors (15 pilocytic astrocytomas (WHO grade I), 25 astrocytomas (WHO grade II), 30 anaplastic astrocytomas (WHO grade III), and 38 glioblastomas (WHO grade IV) included in our series. These compartments were tumors (nonperivascular tumor astrocytes), perivascular tumor astrocytes, and blood vessel walls. Clear differences were observed between the pilocytic and the diffuse astrocytic tumors. Furthermore, malignant progression in the latter category was paralleled by a decrease in cells' ability to bind distinct sugar epitopes, especially the D-GalNAc(alpha1-3)-D-GalNAc-beta1-R determinant of the Forssman pentasaccharide in tumors, the alpha-L-fucose in perivascular tumor areas, and the beta-D-glucose in tumor vessel walls. Markedly, the level of binding site expression for alpha-D-mannose decreased in the tumors, the perivascular tumor areas, and the vessel walls. These glycohistochemical results imply the functional relevance of protein-carbohydrate interactions in this tumor system.

Limiting the number of trees in random forests

The aim of this paper is to propose a simple procedure that a priori determines a minimum number of classifiers to combine in order to obtain a prediction accuracy level similar to the one obtained with the combination of larger ensembles. The procedure is based on the McNe- mar non-parametric test of significance. Knowing a priori the minimum size of the classifier ensemble giving the best prediction accuracy, constitutes a gain for time and memory costs especially for huge data bases and real-time applications. Here we applied this procedure to four multiple classifier systems with C4.5 decision tree (Breiman's Bagging, Ho's Random subspaces, their combination we labeled ‘Bagfs', and Breiman's Random forests) and five large benchmark data bases. It is worth noticing that the proposed procedure may easily be extended to other base learning algorithms than a decision tree as well. The experimental results showed that it is possible to limit significantly the number of trees. We also showed that the minimum number of trees required for obtaining the best prediction accuracy may vary from one classifier combination method to another.

2000

Identification by quantitative chromatin pattern analysis of patients at risk for recurrence of superficial transitional bladder carcinoma.

PURPOSE: Based on the actual clinical outcomes of 132 fully documented patients with superficial transitional cell carcinoma of the bladder, we characterize the risk of recurrence and/or progression by computer assisted image microscopy applied to Feulgen stained nuclei. MATERIALS AND METHODS: Each tumor was characterized by the conventional grading and staging systems as well as by cytometry generated variables describing nuclear DNA content, nuclear morphometry and chromatin patterns. These data were submitted to discriminant analysis to establish a model distinguishing between 2 groups of patients. Group 1 included cases with remission for more than 60 months and group 2 cases presented with recurrence with or without progression within 12 months of transurethral bladder resection. This latter model was then validated by Kaplan-Meyer analysis of the full data set. RESULTS: As evidenced by Kaplan-Meier analysis, the discriminant factor generated by discriminant analysis of cytometry generated variables provided a cutoff value for distinguishing between low and high risks of recurrence (p <0.00001). In contrast, conventional grading and staging systems were not able to make such efficient distinction. CONCLUSIONS: These 2 groups can be used as references with which new cases can be compared to prognosticate disease behavior independently of histopathological grading and/or clinical staging.

In vitro and in vivo pharmacological characterizations of the antitumor properties of two new olivacine derivatives, S16020-2 and S30972-1.

S16020-2, a new olivacine derivative and a topoisomerase II inhibitor, has recently entered clinical trials. New analogues and derivatives have been synthesized from the S16020-2 compound. Preliminary data indicate that S30972-1, one of these S16020-2 derivatives, may exhibit a comparatively higher level of antitumor potency associated with an improved therapeutic index than does S16020-2. The antitumor activities of S16020-2 and S30972-1 were therefore characterized both in vitro and in vivo, with Adriamycin and etoposide chosen as reference compounds. The in vitro data show that S30972-1 is a topoisomerase II inhibitor, mediating its activity through an ATP-dependent mechanism such as S16020-2. The two olivacine derivatives exhibited similar activities in vitro at the levels of the global growth of six human cancer cell lines, of the induction of apoptosis, and of the G2 cell cycle phase arrest. The in vivo antitumor activity characterization included the use of two murine leukemia types (P388-LEU and L1210-LEU), two murine lymphoma-like models (P388-LYM and L1210-LYM), two mammary adenocarcinomas (MXT-HI and MXT-HS), and one melanoma (B16). The data show that S30972-1 is actually more efficient in vivo than S16020-2, a feature that may relate to the fact that S30972-1 is less toxic than S16020-2. The S30972-1 compound exhibited in vivo a level of antitumor activity that was also actually higher than that exhibited by Adriamycin and similar to that exhibited by etoposide.

Labeled neoglycoproteins and human lectins as diagnostic and potential functional markers in salivary glands of patients with Sjögren's syndrome.

OBJECTIVE: The profile of glycans and their recognition by endogenous receptors (lectins) are increasingly attributed to disease process. Monitoring this can provide information on the pathogenesis of Sjögren's syndrome (SS). Commonly, plant lectins are employed for phenomenological glycan mapping. To go beyond this approach restricted to binding of exogenous probes, new markers measure ligand properties of glycans to human (not plant) lectins and the presence of sugar receptors completing a protein-carbohydrate recognition system. Carrier-immobilized sugar epitopes (neoglycoproteins) and purified human lectins establish this innovative panel. METHODS: The host defence molecules mannan binding lectin, serum amyloid P component, and the macrophage migration inhibitory factor-binding sarcolectin, selected for their involvement in cell destructive mechanisms, were purified and labeled. The plant lectins SNA and MAA were employed to monitor regulation of potential ligand sites for I-type lectins and galectins. Asialofetuin was tested as a "pan-galectin selective" probe. The specific binding characteristics were determined by quantitative morphometry and statistical analysis. RESULTS: Diagnostic information emerged from this analysis. The percentage of stained tissue area was significantly different between SS and control specimens after processing with GlcNAc and Man-bearing neoglycoproteins and the 2 tested serum lectins. For separation of cases of primary and secondary SS, the staining intensity with the asialoglycoprotein, sarcolectin, and the exogenous alpha2,6-sialylated glycan-binding lectin SNA was statistically significant. CONCLUSION: Saccharide-presenting probes to measure the cellular capacity to bind glycan epitopes and human lectins as sensors for endogenous binding sites have proven to be useful as diagnostic tools. We suggest the differences we observed reflect aberrations from the normal cellular homeostasis with relevance for the pathogenesis of SS and its manifestation as a primary or secondary syndrome.

S100 proteins in Corpora amylacea from normal human brain.

Corpora amylacea (C.A.) also named polyglucosan bodies (P.B.) are one of the hallmarks of normal brain aging. Although their functions are not yet clear, C.A. increase in number in patients suffering from neurodegenerative diseases. C.A. contain 88% of hexoses and 4% of proteins. Most of the proteins in C.A. are aging or stress proteins such as heat shock proteins, ubiquitinated proteins and advanced glycation end products which are also proinflammatory products. Stimulated by the potential role played by some S100 proteins in the inflammatory process which may be triggered in C.A., we investigated, by immunohistochemistry, the presence of different S100 proteins (S100A1, S100A2, S100A3, S100A4, S100A5, S100A6, S100A8, S100A9, S100A12 and S100B) in C.A. from normal human brain. Among the ten S100 proteins analyzed, nine (S100A) were detected in C.A. Three S100 proteins (S100A8, S100A9, S100A12) which are highly expressed in activated macrophages and used as inflammatory markers were detected in C.A. S100A8 was, in addition, found in thick neuronal processes from the pons. One (S100B) could not be found in C.A. although it was highly expressed in astrocytes. In C.A., the staining intensity was estimated by computer-assisted microscopy and gave the following order: S100A1 congruent withS100A8 congruent with S100A9>S100A5> or =S100A4>S100A12>S100A6> S100A2=S100A3. The potential inflammatory role played by S100 proteins in C.A. is discussed.

Glycohistochemical characteristics of nasal polyps from patients with and without cystic fibrosis.

OBJECTIVE: To investigate whether cystic fibrosis (CF)-related nasal polyps exhibit significantly distinct glycohistochemical characteristics when compared with single vs massive nasal polyps obtained from patients without CF. DESIGN: Glycohistochemical characteristics were identified by means of 8 histochemical probes, including 5 plant lectins (peanut, gorse seed, wheat germ, Maackia amurensis, and Sambucus nigra agglutinins), 2 animal lectins (14- and 16-kd galectins), and 1 neoglycoprotein (exposing the Thomsen-Friedenreich antigen). The binding of the 8 glycohistochemical markers was determined by means of computer-assisted microscopy. For each probe, 3 quantitative parameters were computed: the labeling index, which describes the percentage of tissue area specifically stained by a given marker; the mean optical density, which reflects the staining intensity; and the concentrational heterogeneity, which characterizes the level of heterogeneity of the staining intensity. SUBJECTS: A series of 61 nasal mucosa specimens was analyzed, including 6 normal cases, 23 single and 18 massive polyposis cases without CF, and 14 nasal polyps associated with CF. RESULTS: Normal and polyposal nasal mucosa differed in terms of the amounts and linkage types of sialic acids (revealed by the wheat germ, M amurensis, and S nigra agglutinins) rather than the characteristics of galactoside expression (monitored with the peanut agglutinin and 2 animal galectins). In contrast, nasal polyps markedly differed between patients with and without CF with respect to galactoside expression (revealed by the peanut agglutinin and the 14-kd galectin) and the display of binding site(s) for the neoglycoprotein. CONCLUSION: Normal and polyposal nasal mucosa differ essentially in sialic acid presentation, while nasal polyps from patients with CF have a higher level of various lectin-reactive galactoside residues than nasal polyps from those without CF.

Characterization of steroid hormone sensitivity in human breast cancers maintained ex vivo under organotypical culture conditions.

PURPOSE: The methodology we propose combines the immunohistochemical determination of the oestrogen and progesterone receptors (ER and PgR) with the characterization of the oestradiol- and progesterone-induced influence on cell proliferation in breast cancers in order to characterize their steroid hormone sensitivity at both the "static" and "dynamic" level. METHODS: ER and PgR have been immunohistochemically quantified by means of computer-assisted microscopy. Cell proliferation has been determined by means of tritiated thymidine autoradiography in tumour samples maintained in vitro as organotypic cultures. A series of 14 patients was investigated. RESULTS: Of the 14 breast cancers under study, one with an unequivocally "very ER-rich"/"very PgR-rich" immunohistochemical phenotype totally failed to exhibit any modification in its cell proliferation level after both oestradiol and progesterone stimulation. Two cases definitively associated with an "ER-poor"/"PgR-poor" immunohistochemical phenotype nevertheless responded noticeably to the dynamic stimulation of their cell proliferation by oestradiol and progesterone. While our series of cases covers 14 patients only, it suffices to demonstrate the limits of ER and PgR determination in characterizing steroid hormone sensitivity in breast cancer. DISCUSSION: The present work therefore presents an in vitro approach to test growth regulation of human breast cancer by steroid hormones. The clinical value of the present approach should be further determined by showing that steroid hormone-induced modifications in cell proliferation level are actually associated with clinical response.

Characterization of ligands for galectins, natural galactoside-binding immunoglobulin G subfractions and sarcolectin and also of the expression of calcyclin in thyroid lesions.

The purpose of this study was to characterize ligands for galectins, natural galactoside-binding immunoglobulin G subfractions and sarcolectin and also the expression of calcyclin in various benign and malignant thyroid lesions. The extent of the binding of eight glycochemical probes was quantitatively assessed using computer-assisted microscopy on 76 thyroid lesions including 10 not-otherwise-specified multinodular goiters (S_MNG), 11 multinodular goiters with adenomatous hyperplasia (AH_MNG), 8 normomacrovesicular (NM_ADE) and 12 microvesicular (MIC_ADE) adenomas, and 9 papillary (P_CAR), 10 follicular variants of papillary (FvarP_CAR), 7 follicular (F_CAR) and 9 anaplastic (A_CAR) carcinomas. The 8 histochemical probes included 5 animal lectins (including galectins and sarcolectin), 1 polyclonal antibody (raised against calcyclin) and 2 immunoglobulin G subfractions from human serum with selectivity to alpha- and beta-galactosyl residues. The results show that multinodular goiters with adenomatous hyperplasia exhibited histochemical characteristics intermediate to those of normal multinodular goiters and microvesicular adenomas. Normomacrovesicular adenomas behaved very distinctly from microvesicular ones. Microvesicular adenomas were more closely related to differentiated thyroid carcinomas than any other type of benign thyroid lesions of epithelial origin. Papillary and follicular carcinomas seemed to represent the two extremes of the same biological entity with the follicular variant of the papillary carcinoma serving as a biological link between these two extremes. Anaplastic carcinomas behaved in a significantly different manner when compared to the differentiated forms of thyroid carcinomas. The results suggest that the patterns of expression of the glycoconjugates investigated in the present study may constitute useful tools for characterizing lesions in the human thyroid.

Homocamptothecin, an E-ring-modified camptothecin, exerts more potent antiproliferative activity than other topoisomerase I inhibitors in human colon cancers obtained from surgery and maintained in vitro under histotypical culture conditions.

Topoisomerase I (Topo I) is overexpressed in cancer colon tissues compared with normal colon tissues. Several anti-Topo I inhibitors are already successfully used in the clinic. We illustrate here the antiproliferative activity of a new class of Topo I inhibitors, i.e., E-ring-modified camptothecins with enhanced lactone stability (L. Lesueur-Ginot et al., Cancer Res., 59: 2939-2943, 1999). Forty-three human colon cancers were obtained from surgical resection and maintained under organotypical culture conditions for 48 h. Cell proliferation was assessed in these ex vivo tumor tissue cultures by tritiated thymidine autoradiography. As a validation of the methodology, we first analyzed in our model the antiproliferative activity of two clinically active topoisomerase II (Topo II) inhibitors, Adriamycin and etoposide, which are not active for colon cancers; and three Topo I inhibitors, camptothecin (CPT) and two clinically active compounds (especially for colon cancers), i.e., topotecan and the active metabolite of irinothecan, SN-38. We then compared the antiproliferative activity of CPT, topotecan, and SN-38 against those of two investigational E-ring-modified camptothecins, i.e., BN80245 and BN80915. Three concentrations (1, 10, and 100 nM) were studied for each compound. The results indicate that the three Topo I inhibitors used as references, i.e., CPT, irinothecan, and SN-38, were much more active than the two Topo II inhibitors, i.e., Adriamycin and etoposide, with SN-38 being the most efficient. The two investigational compounds BN80245 and BN80915 exerted higher antiproliferative activity than the three anti-Topo I reference compounds, with the highest activity observed for BN80915.

Discrimination between dysplastic and malignant epithelium of the ampulla of vater based on quantitative image cytometric data.

OBJECTIVE: To assess the ability to associate histopathologic grading with objective criteria obtained by nuclear image cytometry in epithelium of the ampulla of Vater. STUDY DESIGN: Forty-one resected ampullary specimens were studied, including 8 dysplastic ampullomas together with 22 well-differentiated and 11 poorly differentiated ampullary adenocarcinomas. The nuclei were Feulgen stained and analyzed using a computer-assisted microscope, which generated 38 quantitative variables describing chromatin texture and nuclear DNA content (DNA ploidy level). These variables were explored by discriminant analysis to determine the most stable and informative variables. Univariate analysis was performed on the four most informative ones. The whole set of variables was also subjected to principal component analysis in order to characterize intragroup and intergroup heterogeneity. RESULTS: The univariate analysis defined two morphonuclear variables (related to nuclear chromatin distribution) discriminating between dysplasia and well-differentiated cancers. Aneuploidy occurrence was associated with discrimination between well-differentiated and poorly differentiated cancers. CONCLUSION: While alterations in chromatin distribution may be an early event in the malignant degeneration of this epithelium, alterations in nuclear DNA content should correspond to a later phenomenon. Quantification of these features can be exploited to assist in diagnosis.

Big prolactin 60 kDa is overexpressed in salivary glandular epithelial cells from patients with Sjögren's syndrome.

Characterization of endogenous synthesis of prolactin (PRL) proteins and their cellular localization in labial salivary glands of patients with Sjogren's syndrome (SS) were achieved. PRL, PRL-receptors (PRL-R), and S100A6 protein were detected by immunohistochemistry. In situ prolactin synthesis was investigated in controls and SS patients by ex vivo incubation of minor salivary glands biopsies and immunoprecipitation assay. Increased PRL-immunoreactivity was found in cytoplasmic acinar epithelial cells in SS patients compared with normal subjects. PRL-R was distributed only in ductal epithelial cells in which S100A6 protein (a PRL-R-associated protein) was also present. PRL, PRL-R, or S100A6-immunoreactivity was not detected in infiltrating mononuclear cells. Immunoprecipitation demonstrated that PRL synthesis occurred in minor salivary glands with increased synthesis of two distinct PRL-like proteins (one major band at 60 kDa and a minor at 16 kDa) in SS glands compared with normal glands. Expression of PRL gene was demonstrated in SS salivary glands using RT-PCR. A positive correlation was found between the presence of PRL-like proteins in acinar epithelial cells of SS patients and clinical extraglandular manifestations. The presence of anti-Ro and anti-La antibodies also positively correlated with a higher percentage of PRL in acinar epithelial cells. In conclusion, PRL-like proteins are synthetized and overexpressed in glandular epithelial cells of labial salivary glands from SS patients and correlate with the aggressiveness of the disease.

Improving accuracy in the grading of renal cell carcinoma by combining the quantitative description of chromatin pattern with the quantitative determination of cell kinetic parameters.

The determination of grade and stage in renal cell carcinomas (RCCs) often fails to predict the actual clinical outcome for individual patients. The aim of the present work was to investigate whether it is possible to significantly improve the prognostic accuracy of the grading system by using the combination of two independent computer-assisted microscopy techniques. The first technique relates to the quantitative description of morphonuclear and nuclear DNA content features by means of the image analysis of Feulgen-stained cell nuclei, and the second quantitatively characterizes tumor growth by means of different cell kinetic parameters. These parameters consist of a duplication of a time-related parameter determined by means of the technique of using silver-stained proteins in interphase nucleolar organizer regions (AgNOR), a proliferation index determined by means of MIB-1 immunohistochemistry, and an apoptotic index determined by means of the terminal dUTP nick end labeling technique. The prognostic value of these quantitative features was investigated in a series of 60 RCCs. The quantitative analysis of Feulgen-stained nuclei made it possible to identify subgroups of patients with significantly different prognoses in both grade II and grade III RCCs. We labeled the RCCs associated with the most favorable prognoses as grade II- and III- and those with the least favorable ones as grade II+ and III+. The two most important kinetic variables to identify patients with different clinical outcomes were the MIB-1 index and the mean AgNOR area in the MIB-1-positive cells. Three significantly different survival curves were obtained for the 53 grade II and III RCC patients. Our results show that conventional RCC grading can be significantly improved by the quantitative analysis of Feulgen-stained nuclei, by cell kinetic parameter determination, and, more importantly, by combining the proliferation index with the mean AgNOR area parameter.

Differential expression of S100 calcium-binding proteins characterizes distinct clinical entities in both WHO grade II and III astrocytic tumours

The computer-assisted microscopic analysis of Feulgen-stained nuclei enabled us to identify two subgroups of astrocytomas (WHO grade II) and two subgroups of anaplastic astrocytomas (WHO grade III) with significantly distinct clinical outcomes (Decaestecker et al. Brain Pathol 1998; 8: 29-38). The astrocytomas labelled in the present study as typical (TYP-ASTs) behaved clinically like real astrocytomas while atypical astrocytomas (ATYP-ASTs) behaved similarly to anaplastic astrocytomas. The anaplastic astrocytomas that we labelled as typical (TYP-ANAs) behaved clinically like anaplastic astrocytomas while atypical ones (ATYP-ANAs) behaved like glioblastomas. In the present study, we investigate whether some biological characteristics could be evidenced across these four groups of TYP- and ATYP-ASTs and TYP- and ATYP-ANAs. The data show that the levels of expression (immunohistochemically assayed and quantitatively determined by means of computer-assisted microscopy) of vimentin, the glial fibrillary acidic protein and the platelet-derived growth factor-alpha did not differ significantly across these four groups of astrocytic tumours. The level of cell proliferation (determined by means of both the anti-proliferating cell nuclear antigen and the anti-MIB-1 antibodies; P < 0.001 to P < 0.0001) differed very significantly between the astrocytomas and anaplastic astrocytomas, but not between the typical and atypical variants identified in each group. In sharp contrast, the levels of expression of the S100A3 and S100A5 proteins differed markedly in the solid tumour tissue in relation to the astrocytic tumour types and grades. In addition, while the levels of expression of S100A6 did not change in the astrocytic tumour tissue in relation to histopathological grade, the levels of expression of this S100 protein (but not those of S100A3 and S100A5) differed markedly in the blood vessel walls according to whether these vessels originated from low- or high-grade astrocytic tumours.

How could static telepathology improve diagnosis in neuropathology?

