24 research outputs found

    User-centered visual analysis using a hybrid reasoning architecture for intensive care units

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    One problem pertaining to Intensive Care Unit information systems is that, in some cases, a very dense display of data can result. To ensure the overview and readability of the increasing volumes of data, some special features are required (e.g., data prioritization, clustering, and selection mechanisms) with the application of analytical methods (e.g., temporal data abstraction, principal component analysis, and detection of events). This paper addresses the problem of improving the integration of the visual and analytical methods applied to medical monitoring systems. We present a knowledge- and machine learning-based approach to support the knowledge discovery process with appropriate analytical and visual methods. Its potential benefit to the development of user interfaces for intelligent monitors that can assist with the detection and explanation of new, potentially threatening medical events. The proposed hybrid reasoning architecture provides an interactive graphical user interface to adjust the parameters of the analytical methods based on the users' task at hand. The action sequences performed on the graphical user interface by the user are consolidated in a dynamic knowledge base with specific hybrid reasoning that integrates symbolic and connectionist approaches. These sequences of expert knowledge acquisition can be very efficient for making easier knowledge emergence during a similar experience and positively impact the monitoring of critical situations. The provided graphical user interface incorporating a user-centered visual analysis is exploited to facilitate the natural and effective representation of clinical information for patient care

    Activation of mutated TRPA1 ion channel by resveratrol in human prostate cancer associated fibroblasts (CAF)

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    Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, endothelial cells, blood cells and cancer-associated fibroblasts (CAF), the main source of growth factors. The latter cells might modify in the TME the impact of RES on tumor cells via secreted factors. Recent data clearly show the impact of CAF on cancer cells apoptosis resistance via secreted factors. However, the effects of RES on PCa CAF have not been studied so far. We have investigated here for the first time the effects of RES on the physiology of PCa CAF in the context of TME. Using a prostate cancer CAF cell line and primary cultures of CAF from prostate cancers, we show that RES activates the N-terminal mutated Transient Receptor Potential Ankyrin 1 (TRPA1) channel leading to an increase in intracellular calcium concentration and the expression and secretion of growth factors (HGF and VEGF) without inducing apoptosis in these cells. Interestingly, in the present work, we also show that when the prostate cancer cells were co-cultured with CAF, the RES-induced cancer cell apoptosis was reduced by 40%, an apoptosis reduction canceled in the presence of the TRPA1 channel inhibitors. The present work highlights CAF TRPA1 ion channels as a target for RES and the importance of the channel in the epithelial-stromal crosstalk in the TME leading to resistance to the RES-induced apoptosis

    Une occupation mĂ©diĂ©vale Ă  Neuilly-la-ForĂȘt (Calvados)

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    A trial excavation in advance of construction of the new D195 revealed of a stone building. Sample excavation of the occupation levels and of a pit produced pottery of the XIth-XIIth centuries.Dans le cadre du diagnostic archĂ©ologique rĂ©alisĂ© sur le futur tracĂ© de la route dĂ©partementale 195, les restes d'un bĂątiment en pierre ont Ă©tĂ© mis au jour. La fouille d'un lambeau de son sol d'occupation et d'une fosse silo a permis l'Ă©tude d'un petit corpus cĂ©ramique, constituĂ© principalement de ouĂŻes, datĂ© des XIĂšme-XIIĂšme siĂšcles.Marcigny Cyril, Paez-Rezende Laurent, Allart Eric, De Saint Jores Jean-Xavier. Une occupation mĂ©diĂ©vale Ă  Neuilly-la-ForĂȘt (Calvados). In: Revue archĂ©ologique de l'ouest, tome 13, 1996. pp. 169-176

    Involvement of Ion Channels in Endothelin-1-induced Signalling in Human Prostate Cancer Cells

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    Objective: Endothelin-1 (ET-1), a potent vasoconstrictor secreted primarily by endothelial and various epithelial cancercells has been implicated in prostate cancer progression and the ET axis has been suggested to represent a novel andexciting target in the treatment of prostate cancer (PCa). ET-1, acting primarily through the endothelin receptors (ETRs)is integrally involved in multiple facets of PCa progression, including cell growth, inhibition of apoptosis, angiogenesis anddevelopment of bone metastases. ET-1 and ETRs are expressed in PCa tissues and their expression is modulated duringthe evolution of these cancers. The purpose of the present work was to study the effects of ET-1 on proliferation of humanPCa cells PC-3 and the mechanisms by which the activation of ETRs may promote the PCa cells growth.Methods: Prostate cancer cell lines and primary cultured epithelial cells from prostate cancer, RT-PCR and calciumimaging techniques were used to study the expression and functionality of the Endothelin receptors and involvement ofion channels in the effects of ET-1 in prostate cancer cells.Results: We show for the first time that the application of ET-1 induces a dose-dependent cell proliferation andan increase in intracellular free Ca2+ concentrations ([Ca2+]i) via a mobilisation of the internal calcium stores and bya capacitative calcium entry (CCE). These effects of ET-1 were completely abolished by BQ123, a selective ETARantagonist, but not by BQ788, a selective ETBR antagonist. By use of pharmacological inhibitors and siRNA targetingcalcium-activated (IKCa1 and BKCa) potassium channels and calcium channels (TRPC1, TRPV6, Orai1), we showedthat these ion channels play an important role in calcium entry and cell proliferation induced by ET-1 in PCa cells.Conclusion: These results suggest that these ions channels evidenced here might constitute potential targets toblock the ET axis in human prostate cancers

