Dimension matters when modeling network communities in hyperbolic spaces

Over the last decade, random hyperbolic graphs have proved successful in providing geometric explanations to many key properties of real-world networks, including strong clustering, high navigability, and heterogeneous degree distributions. Although a few studies have shown that hyperbolic models can generate community structures, another salient feature observed in real networks, we argue that the current models are overlooking the choice of the latent space dimensionality that is required to adequately represent data with communities. We show that there is an important qualitative difference between the lowest-dimensional model and its higher-dimensional counterparts with respect to how similarity between nodes restricts connection probabilities. Since more dimensions also increases the number of nearest neighbors for angular clusters representing communities, considering only one more dimension allows us to generate more realistic and diverse community structures

Has Toxicity Testing Moved into the 21st Century? A Survey and Analysis of Perceptions in the Field of Toxicology.

BackgroundTen years ago, leaders in the field of toxicology called for a transformation of the discipline and a shift from primarily relying on traditional animal testing to incorporating advances in biotechnology and predictive methodologies into alternative testing strategies (ATS). Governmental agencies and academic and industry partners initiated programs to support such a transformation, but a decade later, the outcomes of these efforts are not well understood.ObjectivesWe aimed to assess the use of ATS and the perceived barriers and drivers to their adoption by toxicologists and by others working in, or closely linked with, the field of toxicology.MethodsWe surveyed 1,381 toxicologists and experts in associated fields regarding the viability and use of ATS and the perceived barriers and drivers of ATS for a range of applications. We performed ranking, hierarchical clustering, and correlation analyses of the survey data.ResultsMany respondents indicated that they were already using ATS, or believed that ATS were already viable approaches, for toxicological assessment of one or more end points in their primary area of interest or concern (26-86%, depending on the specific ATS/application pair). However, the proportions of respondents reporting use of ATS in the previous 12 mo were smaller (4.5-41%). Concern about regulatory acceptance was the most commonly cited factor inhibiting the adoption of ATS, and a variety of technical concerns were also cited as significant barriers to ATS viability. The factors most often cited as playing a significant role (currently or in the future) in driving the adoption of ATS were the need for expedited toxicology information, the need for reduced toxicity testing costs, demand by regulatory agencies, and ethical or moral concerns.ConclusionsOur findings indicate that the transformation of the field of toxicology is partly implemented, but significant barriers to acceptance and adoption remain. https://doi.org/10.1289/EHP1435

Control of light transmission through opaque scattering media in space and time

We report the first experimental demonstration of combined spatial and temporal control of light trajectories through opaque media. This control is achieved by solely manipulating spatial degrees of freedom of the incident wavefront. As an application, we demonstrate that the present approach is capable to form bandwidth-limited ultrashort pulses from the otherwise randomly transmitted light with a controllable interaction time of the pulses with the medium. Our approach provides a new tool for fundamental studies of light propagation in complex media and has potential for applications for coherent control, sensing and imaging in nano- and biophotonics

Implication du PAR-2 dans le remodelage musculaire lisse bronchique de la physiopathologie de l'asthme

La cellule musculaire lisse (CML) a un rôle pivot dans la physiopathologie de l asthme. Dans ce travail de thèse nous avons pu mettre en avant l implication du récepteur de type 2 activé par les protéases (PAR-2) dans une composante majeure du remodelage bronchique : la prolifération musculaire lisse. Dans le premier travail, nous avons montré une augmentation de l expression du PAR-2 au niveau des CML bronchiques d asthmatiques in vitro. La réponse calcique est dépendante du niveau d expression du récepteur, mais n influence pas la réponse proliférante. La stimulation répétée du PAR-2 augmente la prolifération des seules CML d asthmatiques, par un mécanisme dépendant de la voie ERK. Dans le second travail, nous avons montré que la production basale d un épithélium reconstitué entraine une prolifération plus importante des CML d asthmatiques comparée aux CML de témoins. Une augmentation supplémentaire de la prolifération des seules CML d asthmatiques a été observée, après activation par le surnageant d épithélium stimulé par des acariens de maison comparé au surnageant épithélial non stimulé. Ce mécanisme est dépendant du PAR-2 épithélial, qui induit la production de leucotriènes C4, sur des CML dont l expression du récepteur (CysLTR1) est augmentée chez l asthmatique. Ces résultats apportent de nouvelles connaissances dans le remodelage musculaire lisse bronchique de l asthmatique et met en avant le PAR-2 comme cible thérapeutique potentielle.Smooth muscle cells (SMC) play an important role in asthma pathophysiology. In this thesis, we have highlighted the involvement of protease activated receptor type-2 (PAR-2) in SMC proliferation, which is a major component of airway remodeling. In the first study, we have shown an increased expression of PAR-2 in asthmatic bronchial SMC in vitro. Calcium response is dependent on the expression level of PAR-2, which does not affect the proliferative response. Repeated stimulation of PAR-2 increases the proliferation of asthmatics SMC only, by an ERK-dependent mechanism. In the second study, we have demonstrated that the basal production of reconstituted epithelium leads to a greater proliferation of asthmatics SMC compared to controls. Increased proliferation of asthmatics SMC only was observed, after stimulation with supernatant of the epithelium stimulated by house dust mites (HDM) compared to unstimulated epithelial supernatant. This mechanism is epithelial PAR-2-dependent, which induces the production of leukotrienes C4, whose receptor expression (CysLTR1) is increased in asthmatics SMC. These results provide new insights into bronchial smooth muscle remodeling in asthma and highlights the PAR-2 as a potential therapeutic target.BORDEAUX2-Bib. électronique (335229905) / SudocBORDEAUX1-Bib.electronique (335229901) / SudocSudocFranceF