The present paper reports our experience with, and our opinion of static telepathology as applied to neuropathology by means of the PHAROS acquisition system and conventional telephone data transmission (modem). The classical procedure of expert consultation based on surface mailing of histological slides is routinely performed, especially in highly specialized fields of pathology. Telepathology is an easy means of sharing scientific expertise at international level and could thus improve diagnosis particularly in neuropathology, where certain tumor types are very rare and complex to diagnose. Dynamic telepathology allows the referring pathologist to capture by himself images supporting their diagnosis. Using static telepathology the pathologist could be limited in diagnosis by problems in fields selection. We devoted a whole year to collecting all the technical parameters characterizing the use of digitized neuropathological data files in order to investigate the feasibility of telepathology and the extent to which its use could improve diagnoses. Our results on a series of 38 histological brain examinations illustrate how we successfully established an international connection between two departments of pathology in Belgium and the USA. The referring pathologists gave diagnoses in 35 cases and deferred only 3. Despite a time-consuming procedure for the telepathology session of a few cases, this tool provides easy access to expert diagnosis and real-time discussion, both of which are of considerable interest and offer significant improvements in neuropathology.

Characterization of TNP-470-induced modifications to cell functions in HUVEC and cancer cells.

The aim of the present work is to characterize (both in vitro and in vivo) the influence of TNP-470 on different cell functions involved in angiogenesis and, more particularly, on endothelial cell growth, cell migration and vessel formation. In addition, a possible direct anti-tumor activity was investigated. To this end, we made use in vitro of human umbilical cord endothelial vein (HUVEC) cells and two human cancer cell lines. The TNP-470 effects on the growth of cancer cell lines were compared to those of Taxol (an inhibitor of microtubule depolymerization), a cytotoxic reference which also displays strong antiogenic activity at low (non-toxic) doses. The in vitro effects were characterized on the mouse mammary MXT adenocarcinoma, on which we also characterized the influence of three clinically active anti-tumor compounds (as cytotoxic references). The purpose of this part of the study was to determine the actual TNP-470-related anti-tumor activity and to evaluate the possible toxic side-effects at the doses at which this compound induces tumor growth inhibition. These investigations were completed by analyzing the TNP-470 effects on HUVEC cell motility and in vitro and in vivo vessel formation. The results show that in vitro, TNP-470 inhibited the growth not only of HUVEC, but also of neoplastic cells. Furthermore, TNP-470 clearly inhibited in vitro endothelial cell motility (p<10(-5)). However, it had only a minor effect (p=0.02) on the formation of HUVEC cell networks on Matrigel(R). In vivo, TNP-470 was able to inhibit tumor growth (on the MXT model) at a dose (50 mg/kg) associated with toxic side-effects. Histological examination showed a significant inhibition of vessel formation (p<0.001) at high (toxic) and intermediary (non-toxic) doses (50 and 20 mg/kg). However, we also observed that TNP-470 stimulated lymphocyte proliferation. Thus, care must be taken with the TNP-470 compound in combination with other anti-tumoral agents in order to avoid certain unfortunate clinical complications.

Different ways of weakening decision trees and their impact on classification accuracy of DT combination

Recent classifier combination frameworks have proposed several ways of weakening a learning set and have shown that these weakening methods improve prediction accuracy. In the present paper we focus on learning set sampling (Breiman's bagging) and random feature subset selections (Bay's Multiple Feature Subsets). We present a combination scheme labeled 'Bagfs', in which new learning sets are generated on the basis of both bootstrap replicates and selected feature subsets. The performances of the three methods (Bagging, MFS and Bagfs) are assessed by means of a decision-tree inducer (C4.5) and a majority voting rule. In addition, we also study whether the way in which weak classifiers are created has a significant influence on the performance of their combination. To answer this question, we undertook the strict application of the Cochran Q test. This test enabled us to compare the three weakening methods together on a given database, and to conclude whether or not these methods differ significantly. We also used the McNemar test to compare algorithms pair by pair. The first results, obtained on 14 conventional databases, show that on average, Bagfs exhibits the best agreement between prediction and supervision. The Cochran Q test indicated that the weak classifiers so created significantly influenced combination performance in the case of at least 4 of the 14 databases analyzed. © Springer-Verlag Berlin Heidelberg 2000.

The Local Wavelet Transform: a memory-efficient, high-speed architecture optimized to a Region-Oriented ZeroTree coder

1999

Computer-assisted analysis of epiluminescence microscopy images of pigmented skin lesions.

BACKGROUND: Epiluminescence microscopy (ELM) is a noninvasive clinical tool recently developed for the diagnosis of pigmented skin lesions (PSLs), with the aim of improving melanoma screening strategies. However, the complexity of the ELM grading protocol means that considerable expertise is required for differential diagnosis. In this paper we propose a computer-based tool able to screen ELM images of PSLs in order to aid clinicians in the detection of lesion patterns useful for differential diagnosis. METHODS: The method proposed is based on the supervised classification of pixels of digitized ELM images, and leads to the construction of classes of pixels used for image segmentation. This process has two major phases, i.e., a learning phase, where several hundred pixels are used in order to train and validate a classification model, and an application step, which consists of a massive classification of billions of pixels (i.e., the full image) by means of the rules obtained in the first phase. RESULTS: Our results show that the proposed method is suitable for lesion-from-background extraction, for complete image segmentation into several typical diagnostic patterns, and for artifact rejection. Hence, our prototype has the potential to assist in distinguishing lesion patterns which are associated with diagnostic information such as diffuse pigmentation, dark globules (black dots and brown globules), and the gray-blue veil. CONCLUSIONS: The system proposed in this paper can be considered as a tool to assist in PSL diagnosis.

Determination of the levels of expression of sarcolectin and calcyclin and of the percentages of apoptotic but not proliferating cells to enable distinction between recurrent and nonrecurrent cholesteatomas.

OBJECTIVES: To investigate in a series of cholesteatomas 1. whether subgroups of cholesteatomas with specific proliferative/apoptotic features exhibit distinct differentiation markers and 2. whether these different subgroups identified at the biological level relate to specific groups of clinically identified cholesteatomas. STUDY DESIGN: Analysis of 55 cholesteatomas resected by the same surgeon, by means of canal wall up and canal wall down surgical procedures. METHODS: Two differentiation markers were used: biotinylated sarcolectin (to identify sarcolectin-binding sites) and a monoclonal antibody directed against calcyclin (which is the S100A6 protein). The growth pattern in cholesteatomas was characterized at three distinct levels: 1. the cell proliferation level determined by means of the MIB-1 antibody, which enables the Ki-67 cell-cycle-related antigen to be identified on archival material; 2. the apoptosis level determined by means of the in situ labeling of nuclear DNA fragmentation (TUNEL staining); and 3. the p53 tumor suppressor gene-related product determined by means of p53 immunohistochemistry. RESULTS: The cholesteatomas that exhibited the highest proportion of apoptotic cells were those which exhibited the highest level of sarcolectin-binding sites (i.e., sialic acids). In contrast, the cholesteatomas exhibiting the lowest level of both proliferation and apoptosis showed the highest level of calcyclin. Recurrent cholesteatomas can be identified from nonrecurrent ones on the basis of three features, namely, the level of apoptotic cells, the way in which the apoptotic cells are distributed (i.e., homogeneously vs. heterogeneously), and the percentage of calcyclin-positive cells. CONCLUSIONS: The present data emphasize the existence of distinct subgroups of cholesteatomas identifiable at both cell kinetic and differentiation levels. Some of the biological variables used here to identify distinct biological subgroups of cholesteatomas in turn enabled some biological variables to be identified, so making it possible to classify the cholesteatomas in terms of recurrence versus nonrecurrence.

Grading dysplasia in colorectal adenomas by means of the quantitative binding pattern determination of Arachis hypogaea, Dolichos biflorus, Amaranthus caudatus, Maackia amurensis, and Sambucus nigra agglutinins.

The current study deals with the setting up of a new tool that enables the benign versus the malignant nature of colorectal adenomas to be determined accurately. The 2 objectives are to determine (1) whether adenomas should, or should not, be included in a 2- or a 3-tier grading system, and (2) whether severe dysplasias and carcinomas in situ share common or different biological characteristics. The levels of expression of different types of glycoconjugates were characterized in a series of 166 colorectal specimens, including 14 normal, 90 dysplastic, and 62 cancerous cases. The glycoconjugate expressions were demonstrated for 5 lectins, namely, Arachis hypogaea (PNA), Dolichos biflorus (DBA), Amaranthus caudatus (ACA), Maackia amurensis (MAA) and Sambucus nigra (SNA). The glycoconjugates demonstrated by these 5 lectins belong to the family of the Thomsen-Friedenreich antigens. The binding patterns of the 5 lectins were quantitatively determined by means of computer-assisted microscopy. The quantitative data were submitted to discriminant analyses. Our results show that the specific glycochemical staining patterns could be identified unambiguously and without misclassification between benign (normal and low dysplasia) and malignant (ie, either as moderate/severe dysplasia, carcinoma in situ, or cancer) cases. The data also strongly suggested that (1) dysplasias seem to be distinguishable in 2 instead of 3 groups, that is, low versus moderate/severe (high); and (2) moderate/severe dysplasias are biologically distinct from carcinomas in situ. The methodology developed can be applied directly in routine diagnosis to identify moderate/severe dysplasia specimens already exhibiting features common to carcinomas, and which therefore should be treated consistently in view of the fact that our data strongly suggest that most moderate/severe dysplasias are still benign, whereas carcinomas in situ are real carcinomatous lesions.

A pilot study for identifying at risk thyroid lesions by means of a decision tree run on clinicocytological variables.

Fine-needle aspiration biopsy (FNAB) is safe, inexpensive, minimally invasive, and highly accurate in the diagnosis of nodular diseases of the thyroid. However, FNAB does not provide a reliable benign versus malignant diagnosis for 100% of the cases analysed. It is possible to increase the accuracy of the cytological diagnosis by means of information contributed by different clinical variables. In the present study we evaluate the diagnostic value of 10 variables in addition to FNAB on a series of 218 specimens for which we obtained histological diagnoses including 37 cancers (17%). The diagnostic information contributed by these variables was analyzed by means of the Decision Tree technique, an artificial intelligence-related method which forms part of the Supervised Learning algorithms. The results show that Decision Trees enable some subpopulations of patients with uncertain FNAB results to be characterized.

Galectin-1 and galectin-3 binding pattern expression in renal cell carcinomas.

We studied 2 families of molecules whose role remains uncharacterized or obscure in the progress of renal cell carcinoma (RCC): galectins, a major class of glycoproteins, and the Thomsen-Friedenreich (T) antigen. We characterized the level of expression of galectin-1 and galectin-3 and their respective binding sites in a series of 74 RCCs. We also characterized the level of expression of laminin, a natural ligand for galectins. Finally, we characterized the level of T antigen expression and the T antigen binding sites. All levels of expression were quantitatively determined by using computer-assisted microscopy on immunohistochemically or glycohistochemically stained slides. A small concentration of galectin-1 binding sites or a large concentration heterogeneity of galectin-3 can be associated with unfavorable prognoses for patients with grade II or III RCCs. In contrast, T antigen and T antigen binding sites revealed no change across the 2 RCC groups that exhibited different clinical outcomes. We established discriminant scores that permitted a clear distinction between the 2 RCC groups analyzed. Modifications to the expression of galectin-1 and galectin-3, but not of T antigen, parallel an increase in RCC aggressiveness. Galectins represent a family of molecules with a meaningful role in RCC progression.

Galectin-3 and galectin-3-binding site expression in human adult astrocytic tumours and related angiogenesis

Using computer-assisted microscopy, the present work aimed to quantitatively characterize the level of the histochemically detectable expression of galectin-3 and galectin-3-binding sites in sections of a series of 84 astrocytic tumours (including 22 grade II, 21 grade III and 41 grade IV specimens) and seven non-tumoural specimens used as controls. The presence of galectin-3 and reactive sites for this lectin were monitored by means of a specific polyclonal anti-galectin-3 antibody (aGal3) and biotinylated galectin-3 (Gal3), respectively. The pattern of expression of galectin-3-binding sites is compared to the pattern of expression of laminin (a potential galectin-3 ligand) revealed using a biotinylated anti-laminin antibody (aLam). Three variables quantitatively characterizing histochemical staining reactions were evaluated by means of computer-assisted microscopy for each of the 3 probes under study (aGal3, Gal3 and aLam). The labelling index (LI) is the percentage of tissue area specifically stained by a histochemical probe. The mean optical density (MOD) denotes staining intensity. The concentration heterogeneity (CH) feature expresses the concentrational spread of individual fields. The data obtained in the present study show that: (i) white matter of a non-tumoural brain expresses galectin-3 (and also galectin-3-binding sites); (ii) the level of galectin-3 expression significantly decreases in the majority of tumour astrocytes from low to high grade astrocytic tumours; while (iii) some tumour cell clones expressing high amounts of galectin-3 emerged with increasing levels of malignancy; and (iv) the level of accessible galectin-3-binding sites was apparently not heavily modified in the course of malignancy progression. In conclusion, the results obtained in the present study show that human astrocytic tumours are very heterogenous in their galectin-3 levels of expression. If high levels of galectin-3 determine the invasiveness potential of a tumour cell, then within a heterogenous tumour the presence of even a small, but actively proliferating number of tumour cell clones expressing high levels of galectin-3 can be expected to lead to tumour invasiveness.

In vitro motility evaluation of aggregated cancer cells by means of automatic image processing.

BACKGROUND: Set up of an automatic image processing based method that enables the motility of in vitro aggregated cells to be evaluated for a number of hours. METHODS: Our biological model included the PC-3 human prostate cancer cell line growing as a monolayer on the bottom of Falcon plastic dishes containing conventional culture media. Our equipment consisted of an incubator, an inverted phase contrast microscope, a Charge Coupled Device (CCD) video camera, and a computer equipped with an image processing software developed in our laboratory. This computer-assisted microscope analysis of aggregated cells enables global cluster motility to be evaluated. This analysis also enables the trajectory of each cell to be isolated and parametrized within a given cluster or, indeed, the trajectories of individual cells outside a cluster. RESULTS: The results show that motility inside a PC-3 cluster is not restricted to slight motion due to cluster expansion, but rather consists of a marked cell movement within the cluster. CONCLUSIONS: The proposed equipment enables in vitro aggregated cell motility to be studied. This method can, therefore, be used in pharmacological studies in order to select anti-motility related compounds. The compounds selected by the equipment described could then be tested in vivo as potential anti-metastatic.

Galectin fingerprinting in tumor diagnosis. Differential expression of galectin-3 and galectin-3 binding sites, but not galectin-1, in benign vs malignant uterine smooth muscle tumors.

Cell-matrix interactions are governed by a distinct set of proteins, with 2 nonintegrin laminin-binding proteins, galectin-1 and galectin-3, providing 1 aspect. The expression patterns of laminin and the 2 galectins and galectin binding sites were quantitatively determined by means of computer-assisted microscopy with the aim of differentiating between 16 leiomyomas and 10 leiomyosarcomas of the uterus. Three quantitative variables were computed for each of the 5 histochemical markers: labeling index, which describes the percentage of tissue area specifically stained by a given marker; mean optical density which reflects the concentration of the marker; and concentrational heterogeneity, which characterizes the degree of heterogeneity of the marker distribution in the tumor tissue areas. The results reveal evident differences in the galectin-3-related parameters in the 2 tumors groups. Whereas the concentration of galectin-3 binding sites was significantly (P = .01) weaker in the leiomyosarcomas than in the leiomyomas, the percentages of tumor tissue expressing galectin-3 (P = .02) and its binding sites (P = .002) were significantly higher in the leiomyosarcomas than in the leiomyomas. Although significantly (P = .02) higher, the concentration of laminin was more heterogeneously distributed (P = .01) in the leiomyosarcomas than in the leiomyomas. In contrast, the levels of expression of galectin-1 and its accessible binding sites remained similar for both the leiomyomas and the leiomyosarcomas. Finally we document how the levels of expression of galectin-3 and its binding sites can be of assistance in reliably differentiating leiomyomas from leiomyosarcomas.

D-mannose and N-acetylglucosamine moieties and their respective binding sites in salivary glands of Sjögren's syndrome.

OBJECTIVE: Sjögren's syndrome (SS) is an autoimmune exocrinopathy. The mannose binding lectin (MBL), a pluripotent molecule of the innate immune system, is involved in the pathogenesis of autoimmune diseases. We investigated whether specific ligands for MBL and MBL related structures could be reliable markers in cases of SS. METHODS: The labial salivary glands of 19 patients fulfilling the diagnostic criteria for primary (n=11) and secondary SS (n=8) were studied. Seven healthy women served as controls. Computer assisted microscopy was employed to determine quantitatively the percentage of positive structures (acini, ducts, and interlobular connective tissue), the staining intensity, and the level of staining heterogeneity for 4 glycohistochemical probes including wheat germ agglutinin and concanavalin (Con A) as lectins, and mannose and N-acetylglucosamine as parts of neoglycoproteins. The data were evaluated by discriminant analysis. RESULTS: The data strongly suggest that MBL related structures, if not MBL itself, could play distinct roles in the pathogenesis of primary versus secondary SS. Further, quantitative determination of the level of expression of D-mannose and N-acetylglucosamine and their respective binding sites in labial salivary gland acini offers a powerful diagnostic tool for distinguishing primary from secondary SS. CONCLUSION: In SS labial salivary glands, determination of the level of acceptor sites for wheat germ agglutinin, Con A, D-mannose, and N-acetylglucosamine provides information on the roles played by glycoforms in SS. The methodology and data described in this paper should provide pathologists with objective diagnostic markers for SS. Our results should enhance the biological understanding of this pathology.

Improving the prognostic value of histopathological grading and clinical staging in renal cell carcinomas by means of computer-assisted microscopy.

The present work aims to refine prognosis in cases of renal cell carcinoma (RCC) by integrating a variety of parameters with the prognostic information provided by histopathological grading and clinical staging, carried out on a series of 97 RCCs. To this end, Feulgen-stained RCC cell nuclei were characterized by means of 38 variables describing nuclear DNA ploidy levels and morphology. All of these data were subjected to a principal components analysis. On the basis of this multivariate analysis, Fuhrman grade II was subdivided into grades II- and II+, and Fuhrman grade III into grade III- and III+. The same kind of subcategorization was performed in the case of the T2 and T3 clinical stages. The results show that the classification into grade II- and III- RCCs correspond to a more favourable prognosis than grade II+ and III+, to which shorter survival periods were attributable. Similar results were obtained for the subcategorization of the T2 and T3 clinical stages. Very simple biological characterizations of these grade- or stage-related RCC groups were obtained by means of a decision tree approach applied to the cytometry-generated variables. The resulting classification rules were validated on a new series of 18 patients and enabled very accurate predictions of survival.

Sialic acid residues in the labial salivary glands from Sjögren's syndrome patients.

OBJECTIVE: To investigate the composition and expression of sialic acid in the labial salivary glands (LSG) in Sjögren's syndrome (SS). METHODS: LSG of 19 patients with primary SS (n = 11) or secondary SS (n = 8) were studied. Specimens from 7 healthy women served as controls. Computer-assisted microscopy was employed to quantitatively determine the percentage of positive structures, the staining intensity and the heterogeneity for the 4 biotinylated plant lectins Tritricum vulgaris L. (WGA), Maackia amurensis (MAA), Sambucus nigra (SNA) and Canavalia ensiformis L. (Con A). RESULTS: In the acini there was a significant decrease in the staining heterogeneity of WGA in SS compared to controls; the same was observed with respect to MAA staining in the connective tissue and extralobular ducts. In the intralobular ducts, primary SS differed from normal and secondary SS mainly in terms of a decrease in the percentage of positively labeled MAA tissue. In addition, Con A stained acinar cells were significantly more numerous in secondary SS compared with primary SS. CONCLUSION: Differences in the degree of glycoconjugate sialylation were found in SS labial salivary glands, and may play a role in the disease process.

In vitro influence of lectins and neoglycoconjugates on the growth of three human sarcoma cell lines.

PURPOSE: The aim of our study is to investigate the in vitro effects of plant lectins, galectins and neoglycoconjugates on the proliferation of three human sarcoma cell lines. METHODS: Proliferation was assessed by means of the tetrazolium derivative reduction (MTT) assay. In addition, glycohistochemistry was used to make visible the plant-lectin-specific binding sites; the intensity of the lectin binding pattern was quantified by means of image analysis. RESULTS: Depending on the cell lines, the staining intensity and the percentage of labelled cells were different. With respect to growth modulation, the cell lines also responded differently to the probes used. Besides a predominant inhibitory effect elicited by the probes at 50 microg/ml, dose-dependent effects, including growth stimulation, were detectable in several instances. These effects relate to the animal galectins tested and several neoglycoconjugates, e.g. the lactose- and blood-group-A-trisaccharide-bearing probes. CONCLUSIONS: Endogenous lectins and lectin-reactive cellular glycoconjugates can apparently affect the regulation of the growth of human sarcoma cells. We suggest that these results are relevant for further histopathological monitoring in correlation with prognosis and in vitro assays to reveal possible clinical applications.

