Multiconfiguration GPR measurements for geometric fracture characterization in limestone cliffs (Alps)

Until now, geophysical methods have been rarely used to investigate vertical limestone cliffs, mainly due to the extreme conditions for data acquisition. Nevertheless, these techniques are the only available methods which could provide information on the internal state or a rock mass in terms of discontinuities, which play a major role in rock-fall hazards. In this case study, detailed GPR measurements were carried out on a test site with different acquisition configurations deployed on vertical cliff faces. Conventional 2D profiles, common midpoints (CMP) and transmission data were acquired to evaluate the potential of radar waves to improve the characterization of the geometry and properties of the main discontinuities (fractures) within the massif. The results show that the 3D geometry of fractures, which is a crucial parameter for stability assessment, can be retrieved by combining vertical and horizontal profiles performed along the cliff. CMP profiles acquired along the cliff allow a velocity profile to be obtained as a function of depth. Finally, transmission experiments, which generate complex radargrams, have provided valuable and quantitative information on the rock mass, through the modelling of the waves generated. On the other hand, a velocity tomography obtained from the first arrivals travelling through the rock mass from the transmitters to the receivers, shows an image of the investigated zone with a poor resolution

Acoustic to Electric Pitch Comparisons in Cochlear Implant Subjects with Residual Hearing

The aim of this study was to assess the frequency-position function resulting from electric stimulation of electrodes in cochlear implant subjects with significant residual hearing in their nonimplanted ear. Six cochlear implant users compared the pitch of the auditory sensation produced by stimulation of an intracochlear electrode to the pitch of acoustic pure tones presented to their contralateral nonimplanted ear. Subjects were implanted with different Clarion® electrode arrays, designed to lie close to the inner wall of the cochlea. High-resolution radiographs were used to determine the electrode positions in the cochlea. Four out of six subjects presented electrode insertions deeper than 450°. We used a two-interval (one acoustic, one electric), two-alternative forced choice protocol (2I-2AFC), asking the subject to indicate which stimulus sounded the highest in pitch. Pure tones were used as acoustic stimuli. Electric stimuli consisted of trains of biphasic pulses presented at relatively high rates [higher than 700 pulses per second (pps)]. First, all electric stimuli were balanced in loudness across electrodes. Second, acoustic pure tones, chosen to approximate roughly the pitch sensation produced by each electrode, were balanced in loudness to electric stimuli. When electrode insertion lengths were used to describe electrode positions, the pitch sensations produced by electric stimulation were found to be more than two octaves lower than predicted by Greenwood's frequency-position function. When insertion angles were used to describe electrode positions, the pitch sensations were found about one octave lower than the frequency-position function of a normal ear. The difference found between both descriptions is because of the fact that these electrode arrays were designed to lie close to the modiolus. As a consequence, the site of excitation produced at the level of the organ of Corti corresponds to a longer length than the electrode insertion length, which is used in Greenwood's function. Although exact measurements of the round window position as well as the length of the cochlea could explain the remaining one octave difference found when insertion angles were used, physiological phenomena (e.g., stimulation of the spiral ganglion cells) could also create this difference. From these data, analysis filters could be determined in sound coding strategies to match the pitch percepts elicited by electrode stimulation. This step might be of main importance for music perception and for the fitting of bilateral cochlear implant

The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8/10 activates the epithelial sodium channel (ENaC) in vitro

TMPRSS3 encodes a transmembrane serine protease that contains both LDLRA and SRCR domains and is mutated in non-syndromic autosomal recessive deafness (DFNB8/10). To study its function, we cloned the mouse ortholog which maps to Mmu17, which is structurally similar to the human gene and encodes a polypeptide with 88% identity to the human protein. RT-PCR and RNA in situ hybridization on rat and mouse cochlea revealed that Tmprss3 is expressed in the spiral ganglion, the cells supporting the organ of Corti and the stria vascularis. RT-PCR on mouse tissues showed expression in the thymus, stomach, testis and E19 embryos. Transient expression of wild-type or tagged TMPRSS3 protein showed a primary localization in the endoplasmic reticulum. The epithelial amiloride-sensitive sodium channel (ENaC), which is expressed in many sodium-reabsorbing tissues including the inner ear and is regulated by membrane-bound channel activating serine proteases (CAPs), is a potential substrate of TMPRSS3. In the Xenopus oocyte expression system, proteolytic processing of TMPRSS3 was associated with increased ENaC mediated currents. In contrast, 6 TMPRSS3 mutants (D103G, R109W, C194F, W251C, P404L, C407R) causing deafness and a mutant in the catalytic triad of TMPRSS3 (S401A), failed to undergo proteolytic cleavage and activate ENaC. These data indicate that important signaling pathways in the inner ear are controlled by proteolytic cleavage and suggest: (i) the existence of an auto-catalytic processing by which TMPRSS3 would become active, and (ii) that ENaC could be a substrate of TMPRSS3 in the inner ea

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Bioécologie et dynamique de population de collemboles

dissertn: Diss. Doct

Intérêt de l'utilisation de liposomes en vaccinologie antitumorale (exemple des liposomes mimant les exosomes de cellules dendritiques)

