Sema3E/Plexin-D1 Mediated Epithelial-to-Mesenchymal Transition in Ovarian Endometrioid Cancer

Cancer cells often employ developmental cues for advantageous growth and metastasis. Here, we report that an axon guidance molecule, Sema3E, is highly expressed in human high-grade ovarian endometrioid carcinoma, but not low-grade or other ovarian epithelial tumors, and facilitates tumor progression. Unlike its known angiogenic activity, Sema3E acted through Plexin-D1 receptors to augment cell migratory ability and concomitant epithelial-to-mesenchymal transition (EMT). Sema3E-induced EMT in ovarian endometrioid cancer cells was dependent on nuclear localization of Snail1 through activation of phosphatidylinositol-3-kinase and ERK/MAPK. RNAi-mediated knockdown of Sema3E, Plexin-D1 or Snail1 in Sema3E-expressing tumor cells resulted in compromised cell motility, concurrent reversion of EMT and diminished nuclear localization of Snail1. By contrast, forced retention of Snail1 within the nucleus of Sema3E-negative tumor cells induced EMT and enhanced cell motility. These results show that in addition to the angiogenic effects of Sema3E on tumor vascular endothelium, an EMT strategy could be exploited by Sema3E/Plexin-D1 signaling in tumor cells to promote cellular invasion/migration

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

Molecular and pathological signatures of epithelial–mesenchymal transitions at the cancer invasion front

Reduction of epithelial cell–cell adhesion via the transcriptional repression of cadherins in combination with the acquisition of mesenchymal properties are key determinants of epithelial–mesenchymal transition (EMT). EMT is associated with early stages of carcinogenesis, cancer invasion and recurrence. Furthermore, the tumor stroma dictates EMT through intensive bidirectional communication. The pathological analysis of EMT signatures is critically, especially to determine the presence of cancer cells at the resection margins of a tumor. When diffusion barriers disappear, EMT markers may be detected in sera from cancer patients. The detection of EMT signatures is not only important for diagnosis but can also be exploited to enhance classical chemotherapy treatments. In conclusion, further detailed understanding of the contextual cues and molecular mediators that control EMT will be required in order to develop diagnostic tools and small molecule inhibitors with potential clinical implications

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Impact d'évènements extrêmes sur des dispositifs houlomoteur adossés à des structures de protection côtière

The present work aims to describe and evaluate the loads exerted by severe breaking waves onto coastal protection structures. To carry on with this investigation, the numerical tool-box OpenFOAM is employed and the problematic is regarded from different perspectives. First, the physics of an idealised impulsive event between a fluid and a solid is investigated using different configurations. The associated simulations are designed to study the role of air during these academic impact configurations. Secondly, a solitary wave is used to evaluate the performance of the solver to reproduce realistic wave breaking onto a vertical wall and evaluate the related impact pressure records. The computed results are validated against experimental data previously obtained at IRPHE, Marseille (France). Finally, an irregular sea state is simulated using large spatial and temporal scales to evaluate the induced wave loads on an oscillating water column structure. These simulations are compared and validated with experimental results obtained in the large flume tank (GWK) at Hanover (Germany).Ce travail a pour objectif de décrire et évaluer les impacts de vagues extrêmes sur des structures de protection côtière. Dans le cadre de ces recherches, la suite logicielle OpenFOAM est utilisée et la problématique est étudiée suivant différentes perspectives. Dans un premier temps, la physique d'un événement impulsif idéalisé entre un fluide et un solide est étudiée en utilisant différentes configurations. Les simulations associées sont conçues pour étudier le rôle de l’air durant ces configurations d'impact académiques. Deuxièmement, une vague solitaire est utilisée pour évaluer la performance du solveur afin de reproduire des impacts de vague réalistes sur un mur vertical et d'évaluer les pressions d’impact associées. Les résultats numériques sont validés à l’aide de données expérimentales obtenues antérieurement à l'IRPHE, Marseille (France) . Enfin, un état de mer irrégulier est simulé en utilisant une large gamme d'échelles spatiales et temporelles afin d'évaluer les chargement induits par ces vagues sur une structure de colonne d’eau oscillante. Ces simulations sont comparées et validées avec des résultats expérimentaux obtenus dans le grand canal à houle GWK de Hannovre (Allemagne)

Impact d'évènements extrêmes sur des dispositifs houlomoteur adossés à des structures de protection côtière