The influence of L-triiodothyronine, L-thyroxine, estradiol-17β, the luteinizing-hormone-releasing hormone, the epidermal growth factor and gastrin on cell proliferation in organ cultures of 35 benign and 13 malignant human thyroid tumors

PURPOSE: To characterize the influence of six factors on human thyroid tissues at the cell-proliferation level. These six factors were the epidermal growth factor (EGF), the luteinizing-hormone-releasing hormone (LHRH), triiodothyronine, thyroxine, estradiol and gastrin. METHODS: Forty-eight human thyroid specimens were obtained from surgical resection and maintained alive for 48 h ex vivo (in vitro) under organotypic culture conditions. These specimens comprised 35 benign cases (17 multinodular goiters and 18 adenomas) and 13 cancers. Cell proliferation in the control and treated conditions (at a 5 nM dose) was assessed by means of the thymidine labeling index, which enables the percentage of cells in the S phase of the cell cycle to be determined in accordance with autoradiographic procedures. RESULTS: The results show that, of the six factors tested here, EGF significantly (P < 0.05 to P < 0.001) increased cell proliferation in the greatest number of cancers as compared to what happened with the remaining five. Each of these six factors significantly increased or decreased proliferative cell activity in some 10%-30% of the cases under study. CONCLUSIONS: Triiodothyronine, thyroxine, LHRH and gastrin may increase or decrease cell proliferation in human thyroid tissues, whether benign or malignant, to the same extent as other hormones and/or growth factors such as thyrotropin, EGF, insulin-like growth factor 1, transforming growth factor beta1 and estradiol the effects of which on thyroid cell proliferation are already well documented in the literature.

Supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas and glioblastomas are characterized by a differential expression of S100 proteins.

The levels of expression of the S100A1, S100A2, S100A3, S100A4, S100A5, S100A6 and S100B proteins were immunohistochemically assayed and quantitatively determined in a series of 95 astrocytic tumors including 26 World Health Organization (WHO) grade I (pilocytic astrocytomas), 23 WHO grade II (astrocytomas), 25 WHO grade III (anaplastic astrocytomas) and 21 WHO grade IV (glioblastomas) cases. The level of the immunohistochemical expression of the S100 proteins was quantitatively determined in the solid tumor tissue (tumor mass). In addition twenty blood vessel walls and their corresponding perivascular tumor astrocytes were also immunohistochemically assayed for 10 cases chosen at random from each of the four histopathological groups. The data showed modifications in the level of S100A3 protein expression; these modifications clearly identified the pilocytic astrocytomas from WHO grade II-IV astrocytic tumors as a distinct biological group. Modifications in the level of S100A6 protein expression enabled a clear distinction to be made between low (WHO grade I and II) and high (WHO grade III and IV) grade astrocytic tumors. Very significant modifications occurred in the level of S100A1 protein expression (and, to a lesser extent, in their of the S100A4 and S100B proteins) in relation to the increasing levels of malignancy. While the S100A5 protein was significantly expressed in all the astrocytic tumors (but without any significant modifications in the levels of malignancy), the S100A2 protein was never expressed in these tumors. These data thus indicate that several S100 proteins play major biological roles in human astrocytic tumors.

An efficient VLSI architecture for the 2-D Wavelet Transform with Novel Image Scan

A Scalable Architecture for MPEG-4 Wavelet Quantization

Optimal Memory Organization for scalable texture codecs in MPEG-4

1998

Corporeal veno-occlusive dysfunction: a distal arterial pathology?

Alteration of intracavernous smooth muscle cells has been demonstrated in patients with pure venous leakage. This modification seems correlated with reduction of intracavernous oxygen tension. However, Doppler imaging of the cavernous arteries in these patients is normal. To understand the ischemic factor we studied the endothelium of the terminal arteries with computerized image analysis and immunohistochemical staining with 2 types of lectin in patients with venous leakage and those with normal erections. Lectins are glycoproteins that can be used as histological markers to monitor functional and pathological changes.

Use of image cytometry to classify biliary and ampullary adenocarcinomas.

OBJECTIVE: To create an objective classification system to perform TNM classification of ampullary adenocarcinoma and cholangiocarcinoma using image cytometric data derived from Feulgen-stained tumor nuclei. STUDY DESIGN: Surgically resected cases of ampullary adenocarcinoma and cholangiocarcinoma with established TNM classifications were selected on the basis of available formalin-fixed, paraffin-embedded tissue. Fifteen numerical variables related to morphometric, densitometric and textural features of each tumor nucleus were recorded. We employed a methodology based on multivariate statistical tools to characterize the association of morphonuclear variables with TNM classification. The first step consisted of identifying and selecting representative nuclei of each T class. From this "purified" data set an objective classification system was created. The classification system was assessed using internal and external validation. RESULTS: Employing ANOVA, all 15 variables were significantly associated with T classification, 11 of 15 with N and 4 with M. Multivariate analysis was employed to distinguish between T1, T2 and T3 lesions. Our methodology correctly classified 76% of T1 nuclei, 47% of T2 nuclei and 84% of T3 nuclei. Heterogeneity within an individual tumor was defined in 61% of cases included in the training set. Complete concordance between pathologic classification and the classification system was observed in 71% of an independent validation.

Gastrin inhibits motility, decreases cell death levels and increases proliferation in human glioblastoma cell lines.

Whether they are of low or high histopathological grade, human astrocytic tumors are characterized by a marked propensity to diffuse into large areas of normal brain parenchyma. This invasion relates mainly to cell motility, which enables individual cell migration to take place. The present study characterizes in vitro the gastrin-mediated effects on both the growth (cell proliferation vs. cell death) and motility dynamics of the human U87 and U373 glioblastoma cell lines. A computer-assisted phase-contrast microscope was used to track the number of mitoses versus cell deaths every 4 min over a 72-h period and so to quantitatively describe the trajectories of living U373 and U87 cells growing on plastic supports in culture media both with and without the addition of 0.1, 5, or 100 nM gastrin. While 5 or 100 nM gastrin only weakly (p < .05 to p < .01) increased cell proliferation in the U87 cell line and not in U373 one, it very significantly (p < .001) inhibited the amount of cell death at 5 and 100 nM in both the U87 and U373 lines. In addition, 5 nM gastrin markedly inhibited cell mobility in U87 (p < .00001) and U373 (p < .0001) glioblastoma models. All these data strongly suggest that gastrin plays a major role in the biological behavior of the in vitro U87 and U373 human glioblastoma cell lines in matters concerning their levels of cell motility and growth dynamics.

Setting up of an original computer-assisted methodology to characterize in vitro drug-induced anti-angiogenic effects.

The development of angiogenesis within a tumor brings on a sequence of extremely complex molecular events. We have developed a methodology which enables a wide set of biological parameters to be quantitatively determined in the field of anti-angiogenesis pharmacology. This methodology which includes a video cell tracking device, is unique because it offers the possibility of evaluating the specific influence of a given compound with potential anti-angiogenic properties on cell cycle kinetics, cell death, global cell line growth, and cell motility. We chose TNP-470, a synthetic analogue of fumagilin, to test our methodology on HUVEC cell lines taken from various human umbilical cord veins. The experiments carried out with TNP-470 did not confirm all the data reported in the literature. Our results show that i) TNP-470 could be considered as a cytotoxic agent; ii) this compound had an apparently marginal cytostatic effect; and iii) it did not increase the apoptosis level. Our methodology also revealed that the HUVEC cell lines are very heterogeneous in terms of different biological parameters. This highlights the problem of the reproductibility of the result.

Growth inhibition of human in vitro and mouse in vitro and in vivo mammary tumor models by retinoids in comparison with tamoxifen and the RU-486 anti-progestagen.

Retinoids constitute a very promising class of agents for the chemoprevention or treatment of breast cancer. These retinoids exert their biological activity through two distinct classes of retinoic acid (RA) receptors (R), the RAR isotypes (alpha, beta, and gamma) and the three RXR isotypes (alpha, beta, and gamma) and their numerous isoforms which bind as RXR/RAR heterodimers to the polymorphic cis-acting response elements of RA target genes. With respect to these numerous receptor sub-types, the retinoid-induced effects at the biological level include marked modifications with respect to both cell proliferation and cell death (apoptosis), and also in the induction of differentiation processes. The present study aims to characterize the effect which four retinoids (TTNPB, 9-cis-RA, LGD 1069, 4-HPR) with distinct RAR/RXR binding properties induced on various in vitro and in vivo mouse and human breast cancer models. The experiments with the retinoids were carried out in comparison with the anti-estrogen tamoxifen and the anti-progestagen RU-486 compounds. The results show that the 6 compounds under study were markedly more efficient in terms of growth inhibition in the human T-47D cell line when maintained under anchorage-independent culture conditions than when maintained under anchorage-dependent ones. While RU-486 exhibited a weak statistically significant (p < 0.05) influence on the growth of the T-47D stem cells, tamoxifen had a marked inhibitory influence on the growth of these cells. Of the four retinoids, 4-HPR was the least effective since the lowest doses tested (1 and 0.1 nM) exhibited no statistically (p > 0.05) significant influence on the growth of the stem cells. The most efficient retinoid was TTNPB. It was only at the highest dose (10 microM) that tamoxifen and RU-486 showed a weak inhibitory influence on the growth of the T-47D non-stem cells while all 4 retinoids exerted a significant inhibitory influence on the growth of these non-stem cells, with 4-HPR being the most efficient (P < 0.001) at the highest dose, but ineffective (P > 0.05) at the lowest. Tamoxifen and TTNPB were tested in vivo on hormone-sensitive (HS) and hormone-insensitive (HI) strains of the MXT murine mammary carcinoma. While TTNPB appeared to be equally efficient in terms of growth inhibition in both MXT-HS and MXT-HI models, tamoxifen had only a marginal inhibitory influence on the growth of the MXT-HI strain but did inhibit growth in the case of the MXT-HS one. TTNPB was markedly more efficient than tamoxifen in terms of both inhibiting the cell proliferation level (measured by means of computer-assisted microscopy applied to Feulgen-stained nuclei, a method which enables the percentage of cells in the S phase of the cell cycle to be determined) and triggering cell death (measured by means of the determination of the transglutaminase activity) in both the MXT-HI and MXT-HS models. The very significant TTNPB-induced inhibition of the macroscopic MXT-HS growth rate relates to the triggering of cell death (apoptosis) rather than to an inhibition of cell proliferation. All these results clearly indicate that retinoids are very efficient agents against breast cancer, at least as efficient as tamoxifen.

Characterization of astroglial versus oligodendroglial phenotypes in glioblastomas by means of quantitative morphonuclear variables generated by computer-assisted microscopy.

The current WHO classification places glioblastomas in the astrocytoma category. However, whether or not glioblastomas also show oligodendroglial differentiation remains a matter of controversy. This study investigates, at the morphonuclear level, the hypothesis that some glioblastomas (GBMs) may also represent the ultimate level of malignancy in the oligodendroglial lineage. Using a series of 164 GBMs, we sought to ascertain whether any of these GBMs exhibited phenotypical characteristics that were more closely related to oligodendroglial lineages than astrocytic lineages. Phenotypical features were quantitatively determined by means of the computer-assisted microscope analysis of Feulgen-stained nuclei, a process that made it possible to quantitatively describe the patterns of the cell nuclei (and, more specifically, of their chromatin) through 16 variables, and the distribution of the nuclear DNA content (DNA ploidy) through 8 variables. The phenotypical characteristics typical of astrocytic and oligodendroglial tumors were analyzed by means of Discriminant Analysis, a statistical multivariate analysis, performed on a series of 65 astrocytic and oligodendroglial tumors. This series consisted of 14 WHO grade II and 19 grade III astrocytomas and 24 WHO grade II and 8 grade III oligodendrogliomas. This multivariate analysis enabled an accurate model to be produced that distinguished between astrocytomas and oligodendrogliomas on the basis of 5 cytometry-generated variables. This model was used to characterize the phenotype of each of the 164 glioblastomas. The results show that of these 164 glioblastomas, 6 (about 3.5%) displayed phenotypes that were very similar to oligodendrogliomas, and 141 displayed phenotypes that were very similar to astrocytomas. The phenotypes of the 17 remaining GBMs were too ambiguous to be categorized as having a pure astrocytic or oligodendroglial lineage.

Discrimination between chronic pancreatitis and pancreatic adenocarcinoma using artificial intelligence-related algorithms based on image cytometry-generated variables.

The incidence of pancreatic adenocarcinomas (PA) is increased in the setting of chronic pancreatitis. Distinguishing chronic pancreatitis from pancreatic adenocarcinomas is often difficult, and is based on routine brush cytological specimens provided during endoscopic retrograde cholangiopancreatography (ERCP). Reactive epithelial changes in chronic pancreatitis may appear similar to those of a well-differentiated cancer. Brush cytology specimens were obtained during ERCP from 49 patients with diseases for which the differential diagnosis included chronic pancreatitis and/or pancreatic adenocarcinoma Image cytometry was performed involving the assessment of between 200-400 Feulgen-stained nuclei per case; for each case, 40 quantitative cytometric variables were generated. Data analysis was performed using artificial intelligence methods of data classification that produced decision trees and production rule systems. Different classification models were produced for a subset of 34 patients. The best models were identified by the use of a sampling technique (leave-one-out), and were tested on the remaining 15 patients. These models were based on 5 of the 40 variables associated with a significant discriminatory function. Pancreatic adenocarcinoma was diagnosed in the training data set of 34 patients during a leave-one-out process with an estimated sensitivity of 91% and specificity of 87%. Both sensitivity and specificity were 80% in the independent test set of 15 patients. We conclude that inflammatory and malignant pancreatic epithelia exhibit distinct morphological features that can be distinguished by decision tree-based classifiers employing image-cytometric numerical data.

Prognostic value of stem cell line identification for renal cell carcinomas.

OBJECTIVE: To investigate the prognostic value of nuclear DNA content (DNA ploidy level) in a series of 95 renal cell carcinomas (RCCs). STUDY DESIGN: Eight variables were used to characterize DNA ploidy levels. They included DNA index and seven others characterizing the presence of specific stem cell lines in each of the 95 RCCs under study. All these variables were determined by means of computer-assisted microscopy applied to Feulgen-stained nuclei. The actual information contributed by each of the eight variables was determined by means of univariate statistical analyses. RESULTS: The results showed that in the DNA ploidy-related eight variables, the presence of at least 4% aneuploid nuclei with > 5C DNA content was associated with the most significant prognostic value in RCCs with intermediate (T2, T3) invasion levels. CONCLUSION: The present study clearly showed that stem cell line characterization, and particularly the presence of highly aneuploid cells (with > 5C DNA content), is associated in RCCs with significant prognostic value. This kind of marker may help the identification of patients who will develop metastases after surgery and for whom adjuvant therapy might thus be indicated.

Image cytometry as a discriminatory tool for cytologic specimens obtained by endoscopic retrograde cholangiopancreatography.

BACKGROUND: Routine brush cytology is relatively insensitive for the diagnosis of biliary and pancreatic malignancy. Sensitivity can be improved by measuring DNA and proliferation. The goal of this study was to assess the discriminatory capacity of image cytometry using pancreaticobiliary brush cytology specimens obtained during endoscopic retrograde cholangiopancreatography (ERCP). Analysis included morphometry, DNA quantification, and characterization of nuclear chromatin distribution and condensation. METHODS: Brush cytology specimens were obtained during ERCP from 22 chronic pancreatitis specimens, 11 pancreatic adenocarcinoma specimens, 13 primary sclerosing cholangitis specimens, and 11 cholangiocarcinoma specimens and contrasted with 25 normal epithelia specimens. A SAMBA 2005 image processor was used to analyze Feulgen stained chromatin density and distribution. Discriminant analysis of 37 morphonuclear variables was performed to characterize differences between: 1) chronic pancreatitis and pancreatic adenocarcinoma, and 2) primary sclerosing cholangitis and cholangiocarcinoma. RESULTS: Chronic pancreatitis was distinguished from pancreatic adenocarcinoma (P < or = 0.001); sensitivity and specificity were both estimated to be 82%. Primary sclerosing cholangitis was distinguished from cholangiocarcinoma (P < or = 0.01); sensitivity and specificity were estimated to be 82% and 85%, respectively. CONCLUSIONS: Multiparameter image cytometry has potential as an adjuvant diagnostic technique in patients with pancreaticobiliary malignancy.

Direct relationship between hormone sensitivity level and growth pattern. Evidence in 18 gastrointestinal neoplastic cell lines.

OBJECTIVE: We investigated whether a relationship exists in terms of growth pattern and hormone sensitivity in 18 gastrointestinal neoplastic cell lines. Hormones studied included gastrin, epidermal growth factor, estradiol and luteinizing hormone-releasing hormone. STUDY DESIGN: The growth patterns were assessed by means of computer-assisted microscope analysis of Feulgen-stained nuclei combined with the mathematical Delaunay triangulation and Voronoi paving techniques. This methodology enabled four variables characterizing the cell colony patterns to be computed. The information contributed by these variables was analyzed by means of discriminant analysis and the decision tree technique. RESULTS: Each phenotype (sensitivity level) exhibited distinct growth pattern (or cell colony) characteristics in the case of each hormone and/or growth factor under study. Furthermore, the sensitivity of the gastrointestinal cell lines to a given hormone (or growth factor) appeared to be peculiar to the hormone (or growth factor). CONCLUSION: A direct relationship seems to exist between growth pattern and hormone sensitivity levels in gastrointestinal cancers, particularly colorectal.

Determination of growth fraction and cell density to evaluate the potential growth of human oligodendroglial and astrocytic tumours.

The object of this work was PURPOSE: to develop a methodology that enables net tumour growth, a balance between actual tumour growth and tumour cell loss, to be approximately evaluated. METHODS: The methodology proposed relies on detecting the growth fraction immunohistochemically by means of MIB-1 antibody labelling combined with cell density determination, carried out on 5-microm-thick Feulgen-stained histological sections with computer-assisted microscopy. The series investigated included 25 oligodendrogliomas (OLG-II), 9 anaplastic oligodendrogliomas (OLG-III). 13 astrocytomas (AST), 14 anaplastic astrocytomas (ANA) and 8 mixed oligoastrocytomas (OLG-AST). RESULTS: The results show that the biological characteristics of some cases were in total accordance with their histopathological diagnoses. This was the case for the "weakly proliferating weakly dense" OLG-II and AST-II tumours, and for the "highly proliferating highly dense" OLG-III and AST-III ones. In contrast, the biological characteristics of some cases seemed to contradict the histopathological case labels. This was the case for the "highly proliferating highly dense" OLG-II and AST-II tumours, the biological aggressiveness of which would be undervalued on the basis of the morphology-based grading system alone, and also for the "weakly proliferating weakly dense" OLG-III and AST-III tumours, the aggressiveness of which would be overvalued. CONCLUSIONS: Combining the determinations of the MIB-1 and the cell density variables appears to be satisfactory in terms of the cell kinetic characterization of glial tumours as a complement to the prognostic information given by a morphology-based grading system alone.

The in vitro influence of eight hormones and growth factors on the proliferation of eight sarcoma cell lines.

Little is known about the regulation of sarcoma proliferation by hormones and/or growth factors. We therefore characterised the in vitro proliferative influence on eight sarcoma cell lines of the platelet-derived growth factor, the insulin-like growth factor 1, triiodothyronine, the epidermal growth factor, the luteinising-hormone-releasing hormone, progesterone, gastrin and 17 beta-oestradiol. The influence of the different factors on the proliferation of sarcoma cell lines was measured by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Two culture media were studied: (1) a nutritionally poor medium containing 2% of fetal calf serum and (2) a nutritionally rich one containing 5% or 10% FCS both with and without the addition of non-essential amino acids. The results were analysed either by conventional statistical analyses or by a classification method based on a decision-tree approach developed in Machine Learning. This latter method was also compared to other classifiers (such as logistic regression and k nearest neighbours) with respect to its accuracy of classification. Monovariate statistical analysis showed that each of the eight cell lines exhibited sensitivity to at least one factor, and each factor significantly modified the proliferation of five or six of the eight cell lines under study. Of these eight lines one of fibrosarcoma origin was the most "factor-sensitive". Decision-tree-related data analysis enabled the specific pattern of factor sensitivity to be characterised for the three histological types of cell line under study. The effects of hormone and growth factors are significantly influenced by the type of culture medium used. The method used appeared to be an accurate classifier for the kind of data analysed. Sarcoma proliferation can be modulated, at least in vitro, by various hormones and growth factors, and the proliferation of each histopathological type exhibited a distinct sensitivity to different hormone and/or growth-factors.

Improving morphology-based malignancy grading schemes in astrocytic tumors by means of computer-assisted techniques

We propose an original methodology which improves the accuracy of the prognostic values associated with conventional morphologically-based classifications in supratentorial astrocytic tumors in the adult. This methodology may well help neuropathologists, who must determine the aggressiveness of astrocytic tumors on the basis of morphological criteria. The proposed methodology comprises two distinct steps, i.e. i) the production of descriptive quantitative variables (related to DNA ploidy level and morphonuclear aspects) by means of computer-assisted microscopy and ii) data analysis based on an artificial intelligence-related method, i.e. the decision tree approach. Three prognostic problems were considered on a series of 250 astrocytic tumors including 39 astrocytomas (AST), 47 anaplastic astrocytomas (ANA) and 164 glioblastomas (GBM) identified in accordance with the WHO classification. These three problems concern i) variations in the aggressiveness level of the high-grade tumors (ANA and GBM), ii) the detection of the aggressive as opposed to the less aggressive low-grade astrocytomas (AST), and iii) the detection of the aggressive as opposed to the less aggressive anaplastic astrocytomas (ANA). Our results show that the proposed computer-aided methodology improves conventional prognosis based on conventional morphologically-based classifications. In particular, this methodology enables some reference points to be established on the biological continuum according to the sequence AST-->ANA-->GBM.