Sensitivity of the correlation between the depth of shower maximum and the muon shower size to the cosmic ray composition

The composition of ultra-high energy cosmic rays is an important issue in astroparticle physics research, and additional experimental results are required for further progress. Here we investigate what can be learned from the statistical correlation factor r between the depth of shower maximum and the muon shower size, when these observables are measured simultaneously for a set of air showers. The correlation factor r contains the lowest-order moment of a two-dimensional distribution taking both observables into account, and it is independent of systematic uncertainties of the absolute scales of the two observables. We find that, assuming realistic measurement uncertainties, the value of r can provide a measure of the spread of masses in the primary beam. Particularly, one can differentiate between a well-mixed composition (i.e., a beam that contains large fractions of both light and heavy primaries) and a relatively pure composition (i.e., a beam that contains species all of a similar mass). The number of events required for a statistically significant differentiation is ~ 200. This differentiation, though diluted, is maintained to a significant extent in the presence of uncertainties in the phenomenology of high energy hadronic interactions. Testing whether the beam is pure or well-mixed is well motivated by recent measurements of the depth of shower maximum.Comment: Accepted for publication in Astroparticle Physics, LA-UR-12-2008

A C. elegans Screening Platform for the Rapid Assessment of Chemical Disruption of Germline Function

Background: Despite the developmental impact of chromosome segregation errors, we lack the tools to assess environmental effects on the integrity of the germline in animals. Objectives: We developed an assay in Caenorhabditis elegans that fluorescently marks aneuploid embryos after chemical exposure. Methods: We qualified the predictive value of the assay against chemotherapeutic agents as well as environmental compounds from the ToxCast Phase I library by comparing results from the C. elegans assay with the comprehensive mammalian in vivo end point data from the ToxRef database. Results: The assay was highly predictive of mammalian reproductive toxicities, with a 69% maximum balanced accuracy. We confirmed the effect of select compounds on germline integrity by monitoring germline apoptosis and meiotic progression. Conclusions: This C. elegans assay provides a comprehensive strategy for assessing environmental effects on germline function

3He/4He Ratio in Olivines from Linosa, Ustica, and Pantelleria Islands (Southern Italy)

We report helium isotope data for 0.03–1 Ma olivine-bearing basaltic hawaiites from three volcanoes of the southern Italy magmatic province (Ustica, Pantelleria, and Linosa Islands). Homogenous H3e/H4e ratios (range: 7.3–7.6 Ra) for the three islands, and their similarity with the ratio of modern volcanic gases on Pantelleria, indicate a common magmatic end-member. In particular, Ustica (7.6±0.2 Ra) clearly differs from the nearby Aeolian Islands Arc volcanism, despite its location on the Tyrrhenian side of the plate boundary. Although limited in size, our data set complements the large existing database for helium isotope in southern Italy and adds further constraints upon the spatial extent of intraplate alkaline volcanism in southern Mediterranea. As already discussed by others, the He-Pb isotopic signature of this magmatic province indicates a derivation from a mantle diapir of a OIB-type that is partially diluted by the depleted upper mantle (MORB mantle) at its periphery