La recherche sur le cancer a pour vocation de permettre de trouver de nouveaux moyens de combattre ce mal. Une des voies possibles pour lutter contre le cancer est de stimuler le système immunitaire, afin que l'organisme rejette lui-même ses tumeurs. La conception d'un outil d'immunothérapie active, autrement dit d'un " vaccin antitumoral ", semble être aujourd'hui à portée de main. Nous discutons ici du portrait d'un vaccin antitumoral idéal, qui serait capable d'orienter la réponse immunitaire pour lutter contre la cible qui aurait été choisie. Ce portrait robot nous permet de justifier que l'utilisation de liposomes pourrait permettre la conception d'un outil efficace. Nous illustrons cela par quelques exemples publiés. Enfin, nous présentons les résultats préliminaires obtenus en utilisant des liposomes possédant la composition lipidique des exosomes de cellules dendritiques, qui sont des vésicules naturellement présentes dans l'organisme, et impliquées dans l'immunité. L'étude de ces " Lipex " permettra de mieux comprendre les propriétés des exosomes, et servira de point de départ à la conception d'un outil d'immunothérapie active antitumorale.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Amélioration des performances des recyclés en domaine routier par optimisation des unités de traitement

Amélioration des performances des recyclés en domaine routier par optimisation des unités de traitemen

CHE-14, a protein with a sterol-sensing domain, is required for apical sorting in C. elegans ectodermal epithelial cells

BACKGROUND: Polarised trafficking of proteins is critical for normal expression of the epithelial phenotype, but its genetic control is not understood. The regulatory gene lin-26 is essential for normal epithelial differentiation in the nematode Caenorhabditis elegans. To identify potential effectors of lin-26, we characterised mutations that result in lin-26-like phenotypes. Here, we report the phenotypic and molecular analysis of one such mutant line, che-14. RESULTS: Mutations in che-14 resulted in several partially penetrant phenotypes affecting the function of most epithelial or epithelial-like cells of the ectoderm, including the hypodermis, excretory canal, vulva, rectum and several support cells. The defects were generally linked to the accumulation of vesicles or amorphous material near the apical surface, suggesting that secretion was defective. The CHE-14 protein showed similarity to proteins containing sterol-sensing domains, including Dispatched, Patched and NPC1. A fusion protein between full-length CHE-14 and the green fluorescent protein became localised to the apical surface of epithelial cells that require che-14 function. Deletions that removed the predicted transmembrane domains or extracellular loops of CHE-14 abolished apical localisation and function of the protein. CONCLUSIONS: We propose that CHE-14 is involved in a novel secretory pathway dedicated to the exocytosis of lipid-modified proteins at the apical surface of certain epithelial cells. Our data raise the possibility that the primordial function of proteins containing a sterol-sensing domain is to control vesicle trafficking: CHE-14 and Dispatched in exocytosis, Patched and NPC1 in endocytosis

Performance assessment and ranking of natural and recycled granular materials for road subbase layers by precision cyclic triaxial testing (EN 13286-7)

The cyclic load triaxial test is a laboratory test that allows investigating the mechanical behaviour (resilient and permanent strains) of unbound granular materials used in subbase and capping layers of roads. The resilient modulus and permanent strains are required to assess material performance and serve as key input properties in modelling and designing roads. This paper will present the investigation of resilient and permanent strains as specified by European standard EN 13286-7, for a limestone aggregate and recycled materials (one crushed concrete aggregate and two blended crushed waste aggregates) used in subbases and capping layers of road structures in Belgium. Method B (constant confining pressure) was used in most of the tests for resilient strains. The influence of water content was also analysed. Permanent strains were analysed after conditioning by 20,000 cycles of single-stage loading. The paper will also present the results obtained on the limestone aggregate only in analysing resilient strains with both axial and confining cyclic loading – method A. The resilient moduli were deduced from the test results and compared to those obtained with method B. The calibration of the LDT’s in air proved to remain valid when they were used in water (variable confining pressure tests). The natural and recycled materials were ranked starting from the characteristic values of resilient modulus and characteristic permanent axial strain. This ranking based on a mechanistic approach was compared with conventional ranking based on indicative properties determined in empirical tests. This research work produced an excellent set of findings for the mechanical characterization of unbound subbase materials through the cyclic triaxial test, thus contributing to a more widespread and common use of recycled materials in geotechnical engineering

Exploring the link between spectral variance and upper canopy taxonomic diversity in a tropical forest: influence of spectral processing and feature selection

International audienceThe rapid loss of biodiversity in tropical rainforests calls for new remote sensing approaches capable of providing rapid estimates of biodiversity over large areas. Imaging spectroscopy has shown potential for the estimation of taxonomic diversity, but the link with spectral diversity has not been investigated extensively with experimental data so far. We explored the relationship between taxonomic diversity and visible to near infrared spectral variance derived from various spectral processing techniques by means of a labeled dataset comprising 2000 individual tree crowns from 200 species from an experimental tropical forest station in French Guiana. We generated a set of artificially assembled communities covering a broad range of taxonomic diversity from this experimental dataset. We analyzed the impact of various processing steps: spectral normalization, spectral transformation through principal component analysis, and feature selection. Correlation between taxonomic diversity and inter-specific spectral variance was strong. Correlation was lower with total spectral variance, with or without normalization and transformation. Dimensionality reduction through feature selection resulted in dramatic improvement of the correlation between Shannon index and spectral variance. While airborne diversity mapping of tropical forest may not be at hand yet, our results confirm that spectral diversity metrics, when computed on properly preprocessed and selected spectral information can predict taxonomic diversity in tropical ecosystems