Quantitative glycohistochemistry defines new prognostic markers for cancers of the oral cavity.

BACKGROUND: Histopathologic grading and clinical staging cannot provide a precise prognosis of oral cavity cancer patients. The use of glycohistochemical markers may improve the level of prognostic accuracy of such conventional classification systems. METHODS: Computer-assisted microscopy was employed in a series of 40 oral cavity cancers to determine quantitatively the percentage of positive cells, the staining intensity, and the level of staining heterogeneity for 3 glycohistochemical markers, including peanut agglutinin (PNA), Thomsen-Friedenreich antigen (T antigen) as part of a neoglycoprotein, and sarcolectin. Data were evaluated by discriminant analysis. RESULTS: Although the level of differentiation (P < 0.01 to P < 0.001) and the T variable of the TNM staging system (P < 0.05 to P < 0.01) related mainly to the level of expression of the acceptor sites for PNA and the T antigen, the patient survival period (P < 0.05) was largely a fraction of the level of expression of the acceptor sites for the carrier-immobilized T antigen and for sarcolectin. CONCLUSIONS: In oral cavity cancer, determining the level of acceptor sites for PNA, T antigen, and sarcolectin provides useful information on histopathologic differentiation, clinical staging, and survival. Because these processes of determination were carried out quantitatively, a discriminant model was set up, which enabled the level of oral cavity cancer aggressiveness to be characterized precisely. The current methodology described in this article should therefore afford pathologists original and quantitative (and thus objective) prognostic markers for oral cavity cancers.

The chromatin pattern of cell nuclei is of prognostic value for renal cell carcinomas.

Using a series of 105 renal cell carcinomas (RCCs) we investigated whether features quantitatively describing the appearance of Feulgen-stained nuclei and, more particularly, of their chromatin (on the basis of computer-assisted microscopy) can contribute any significant prognostic information. Thirty morphonuclear and 8 nuclear DNA content-related variables were thus generated. The actual prognostic values of this set of cytometric variables was compared (by means of discriminant statistical analysis) to conventional diagnostic and/or prognostic markers including histopathological grades, tumour invasion levels and the presence or absence of metastases. We obtained complete clinical follow-ups for 49 of the 105 RCC patients under study, making it possible to define a subset of patients with a bad prognosis (i.e., who died in the 12 months following nephrectomy) and a subset of patients with a good prognosis (i.e., who survived at least 24 months following nephrectomy). An original method of data analysis related to artificial intelligence (decision tree induction) enabled a strong prognostic model to be set up. In the case of 10 new patients, this model identified all the dead patients as having a bad survival status, with a total of 8 correct predictions. Another prognostic model similarly generated enabled the correct predictions to be confirmed.

Applications of lectins and neoglycoconjugates in histology and pathology.

The biological importance of oligosaccharide sequences in many different settings is undeniable. Glycan histochemistry has brought together the histological and biochemical approaches and provided insight into the mutual importance of both approaches. The aim of the authors is to take a look at a number of ways in which modern glycohistochemistry contributes to acquiring knowledge about the key role played by carbohydrates in the physiology of vertebrate tissues and human disease. The versatility of lectin and neoglycoconjugate histochemical procedures is emphasized.

1997

Algorithm analysis of lectin glycohistochemistry and Feulgen cytometry for a new classification of nasal polyposis

The aim of this study is to present a new classification of nasal polyps. This classification is based both on morphologic criteria relating to morphonuclear features from isolated Feulgen-stained nuclei and on glycohistochemical characteristics from histologic slides submitted to three lectins (peanut, wheat germ, and gorse seed agglutinins) and one neoglycoconjugate glycohistochemical stain. While the morphonuclear features (including 30 variables) relate essentially to chromatin pattern, the glycohistochemical stains (including 16 variables) are linked to the presence of specific carbohydrate moieties in cell membranes and cytoplasm. Forty-nine nasal polyps, including single polyps, diffuse polyposis, cystic fibrosis-related polyposis, and aspirin idiosyncracy-related polyposis associated with asthma, were thus characterized. All the variables were obtained quantitatively by means of computer-assisted microscopy. Two complementary methods of data classification were used to determine the actual diagnostic value contributed by each quantitative variable, namely, discriminant analysis, which forms part of multifactorial statistical analysis, and the decision tree technique, which is an artificial intelligence-related algorithm. The data so obtained show that our morphologic classification of nasal polyps fits in with the classification of nasal polyps defined on the basis of clinical criteria.

Determination of proliferative activity in nasal polyps.

AIMS: To determine the level of proliferative activity in 39 nasal polyps with clear cut distinct clinical behaviour patterns. METHODS: The 39 nasal polyps included 11 polyps labelled as "single" and taken from the lateral nasal wall and the middle turbinate; 12 polyps labelled as "massive" and relating to diffuse polyposis involving the entire nasal cavity; six polyps labelled as "ASA" and relating to nasal polyps from patients with acetylsalicylic acid intolerance and asthma; and 10 polyps from cystic fibrosis related polyposis. Cell proliferation was determined by two independent methods: first, the computer assisted microscope analysis of isolated Feulgen stained nuclei for the measurement of the percentage of cells in the S phase of the cell cycle; and second, the immunohistochemical evaluation of a proliferation associated protein by means of the MIB 1 monoclonal antibody. RESULTS: The cystic fibrosis related polyposis exhibited the highest proliferative activity of all the clinically identified nasal polyp groups. Acute inflammatory nasal polyps exhibited a higher cell proliferation than chronic ones. The results also show that while the immunohistochemical determination of cell proliferation by means of the MIB 1 monoclonal antibody is a valuable tool in determining cell proliferation in nasal polyps, the cytometrical image analysis of Feulgen stained nuclei is not useful for this purpose. CONCLUSION: Cell proliferation activity identifies cystic fibrosis as being distinct from the other nasal polyp groups.

Correlation between gender and cytomorphonuclear characteristics in human melanomas and in vitro evidence of sex steroid-induced modifications in the morphonuclear characteristics of three human melanoma cell lines.

The influence of gonadal steroids on human melanoma still remains a controversial issue. The aim of our study was to investigate whether sex steroids may influence the biological characteristics of human melanoma. Such biological characteristics were monitored at the morphological level by means of computer-assisted microscope analysis of Feulgen-stained nuclei, which provides 28 quantitative variables describing the nucleus morphometry (size, anisonucleosis level) and chromatin pattern. This methodology was used to characterize the morphonuclear features in a series of 69 human melanomas (from formalin-fixed paraffin embedded tissues) including 28 male, 17 premenopausal and 24 postmenopausal female patients, and to investigate the effect of two sex steroids (5-alpha-dihydrotestosterone [DHT] and 17-beta-oestradiol [E2]) on three human melanoma in vitro models--the HT-144, SK-MEL-28 and C32 cell lines. The results show that the morphonuclear characteristics of melanoma originating from male and female patients are very distinct (P < 0.01). This difference is still more marked (P < 0.0005) when only premenopausal female patients are compared with male patients. The in vitro data show that both DHT and E2 are able to modify markedly (P < 0.001 to P < 0.0001) the nucleus morphometry and chromatin pattern of the three cell lines. Although the mechanism and the physiological outcome are still unknown, the present work shows that there is in vivo and in vitro evidence that the biological behaviour of human melanoma is influenced by sex steroids.

Classification strategies for the grading of renal cell carcinomas, based on nuclear morphometry and densitometry.

The various grading systems proposed for renal cell carcinomas all suffer from problems related to inter-observer variability. Some of these grading systems are based, either partially or wholly, on morphonuclear criteria, such as nuclear size and shape, anisonucleosis, and chromatin pattern. These criteria can be quantitatively (and thus objectively) evaluated by means of the computer-assisted microscopic analysis of Feulgen-stained nuclei. In the present work, 39 quantitative variables, including two morphometric, 28 chromatin pattern-related, and nine DNA ploidy level-related, were computed for 65 renal cell carcinomas. The actual diagnostic information contributed by each variable was determined by means of multifactorial statistical analysis (discriminant analysis) and two artificial intelligence-related methods of data classification (the decision tree and production rule methods). The results show that quantitative information, as provided by the computer-assisted microscopy of Feulgen-stained nuclei and analysed by means of artificial intelligence-related methods of data classification, contributes significant diagnostic information for the grading of renal cell carcinoma, thus reducing the problem of inter-observer reproducibility.

Ploidy level determination and quantitative chromatin pattern description in pregnancy-associated breast cancers.

The present study deals with the characterization of hormone-sensitivity in pregnancy-associated breast cancers (PBCs). This characterization was carried out in 22 PBCs as opposed to 88 non-pregnancy-associated breast cancers (NPBCs). For this study, we used the digital cell image analysis of Feulgen-stained nuclei to assess the type of hormone-sensitivity. In a previous study it was demonstrated that the chromatin pattern in breast cancers is related to the amounts of estrogen receptors they contain. Our results demonstrated that the quantitative description of the chromatin pattern by means of 15 parameters (relating to morphometric, densitometric, and textural features) made it possible to identify typical cell nuclei populations in the PBC and NPBC groups. The use of specific statistical analyses (principal-components and discriminant) made it possible to quantify the proportion of each cell nucleus type in the PBCs. Furthermore, of the 22 PBCs under study, 13 contained a large majority of cell nuclei whose chromatin pattern was characteristic of hormone-sensitive cells, while 5 cases contained a large majority of typically hormone-insensitive ones. The remaining 4 cases contained a relatively similar proportion of typically hormone-sensitive and insensitive cell nuclei. The quantitative chromatin pattern description thus made it possible to characterize the hormone-sensitivity level in PBCs, whereas DNA ploidy level determination did not enable any such characterization to be carried out. The chromatin pattern assay described here, which enables hormone-sensitive pregnancy-associated breast cancers to be identified from hormone-insensitive ones independently from biochemical assays, should help the physician regarding therapy adaptation.

Contribution of quantitative lectin histochemistry to characterizing well-differentiated, dedifferentiated and poorly differentiated liposarcomas.

OBJECTIVE: To find new diagnostic markers in the group of lipomatous tumors. STUDY DESIGN: The histochemical lectin staining pattern was characterized in a series of 45 lipomatous lesions, including 10 typical lipomas, 6 atypical lipomas, 8 well-differentiated, 6 myxoid, 5 dedifferentiated and 10 pleomorphic liposarcomas. Three lectins were used-peanut (Arachis hypogaea) agglutinin, which binds to terminal Gal(beta 1,3)GalNAc residues; wheat germ (Triticum vulgare) agglutinin (s-WGA, the succinylated form of WGA), which binds to ((1-4)-D-GlcNAc)n and Neu5NAc residues; and jack bean (Concanavalia ensiformis) agglutinin which binds to alpha-D-Man and alpha-D-Glc residues. Histochemical staining was quantitatively measured by means of a cell image processor. RESULTS: In the case of certain carbohydrate residues, typical lipomas closely resemble atypical lipomas, which in turn closely resemble well-differentiated liposarcomas; typical lipomas differ significantly from well-differentiated liposarcomas. This indicates that atypical lipomas, or at least some of them, could represent a biologic link between typical lipomas and well-differentiated liposarcomas. While well-differentiated and pleomorphic liposarcomas differed significantly from each other, the poorly differentiated component of dedifferentiated liposarcomas included histochemical lectin properties, which were common to both well-differentiated and pleomorphic liposarcomas. CONCLUSION: Some atypical lipomas exhibit glycohistochemical characteristics that are common to those of well-differentiated liposarcoma. The poorly differentiated component of dedifferentiated liposarcomas remains more differentiated in terms of glycohistochemical markers than do poorly differentiated pleomorphic liposarcomas.

Decision tree induction: a useful tool for assisted diagnosis and prognosis in tumor pathology.

The aim of the present work is to show that decision tree induction algorithms are a useful tool for extracting reliable information from data series, with the objective of assisting pathologists in identifying specific diagnostic and prognostic markers in various types of tumor pathologies. In terms of accuracy, we show that the decision tree technique exceeds other more sophisticated techniques, such as multilayer neural networks. Furthermore, because of the case with which decision tree results can be interpreted (logical classification rules), new methodologies can be readily developed to further assist in analyzing complex data that mix heterogeneous features. In this paper, we illustrate such capabilities in the context of different complex diagnostic and/or prognostic problems in tumor pathology relating to bladder, astrocytomas, and adipose tissues.

Quantitative chromatin pattern description in Feulgen-stained nuclei as a diagnostic tool to characterize the oligodendroglial and astroglial components in mixed oligo-astrocytomas.

The oligoastrocytoma, as a mixed glioma, represents a nosologic dilemma with respect to precisely defining the oligodendroglial and astroglial phenotypes that constitute the neoplastic cell lineages of these tumors. In this study, cell image analysis with Feulgen-stained nuclei was used to distinguish between oligodendroglial and astrocytic phenotypes in oligodendrogliomas and astrocytomas and then applied to mixed oligoastrocytomas. Quantitative features with respect to chromatin pattern (30 variables) and DNA ploidy (8 variables) were evaluated on Feulgen-stained nuclei in a series of 71 gliomas using computer-assisted microscopy. These included 32 oligodendrogliomas (OLG group: 24 grade II and 8 grade III tumors according to the WHO classification), 32 astrocytomas (AST group: 13 grade II and 19 grade III tumors), and 7 oligoastrocytomas (OLGAST group). Initially, image analysis with multivariate statistical analyses (Discriminant Analysis) could identify each glial tumor group. Highly significant statistical differences were obtained distinguishing the morphonuclear features of oligodendrogliomas from those of astrocytomas, regardless of their histological grade. When compared with the 7 mixed oligoastrocytomas under study, 5 exhibited DNA ploidy and chromatin pattern characteristics similar to grade II oligodendrogliomas, I to grade III oligodendrogliomas, and I to grade II astrocytomas. Using multifactorial statistical analyses (Discriminant Analysis combined with Principal Component Analysis). It was possible to quantify the proportion of "typical" glial cell phenotypes that compose grade II and III oligodendrogliomas and grade II and III astrocytomas in each mixed glioma. Cytometric image analysis may be an important adjunct to routine histopathology for the reproducible identification of neoplasms containing a mixture of oligodendroglial and astrocytic phenotypes.

Nearest-neighbor classification for identification of aggressive versus nonaggressive low-grade astrocytic tumors by means of image cytometry-generated variables.

The authors investigated whether cytometry-related variables generated by means of computer-assisted microscopic analysis of Feulgen-stained nuclei can contribute significant information toward the characterization of low-grade astrocytic tumor aggressiveness. This investigation was conducted using the nearest-neighbor rule (a traditional classification method used in pattern recognition) to analyze a series of 250 supratentorial astrocytic tumors from adult patients. This series included 39 low-grade astrocytomas and 211 high-grade astrocytic tumors (including 47 anaplastic astrocytomas and 164 glioblastomas multiforme [GBMs]). The results show that the 3-nearest-neighbors rule enabled a subgroup of "atypical" astrocytomas to be distinguished from the "typical" tumors. The atypical astrocytoma species exhibited a DNA content (DNA ploidy level) and morphonuclear characteristics that were statistically more similar to the characteristics of GBMs than to those exhibited by the typical astrocytomas. An analysis of survival data revealed that patients with atypical astrocytomas survived for a significantly shorter period (p < 0.001) than patients with typical lesions of this kind. In fact, patients with atypical astrocytomas had a survival period similar to that of patients with anaplastic astrocytomas, whereas patients with typical astrocytomas had a survival period significantly longer (p < 0.0001) than those associated with anaplastic astrocytomas and GBMs.

The combined determination of proliferative activity and cell density in the prognosis of adult patients with supratentorial high-grade astrocytic tumors.

Tumor growth represents the ratio between cell gain (number of mitoses per unit of time, i.e., proliferative activity) and cell loss (number of cell deaths during the same unit of time). While in adults, proliferative activity parallels the level of malignancy in astrocytic tumors and therefore represents a useful diagnostic marker, cell loss has never been concomitantly assessed in tumors of this type. We hypothesize that cell density assessable on histologic slides represents the ratio between cell gain and cell loss. This hypothesis concerns only the diffuse type of astrocytic tumors. Proliferative activity (assessed by MIB1 antigen immunostain) and cell density were thus quantitatively assessed by means of a cell image processor in a series of 54 supratentorial astrocytic tumors of adult patients, which included 15 astrocytomas (ASTs), 18 anaplastic astrocytomas (ANAs), and 21 glioblastomas (GBMs). The results show that proliferative activity and cell density were highly correlated (P = .003) and that both correlated with histopathologic grade. The patients with a high-grade astrocytic tumor (i.e., ANA or GBM) that exhibited a low level of proliferative activity but high cell density survived for significantly shorter periods than did patients with a tumor that exhibited low proliferative activity and low cell density (P = .002). The patients with a high-grade astrocytic tumor that exhibited high proliferative activity and high cell density survived for significantly less time than did the patients with a tumor that exhibited high proliferative activity but low cell density (P < .05). A marked difference in survival periods was observed between the patients with a high-grade astrocytic tumor that exhibited a low level of proliferative activity and low cell density and the patients with a tumor that exhibited a high level of proliferative activity and high cell density (P < .001). The concomitant determination of proliferative activity and cell density seems likely to enable determination of the few adult patients who have high-grade astrocytic tumors and who will survive for a considerable period (several years).

Dynamic characterization of glioblastoma cell motility.

The cell motility dynamic of two glioblastoma cell lines (U373 and U87) was studied by means of an automatic video-cell-tracking-system enabling each cell in a colony to be tracked for several hours. Twenty-five experiments were performed on both models growing on three different supports (glass, plastic and Matrigel). Cell motility was significantly different in each cell line and also for different growth support in a given cell line. We observed that U87 cells are significantly (p < 0.00001) less motile than U373 cells. The most favorable growth supports for cell motility studies were Matrigel and glass. A significant (p < 0.001) correlation between cell colony density and cell motility was highlighted, with isolated cells exhibiting a motility level distinct from the one observed for colonies. The present methodology, which enabled cell motility to be quantified in human glioblastoma cells, represents an original tool for identifying new classes of compounds able to reduce glioblastoma cell motility and cell migration potential into the brain.

Characterization of the nuclear deoxyribonucleic acid content and nuclear morphometry in 71 primary cutaneous melanomas.

BACKGROUND: While the determination of nuclear deoxyribonucleic acid (DNA) content (DNA ploidy level) and nuclear morphometry characterization has proved to be of prognostic value in melanocytic lesions, there are several ways of performing these determinations. OBJECTIVE: To identify which of 9 DNA ploidy- and 2 nuclear morphometry-related variables are of prognostic and/or diagnostic value in 71 primary melanomas. METHODS: Histological typing, Breslow depth determination, the evaluation of Clark's level of invasion and the 11 quantitative variables (calculated in Feulgen-stained nuclei using computer-assisted microscope analysis) determined for each melanoma were submitted to discriminant analysis. RESULTS: The discriminant analysis of image cytometric variables enabled specific cell subpopulations to be identified in histological and the Breslow-related groups, but not in the Clark-related ones. CONCLUSION: The characterization of melanoma heterogeneity by means of the identification of specific DNA ploidy level-related cell subpopulations in specific Breslow-related groups enables the problem of intra- and interobserver variability in Breslow depth determination to be reduced and therefore can help dermatologists in their daily routine.

Computer-Assisted Microscope Analysis of Feulgen-Stained Nuclei in Gonadotroph Adenomas and Null-Cell Adenomas of the Pituitary Gland.

The current classification of clinically nonfunctioning pituitary adenomas is based on immunocytochemical and ultrastructural studies. However, a number of cases have less distinctive features that cannot be easily conformed with the prevailing morphologic classifications. The diagnostic information contributed by the determination of the nuclear DNA content (DNA ploidy level) and quantitative chromatic pattern description as opposed to the morphofunctional diagnosis in clinically nonfunctioning adenomas was consequently investigated in a series of 71 pituitary adenomas, including 31 null-cell adenomas, 35 gonadotropin adenomas, and 5 nonfunctioning adenomas that were not examined by electron microscopy. DNA ploidy level (8 variables) and quantitative chromatin pattern description (30 variables) were carried out by means of the computer-assisted microscope analysis of 80-1600 Feulgen-stained nuclei analyzed/case. The diagnostic information contributed by the 38 quantitative variables was determined by multifactorial statistical analysis (i.e., Discriminant Analysis). This computer-assisted classification significantly differentiated nulLcell adenomas from gonadotropin adenomas (p = 0.0025). In addition, it was able to differentiate three major subtypes of nonfunctioning adenomas on the basis of their immunohistochemical profiles. These were the immunonegative adenomas, the follicle-stimulating hormone (FSH)-positive adenomas, and the a-subunit (a) and/or luteiwizing hormone (LH)-positive adenomas (p < 0.0001 to p < 0.001). We thus suggest that the cytometric image analysis of Feulgen-stained nuclei can contribute on the discrimination of subtypes of clinically nonfunctioning pituitary adenomas.

