572 research outputs found
Analyse des mutations des domaines ISDR et V3 de la protéine NS5A du virus de l'hépatite C avant le traitement par l'interféron avec ou sans ribavirine
Aim of the study. â The hepatitis C virus (HCV) non-structural NS5A protein has been controversially implicated in the resistance of HCV to interferon therapy in clinical studies. In Japan, mutations in the interferon sensitivity-determining region (ISDR) in the NS5A gene were associated with response to interferon therapy in patients infected with genotype 1b. In contrast, studies from Europe did not confirm such association. More recently, it has been suggested that the V3 domain outside the putative ISDR might also have amino acids changes that may be involved in the resistance to IFN. In this study, the relationship between NS5A mutations in ISDR and V3 domains and virological response to therapy were investigated.
Materials and methods. â The NS5A gene was sequenced from 35Â HCV genotype 1b infected patients at D0 of a prospective clinical trial of interferon therapy and interferon plus Ribavirin combination therapy.
Results. â In the ISDR domain, we did not observe any significant differences in amino acids changes between responders (1.7 ± 1.8, n = 19, range 0â6) and non-responders (1.1 ± 0.8, n = 14, range: 0â3), (P = 0.483), to therapy before the beginning of treatment. In the V3 domain, we found more mutations in responders (6.5 ± 1.9, range: 2â11) than in non-responders (4.7 ± 1.2, range: 3â8) (P = 0.0013), before the beginning of treatment.
Conclusion. â Our results confirm that, in Europe, the ISDR domain is not predictive for treatment success but suggest that the V3 domain have greater variability in responders than non-responders
Probing material nonlinearity at various depths by time reversal mirrors
International audienceIn this letter, the time reversal mirror is used to focus elastic energy at a prescribed location and to analyze the amplitude dependence of the focus signal, thus providing the nonlinearity of the medium. By varying the frequency content of the focused waveforms, the technique can be used to probe the surface, by penetrating to a depth defined by the wavelength of the focused waves. The validity of this concept is shown in the presence of gradual and distributed damage in concrete by comparing actual results with a reference nonlinear measurement and X ray tomography images
Intensity-Based Registration of Freehand 3D Ultrasound and CT-scan Images of the Kidney
This paper presents a method to register a pre-operative Computed-Tomography
(CT) volume to a sparse set of intra-operative Ultra-Sound (US) slices. In the
context of percutaneous renal puncture, the aim is to transfer planning
information to an intra-operative coordinate system. The spatial position of
the US slices is measured by optically localizing a calibrated probe. Assuming
the reproducibility of kidney motion during breathing, and no deformation of
the organ, the method consists in optimizing a rigid 6 Degree Of Freedom (DOF)
transform by evaluating at each step the similarity between the set of US
images and the CT volume. The correlation between CT and US images being
naturally rather poor, the images have been preprocessed in order to increase
their similarity. Among the similarity measures formerly studied in the context
of medical image registration, Correlation Ratio (CR) turned out to be one of
the most accurate and appropriate, particularly with the chosen non-derivative
minimization scheme, namely Powell-Brent's. The resulting matching transforms
are compared to a standard rigid surface registration involving segmentation,
regarding both accuracy and repeatability. The obtained results are presented
and discussed
How a plantar pressure-based, tongue-placed tactile biofeedback modifies postural control mechanisms during quiet standing
The purpose of the present study was to determine the effects of a plantar
pressure-based, tongue-placed tactile biofeedback on postural control
mechanisms during quiet standing. To this aim, sixteen young healthy adults
were asked to stand as immobile as possible with their eyes closed in two
conditions of No-biofeedback and Biofeedback. Centre of foot pressure (CoP)
displacements, recorded using a force platform, were used to compute the
horizontal displacements of the vertical projection the centre of gravity
(CoGh) and those of the difference between the CoP and the vertical projection
of the CoG (CoP-CoGv). Altogether, the present findings suggest that the main
way the plantar pressure-based, tongue-placed tactile biofeedback improves
postural control during quiet standing is via both a reduction of the
correction thresholds and an increased efficiency of the corrective mechanism
involving the CoGh displacements
Validation and data characteristics of methane and nitrous oxide profiles observed by MIPAS and processed with Version 4.61 algorithm
The ENVISAT validation programme for the atmospheric instruments MIPAS, SCIAMACHY and GOMOS is based on a number of balloon-borne, aircraft, satellite and ground-based correlative measurements. In particular the activities of validation scientists were coordinated by ESA within the ENVISAT Stratospheric Aircraft and Balloon Campaign or ESABC. As part of a series of similar papers on other species [this issue] and in parallel to the contribution of the individual validation teams, the present paper provides a synthesis of comparisons performed between MIPAS CH4 and N2O profiles produced by the current ESA operational software (Instrument Processing Facility version 4.61 or IPF v4.61, full resolution MIPAS data covering the period 9 July 2002 to 26 March 2004) and correlative measurements obtained from balloon and aircraft experiments as well as from satellite sensors or from ground-based instruments. In the middle stratosphere, no significant bias is observed between MIPAS and correlative measurements, and MIPAS is providing a very consistent and global picture of the distribution of CH4 and N2O in this region. In average, the MIPAS CH4 values show a small positive bias in the lower stratosphere of about 5%. A similar situation is observed for N2O with a positive bias of 4%. In the lower stratosphere/upper troposphere (UT/LS) the individual used MIPAS data version 4.61 still exhibits some unphysical oscillations in individual CH4 and N2O profiles caused by the processing algorithm (with almost no regularization). Taking these problems into account, the MIPAS CH4 and N2O profiles are behaving as expected from the internal error estimation of IPF v4.61 and the estimated errors of the correlative measurements