    Characterization of Human Colon Organoids From Inflammatory Bowel Disease Patients

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    International audienceInflammatory Bowel Diseases (IBD) are chronic inflammatory disorders, where epithelial defects drive, at least in part, some of the pathology. We reconstituted human intestinal epithelial organ, by using three-dimension culture of human colon organoids. Our aim was to characterize morphological and functional phenotypes of control (non-IBD) organoids, compared to inflamed organoids from IBD patients. The results generated describe the epithelial defects associated with IBD in primary organoid cultures, and evaluate the use of this model for pharmacological testing of anti-inflammatory approaches. Human colonic tissues were obtained from either surgical resections or biopsies, all harvested in non-inflammatory zones. Crypts were isolated from controls (non-IBD) and IBD patients and were cultured up to 12-days. Morphological (size, budding formation, polarization, luminal content), cell composition (proliferation, differentiation, immaturity markers expression), and functional (chemokine and tight junction protein expression) parameters were measured by immunohistochemistry, RT-qPCR or western-blot. The effects of inflammatory cocktail or anti-inflammatory treatments were studied in controls and IBD organoid cultures respectively. Organoid cultures from controls or IBD patients had the same cell composition after 10 to 12-days of culture, but IBD organoid cultures showed an inflammatory phenotype with decreased size and budding capacity, increased cell death, luminal debris, and inverted polarization. Tight junction proteins were also significantly decreased in IBD organoid cultures. Inflammatory cytokine cocktail reproduced this inflammatory phenotype in non-IBD organoids. Clinically used treatments (5-ASA, glucocorticoids, anti-TNF) reduced some, but not all parameters. Inflammatory phenotype is associated with IBD epithelium, and can be studied in organoid cultures. This model constitutes a reliable human pre-clinical model to investigate new strategies targeting epithelial repair

    Transient Receptor Potential Channel Expression Signatures in Tumor-Derived Endothelial Cells: Functional Roles in Prostate Cancer Angiogenesis

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    International audienceTransient receptor potential (TRP) channels control multiple processes involved in cancer progression by modulating cell proliferation, survival, invasion and intravasation, as well as, endothelial cell (EC) biology and tumor angiogenesis. Nonetheless, a complete TRP expression signature in tumor vessels, including in prostate cancer (PCa), is still lacking. Methods: In the present study, we profiled by qPCR the expression of all TRP channels in human prostate tumor-derived ECs (TECs) in comparison with TECs from breast and renal tumors. We further functionally characterized the role of the ‘prostate-associated’ channels in proliferation, sprout formation and elongation, directed motility guiding, as well as in vitro and in vivo morphogenesis and angiogenesis. Results: We identified three ‘prostate-associated’ genes whose expression is upregulated in prostate TECs: TRPV2 as a positive modulator of TEC proliferation, TRPC3 as an endothelial PCa cell attraction factor and TRPA1 as a critical TEC angiogenic factor in vitro and in vivo. Conclusions: We provide here the full TRP signature of PCa vascularization among which three play a profound effect on EC biology. These results contribute to explain the aggressive phenotype previously observed in PTEC and provide new putative therapeutic targets

    Reconstruire le Nord – Pas-de-Calais aprùs la Seconde Guerre mondiale (1944-1958)

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    De 1940 Ă  la fin du second conflit mondial, le Nord et le Pas-de-Calais subissent plusieurs vagues de destruction. Reconstruire la rĂ©gion est un processus complexe, d'autant que la guerre aggrave une situation dĂ©jĂ  difficile – dĂšs 1939 de nombreuses villes nordistes avaient dĂ©jĂ  besoin de se moderniser. Relever les ruines ne suffit pas, un immense effort d'Ă©dification d’infrastructures et de logements neufs s’impose. Cependant, les rĂ©sultats d’une telle entreprise apparaissent mitigĂ©s : la lenteur de cette seconde Reconstruction condamne beaucoup d’habitants Ă  vivre des annĂ©es dans des bĂątiments provisoires et de surcroĂźt peu esthĂ©tiques. Faut-il rĂ©viser ce jugement stylistique ? Le bilan Ă©conomique semble tout aussi incertain. Les dĂ©fis Ă©taient peut-ĂȘtre trop importants pour une rĂ©gion ravagĂ©e deux fois en une gĂ©nĂ©ration. Mais les principes adoptĂ©s pour le relĂšvement de l’économie ne portent-ils pas aussi leur part de responsabilitĂ©

    Projet Collectif de Recherches PALEHAUTS. Enrichissement du cadre chronostratigraphique et archéologique des sites paléolithiques historiquement et récemment découverts en Hauts-de-France. Bilan de l'année probatoire 2018

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    Ce rapport de dĂ©compose en trois sections, la premiĂšre rassemble la documentation administrative, la seconde rappelle la problĂ©matique gĂ©nĂ©rale du projet, prĂ©sente les rĂ©sultats obtenus lors de l’annĂ©e probatoire 2018 et le bilan, la derniĂšre section regroupe diffĂ©rents inventaires et compte-rendu derĂ©unions. Sauf mention contraire les textes et la mise en page sont rĂ©alisĂ©s par Emilie Goval
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