Finding prototypes for nearest neighbour classification by means of gradient descent and deterministic annealing

1996

Does any correlation exist between the Gleason classification system and the computer-assisted microscope analysis of Feulgen-stained nuclei features in human prostate adenocarcinoma?

Grading prostatic adenocarcinomas remains an important problem. Various systems exist (including those proposed by Gleason) but none of these systems seems able to reliably predict either the lethal potential of a tumor in an individual patient or the responsiveness of an individual tumor to various forms of therapy. The most frequently used grading system, as proposed by Gleason, is essentially based on the description of tumor growth pattern. The aim of the present work is therefore to investigate whether the quantitative description of morphonuclear features (including cell anaplasia) and the DNA ploidy level can contribute significant information to the Gleason grading, thus partly at least reducing its subjective nature. This quantitative description was carried out by means of the Feulgen-stained nuclei image cytometry computation of 24 variables in 101 prostatic adenocarcinomas. The results show that both DNA ploidy- and morphonuclear-related variables were weak discriminators for the various grades of the Gleason classification system, and particularly between the high (Gleason 4 and 5) and the other Gleason-grades, i.e. the low (Gleason 1 and 2) and intermediate (Gleason 3) ones. The morphonuclear evidence of anaplasia is thus not redundant data on tumor growth pattern and may be expected to provide additional diagnostic information.

The characterization of biological features in dedifferentiated liposarcomas by means of principal components and discriminant analyses of 25 computer-generated variables from Feulgen-stained nuclei and histological slides

Quantitative measurements of desmin and vimentin immunostains and cell density in leiomyomas and leiomyosarcomas.

The distinction between benign and malignant smooth muscle tumours relying on histological features such as the mitotic index and pleomorphism remains a generally acknowledged difficulty in modern pathology. A cell image processor was therefore used to quantitatively assess the desmin and vimentin immunostain in 39 smooth muscle tumours which included 26 benign (leiomyomas) and 13 malignant (leiomyosarcomas) cases. The 13 leiomyosarcomas were primary (non-recurrent and non-metastatic). Ploidy level and cell density were also assessed on each of these 39 tumours by means of the computer-assisted microscopic analysis of 5-microns thick Feulgen-stained histological sections. The results show that while neither the ploidy level determination nor the quantitative assessment of the vimentin immunostain made it possible to distinguish between leiomyomas and leiomyosarcomas, cell density determination and the quantitative assessment of the desmin immunostain enabled such a distinction to be made. Indeed, the leiomyomas exhibited a much higher level of desmin positivity than the leiomyosarcomas, as did diploid tumours as compared to the aneuploid (benign or malignant) ones. Furthermore, the leiomyoma group exhibited a significantly lower mean cell density value than the leiomyosarcoma group. The present study further confirms the lack of relationship between ploidy level and cytological malignancy in smooth muscle tumours.

Image cytometry analysis of Feulgen-stained nuclei in 72 lipomatous lesions including atypical lipomas and well-differentiated liposarcomas.

Well-differentiated lipomatous tumors constitute a histopathologic category whose nomenclature has been controversial, particularly with respect to the distinction between atypical lipomas of the extremities and well-differentiated liposarcomas of the retroperitoneum. To determine whether there were differences in image analytic parameters between these neoplasms, 72 lesions including 21 typical lipomas, 7 atypical lipomas, 16 retroperitoneal and 5 nonretroperitoneal well-differentiated, 9 dedifferentiated, and 14 pleomorphic liposarcomas were submitted to the computer-assisted microscopic analysis of Feulgen-stained nuclei. This methodology enabled four groups of variables to be calculated. These included: (1) quantitative chromatin pattern description (14 variables); (2) the measurement of proliferative activity (1 variable); (3) nuclear DNA content (DNA ploidy level, 5 variables); and (4) the measurement of cell density and topographical cell nuclei organization (2 variables). The results strongly suggest that atypical lipomas, whether superficial or deep, and well-differentiated liposarcomas, whether retroperitoneal or not, belong to the same category in terms of the variables analyzed.

The contribution of image cytometry and artificial intelligence-related methods of numerical data analysis for adipose tumor histopathologic classification.

Thirty-five lipomatous tumors were quantitatively described using 47 variables generated by means of computer-assisted microscope analysis. Of these 47 quantitative variables, 27 were computed on Feulgen-stained specimens (25 on cytologic and 2 on histologic samples) and, of the remaining 20, 8 related to vimentin and S-100 protein immunostaining patterns and the other 12 to the glycohistochemical staining patterns of peanut agglutinin, succinylated wheat germ agglutinin, and concavalin A agglutinin. The 35 lipomatous tumors included 6 atypical lipomas and 8 well differentiated, 5 dedifferentiated, 6 myxoid, and 10 pleomorphic liposarcomas. The actual diagnostic value contributed by each of the 47 variables with respect to the 5 lipomatous tumor groups was determined by means of the decision tree technique, an artificial intelligence-related algorithm that forms part of the supervised learning algorithms. Of the 47 quantitative variables, the decision tree technique retained 8: i.e., 2 tissue architecture-, 2 DNA ploidy level-, 2 morphonuclear-, 1 lectin histochemical-, and 1 vimentin immunostain-related variables. The decision tree technique made use of these 8 variables to set up logical rules that make it possible to identify atypical lipomas from well differentiated liposarcomas, on the one hand, and dedifferentiated liposarcomas from those that are well differentiated and pleomorphic, on the other. Thus, the combination of an artificial intelligence algorithm analyzing quantitative variables generated by means of the computer-assisted microscope analysis of cytologic and histologic samples from lipomatous tumors can be considered an expert system contributing significant diagnostic information to conventional diagnosis.

Methodological aspects of using decision trees to characterise leiomyomatous tumors.

The aim of the present work is to present the potential uses of a classification technique labeled the "decision tree" for tumor characterisation when faced with a large number of features. The decision tree technique enables multifeature logical classification rules to be produced by determining discriminatory values for each feature selected. In this report, we propose a methodology that used decision trees to compare and evaluate the information contributed by different types of features for tumor characterisation. This methodology is able to produce a set of hypotheses related to a diagnosis and or prognosis problem. For example, hypotheses can be producted (on the basis of a set of descriptive features) to explain why tumor cases belong to a given histopathological group. To illustrate our purpose, this methodology was applied to the difficult problem of leiomyomatous tumour diagnosis. The aim was to illustrate what kind of diagnostic information can be extracted from a sample data set including 23 smooth muscle tumors (14 benign leiomyomas and 9 malignant leiomyosarcomas) described by a large set of computer-assisted, microscope-generated features. Three groups of features were used relating to: (1) ploidy level determination (10 features), (2) quantitative chromatin pattern description (15 features), and (3) immunohistochemically related antigen specificities (6 features). All these features were quantified by digital cell image analysis. The results suggest that an objective distinction between leiomyomas and leiomyosarcomas can be established by means of simple logical rules depending on only a few features among which the immunohistochemically revealed antigen expression of desmin plays a preponderant part. One of the combinations of features proposed by the methodology is interesting for pathologists, because it includes two features describing the appearance of a nucleus in terms of chromatin distribution homogeneity and density, two features widely used by pathologists in tumor-grading systems.

The computer-assisted microscope analysis of Feulgen-stained nuclei linked to a supervised learning algorithm as an aid to prognosis assessment in invasive transitional bladder cell carcinomas.

The aim of the present work is to ascertain whether additional information to grading and staging can be obtained for the prognosis of invasive bladder tumours (T2, T3, T4) by means of two computer-assisted methodologies. The first methodology relates to the digital image analysis of Feulgen-stained nuclei and the second to a supervised learning algorithm named Decision Tree. The digital image analysis of Feulgen-stained nuclei generated 11 variables for nuclear DNA content and 15 for quantitatively describing chromatin pattern. These 26 variables were submitted to a Decision Tree technique which produces multi-attribute logical classification rules by selecting informative variables and determining discriminatory values for each of them. A series of 41 patients for which the majority of the T2 bladder tumours (68%) were associated with a 'good' prognosis (remission) while the majority of the T3-T4 ones (77%) were associated with a 'bad' one (clinical progression or death) were submitted to the proposed approach. The results show that the decision tree was able to characterise the tumours associated with a 'bad' prognosis in the T2 sub-group (32%) and the tumours associated with a 'good' prognosis in the T3-T4 one (23%), by using only few image-generated variables (added to the clinical stage).

The use of the decision tree technique and image cytometry to characterize aggressiveness in World Health Organization (WHO) grade II superficial transitional cell carcinomas of the bladder.

The aggressiveness of human bladder tumours can be assessed by means of various classification systems, including the one proposed by the World Health Organization (WHO). According to the WHO classification, three levels of malignancy are identified as grades I (low), II (intermediate), and III (high). This classification system operates satisfactorily for two of the three grades in forecasting clinical progression, most grade I tumours being associated with good prognoses and most grade III with bad. In contrast, the grade II group is very heterogeneous in terms of their clinical behaviour. The present study used two computer-assisted methods to investigate whether it is possible to sub-classify grade II tumours: computer-assisted microscope analysis (image cytometry) of Feulgen-stained nuclei and the Decision Tree Technique. This latter technique belongs to the Supervised Learning Algorithm and enables an objective assessment to be made of the diagnostic value associated with a given parameter. The combined use of these two methods in a series of 292 superficial transitional cell carcinomas shows that it is possible to identify one subgroup of grade II tumours which behave clinically like grade I tumours and a second subgroup which behaves clinically like grade III tumours. Of the nine ploidy-related parameters computed by means of image cytometry [the DNA index (DI), DNA histogram type (DHT), and the percentages of diploid, hyperdiploid, triploid, hypertriploid, tetraploid, hypertetraploid, and polyploid cell nuclei], it was the percentage of hyperdiploid and hypertetraploid cell nuclei which enabled identification, rather than conventional parameters such as the DI or the DHT.

Image cytometry characterization of ploidy level, proliferative activity and chromatin pattern in 50 nasal polyps

A computer-assisted microscope analysis of Feulgen-stained nuclei was carried out on a series of 50 nasal polyps in order to try to identify specific biological subgroups. The present series of 50 nasal polyps includes single polyps both associated (n=9) and unassociated (n=9) with allergy and diffuse polyposis both associated (n=7) and unassociated (n=9) with allergy, cystic fibrosis (n=9) and ASA (aspirin-sinusitis-asthma) related polyposis (n=7). The computer-assisted microscope analysis provides 36 quantitative variables which include 1 variable describing proliferative activity, 9 describing the nuclear desoxyribonucleic acid distribution (DNA ploidy level) and 26 describing nucleus morphology, i.e. its size and chromatin pattern. The results show that the methodology proposed here enabled four major groups of nasal polyps to be identified, i.e. diffuse polyposis associated with allergy, cystic fibrosis-related polyposis, single polyps both associated and unassociated either with allergy and a fourth group including diffuse polyposis not associated with allergy and ASA-related polyposis. These four groups of nasal polyps differed markedly in their morphonuclear characteristics, but not in the proliferative activity- and DNA ploidy- related variables.

The value of nuclear DNA and texture analysis by digital image processing in the diagnosis of lipomatous and leiomyomatous tumours.

The present study investigates whether the quantitative chromatin pattern description carried out by means of the digital cell image analysis of Feulgen-stained nuclei can contribute valuable diagnostic information on sarcomas. A series of 77 soft tissue tumours was consequently studied. This series included 9 benign lipomas versus 26 malignant liposarcomas and 26 benign leiomyomas versus 16 malignant leiomyosarcomas. Of the 26 liposarcomas, 14 were primary and 12 recurrent tumours. Of the 16 leiomyosarcomas, 13 were primary and three recurrent tumours. The results show that the combined use of principal-components analysis and the discriminant analyses of digital data obtained by means of the computer-assisted microscope analysis of Feulgen-stained nuclei made it possible to obtain a clear-cut distinction between the three histopathological groups relating to the lipoma/liposarcoma group of soft tumours. In contrast, while a clear-cut distinction could be made between the recurrent leiomyosarcomas and the primary leiomyosarcomas, such a distinction was not possible between the benign leiomyomas and the malignant primary leiomyosarcomas. This feature, along with previous ones obtained through DNA ploidy level determination, suggests to us that leiomyomas, or at least some of them, are in the process of malignant transformation. In other words, leiomyomas might be the pre-malignant counterpart of leiomyosarcomas, a feature that the present results do not suggest for lipomas versus liposarcomas.

1995

Stereotactic biopsies from astrocytic tumors. Diagnostic information contributed by the quantitative chromatin pattern description.

OBJECTIVE: To reduce the problem of heterogeneity in astrocytic tumors by means of computer-assisted microscope analysis of Feulgen-stained nuclei. STUDY DESIGN: Thirty-eight glial tumors for which we obtained 227 stereotactic biopsies were subjected to digital cell image analysis of Feulgen-stained nuclei. This series of 38 glial tumors included 36 supratentorial astrocytic tumors (13 astrocytomas, 7 anaplastic astrocytomas and 16 glioblastoma multiformes) and 2 grade 3 astrocytic tumors of the cerebellum. RESULTS: The results suggest a new methodology, enabling the biologic characteristics of the brain parenchymal area surrounding a given glial tumor to be characterized. This methodology relies on the performance of three successive steps. The first is quantitative characterization of nuclear morphology and its chromatin pattern by means of 15 morphonuclear variables. This characterization is carried out by means of the computer-assisted microscope analysis of Feulgen-stained nuclei. The second step consists of setting up morphonuclear data banks, with each process giving the precise portrait of a given cell nuclear population. This process is carried out by means of multivariate analysis, taking into account the 15 variables mentioned above. Multivariate analysis includes principal components analysis followed by the canonical transformation of the data. The third step consists of testing unknown cases against these morphonuclear data banks. This is carried out by means of linear discriminant analysis, which enables the various cell nuclear types in the stereotactic biopsy to be quantified. CONCLUSION: The present methodology makes it possible to investigate whether infiltrating tumor cells are present in or absent from the parenchymal brain area surrounding a glial tumor. It can therefore contribute additional information to that contributed by computed tomography and/or magnetic resonance imaging with respect to the precise delineation of the volume of a brain tumor. This delineation must be as precise as possible to allow total surgical resection of the tumor and prevention of its recurrence.

Identification of high versus lower risk clinical subgroups in a group of adult patients with supratentorial anaplastic astrocytomas.

The present work investigates whether computer-assisted techniques can contribute any significant information to the characterization of astrocytic tumor aggressiveness. Two complementary computer-assisted methods were used. The first method made use of the digital image analysis of Feulgen-stained nuclei, making it possible to compute 15 morphonuclear and 8 nuclear DNA content-related (ploidy level) parameters. The second method enabled the most discriminatory parameters to be determined. This second method is the Decision Tree technique, which forms part of the Supervised Learning Algorithms. These two techniques were applied to a series of 250 supratentorial astrocytic tumors of the adult. This series included 39 low-grade (astrocytomas, AST) and 211 high-grade (47 anaplastic astrocytomas, ANA, and 164 glioblastomas, GBM) astrocytic tumors. The results show that some AST, ANA and GBM did not fit within simple logical rules. These "complex" cases were labeled NC-AST, NC-ANA and NC-GBM because they were "non-classical" (NC) with respect to their cytological features. An analysis of survival data revealed that the patients with NC-GBM had the same survival period as patients with GBM. In sharp contrast, patients with ANA survived significantly longer than patients with NC-ANA. In fact, the patients with ANA had the same survival period as patients who died from AST, while the patients with NC-ANA had a survival period similar to those with GBM. All these data show that the computer-assisted techniques used in this study can actually provide the pathologist with significant information on the characterization of astrocytic tumor aggressiveness.

The combination of a decision tree technique with the computer-assisted microscope analysis of Feulgen-stained nuclei to assess aggressiveness in lipomatous and smooth muscle tumors.

The present study describes a computer-assisted methodology whose purpose is to reduce the degree of subjectivity in the diagnosis of soft tissue tumors. This methodology associates three complementary techniques, namely digital cell image analysis, the discretisation of numerical data and a Decision Tree technique (DT). The first technique relies on the use of the digital cell image analysis of Feulgen-stained nuclei, a technique which makes possible a quantitative and thus objective description of nuclei with the help of 24 numerical parameters (15 morphonuclear and 9 DNA content- (ploidy level and proliferation activity) related). The second technique transforms each numerical parameter into an ordinal one with a small number of values (2 to 4) so that only the relevant physical significance of the parameters is retained. The Decision Tree technique generates classification rules on the basis of the discretised parameters quoted above. This methodology was applied to 53 human soft tissue tumors which included 26 lipomatous tumors (13 malignant liposarcomas and 13 benign lipomas) and 27 smooth muscle tumors (11 malignant leiomyosarcomas and 16 benign leiomyomas). The results show that a distinction between benign (lipoma) and malignant (liposarcoma) lipomatous tumors can easily be made by means of simple logical rules depending on only four discretised cytological parameters (two ploidy- and two morphonuclear-related). In contrast, no stable or predictive characterisation can be obtained with respect to the difference between leiomyosarcomas and the leiomyomas. Hence, while lipomas and liposarcomas appeared to be two completely distinct biological entities, leiomyomas and leiomyosarcomas seem to involve a continuous biological process.

The combined use of the decision tree technique and the computer-assisted microscope analysis of Feulgen-stained nuclei as an aid for astrocytic tumour aggressiveness characterization

Multiple-knowledge representations in concept learning

This paper investigates a general framework tor learning concepts that allows to generate accurate and comprehensible concept representations. It is known that biases used in learning algorithms directly affect their performance as well as their comprehensibility. A critical problem is that, most of the time, the most “comprehensible” representations are not the best performer in terms of classification! In this paper, we argue that concept learning systems should employ Multiple-Knowledge Representation: a deep knowledge level optimised from recognition (classification task) and a shallow one optimised for comprehensibility (description task). Such a model of concept learning assumes that the system can use an interpretation function of the deep knowledge level to build an approximately correct comprehensible description of it. This approach is illustrated through our GEM system which learns concepts in a numerical attribute space using a Neural Network representation as the deep knowledge level and symbolic rules as the shallow level.

1993

Etude anatomique et extensométrique concernant la collerette d'appui et le manche de la prothèse

Apprentissage et outils statistiques en classification conceptuelle incrémentale

1991

Search for the intersection polygon of any two polygons: Application to the garment industry

One of the biggest problems usually encountered by the clothes manufacturer consists of placing various pattern parts on a rectangular area in such a way that the waste of material between the pieces is minimized. To bring some automated help in this field, computer programs need first to handle the complicated contours of the pieces. One needs not only to check the overlap of two contiguous patterns, but also to compute their precise area of intersection, allowing in this way the use of some kind of combinatorial optimization. In a wider context, it is possible to design a general purpose algorithm, able to build the complete structure representing the intersection of two polygons. It is remarkable that the same algorithm can also be used, with only a few modifications, to compute the union and the difference of any two polygons. Copyright © 1991, Wiley Blackwell. All rights reserved

Traitement d'images et utilisation de la CAO pour la fabrication de prothèses

Description contrasting in incremental concept formation

This study evaluates the impact of concept descriptions on the behaviour and performance of concept formation processes (in which the data is either noisy or noise-free). Using a common architecture (ADECLU), different concept definitions are envisaged. These descriptions are of symbolic/numeric type, including statistical indices. The use of these indices introduces a “contrasting” between concept descriptions and reduces the effect of noise on predictive performance.

1990

Hormone and protein excretion responses to maximal exercise in humans

The increases in plasma renin activity (PRA) and in the plasma concentration in angiotensin II (AII), aldosterone (ALDO), vasopressin (ADH) after exercise were compared to the urine protein excretion of well-hydrated healthy subjects submitted to a 2-min supramaximal bicycle exercise. Venous blood and urine samples were obtained at rest and after exercise. PRA, AII and ALDO were increased to about 4, 2 and 2-fold respectively of the resting basal values. ALDO continued to rise following exercise while PRA and AII returned to resting values (P < 0.05). Urine total protein, albumin and β2-microglobulin (β2-m) increased 7, 38 and 162-fold during the first 20 min postexercise period respectively. The enhanced total protein, albumin and (β2-m) excretion were related to a decrease in plasma volume at 20 min postexercise. A positive relationship (r = 0.515; P < 0.05) after exercise was observed between albumin excretion and PRA. No correlation was noted between the PRA-AII-ALDO system and the β2-m excretion following exercise. It was concluded that: 1) postexercise proteinuria was negatively correlated with the reduction in plasma volume; 2) the PRA-AII-ALDO system does not develop concomitantly with this transient kidney impairment.

1988

Indirect evidence of glomerular/tubular mixed-type postexercise proteinuria in healthy humans.

