Construction et exploration de configurations spatiales : comparaison experts-novices

This paper presents two experiments which the aim is to examine the effects of using Information New Technology (INT) on individual\u27s cognitive processing. The first experiment\u27s results show that level expertise didn\u27t affect processing capacities of working memory, neither visuo-spatial imagery abilities (for short-range forecasts). In return, data collected in the second experiment emphasize differences between expert and novice in the way of using INT, specially Internet web site. Indeed, experts implement systematic exploration strategies, which are regulated by semantical information processing

Spotting effect in microarray experiments

BACKGROUND: Microarray data must be normalized because they suffer from multiple biases. We have identified a source of spatial experimental variability that significantly affects data obtained with Cy3/Cy5 spotted glass arrays. It yields a periodic pattern altering both signal (Cy3/Cy5 ratio) and intensity across the array. RESULTS: Using the variogram, a geostatistical tool, we characterized the observed variability, called here the spotting effect because it most probably arises during steps in the array printing procedure. CONCLUSIONS: The spotting effect is not appropriately corrected by current normalization methods, even by those addressing spatial variability. Importantly, the spotting effect may alter differential and clustering analysis

A multiparameter panel method for outcome prediction following aneurysmal subarachnoid hemorrhage

Purpose: Accurate early anticipation of long-term irreversible brain damage during the acute phase of patients with aneurysmal subarachnoid hemorrhage (aSAH) remains difficult. Using a combination of clinical scores together with brain injury-related biomarkers (H-FABP, NDKA, UFD1 and S100β), this study aimed at developing a multiparameter prognostic panel to facilitate early outcome prediction following aSAH. Methods: Blood samples of 141 aSAH patients from two separated cohorts (sets of 28 and 113 patients) were prospectively enrolled and analyzed with 14months of delay. Patients were admitted within 48h following aSAH onset. A venous blood sample was withdrawn within 12h after admission. H-FABP, NDKA, UFD1, S100β and troponin I levels were determined using classical immunoassays. The World Federation of Neurological Surgeons (WFNS) at admission and the Glasgow Outcome Score (GOS) at 6months were evaluated. Results: In the two cohorts, blood concentration of H-FABP, S100β and troponin I at admission significantly predicted unfavorable outcome (GOS 1-2-3). A multivariate analysis identified a six-parameter panel, including WFNS, H-FABP, S100β, troponin I, NDKA and UFD-1; when at least three of these parameters were simultaneously above cutoff values, prediction of unfavorable outcome reached around 70% sensitivity in both cohorts for 100% specificity. Conclusion: The use of this panel, including four brain injury-related proteins, one cardiac marker and a clinical score, could be a valuable tool to identify aSAH patients at risk of poor outcom

La villa des « Vernes » à La Boisse (Ain) : contribution des fouilles récentes à la compréhensionde l’évolution d’un établissement rural antique et de son espace funéraire

Dans le cadre de l’aménagement d’un diffuseur autoroutier sur la commune de La Boisse (Ain), à une vingtaine de kilomètres au nord-est de Lyon, une opération d’archéologie préventive, réalisée en 2005-2006, a permis d’enrichir la documentation d’une villa du Ier s. après J.-C. Si une partie de cet établissement avait déjà été explorée en 1980 lors de la construction de l’autoroute A42, la fouille a permis de compléter le plan de la pars urbana, et surtout de préciser la datation de l’occupation gallo-romaine. Cette villa de plan classique n’est en effet pas une création ex nihilo ; elle a succédé à deux ensembles architecturaux antérieurs, caractérisés par des constructions en terre et bois. La villa a été abandonnée à l’extrême fin du Ier s. ap. J.-C. ou au début du siècle suivant. Deux structures isolées à caractère funéraire qui, par leur richesse, constituent un unicum régional, sont aussi datées de cette période.As part of the construction of a motorway interchange in the municipality of La Boisse (Ain), about twenty kilometres north-east of Lyon, a preventive archaeology project carried out in 2005–2006 furnished additional information about a villa built in the 1st century AD. Whereas a section of the site had already been explored during the construction of the A42 motorway, the latter excavation not only enabled the plan of the pars urbana to be completed and, above all, it allowed the dating of the Gallo-Roman occupation to be made with precision. This classically laid out villa was not an ex nihiloconstruction: it had been built over two earlier sets of architectural buildings made from wood and mud. The villa was abandoned at the extreme end of the 1st century AD or at the start of the following century. Two isolated, apparently funerary structures – which, through the wealth of their contents, are unique for the region – have also been dated to the same period.Im Rahmen des Baus eines Autobahnverteilers auf dem Gebiet der Gemeinde La Boisse (Departement Ain) etwa 20 km nordöstlich von Lyon, konnte durch eine 2005-2006 durchgeführte Präventivgrabung die Dokumentation einer villa des 1. Jh. n. Chr. bereichert werden. Ein Teil dieses Areals war bereits 1980 anlässlich des Baus der Autobahn A42 erforscht worden, doch die neue Grabung bot Gelegenheit, den Grundriss der pars urbana zu ergänzen, und vor allem die Datierung der gallo-römischen Phase zu präzisieren. Diese villa mit klassischem Grundriss war in der Tat keine Gründung ex nihilo ; sondern sie folgte auf zwei Vorgängerbauten in Holz-Erde-Bauweise. Die villa wurde Ende des 1. Jh. n. Chr. oder Anfang des folgenden Jahrhunderts aufgegeben. Zwei isolierte Grabstrukturen, deren Reichtum in der Region einzig ist, werden ebenfalls in diese Zeit datiert