The present work aims to describe and evaluate the loads exerted by severe breaking waves onto coastal protection structures. To carry on with this investigation, the numerical tool-box OpenFOAM is employed and the problematic is regarded from different perspectives. First, the physics of an idealised impulsive event between a fluid and a solid is investigated using different configurations. The associated simulations are designed to study the role of air during these academic impact configurations. Secondly, a solitary wave is used to evaluate the performance of the solver to reproduce realistic wave breaking onto a vertical wall and evaluate the related impact pressure records. The computed results are validated against experimental data previously obtained at IRPHE, Marseille (France). Finally, an irregular sea state is simulated using large spatial and temporal scales to evaluate the induced wave loads on an oscillating water column structure. These simulations are compared and validated with experimental results obtained in the large flume tank (GWK) at Hanover (Germany).Ce travail a pour objectif de décrire et évaluer les impacts de vagues extrêmes sur des structures de protection côtière. Dans le cadre de ces recherches, la suite logicielle OpenFOAM est utilisée et la problématique est étudiée suivant différentes perspectives. Dans un premier temps, la physique d'un événement impulsif idéalisé entre un fluide et un solide est étudiée en utilisant différentes configurations. Les simulations associées sont conçues pour étudier le rôle de l’air durant ces configurations d'impact académiques. Deuxièmement, une vague solitaire est utilisée pour évaluer la performance du solveur afin de reproduire des impacts de vague réalistes sur un mur vertical et d'évaluer les pressions d’impact associées. Les résultats numériques sont validés à l’aide de données expérimentales obtenues antérieurement à l'IRPHE, Marseille (France) . Enfin, un état de mer irrégulier est simulé en utilisant une large gamme d'échelles spatiales et temporelles afin d'évaluer les chargement induits par ces vagues sur une structure de colonne d’eau oscillante. Ces simulations sont comparées et validées avec des résultats expérimentaux obtenus dans le grand canal à houle GWK de Hannovre (Allemagne)

Numerical simulation of water waves impact on near-shore defensive structures

International audienc

Computations of soliton impact onto a vertical wall: Comparing incompressible and compressible assumption with experimental validation

International audienceThis paper present numerical computations of solitary wave impact on a vertical wall. Different wave breaking cases were studied such as the high-aerated (air-pocket) or low-aerated (flip-through) in order to test the software ability to accurately reproduce the generated wall pressure loads. The numerical toolbox OpenFOAM was used here under the incompressible and compressible assumptions, together with 2D and 3D configurations. First, an idealised test case was used to validate the numerical convergence on an analytical value of the pressure impulse. Pressure impulse convergence was always numerically obtained but the pressure levels never converged under the incompressible assumption. Switching to the compressible assumption, pressure impulse and pressure time series converged both on the idealised test case and on the experimental configuration used. A large variety of spatial and temporal pressure variations were highlighted in this study that enable some physical interpretation of the impact mechanism.

Flat plate pressure impact on a still water surface: The effect of surrounding ambient pressure and plate size

International audienceThe study of the impact between a rigid structure and water has raised the interest of many researchers in these recent years. This problem is relevant to various engineering applications, and particularly in the nautical environment (renewable energy, marine applications...). The present paper details an experimental investigation of rigid circular plates impacts into pure water. The analyses are based on impact pressure temporal signals, pressure impulses and frequency analysis recorded while the plates were impinging the still water surface. The measurement campaigns were carried out at the University Le Havre Normandy’s LOMC laboratory, in a recently developed experimental facility. In the previous experimental and numerical studies, it was observed that the magnitude of the peak slamming pressure is reduced if compared to the theoretical model predicted by von Karman (1929). Similar observations were made here and the decrease was partly attributed to the cushion effect resulting from the presence of an entrapped air layer between the rigid plate and the water free surface. This work aims to study the influence of the cushion effect on the impact pressure by using four rigid circular plates with different diameters in order to modify the volume of the air layer. Initially, the measurements were carried out for an ambient pressure equal to the atmospheric pressure. In a second part of the study, the same measurements were performed for two lower ambient pressures (about 75% and 50% of the atmospheric pressure) in order to minimise the cushion effect. And finally, a frequency analysis is presented with comparisons to theoretical results of Minnaert (1933) in order to correlate the air layer size to the pressure oscillation characteristics. The obtained results were compared with previous experimental and theoretical studies for low impact velocitie

Computations of pressure loads on an oscillating water column with experimental comparison for random waves

International audienceThis paper presents numerical investigations with experimental comparisons of random wave induced loads on the external walls of a large scale Oscillating Water Column (OWC) device. The objective is to investigate the capability of a numerical model that uses the Reynolds Averaged Navier–Stokes (RANS) equations to accurately reproduce extreme wave loads on an OWC. Both incompressible and compressible approximations for the RANS equations are studied in this work with the aim of investigating the limitations of both approaches. After a first characterisation of the random wave propagation processes at the numerical flume, wave loads are analysed. An OWC power take-off (PTO) and in-chamber air compressibility effects are studied using regular waves. Next, an OWC facing irregular waves is studied and compared with experimental data, putting special emphasis on the extreme loads together with the stochastic nature of random waves. The simulation of extreme wave loads on an OWC is validated and the necessity of a compressible model for correct reproduction of an OWC in-chamber flow for certain operating conditions of the PTO is pointed out from the simulations