Hypothetical mechanisms have been postulated to explain the presence of proteins in urine after severe exercise. Recently, it has been shown that several amino acids inhibit tubular protein reabsorption. Seven healthy men, hyperhydrated, were studied during a 2-min bicycle exercise at supramaximal load. The subjects were tested without or with lysine perfusion (0.4 g/kg body wt iv). In both testing conditions, blood lactate increased to 13.8 mmol/l. Total protein urinary excretion increased to 1.10 and 1.67 mg/min, without and with lysine perfusion, compared with 79 micrograms/min at rest. In the meantime, albumin excretion increased 48- and 74-fold, respectively, while beta 2-microglobulin excretion increased 97- and 1,043-fold compared with basal values. The renal clearance of albumin increased to 8.4 microliters/min without lysine and to 12.0 microliters/min with lysine perfusion (rest 0.18). beta 2-Microglobulin clearance increased to 10.0 and 39.3 ml/min, respectively (rest 0.05). These data clearly demonstrate that postexercise proteinuria is of mixed type after exhaustive short-term exertion. Both increased glomerular permeability and partial tubular reabsorption inhibition to proteins appear to be involved.

1987

Design of an Authoring System for Micro Computer

1980

Remaining comments from France on document 97/5 N 642. Working draft specifications for Pascal

1979

Ecriture modulaire d'un compilateur pour un langage structuré simple

Communications publiées lors de congrès ou colloques nationaux et internationaux

A paraître

Robust Structured Light Pattern for Use with a Hologram in 3D Endoscopy

This paper introduces a novel structured light pattern designed to be compatible with the hologram projection. Here is proposed to use a De Bruijn-based sequence and a combination of continuous and dashed lines for the pattern. Dashed lines are coded by a combination of their period and of their duty cycles. It provides 16 different lines which limits to two the required number of lines for identification. The segmentation has been made easier by inserting continuous lines between two dashed lines. As required by the use of holograms, the sequence has been adapted by making it symmetric. It has been improved by guaranteeing a hamming distance equal to two for contiguous lines. The implementation on a virtual model has shown that a subpixel accuracy has been achieved. The aim of this pattern is to be used in 3D endoscopy

AI Guided Panoramic Image Reconstruction

Low-cost plenoptic camera with off-the-shelf components

Consistent Long Sequences Deep Faces

Real-Time Depth-Based Multilayer Image Computation for 3D Displays

Multi-layer displays are a type of 3D display composed of multiple LCD panels arranged in front of a backlight. For generating the layers, iterative methods are commonly employed, which lead to long computational times that are not suitable for real-time 3D imaging systems. This study addresses the challenge of real-time computation of multi-layer images using a depth camera and demonstrates an end-to-end capture to display process. Unlike iterative methods, our approach directly computes the layers. Firstly, we pre-process the depth input. Secondly, we recreate a focal stack by slicing views based on depth and applying blur. Then, we calculate the multi-layer compensation to diminish artifacts from object blur across layers. The entire pipeline, from Kinect to layered 3D display, achieves a frame rate between 20 and 28 frames per second, at the cost of reduced quality in the reproduced views

2024

Single RGBD to Multilayer 3D Display Pipeline

Tensor displays are multiview glasses-free 3D displays composed of a stack of LCD layers. The images displayed on each layer are usually generated from a dense set of viewpoints (light field) or a set of focused images (focal stack). This paper presents an alternative using a single color view with depth for the generation of the images' layers. To do so various single-RGBD pipelines using intermediate data formats to generate the layers' images, including a direct method, are compared. Experiments show that by a single-color view with depth as input, one can provide a quality close to the light field or focal stack pipelines, hence reducing memory storage costs.

From Plenoptic Images to 3D Layered Displays

Plenoptic cameras are equipped with a micro-lens array that allows them to capture multiple viewpoints in the form of a plenoptic image, providing 3D information about the scene. This 3D information can be projected back with a glasses-free 3D display, such as the multi-layer display. However, the current method to generate the multi-layer images require first converting the plenoptic image into multi-view images, resulting in data and computational inefficiencies. Our proposed method directly converts plenoptic images to multi-layer images using a CNN, showing improvements in quality metrics, with an average gain of 1.25 dB for the PSNR (for plenoptic 1.0 camera model).

Toward Real-time Depth-based Layered 3D Display

Multi-layer displays are a type of 3D display composed of multiple LCD panels arranged to generate parallax and facilitate 3D perception. However, generating multi-layer images requires time-consuming algorithms, not adapted for real-time visualization. This study addresses the challenge of real-time computation of multi-layer images using a single view and depth map. We present you a novel and faster approach generating layers. Our complete pipeline runs at a frame rate comprise between 155 and 300 Hz, at the cost of a reduced quality in the reproduced views.

Training Data Selection to Improve Multi-class Instance Segmentation in Digital Pathology

Finding the best channel for tissue segmentation in whole-slide images

In digital pathology, segmentation between tissue and glass slide is a very common pre-processing step in image processing pipelines. It is often presented as relatively trivial, and solved using ad-hoc heuristics that are not always precisely defined nor justified. Most tissue segmentation pipelines start by reducing the color image to a single-channel representation, grayscale being the most common. We show in this study that representations that focus on the colorfulness or entropy offer better separability between tissue and background, and lead to better results in simple thresholding pipelines.

Assessing Local Descriptors for Feature-Based Registration of Whole-Slide Images

Feature-based registration has become increasingly popular in digital pathology for achieving initial global alignment between image pairs. However, the selection of algorithms used in this approach is often not well-justified. Specifically, the choice of local feature descriptor is rarely, if ever, discussed in the context of digital pathology. The majority of feature-based whole-slide image registration methods rely on the SIFT descriptor. In this study, we demonstrate that the choice of descriptor significantly influences the quality of registration results and that the BRIEF descriptor captures more optimal information for histological image registration.

2023

Automatic detection of windows reflection or transparency pollution in TLS acquisitions

Perspective Camera Model for Layer Optimization of 3D Layered Display

Study on Viewpoint-Dependent Time-Multiplexing for Weighted Optimization of 3D Layered Displays

Fibroblast Activation Protein Inhibitor, a Promising Radiotracer inFibrogenesis

Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible interstitial lung diseasefor which biomarker of the fibrotic activity of the disease are lacking. Fibroblast activation protein-α(FAP) is a marker of activated fibroblasts. The development of quinoline-based PET tracers that actas FAP inhibitors (FAPIs) demonstrated promising results in oncology with a high and selectivetumor uptake. In the present study, we evaluated the potential role of FAPI as a biomarker of lungfibrogenesis. Methods: The lung uptake of FAPI and its kinetic was assessed in a mouse model ofpulmonary fibrosis. Thus, intratracheal instillation of bleomycin (0.02U/mouse) was performed onC56BL/6 mice. Control mice received an intratracheal instillation of NaCl 0.9%. FAPI was providedby SOFIE (Totowa, USA) and the radiotracer 18F-FAPI was produced in the department of NuclearMedicine of Erasme Hospital. PET/CT imaging were determined at different timepoints (days 3, 10,16 and 28) after the instillation of bleomycin. A time course of uptake of the radiotracer wasevaluated. The results are presented as the mean standardized uptake value (SUV mean) in thelungs and the calculation of a lung-to-muscle ratio (LMR). To correlate with the PET scan results, theextent of fibrosis was assessed by measuring lung content of hydroxyproline and by evaluating theAshcroft modified scale. Results: The optimal imaging window was determined between 40 and 90minutes after radiotracer injection. Bleomycin-treated mice presented a significantly higher uptakeof 18F-FAPI (both SUV mean and LMR) at days 10 and 16 after instillation as compared to controlmice (p < 0.01). No significant statistical difference was observed at day 3 and day 28 afterinstillation. At day 10 and day 16, a strong correlation between 18F-FAPI uptake and hydroxyprolinelung content was observed, as well as a moderate correlation with the Ashcroft modified score.Conclusions: Our results suggest that FAPI constitutes a promising marker of fibrogenesis whoseexpression can be assessed by PET/CT imaging in a mouse model of lung fibrosis. Interestingly, nosignificant increase of lung FAPI uptake was observed during the initial inflammatory phase afterbleomycin instillation as well as at the later stage when fibrotic changes are established and nolonger grow. 18F-FAPi PET/CT could be a useful tool for preclinical evaluation of antifibrotic drugsand further studies should assess its value in patients with IPF.

Assessment of Multi-Plenoptic 2.0 Camera Depth Maps for DIBR

A Quantitative Evaluation of Trademark Search Engines' Performances through Large-Scale Statistical Analysis

Intellectual Property Offices now offer their users trademark search engines to help them identify earlier trademarks in their register. Such tools have proven to be extremely useful given the growing number of trademarks registered but have never been subjected to thorough evaluation, despite the necessity for openness and accountability in justice systems. Additionally, their performance is unknown, in particular the reliability of their results pertaining to applicable legal rules. In fact, their "black box nature" makes automatic and at-scale evaluation hard to perform directly, which is why we propose a novel method for evaluating their performance using settled case-law for ground truth, and at-scale analysis. Based on this methodology, we evidence the performance for two such systems, the Benelux Office of Intellectual Property (BOIP) and European Union Intellectual Property Office (EUIPO), using 8 126 opposition division decisions from the EUIPO. We show important disparities between the two systems, along with surprisingly good results for EUIPO's system.

2022

3D Tensor Display for Non-Lambertian Content

Tele-Robotics VR with Holographic Vision in Immersive Video

Pattern-free Plenoptic 2.0 Camera Calibration

Extracting Microseismic Ground Motion From Legacy Seismograms

Before digital recordings became available in the 1970s, the ground motion was recorded using ink on white paper, scratching black-smoked paper, or light on photographic paper. While those analog seismic records offer unique continuous observations from the last century, most of them are now stacked and archived in boxes and potentially exposed to physical decay and permanent loss. To preserve those records and ultimately subject them to modern methods of analysis, it is time-sensitive to scan and digitize them. Here, we worked on a method for automatic digitization of paper seismograms using image processing and machine learning to extract microseismic ground-motion periods and amplitudes. We implemented the method on legacy data recorded at the Royal Observatory of Belgium to extract power spectral densities for major storms during the last century, which are compared with modeled microseisms levels computed using a numerical ocean wave model. This further shows how digitizing analog seismograms does not only preserve the scientific legacy but also makes new research possible by bringing analog data to the digital age.

Novel View Synthesis in Embedded Virtual Reality Devices

Abstract Virtual Reality and Free Viewpoint navigation require high-quality rendered images to be realistic. Current hardware assisted raytracing methods cannot reach the expected quality in real-time and are also limited by the 3D mesh quality. An alternative is Depth Image Based Rendering (DIBR) where the input only consists of images and theirassociated depth maps for synthesizing virtual views to the Head Mounted Display (HMD). The MPEG Immersive Video (MIV) standard uses such DIBR algorithm called the Reference View Synthesizer (RVS). We have first implemented a GPU version, called the Realtime accelerated View Synthesizer (RaViS), that synthesizes two virtual views in real-time for the HMD.In the present paper, we explore the differences between desktop and embedded GPU platforms, porting RaViS to an embedded HMD without the need for a separate, discrete desktop GPU. The proposed solution gives a first insight into DIBR View Synthesis techniques in embedded HMDs usingOpenGL and Vulkan, a cross-platform 3D rendering library with support for embedded devices.

Towards non-Lambertian scenes for tensor displays

Tensor displays are screens able to render a light field with correct depth perception without wearing glasses. Such devices have already been shown to be able to accurately render a scene composed of Lambertian objects. This paper presents the model and prototyping of a tensor display with three layers, using re-purposed computer monitors, and extends the light field factorization method to non-Lambertian objects. Furthermore, we examine the relation and limitations between the depth-of-field and the depth range with Lambertian and non-Lambertian scenes. Non-Lambertian scenes contain out-of-range disparities that can not be properly rendered with the usual optimization method. We propose to artificially compress the disparity range of the scene by using two light fields focused on different depths, effectively solving the problem and allowing to render the scene clearly on both simulated and prototyped tensor display.

2021

Processing multi-expert annotations in digital pathology: A study of the Gleason2019 challenge

MPEG Immersive Video tools for Light-Field Head Mounted Displays

Light-Field displays project hundreds of microparallax views for users to perceive 3D without wearing glasses. It results in gigantic bandwidth requirements if all views would be transmitted, even using conventional video compression per view. MPEG Immersive Video (MIV) follows a smarter strategy by transmitting only key images and some metadata to synthesize all the missing views. We developed (and will demonstrate) a realtime Depth Image Based Rendering software that follows this approach for synthesizing all Light-Field micro-parallax views from a couple of RGBD input views.

Depth Image-Based Rendering of non-Lambertian Content in MPEG Immersive Video

In the context of the development of MPEG-I standard for immersive video compression ISO/IEC 23090-12 (MIV), the need of handling scenes with non-Lambertian materials arose. This class of material is omnipresent in natural scenes, but violates all the assumptions on which depth image-based rendering (DIBR) is based. In this paper, we present a view-synthesizer designed to handle non-Lambertian objects with DIBR, replacing the classical depth maps by multi-coefficients non-Lambertian maps. We report the results of the exploration experiments on Future MIV designed to test this rendering method against the classical DIBR approaches, and demonstrate promising results on all the tested sequences.

Multiview from micro-lens image of multi-focused plenoptic camera

Performance analysis of DIBR-based view synthesis with kinect azure

Polynomial Image-Based Rendering for non-Lambertian Objects

Non-Lambertian objects present an aspect which depends on the viewer's position towards the surrounding scene. Contrary to diffuse objects, their features move non-linearly with the camera, preventing rendering them with existing Depth Image-Based Rendering (DIBR) approaches, or to triangulate their surface with Structure-from-Motion (SfM). In this paper, we propose an extension of the DIBR paradigm to describe these non-linearities, by replacing the depth maps by more complete multi-channel ”non-Lambertian maps”, without attempting a 3D reconstruction of the scene. We provide a study of the importance of each coefficient of the proposed map, measuring the trade-off between visual quality and data volume to optimally render non-Lambertian objects. We compare our method to other state-of-the-art image based rendering methods and outperform them with promising subjective and objective results on a challenging dataset.

A Calibration Method for Subaperture Views of Plenoptic 2.0 Camera Arrays

We present a novel methodology to precisely calibrate the subaperture views of an array of plenoptic 2.0 cameras. Such cameras consist of a micro lens array, and the image captured through them is a lenslet image that can be converted to a dense set of pinhole views, the so-called subaperture images. This camera array provides several dense multiview images at some sparse points of 3D space. To find the relative position of those views, simply using structure-from-motion creates misalignments due to the small disparities within each set. Additionally, a traditional calibration using calibration patterns will also fail due to the complicated objectives of plenoptic 2.0 cameras and artifacts when they are converted to subaperture views. In this paper, we propose two calibration steps (a) to register the sparse central subaperture views using Structure-from-Motion which makes it robust to artifacts in the subaperture views, and (b) to register all dense multiview sets per plenoptic camera using camera's lenses specifications, disparity and distance to the scene. These two steps are followed by a novel merging process of the former registrations, to achieve precise calibration parameters for all the subaperture views of the multi-plenoptic array. Experimental results objectively and subjectively demonstrate high accuracy of the calibration. We show a 10% smaller reprojection error than using a naive structure-from-motion approach and verify that our method is suitable for high precision view synthesis applications such as virtual reality and holography.

View Synthesis: LiDAR Camera versus Depth Estimation

Light Field Rendering for non-Lambertian Objects

3D scanner colorization taking into account lighting problems (shadows, overexposures, lighting changes, and lack of light)

2020

Calibration of an inwards spherical light field capturing device

Computer Generated Holography with Depth-based View Synthesis

Thermal Image Super-Resolution Challenge - PBVS 2020

This paper summarizes the top contributions to the first challenge on thermal image super-resolution (TISR), which was organized as part of the Perception Beyond the Visible Spectrum (PBVS) 2020 workshop. In this challenge, a novel thermal image dataset is considered together with state- of-the-art approaches evaluated under a common framework. The dataset used in the challenge consists of 1021 thermal images, obtained from three distinct thermal cameras at different resolutions (low-resolution, mid-resolution, and high-resolution), resulting in a total of 3063 thermal images. From each resolution, 951 images are used for training and 50 for testing while the 20 remaining images are used for two proposed evaluations. The first evaluation consists of downsampling the low-resolution, mid-resolution, and high-resolution thermal images by ×2, ×3 and ×4 respectively, and comparing their super-resolution results with the corresponding ground truth images. The second evaluation is comprised of obtaining the ×2 super-resolution from a given mid-resolution thermal image and comparing it with the corresponding semi-registered high- resolution thermal image. Out of 51 registered participants, 6 teams reached the final validation phase.

MANet: Multi-scale aggregated network for light field depth estimation

Xslit cameras for free navigation with depth image-based rendering

RaViS: Real-time accelerated view synthesizer for immersive video 6DoF VR

3D digitization of the Brussels City Hall and the medieval archangel Michael wind vane: architectural and archaeological exploitation

In order to make the architectural and archaeological study, the roofs, the courtyard and the facades of the Brussels City Hall were digitized with a 3D scanner, coupled with photographic acquisitions. Various elements, such as the main portal tympanum and the archangel Michael, - an exceptionally preserved 5-metre-high medieval metal wind vane that adorned the top of the 96-metre-high tower -, were also digitized in high definition. Numerical surveys shows different colorimetric (variation of colorimetry related to the changes in natural lighting) and geometric defects (erroneous points related to the passages of persons and vehicles, flying points or noises inherent to the acquisition device). A specific and automatic processing pipeline has therefore been developed and applied to correct all this problems. Given the amount of data and operations for creating plans, a software has been developed to present the data as an enriched 2D representation. This is similar to orthophotos complemented by the possibility to navigate in the depth and to vary the rendering mode (color, intensity, orientation ...), to highlight elements (surfaces, edges ...) hardly visible in simple color mode of rendering. Its functionalities allowed the drawing of very precise elevations and to generate projection images in high definition of all buildings parts and also of the archangel statue. Indeed, this survey allowed to draw the entire statue to the real scale and in a completely proportioned way. Archeologists have been able to distinguish the main work components, and they better understand the articulations between its constitutive parts and the various transformations made to the metal statue over the centuries.

2019

Data augmentation for training deep regression for in vitro cell detection

SNOW: Semi-Supervised, NOisy and/or Weak Data for Deep Learning in Digital Pathology

Digital pathology produces a lot of images. For machine learning applications, these images need to be annotated, which can be complex and time consuming. Therefore, outside of a few benchmark datasets, real-world applications often rely on data with scarce or unreliable annotations. Inthis paper, we quantitatively analyze how different types of perturbations influence the results of a typical deep learning algorithm by artificially weakening the annotations of a benchmark biomedical dataset. We use classical machine learning paradigms (semi-supervised, noisy and weak learning) adapted to deep learning to try to counteract those effects, and analyze the effectiveness of these methods in addressing different types of weakness.

Extracting Multi-View Images from Multi-Focused Plenoptic Camera

2018

Free Navigation in Natural Scenery with DIBR: RVS and VSRS in MPEG-I standardization

Natural Scenes Datasets for Exploration in 6DoF Navigation

3D Imaging System Using Multi-Focus Plenoptic Camera and Tensor Display

Artifact Identification in Digital Pathology from Weak and Noisy Supervision with Deep Residual Networks

RGB Guided Thermal Super-Resolution Enhancement

In visual surveillance and security problems, objects can occur in different conditions of illumination and occlusion, therefore thermal images have become a major tool in a large variety of applications. By the reason of their high cost compared to their visual (RGB) counterpart, thermal sensors are used in low-resolution and in low contrast which introduces the necessity to obtain a higher resolution version. In this work, we propose a deep learning model by which to enhance the thermal image resolution guided by RGB images using GAN based model. The results indicate an improvement in resolution enhancement using RGB guided thermal super-resolution models compared to the classical single thermal super-resolution approach.

Multimodal Sensor Fusion In Single Thermal image Super-Resolution

With the fast growth in the visual surveillance and security sectors, thermal infrared images have become increasingly necessary ina large variety of industrial applications. This is true even though IR sensors are still more expensive than their RGB counterpart having the same resolution. In this paper, we propose a deep learning solution to enhance the thermal image resolution. The following results are given:(I) Introduction of a multimodal, visual-thermal fusion model that ad-dresses thermal image super-resolution, via integrating high-frequency information from the visual image.(II) Investigation of different net-work architecture schemes in the literature, their up-sampling methods, learning procedures, and their optimization functions by showing their beneficial contribution to the super-resolution problem.(III) A bench-mark ULB17-VT dataset that contains thermal images and their visual images counterpart is presented.(IV) Presentation of a qualitative evaluation of a large test set with 58 samples and 22 raters which shows that our proposed model performs better against state-of-the-arts.

MPEG-I Coding performance in Immersive VR/AR applications

MPEG-I Coding performance in Immersive VR/AR applications

Depth Image-Based View Synthesis with Multiple Reference Views for Virtual Reality

Scalable light field disparity estimation with occlusion detection

Numérisation 3D de l'Hôtel de Ville de Bruxelles et de la statue du saint Michel : exploitation architecturale et archéologique

2017

MPEG-I immersive video and VR standards

A Graph Based Algorithm for Star Recognition

Toward the realization of six degrees-of-freedom with compressed light fields

Analysis of abdominal movement with Phase Optical Flow: Application to Diffusion imaging.