Decision-Making and Optimization Framework for the Design of Emerging Satellite Constellations
Presented at AIAA SciTech 2023, National Harbor, MD January 23rd -27th, 2023With the parallel increase in global orbital debris due to passive object collisions, as well as in
the number of proposed low earth orbit mega-constellations, in anti-satellite missile tests, and the
fielding of new satellites, there is an inherent need for a framework to optimize the design of Low
Earth Orbit (LEO) mega-constellations to avoid collisions while maintaining the functionality of
the constellation. In this paper, we aim to provide a framework that unifies these considerations
in the conceptual design phase of mega-constellations. We start with a discussion of metrics
of importance for the design of mega-constellations, namely coverage, collision risk, collision
avoidance, and station-keeping costs. With these metrics defined, we utilize the first principles
of orbital mechanics and statistical models to analyze potential alternative mega-constellation
designs. These designs are then optimized using Non-denominated Sorting Genetic Algorithm
2 (NSGA2) with our own defined objective function to create a repository of Pareto optimal
configurations. We then showcase how a multi-criteria decision-making methodology can be
utilized by a variety of unique stakeholders and subject-matter experts to select an optimal
constellation design for a given scenario. A Pareto Frontier collection with optimal solutions
of 10 constellations was produced by the framework. Radar plots to assess the significance of
the weighted metric of the framework shows several trading options for conceptual designs of
the constellations. We finally discuss the scope, limitations, applications, and future work for
various scenarios
In vivo and ex vivo percutaneous absorption of [14C]-bisphenol A in rats: a possible extrapolation to human absorption?
Bisphenol A (BPA) is a monomer used mainly in the synthesis of polycarbonates and epoxy resins. Percutaneous absorption is the second source of exposure, after inhalation, in the work environment. However, studies on this route of absorption are lacking or incomplete. In this study, percutaneous BPA absorption was measured in vivo and ex vivo in the rat, and ex vivo in humans. An approximately 12-fold difference in permeability between rat skin and human skin was found, with permeability being higher in the rat. In addition, inter- and intra-individual variability of up to tenfold was observed in humans. No accumulation of BPA in the skin was found during exposure. The skin clearance rate following exposure was estimated at 0.4Â ÎŒg/cmÂČ/h. Ex vivo and in vivo percutaneous absorption fluxes of BPA in the rat were in the same range (about 2.0Â ÎŒg/cmÂČ/h), suggesting that extrapolation to the in vivo situation in humans may be possible. The European tolerable daily intake (TDI) of BPA is 50Â ÎŒg/kg body weight. However, many research projects have highlighted the significant effects of BPA in rodents at doses lower than 10Â ÎŒg/kg/day. A 1-h occupational exposure over 2,000Â cmÂČ (forearms and hands) may lead to a BPA absorption of 4Â ÎŒg/kg/day. This is 8% of the European TDI and is very close to the value at which effects have been observed in animals. This absorption must therefore be taken into account when evaluating risks of BPA exposure, at least until more relevant results on the toxicity of BPA in humans are available
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The immune cell landscape in kidneys of patients with lupus nephritis.
Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies
Influences of tongue biomechanics on speech movements during the production of velar stop consonants: a modeling study
This study explores the following hypothesis: forward looping movements of
the tongue that are observed in VCV sequences are due partly to the anatomical
arrangement of the tongue muscles and how they are used to produce a velar
closure. The study uses an anatomically based 2D biomechanical tongue model.
Tissue elastic properties are accounted for in finite-element modeling, and
movement is controlled by constant-rate control parameter shifts. Tongue
raising and lowering movements are produced by the model with the combined
actions of the genioglossus, styloglossus and hyoglossus. Simulations of V1CV2
movements were made, where C is a velar consonant and V is [a], [i] or [u]. If
V1 is one of the vowels [a] and [u], the resulting trajectories describe
movements that begin to loop forward before consonant closure and continue to
slide along the palate during the closure. This prediction is in agreement with
classical data published in the literature. If V1 is vowel [i], we observe a
small backward movement. This is also in agreement with some measurements on
human speakers, but it is also in contradiction with the original data
published by Houde (1967). These observations support the idea that the
biomechanical properties of the tongue could be the main factor responsible for
the forward loops when V1 is a back vowel. In the left [i] context, it seems
that additional factors have to be taken into considerations, in order to
explain the observations made on some speaker
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