Multilineage Differentiation for Formation of Innervated Skeletal Muscle Fibers from Healthy and Diseased Human Pluripotent Stem Cells.

Induced pluripotent stem cells (iPSCs) obtained by reprogramming primary somatic cells have revolutionized the fields of cell biology and disease modeling. However, the number protocols for generating mature muscle fibers with sarcolemmal organization using iPSCs remain limited, and partly mimic the complexity of mature skeletal muscle. Methods: We used a novel combination of small molecules added in a precise sequence for the simultaneous codifferentiation of human iPSCs into skeletal muscle cells and motor neurons. Results: We show that the presence of both cell types reduces the production time for millimeter-long multinucleated muscle fibers with sarcolemmal organization. Muscle fiber contractions are visible in 19-21 days, and can be maintained over long period thanks to the production of innervated multinucleated mature skeletal muscle fibers with autonomous cell regeneration of PAX7-positive cells and extracellular matrix synthesis. The sequential addition of specific molecules recapitulates key steps of human peripheral neurogenesis and myogenesis. Furthermore, this organoid-like culture can be used for functional evaluation and drug screening. Conclusion: Our protocol, which is applicable to hiPSCs from healthy individuals, was validated in Duchenne Muscular Dystrophy, Myotonic Dystrophy, Facio-Scapulo-Humeral Dystrophy and type 2A Limb-Girdle Muscular Dystrophy, opening new paths for the exploration of muscle differentiation, disease modeling and drug discovery

HER3 as biomarker and therapeutic target in pancreatic cancer: new insights in pertuzumab therapy in preclinical models.

International audienceThe anti-HER2 antibody pertuzumab inhibits HER2 dimerization and affects HER2/HER3 dimer formation and signaling. As HER3 and its ligand neuregulin are implicated in pancreatic tumorigenesis, we investigated whether HER3 expression could be a predictive biomarker of pertuzumab efficacy in HER2low-expressing pancreatic cancer. We correlated in vitro and in vivo HER3 expression and neuregulin dependency with the inhibitory effect of pertuzumab on cell viability and tumor progression. HER3 knockdown in BxPC-3 cells led to resistance to pertuzumab therapy. Pertuzumab treatment of HER3-expressing pancreatic cancer cells increased HER3 at the cell membrane, whereas the anti-HER3 monoclonal antibody 9F7-F11 down-regulated it. Both antibodies blocked HER3 and AKT phosphorylation and inhibited HER2/HER3 heterodimerization but affected differently HER2 and HER3 homodimers. The pertuzumab/9F7-F11 combination enhanced tumor inhibition and the median survival time in mice xenografted with HER3-expressing pancreatic cancer cells. Finally, HER2 and HER3 were co-expressed in 11% and HER3 alone in 27% of the 45 pancreatic ductal adenocarcinomas analyzed by immunohistochemistry. HER3 is essential for pertuzumab efficacy in HER2low-expressing pancreatic cancer and HER3 expression might be a predictive biomarker of pertuzumab efficacy in such cancers. Further studies in clinical samples are required to confirm these findings and the interest of combining anti-HER2 and anti-HER3 therapeutic antibodies

A Combined CXCL10, CXCL8 and H-FABP Panel for the Staging of Human African Trypanosomiasis Patients

The actual serological and parasitological tests used for the diagnosis of human African trypanosomiasis (HAT), also known as sleeping sickness, are not sensitive and specific enough. The card agglutination test for trypanosomiasis (CATT) assay, widely used for the diagnosis, is restricted to the gambiense form of the disease, and parasitological detection in the blood and cerebrospinal fluid (CSF) is often very difficult. Another very important problem is the difficulty of staging the disease, a crucial step in the decision of the treatment to be given. While eflornithine is difficult to administer, melarsoprol is highly toxic with incidences of reactive encephalopathy as high as 20%. Staging, which could be diagnosed as early (stage 1) or late (stage 2), relies on the examination of CSF for the presence of parasite and/or white blood cell (WBC) counting. However, the parasite is rarely found in CSF and WBC count is not standardised (cutoff set between 5 and 20 WBC per µL). In the present study, we hypothesized that an early detection of stage 2 patients with one or several proteins in association with clinical evaluation and WBC count would improve staging accuracy and allow more appropriate therapeutic interventions