Development of high-speed and high-quality free-viewpoint video generation system using visual hull (translation of the Japanese title)

High-efficiency free-viewpoint sports video generation using Visual Hull

High-efficiency and high-quality free-viewpoint sports video generation using visual hull (Translation)

2016

Convergent Multi-View Geometric Error Correction with Pseudo-Inverse Projection Homography

Combining known depth map and plain sweeping (translation of the Japanese title)

Detection of correspondence between cameras with different resolutions (translation of the Japanese title)

Modular parallelization framework for multi-stream video processing

Free Viewpoint Video for Sports Events Using Multi-resolution Visual Hull and Micro-facet Billboarding

Dense correspondence point detection between cameras with different resolutions (translation of the Japanese title)

Depth estimation for free-viewpoint video generation by integrating multi-view camera and depth camera (translation of the Japanese title)

Nonuniform Depth Distribution Selection with Discrete Fourier Transform

Efficient MRF-based disocclusion inpainting in multiview video

Multi-view Wide Baseline Depth Estimation Robust to Sparse Input Sampling

Free-viewpoint soccer viewing system using multi-resolution visual hull (translation of the Japanese title)

Color retargeting: interactive time-varying color image composition from time-lapse sequences

Image normalization for quantitative immunohistochemistry in digital pathology

We propose to adapt to immunohistochemistry (IHC) some methods proposed to normalize images from histological slices stained with hematoxylin-eosin (H&E). Our final aim is to provide a coherent quantitative characterization of IHC biomarkers across different IHC batches with possible staining variations. In contrast to H&E, IHC staining strongly varies with the tissue analyzed and the protein targeted, making image normalization challenging. To solve this problem, we added in each IHC batch a slice from a reference tissue microarray (TMA) and then digitalized it to establish an inter-batch normalization transform. A comparison of two methods adapted to the specificity of IHC-stained slides evidences some normalization requirements to make valid IHC biomarker quantification across different staining batches.

New visual coding exploration in MPEG: Super-MultiView and Free Navigation in Free viewpoint TV

Examination of a free-view soccer viewing system using Visual hull and Microfacet billboarding (translation of the Japanese title)

2015

Amplified spontaneous emission injection into an optical fiber with the aid of a nematicon

Amplified Spontaneous Emission (ASE) has become popular for applications like spectroscopy, fiber sensors and imaging that require incoherent light. In our setup ASE is generated in a dye-doped nematic liquid crystal cell and it is then collected into an optical fiber to integrate into the device. We demonstrate that, generating a nematicon from the same fiber, the ASE collection efficiency is increased of almost one order of magnitude thanks to the wave-guiding action of the nematicon that induces the injection into the fiber. Moreover the collected emission is highly linearly polarized parallel to the direction of the liquid crystal director

Examination of essential technologies for the development of a free-view soccer viewing system (translation of the Japanese title)

Player domain extraction for soccer free-viewpoint video using Low-Rank Sparse decomposition (translation of the Japanese title)

Study on compression efficiency of super multiview video data format (translation of the Japanese title)

Study on spatio-temporal interpolation for the generation of multi-view video (translation of the Japanese title)

Mesh generation from depth map using Laplacian as evaluation standard (translation of the Japanese title)

Generalized Inpainting Method for Hyperspectral Image Acquisition

Comparison of Normalized Transfer Functions for Fast Blending-based Color Correction of Scans Acquired under Natural Conditions

Position control of movable multi-lens camera for wide-range free-viewpoint image generation (translation of the Japanese title)

Research on background subtraction for sports video (translation of the Japanese title)

Multi-view soccer video segmentation method using visual hull (translation of the Japanese title)

A Study on Compressed Multi-Resolution Formats for Free View Video Streaming (translation of the Japanese title)

Reconstruction of Compressively Sampled Light Fields Using A Weighted 4D-DCT Basis

Super-Resolution Image Synthesis using The Physical Pixel Arrangement of A Light Field Camera

Rank Analysis of A Light Field for Dual-Layer 3D Displays

High-Throughput Analysis of Tissue-Based Biomarkers in Digital Pathology

Multi-Camera Epipolar Plane Image feature detection for Robust View Synthesis

Research on compression methods for light field camera images for refocus images (translation of the Japanese title)

Player area extraction for soccer video free navigation system (translation of the Japanese title)

Free viewpoint image generation by moving multi-lens camera array (translation of the Japanese title)

Subjective Evaluation of Compression Performance of Synthesis Error Compensated Multiview Video plus Depth

Free-viewpoint Video Synthesis from a Movable 2D Camera Array

Precise Extraction of Players in a Soccer Game

Development of free-viewpoint soccer video system (translation of the Japanese title)

Super Multiview Video - Technology and Applications

Real-time Fullscale Model Colorization and Global Color Quality Evaluation for Rapid Scanning in Uncontrolled Environment

Automated Tissue Microarray Image Processing in Digital Pathology.

Data Format and View Synthesis for Free-viewpoint Video Streaming of Super Multiview Video

View Synthesis Using Superpixel Based Inpainting Capable of Occlusion Handling and Hole Filling

Acquisition and Processing of Ray-Space/Light Field Data

Joint Directional-Positional Multiplexing for Light Field Acquisition by Kronecker Compressed Sensing

Free-Viewpoint Video Synthesis from Mixed Resolution Multi-View Images and Low Resolution Depth Maps

Data Conversion from Multi-View Cameras to Layered Light Field Display for Aliasing-Free 3D Visualization

A practical implementation of free viewpoint video system for soccer games

Multi-viewpoint / free-viewpoint video streaming system with flexible viewpoint switching (translation of the Japanese title)

Depth Image Based Rendering using inpainting based on segmentation (translation of the Japanese title)

A New Physical-Digital Environment for Discussion and Presentation Skills Training

2014

Keynote IWCIM: Image-based 3D scene visualization and Free Viewpoint TV

Basic study for introduction of rotation mechanism in free viewpoint image generation by movable multi-lens camera array (translation of the Japanese title)

Basic study of player domain extraction method for free-viewpoint video generation system of soccer (translation of the Japanese title)

Examination of technologies for practical use of soccer free-viewpoint video generation system (translation of the Japanese title)

Parallax accuracy improvement method for increasing the resolution of light field camera images (translation from the Japanese title)

Improvement of 3D reconstruction from multi-view images using feature point mapping and voxel search (translation of the Japanese title)

Quality evaluation of transparent layer type 3D display by non-negative matrix factorization NMF (translation from the Japanese title)

A study of DIBR method suitable for a wide range of virtual viewpoint movement (translation of the Japanese title)

Examination of restoration method by weighted L1 regularization of ray space compressed and sensed by coded aperture (translation of the Japanese title)

Improvement of accuracy of free-viewpoint video generation system by multi-frame spatio-temporal stereo (translation from the Japanese title)

Basic study of streaming of free-viewpoint video using Multiview Video plus Depth format (translation of the Japanese title)

Real-World Data Analysis - Super Multiview Video Compression and Standardization Activates

Free viewpoint video generation by merging multiple viewpoint images considering the boundary part of the object (translation from the Japanese title)

Examination of super-resolution from a light field camera using a horizontal-vertical parallax map (translation of the Japanese title)

Evaluation of display quality of layered 3D display using live-action multi-lens image with horizontal and vertical parallax (translation from the Japanese title)

Image quality evaluation of View Synthesis using PatchMatch Stereo (translation of the Japanese title)

Multi-frame spatio-temporal stereo in a free-viewpoint video generation system (translation of the Japanese title)

Basic study of 3D reconstruction from multi-viewpoint images using feature point mapping and voxel search (translation of the Japanese title)

Real World Data Compression - Super Multiview Video Compression and Standardization Activities

Real-time Local Stereo Matching using Edge Sensitive Adaptive Windows

Self-Calibration of Large Scale Camera Networks

A Qualitative Comparison of MPEG View Synthesis and Light Field Rendering

Improved depth map generation for efficient transmission of multi-lens stereoscopic video (translation of the Japanese title)

Examination of calculation cost reduction method for speeding up PatchMatch Stereo (translation of the Japanese title)

Analysis of ray space for free viewpoint image generation by movable multi-lens camera (translation of the Japanese title)

Synthesis Error Compensated Multiview Video Plus Depth For Representation of Multiview Video

Multi-sensor data fusion for hand tracking using Kinect and leap motion

Hyperspectral Compressive Sensing

A qualitative comparison of MPEG view synthesis and light field rendering

Lens-free digital in-line holographic imaging for wide field-of-view, high resolution and real-time monitoring of complex microscopic objects

Adaptive Hole Filling for 3D Warping-Based Free View Synthesis

2013

Human Motion Tracking for Rehabilitation using Depth Images and Particle Filter Optimization

Fast Color Correction for Rapid Scanning in Uncontrolled Environment

Human motion tracking for rehabilitation using depth images and particle filter optimization

The algorithm presented here allows the motion tracking of a human subject performing rehabilitation exercises during physiotherapy. The motion is tracked by fitting a model into the observed data, which are depth images coming from one or multiple Kinect sensors. The model consists of a surface mesh morphologically close to the patient's body and an articulated skeleton. The mesh is deformed by linear blend skinning according to the pose of the skeleton. The optimization is performed by particle filtering. Thanks to the graphics pipeline and the computing capabilities of the GPU, our algorithm reaches execution speeds close to real time. When working offline with a model very close to the patient's morphology, the joints locations and rotations are estimated with an average accuracy respectively smaller than a few millimeters and a few degrees.

Foreground Detection Method for Depth Map Stabilization

Effect of Depth Stabilisation on Compression Performance of SECOND-MVD

Hybrid method to extract striation features from ship noise spectrogram

Efficient Transmission of Multiview 3D Video by Plane Approximation of Depth Map

SECOND-MVD: Synthesized Error COmpeNsateD Multiview Video plus Depth

Glasses-free 200-view 3D Video System for Highly Realistic Communication

A New Data Format for Multi-view Video

Virtual Image Generation by Using Super-Resolution

Compression of Multi-View Images Using Hybrid Representation for 200-Inch 3D Display

2012

Plans Extraction From Complex Buildings 3D Acquisitions

Robust structured light pattern for use with a hologram in 3D endoscopy

EfficienT transmission of Multiview 3D Video by Plane Approximation of Depth Map

Adaptive hole filling method for generated free-viewpoint images using 3D warping (translation of the Japanese title)

Interpolation of FTV images by super-resolution (translation of the Japanese title)

A Hybrid Representation for Multiview Images

3D augmented reality applied to the treatment of neuropathic pain.

Virtual viewpoint image synthesis using super-resolution (translation of the Japanese title)

Image Generation of FTV by using Super Resolution

Close-up View Synthesis for Free-Viewpoint Image Generation

Adaptive processing in virtual viewpoint image generation using 3D warping (translation of the Japanese title)

Adaptive hole filling method for generated images using 3D warping (translation of the Japanese title)

Unsupervised vehicle detection in traffic scene using distributed one class classifiers

Adaptive processing for holes caused by free-viewpoint image generation using 3D warping (translation of the Japanese title)

Compressed sensing of ray space in a circular camera array (translation of the Japanese title)

Generating free-viewpoint video and its acceleration (translation of the Japanese title)

Overview of Multi-view Video plus Depth(MVD) Coding

Data Representation for Arbitrary View Synthesis

3D augmented reality applied to the treatment of neuropathic pain

Towards a real-time high-definition depth sensor with hardware-efficient stereo matching

Image registration software data correction algorithm for a hyperspectral imager

Modular sub-wavelength diffractive light modulator for high-definition holographic displays

All-Around Dense Ray Capture by Mirror-Scan of Reduced-Size Images

2011

Tridimensional laser scanning to retrieve engineering site drawings. The experience of the Brussels Park Bunker rehabilitation project.

Geometrical 3D reconstruction using real-time RGB-D cameras

N-View N-Depth coding suitable for free-viewpoint video generation (translation of the Japanese title)

Dynamic visible light communication using an image sensor that can read out partially at high speed (translation of the Japanese title)

FTV coding with global view and depth (translation of the Japanese title)

Forward position viewpoint image generation in circular camera arrangement (translation of the Japanese title)

Coding of depth information suitable for free-viewpoint video generation (translation of the Japanese title)

Free-Viewpoint Image Generation at the Forward Point in Circular Camera Setup

Road-to-vehicle Visible Light Communication UsingHigh-speed Camera in Driving Situation

All-around ray-reproducing 3DTV

Free-viewpoint Image Generation Techniques

Compressive acquisition of ray-space in circular camera arrangement

Global view and depth format for FTV

Traffic sign detection in dual-focal active camera system

Depth Up-sampling for Depth Coding using View Information

Compression of multi-view video and depth information using parallax compensation vector (translation of the Japanese title)

Reconstruction of ray space using radon transformation (translation of the Japanese title)

High-Speed LED Traffic Sign Tracking Method Using Image Sensor with High-Speed Capturing Ability of Partial Area

Free-viewpoint Image Generation from a Video Captured by a Handheld Camera

Novel view synthesis for dynamic scene using moving multi-camera array

Programme and Abstracts

A cross-based filter for fast edge-preserving smoothing

Real-time depth extraction and viewpoint interpolation on FPGA

Real-Time High-Definition Stereo Matching on FPGA

Rectification of Camera Array using Bundle Adjustment

Multi-view Ray acquisition using Camera and Mirror System

Free-viewpoint Image Generation using Moving Object Detection

Free-viewpoint Image Generation By Moving Multi-camera Array

Hierarchical Encoding System of Road-to-Vehicle Communication

Free-viewpoint Image Generation using Structure from Motion

Image Processing Based Road-to-vehicle Visible Light Communication

Parallel Communication Using Visually Non-Lighting LEDs

Resolution Improvement of Free-viewpoint Image Generation

Epipolar Plane Depth Image Representation for FTV

3D space representation using epipolar plane depth image

Reducing Bitrates of Compressed Video with Enhanced View Synthesis for FTV

Color Based Depth Up-Sampling for Depth Compression

Parallel processing method for realtime FTV

2010

Hierarchical Encoding System for Road-to-Vehicle Communication Using LED Traffic Light

Free-viewpoint image generation for static scene by SfM

Free-viewpoint image generation using different focal length camera array

Hierarchical Encoding System for Road-to-Vehicle Communication Using LED Traffic Light

Traffic Sign Detection Based on Shape and Color

Parallel Visible Light Communication Using Visually Non-Lighting LEDs

Free-Viewpoint Image Generation in Static Scene by a Handy Camera

Receiver for a Visible Light Communication System Using a on-Vehicle High-Speed Camera

Multi-View Ray Acquisition Using Hybrid Camera and Mirror System

Probabilistic reliability based view synthesis for FTV

Novel View Synthesis Using Moving Camera Array

Calibration of Camera Array Using Bundle Adjustment

LED Traffic Light Detection Using a High-speed-camera for a Road-to-vehicle Visible Light Communication System

Free-viewpoint image generation for dynamic scene using moving multi-camera array

Free-viewpoint Image Generation using SFM for a Handy Camera

Channel characteristics and receiving system of road-vehicle communication

FTV data compression using depth map

Reliable View Synthesis with Automatic Error Compensation for FTV

Parallel processing method for real-time free-viewpoint image composition (translation of the Japanese title)

Multi-view Ray Acquisition with Hybrid Camera and Mirror System

Study on parallel visible light communication using visually non-lighting LED

Free-viewpoint image generation for dynamic scene using moving multi-camera array

A Data Format for FTV Using Depth information

Influence of quantization of brightness in road-vehicle communication

Free-viewpoint Image Generation for Static Scene by SfM

FTV data format for image generation using depth information (translation of the Japanese title)

Geometric correction of ray space data acquired by a circular camera array (translation of the Japanese title)

Basic study of vehicle-to-vehicle visible light communication using LEDs that are visually unlit (translation of the Japanese title)

Hybrid multi-point ray acquisition system with camera and plane mirror (translation of the Japanese title)

Arbitrary view synthesis using multi-resolution cameras

Long Distance Road Sign Recognition Using an Active Camera System

Visible Light Communication Between LED Array and On-vehicle High Speed Camera

Acquisition of multipoint rays by hybrid acquisition of direct light and reflected light (translation of the Japanese title)

Free viewpoint image generation by tracking natural feature points (translation of the Japanese title)

Error suppression in view synthesis using reliability reasoning for FTV

A New Vision System for Traffic Sign Recognition

High-speed-camera image processing based LED traffic light detection for road-to-vehicle visible light communication

View Synthesis Using Graph Cuts for FTV

In-vehicle receiver for visible light communication using LED traffic lights (translation of the Japanese title)

Novel View Synthesis with Residual Error Feedback for FTV

Detecting man-made structure changes to assist geographic data producers in planning their update strategy, ISPRS

Computerised geometric analysis of a spire coming from a Gothic tabernacle

Ki-67 hot-spots detection on glioblastoma tissue sections

The use of ORFEO toolbox in the context of map updating

LOCOCO: LOw COmplexity COrner detector

An efficient run-time management methodology for stereo matching application

Robust low complexity feature tracking

Joint integral histograms and its appalication in stereo matching

Robust low complexity feature tracking using CUDA

Depth Estimation for Moving Multiple Camera Array

View Generation by Canceling Residual Error for FTV

Identification of Emitting LED Array for Achieving Road-to-Vehicle Communication

Depth Estimation for Moving Multiple Camera Array

A New Method for Traffic Sign Recognition Using Hybrid Camera System

2009

On-Vehicle Receiver for Visible Light Road-to-Vehicle Communication

Free-viewpoint Image Generation using Moving Object Extraction

Ray acquisition and free viewpoint image generation by mobile camera array (translation of the Japanese title)

Free-viewpoint Image Generation by Handy Camera

Super resolution of free-viewpoint images on FTV (translation of the Japanese title)

Ray-Based Acquisition and Reproduction of 360-degree 3D Images

Encoding system based on spatial frequency characteristics of road-vehicle communication

All-around light acquisition method using a small optical system (translation of the Japanese title)

Reconstruction of still scene FTV with a handy camera (translation of the Japanese title)

Visible light communication in-vehicle receiver equipped with a traffic light tracking mechanism (translation of the Japanese title)

Reduction of data volume in ray space acquisition using Radon transform (translation of the Japanese title)

Traffic Sign Recognition Based on Edge Information and Template Matching

Free viewpoint image generation that compensates for depth error (translation of the Japanese title)

Traffic light detection for image sensors for optical communication (translation of the Japanese title)

Tracking of LED Traffic Light for Read-to-Vehicle Communication System

Examination of coding method based on spatial frequency characteristics in parallel optical communication between roads and vehicles (translation of the Japanese title)

Highly efficient acquisition of ray space in linear camera arrangement (translation of the Japanese title)

In-vehicle receiver for visible light communication using LED traffic lights (translation of the Japanese title)

Compensation method for image synthesis error in FTV (translation of the Japanese title)

Real-time video playback system for all-around 3D display (translation of the Japanese title)

Free viewpoint image generation from a handy camera using feature points (translation of the Japanese title)

Examination of road-to-vehicle optical communication using an image sensor for optical communication (translation of the Japanese title)

View synthesis using reliability reasoning for FTV

Traffic Sign Recognition Based on Template Matching

Traffic Signs Recognition Based on Color and Shape Information

View Synthesis using Residual Prediction

Encoding system based on spatial frequency characteristics of road-vehicle communication

Reliability-based Free Viewpoint Image Generation

Free viewpoint image generation by handy camera images using feature points (translation of the Japanese title)

Examination of real-time video playback on an all-around 3D display (translation of the Japanese title)

Traffic Sign Recognition Using Wide Angle Camera Cooperated with Narrow Angle Camera

Reconstruction and Digitalization of an archaeological site, Itanos, Crete

A multi-features stereo vision system for road traffic analysis

This paper presents a method for counting and classifying vehicles on motorway. The system is based on a multi-camera system fixed over the road. Different features (maximum phase congruency and edges) are detected on the two images and matched together with local matching algorithm. The resulting 3D points cloud is processed by maximum spanning tree clustering algorithm to group the points into vehicle objects. Bounding boxes are defined for each detected object, giving an approximation of the vehicles 3D sizes. A complementary 2D quadrilateral detector has been developed to enhance the probability of matching features on vehicle exhibiting little texture such as long vehicles. The algorithm presented here was validated manually and gives 90% of good detection accuracy.

Weakened watershed assembly for remote sensing image segmentation and change detection

A camera auto-calibration algorithm for realtime road traffic analysis

This paper presents a new mono-camera system for traffic surveillance. It uses an original algorithm to obtain automatically a calibration pattern from road lane markings. Movement detection is done with a Σ - Δ background estimation which is a non linear method of background substraction based on comparison and elementary increment/decrement. Foreground and calibration data obtained allow to determine vehicles speed in an efficient manner. Finally, a new method to estimate the height of vehicles is presented.

3D Reconstruction and Digitalization of an
archaeological site, Itanos, Crete

Numérisation 3D de la grotte d'El Castillo (Puente Viesgo)

Influence d'images évocatrices et distractrices sur une tâche de jugement en acoustique des salles

Biomedical Engineer and Phlebologist

Comparaison et évaluation de méthodes de segmentation avec contrainte en vue d'une classification du bâti et des routes

Robust stereo matching with fast normalized cross-correlation over shape-adaptive regions

Real-time stereo matching: a cross-based local approach

Complexity reduction of real-time depth scanning on graphics hardware

Accurate and efficient stereo matching with robust piecewise voting

Interpolation error as a quality metric for stereo: robust, or not?

Migrating real-time depth image-based rendering from traditional to next-gen GPGPU

A high-level kernel transformation rule set for efficient caching on graphics hardware

Real-time accurate stereo with bitwise fast voting on CUDA

2008

An Iterative Approach for 3D Model Generation Using Disparity Maps

A Study of Free Viewpoint Video Realizing 3D Movement of Viewpoint by Horizontal Cameras and a Zenith Camera

Enhanced Multiple Local Ray-spaces Method for Walk-through View Synthesis

3DAV Integrated System Featuring Arbitrary Listening-point and Free Viewpoint Generation

Realtime Walk-through View Generation Using Multilayer Multiview Images

Free viewpoint video generation for walk-through experience using image-based rendering

Cells Tracking by Snakes

In this paper, a cells detection method based on active contours is presented. Active contours or snakes are widely use in image segmentation and tracking problems. Traditionally, active contours initialization is performance manually, this method provides an automatic initialization based on cross correlation. Cell tracking based on active contours provide a faster method to performance this task to multitarget problem. External and internal forces on the image are computed to determinate the action area of the active contours, this task is performance by the Vector Field Convolution (VFC) algorithm.

Improvement of Walk-through Generation Based on Multiple Local Ray-space Representation Using Block Matching

A New Block Matching Method for Ray Space Interpolation

A Method to Represent 3D Movement of Viewpoint for Free Viewpoint Video Using Divided Local Regions

Cell tracking by normalized cross-correlation with image processing

Here, cell tracking task involves normalized cross correlation of the cell target and microscope images. The sensibility of this method was improved applying image processing algorithms prior to the cross correlation task. © 2008 IEEE.

Cell recognition and tracking using nonlinear cross-correlation

Walk-through in Free Viewpoint Video Generation

Moving Camera Calibration Using Generated Model of a Scene

Free Viewpoint Generation Method and Walk-through Experience

A Correction Method of Vertical Disparity in Vertical Movement of Viewpoint for Free Viewpoint Video Using Divided Local Regions

Phase contrast image segmentation by weak watershed transform assembly

Design of an articulated mini-fixation device for proximal interphalangeal joint finger fractures

Digital Integrated Operating Room

Registration and segmentation of head and neck volumes in IMRT applications

Using a Pocket PC as an interaction peripheral for Virtual Realty

Un projet d'ingénierie biomédicale à double objectif pédagogique

Anisotropic local high-confidence voting for accurate stereo correpondence

Cross-layer optimization for multi-user video streaming over IEEE 802.11E HCCA wireless networks

A scalable end-to-end optimized real-time image-based rendering framework on graphics hardware

Scalable stereo matching with locally adaptive polygon approximation

Spatial locality trade-offs of wavelet-based applications in dynamic execution environments

Triple A philosophy applied to multimedia SoC design

Applying SIMD to optical character recognition (OCR)

2007

The Reappearance Method of Vertical Disparity in Free Viewpoint Video Generated from the Circumference Arrangement Multiview Video

Detection of Foreground Using Background Modeling and Iterative Local Matting

The Optimal Color Correction of Multicamera Systems

A Study of Data Compression Method in Generation of Walk-through Videos

Color Correction of Multiview Camera System Using Matched Feature Points

Image Processing for in Vitro Cell Tracking

In this paper, we propose an image processing method able to detect cells trough in vitro phase-contrast video microscopy. Bodies of the cells and image background are very similar; it does not allow having a good performance of tracking process. The proposed method normalizes original image to obtain better object-background contrast, image is equalized to highlight the object to be tracked, and image is threshold in order to obtain a better object-background contrast. Gray Level Morphological Gradient is applied to obtain more defined contours in the areas surrounded by Halos. Dilatation and Erosion were combined to achieve this goal. A subtraction process was applied after dilation of image to obtain borders. © Springer-Verlag Berlin Heidelberg 2007.

Documentation of the El Castillo (Puente Viesgo) cave using 3D scanning

3D and Virtual Reality

Graph Nodes Clustering based on the Commute-Time Kernel

Cell tracking by border-optical hybrid model

We propose an hybrid (image processing-correlation) method to obtain cells detection and cells migration tracking in order to analyze cells behaviors under different conditions. © 2007 OSA.

Channel-aware rate adaptation for energy optimization and congestion avoidance

Adaptive mapping to resource availability for dynamic wavelet-based applications

Platform-scalable task partition and multilevel buffering in multi-processor Plessey corner detector

High-speed stream-centric dense stereo and view synthesis on graphics hardware

Energy-efficient bandwidth allocation for multi-user video streaming over WLAN

Real-time stereo correspondence using a truncated separable Laplacian Kernel approximation on graphics hardware

Fast reliable multi-scale motion region detection in video processing

High-speed dense stereo via directional center-biased windows on graphics hardware

Fast variable center-biased windowing for high-speed stereo on programmable graphics hardware

Fast Variable Center-Biased windowing For High-Speed Stereo on Programmable Graphics Hardware

High-Speed Dense Stereo Via Directional Center-Biased Support Windows on Programmable Graphics Hardware

Modelling energy consumption of an ASIC MPEG-4 simple profile encoder

Network adaptive and energy-efficient multi-user video communication over QoS enabled WLAN

Energy-Efficient Bandwidth Allocation for Multi-user Video streaming over WLAN

Real-Time Stereo Using A Truncated Separable Laplacian Kernel Approximation On Programmable Graphics Hardware

OLGA: On-Line GAming over Heterogeneous Platforms Thanks to Standard Scalable Content

An Integrated Audio-Visual Viewer for a Large Scale Multipoint Cameras and Microphones

2006

Computer assisted needle positioning for liver tumor radiofrequency ablation (RFA)

Detection of Biological Cells in Phase-Contrast Microscopy Images

Arbitrary Listening-point Generation Using Acoustic Transfer Function Interpolation in A Large Microphone and Camera Array

The Sub-band Sound Wave Ray-Space Representation

Multipoint Sound and Image Generation Using Large Microphone and Camera Array

Interactive web-based application for potteries capacity computing

Imaging technologies for avoiding back pain at work

Interactive airway wall thickness measurement from computed tomography data

Apple Stem and Calyx Recognition by Decision Trees

Software-controlled scratchpad mapping strategies for wavelet-based applications

OLGA: On-Line GAming over heterogeneous platforms thanks to standard scalable content

A Content Adaptation Approach for On-Line Gaming on Various Networks and Terminals

Measurements and Modeling of Resource Consumption in Wireless Video Streaming: The Decoder Case

Streaming-Mode MB-Based Integral Image Techniques for Fast Multi-view Video Illumination Compensation

The Sub-band Sound Wave Ray-Space Representation

2005

Multipoint Measuring System for Video and Sound - 100 Cameras and Microphones System

Automatic fluoroscopic Image Calibration for Traumatology Intervention Guidance

The Sound Wave Ray-Space

Arbitrary Listening-point Generation of 3D Sound Wave Field Based on Ray-Space Method

3D Sound Wave Representation Based on Ray-Space Method

Hierarchical Modeling

Real Time L-System Generated Trees Based on Modern Graphics Hardware

Distal locking of intra-medullary nail using non-constrained fluoroscopic images

Modélisation hiérarchique

Hierarchical modeling

Computers and 3D Image Synthesis as Tools for Archaeology

Mitotic Tree Construction by Computer In Vitro Cell Tracking : a Tool for Proliferation and Motility Features Extraction

A content quality driven energy management system for mobile 3D graphics

Alleviating memory bottlenecks by software-controlled data transfers in a data-parallel wavelet transform on a multicore DSP

Mobile multiview video

Exploration of system-level trade-offs for application mapping in multi-processor system-on-chips

Pareto based optimization of multi-resolution geometry for real time rendering

Memory hierarchy energy cost of a direct filtering implementation of the wavelet transform

2004

Adaptive Distributed Source Coding for Multi-view Images

Adaptive Distributed Source Coding of Correlated View Image

Effect of Quality Control on Adaptive Distributed Source Coding for Multi-view Images

Comparison of very high spatial resolution satellite image segmentations

Since 1999, very high spatial resolution data represent the surface of the earth with more details. However, information extraction by computer-assisted classification techniques proves to be very complex owing to the internal variability increase in land-cover units and to the weakness of spectral resolution1, 2, 3. The increase in variability decreases the statistical separability of land-cover classes in the spectral space 4. Per pixel multispectral classification techniques are then insufficient for an extraction of complex categories and spectrally heterogeneous land-cover, like urban areas5. Per region classification was proposed as an alternative approach6, 7. The first step of this approach is the segmentation. A large variety of segmentation algorithms were developed these last 20 years8 and a comparison of their implementation on very high spatial resolution images is necessary. For this study, four algorithms from the two main groups of segmentation algorithms (boundary-based and region-based algorithms) were selected. In order to compare the algorithms, an evaluation of each algorithm was carried out with empirical discrepancy evaluation methods. This evaluation is carried out with a visual segmentation of IKONOS panchromatic images.

Distributed Source Coding of Multiview Images

Towards a Virtual 3D Reconstruction of a Rood-Screen from its Archaeological Fragments

An environment for the analysis and reconstruction of archaeological objects

3D orientation of archaeological fragments coming from a Gothic spire

Traumatology surgical intervention guided by virtual reality

Quality of experience and quality-obeisant energy-awareness in mobile 3D gfx

3D graphics rendering time modeling and control for mobile terminals

Optimization of Multiuser Camera Sensor Network for Arbitrary View Generation

2003

Optimization of Camera Sensor Network for Multiuser

Offset Block Matching for Ray Space Interpolation

Distributed Source Coding for Multi-view Images

Multi View Image Interpolation using Offset Block Matching

Distributed Source Coding for A Robust Camera Sensor Network

An Interpolation Method for Ray Space Data using Offset Blocks

An Adaptive Block Matching Method for Ray-Space Interpolation

Optimized Free View Generation in Camera Sensor Network

Distributed Processing Method for Arbitrary View Generation in Camera Sensor Network

Memory Compaction and Power Optimization for Wavelet-Based Coders

A framework for mapping scalable networked multimedia applications on run-time reconfigurable platforms

Terminal QoS: advanced resource management for cost-effective multimedia applications

Terminal QOS management on run-time reconfigurable platforms

Visual and Complexity Analysis of the Extended Loop Subdivision Scheme

Optimized memory requirements for wavelet-based scalable video codecs

2002

Decentralized Multi View Image Processing in Camera Sensor Network

Arbitrary View Generation using Decentralized Processing in Camera Sensor Network

A Coding Scheme for Multi View Images in Node-to-Center Communication

A Distributed Source Coding for ITS

Observed Information Relationship with Sensor Parameters In Sensor Network

Conception of a navigation system controlling the reduction of long bone fractures treated by external fixation

Wood Analyst©: A new image analysis software adapted for douglas-fir thin cross sections

Complexity Assessment of the AVC Codec with ATOMIUM

Cache misses and energy-dissipation results for JPEG2000 filtering

Initial Memory Complexity Analysis of the AVC Codec

Bitstream Syntax Description Language For 3D MPEG-4 View-Dependent Texture Streaming

Assessment of MPEG-4 VTC and JPEG2000 Dynamic Memory Requirements

A Fast QoS Adaptation Algorithm for MPEG-4 Multimedia Applications

A QoS Framework for Interactive 3D Applications

Real-time 3D applications on mobile platforms with run-time reconfigurable hardware accelerator

Reduced Memory Requirements in Modified JPEG2000 codec

Enabling multimedia QoS control with black-box modeling

Streaming MPEG-4 Textures: A 3D view-dependent approach

Scaling Bandwidth and Complexity of Hybrid MC/DCT Video Codecs

Scalable 3D Graphics Processing in Consumer Terminals

2001

A Local Wavelet Transform implementation versus an optimal Row-Column algorithm for the 2D multilevel decomposition

Real-time simulation of virtual objects impact with shattering

Limiting the Number of Trees in Random Forests

Adjusting the outputs of a classifier to new a priori probabilities may significantly improve classification accuracy: Evidence from a multi-class problem in remote sensing

Characterization of acting filaments in cancer cells by the Hough transform

Amélioration de l'interprétation numérique de l'occupation du sol

Remote Sensing Classification of Spectral, Spatial and Contextual Data Using Multiple Classifier Systems

High-Level cache modelling for 2D-discrete Wavelet Transform Implementations

MPEG-4 Visual Texture Coding: Variform, yet Temperately Complex

2000

Mixing Bagging and Multiple Feature Subsets to Improve Classification Accuracy of Decision Tree Combination

Different Ways of Weakening Decision Trees and Their Impact on Classification Accuracy of DT Combination

Virtual reality based on Conventional X-Rays

Fast software implementation of the MPEG-4 reversible integer wavelet transform on Pentium MMX, Sharc ADSP and Trimedia TM1000

3D Computational Graceful Degradation

1999

Building virtual 3D bone fragments models to control diaphyseal fracture reduction

Implementation of an integer wavelet transform on a parallel TI TMS320C40 platform

An Integer Wavelet Transform Implemented on a Parallel TI TMS320C40 Platform

A Scalable Architecture for MPEG-4 Embedded Zero Tree Coding

Efficient Implementation of Embedded Zero-Tree Wavelet Encoding

Implementation of a scalable MPEG-4 wavelet-based visual texture compression system

Power Exploration For Embedded Zero-Tree Wavelet Encoding

1998

Automatic objects selection in computer-assisted microscopy

A New Technique for Motion Estimation and Compensation of the Wavelet Detail Images

Methodological reduction of Memory Requirements for a VLSI Spaceborne Wavelet Compression Engine

Video Coding Based on Motion Estimation in the Wavelet Detail Images

Arithmetic complexity of Motion Estimation Algorithms

Design of an Arithmetic coder for a Hardware Wavelet compression engine

1997

Contour Image Coding Using Uniform Cubic B-Splines

1996

Two and three-dimensional processing of medical images on a personal computer

Implementation Aspects of FIR filtering in a Wavelet Compression Scheme

Space-filling curves in Advanced Image Compression applications

Reduction of the Memory Requirements for the VLSI implementation of the 2D-Inverse Fast Wavelet Transform, using a Space-filling Curve

1995

Comparisons of different RBF networks for pattern classification

Multiple-Knowledge Representation in Concept Learning

Towards Neuro-Fuzzy Defuzzification in Benelearn '95

Comparing RBF and fuzzy inference systems on theoretical and practical basis

Parallelization of the 2D Fast Wavelet Transform with a space-filling curve image scan

Low-power VLSI Architectures for the 2D Wavelet Transform in Image Compression applications

Chinese Remainder Theorem-based Algorithm for Convolution

A space-filling curve image-scan for the parallelization of the Two-Dimensional Fast Wavelet Transform

A Space-filling curve image scan for Low Power VLSI implementation of Wavelet Coding

A VLSI architecture for the 2-D wavelet transform with novel image scan

1994

Cognitive and Semantic interpretation of a NN classifier using prototypes

How to "secure" the decisions of a NN classifier

A fractal based Region Oriented Color image compression scheme suited for VLSI implementation

An ECG trigger module for the acquisition of cardiac MR Images

1993

Using prototypes to solve problems in neural net classifiers

NNP: a neural net classifier using prototypes

We present a three-layer neural net classifier for multiclass object recognition problems requiring piecewise nonlinear discriminant surfaces. The hidden layer is composed of prototypes of each class. The weights from the input to the hidden layer are the vector descriptions of prototypes (in the input feature space). The output layer neurons represent the classes, the hidden-to-output weights being binary and fixed. They map each prototype neuron to one of the class output neurons. Only the input-to-hidden weights are adapted by an algorithm using deterministic annealing and gradient descent techniques. This algorithm permits the distribution of prototypes in classes while minimising the classification error rate.

1991

Description Contrasting in Incremental Concept Formation

Statistical Strategies in Incremental Conceptual Classification

Incremental Classification, a Multidisciplinary Viewpoint

Chip Design at the Free University Brussels (VUB) : A start-up Experience

1990

Image processing and Application of CAD to the manufacture of prostheses

Formation de concepts en intelligence artificielle

Des des travaux précédents ([Decaes89 a,b][Decaes90]), l'auteure a étudié des mécanismes incrémentaux de "Formation de Concepts", et a développé ADECLU, un système incrémental de "Conceptual Clustering". Dans cet article, l'auteure présente les différentes version de ADECLU et les compare, du point de vue conceptuel et des performances, aux méthodes développées en Analyse Relationnelle (Agrégation et Bloc Sériation) [Marc81, 87][Mich87]

Neural Networks as a new Approach to Image Processing

1989

Incremental Concept Formation with Attribute Selection

Application of CAD / CAM in Prosthetics and Orthotics

Formation incrémentale de concepts par un critère d'adéquation

Application de la CAO. La conception et la fabrication de prothèses et d'orthèses

Application of the " CAD - CAM " in

Incremental concept formation via a suitability criterion

The Morphology of the ECG Measured in Magnetic Fields

1988

Philosophy and Application of CAD-CAM for Ortheses and Prostheses

Participations à des congrès et colloques internationaux

2023

Adaptive Changes in Heart Rate Variability and Cardiac Function during Long-term Spaceflight: Insights from Wearable Devices

Adaptive Changes in Heart Rate Variability and Cardiac Function during Long-term Spaceflight

2021

Un outil en ligne pour l'étude 3D de la sculpture ?

Panorama, une plateforme de recherche à l'ULB, et le projet USINE, webplaterforme3D pour l'étude collaborative de la sculpture

2020

From MPEG immersive video to holography

2017

Robust Disparity Estimation on Sparse Sampled Light Field Images

2016

Free Navigation and Immersive 3D

Keynote 3DTV-CON: Next-generation virtual and augmented reality exploration and standardization

The keynote presents developments over the past ten years in immersive media standards, as well as recent technological breakthroughs in next-generation virtual and augmented reality.For instance, ISO/IEC MPEG and ITU-T VCEG have recently issued the 3D-HEVC multiview video compression standard, which reaches unpreceded compression performances for coding the video streams captured with dense, linear camera arrangements. With the aim of supporting future, high-quality 3D light field displays and Free Navigation virtual/augmented reality applications with sparse, curvelinear camera setups, new coding and view synthesis rendering techniques should be developed.In view of the high challenges, MPEG and JPEG engage in defining a collaboration for developing these next-generation Virtual Reality standards, supporting 360 degree 3D video and virtual walkthrough applications with correct motion parallax and visual accomodation cues. Point Cloud and Light Field technologies are the select candidates to serve this purpose. Commonalities between these technologies will be presented, aiming at identifying the most promising exploration and standardization approaches.

2014

ADAM-17/FHL2 Colocalisation Suggests Interaction and Role of These Proteins in Colorectal Cancer

2010

Indoleamine 2,3-dioxygenase expression is an independent prognostic factor in pT1-4N1Mx staged colorectal cancer

2009

In vivo assessment of temozolomide delivery systems for inhalation therapy of lung cancer

In Vivo Assessment of Temozolomide Local Delivery for Lung Cancer Inhalation Therapy Nathalie Wauthoz, Philippe Deleuze, Julien Hecq, Isabelle Roland, Sven Saussez, Ivan Adanja, Olivier Debeir, Christine Decaestecker, Véronique Mathieu, Karim Amighi Laboratoire de Pharmacie Galénique et de Biopharmacie Director : Karim Amighi Abstract The aim of this study was to compare the efficacy of local drug delivery by inhalation to intravenous delivery in a B16F10 melanoma metastatic lung model. Temozolomide was formulated as a suspension, which was elaborated and evaluated in terms of particle size, shape and agglomeration. An endotracheal administration device was used to aerosolize the suspension. This mode of delivery was evaluated at different temozolomide concentrations and was optimized for the uniformity of delivered dose, the droplet size distribution and the distribution of droplets in vivo. Of the particles in the stabilized suspension, 79% were compatible with the human respirable size range, and this formulation retained 100% in vitro anticancer activity as compared to temozolomide alone in three distinct cancer cell lines. The pulmonary delivery device provided good reproducibility in terms of both the dose delivered and the droplet size distribution. Most of the lung tissues that were exposed to aerosol droplets contained the particles, as revealed by fluorescent microscopy techniques. The global in vivo antitumor activity of the inhaled temozolomide provided a median survival period similar to that for intravenous temozolomide delivery, and three out of twenty-seven mice (11%) survived with almost complete eradication of the lung tumours. The present study thus shows that inhalation of a simple liquid formulation is well tolerated and active against a very biologically aggressive mouse melanoma pulmonary pseudo-metastatic model. This inhalation delivery could be used to deliver other types of anticancer drugs.

2008

Aristolochic acid induces proximal tubule apoptosis, EMT and interstitial cell infiltration

Aristolochic acid induces proximal tubule apoptosis, epithelial to mesenchymal transformation and immuncompetents cells infiltration

2007

Early intratubular epithelial to mesenchymal transition (EMT) after aristolochic acid intoxication

From aristolochic acid intoxication to renal fibrosis

1990

Blocs Sériation de Matrices Binaires par Algorithme Génétique

Le but de cet article est de montrer que l'Algorithme Génétique ("Genetic Algorithms in Search, Optimization and Machine Learning", H. Goldberg, Addison Wesley, 1989.