Mannose-Specific Lectins from Marine Algae: Diverse Structural Scaffolds Associated to Common Virucidal and Anti-Cancer Properties.

To date, a number of mannose-specific lectins have been isolated and characterized from seaweeds, especially from red algae. In fact, man-specific seaweed lectins consist of different structural scaffolds harboring a single or a few carbohydrate-binding sites which specifically recognize mannose-containing glycans. Depending on the structural scaffold, man-specific seaweed lectins belong to five distinct structurally-related lectin families, namely (1) the griffithsin lectin family (beta-prism I scaffold); (2) the Oscillatoria agardhii agglutinin homolog (OAAH) lectin family (beta-barrel scaffold); (3) the legume lectin-like lectin family (beta-sandwich scaffold); (4) the Galanthus nivalis agglutinin (GNA)-like lectin family (beta-prism II scaffold); and, (5) the MFP2-like lectin family (MFP2-like scaffold). Another algal lectin from Ulva pertusa, has been inferred to the methanol dehydrogenase related lectin family, because it displays a rather different GlcNAc-specificity. In spite of these structural discrepancies, all members from the five lectin families share a common ability to specifically recognize man-containing glycans and, especially, high-mannose type glycans. Because of their mannose-binding specificity, these lectins have been used as valuable tools for deciphering and characterizing the complex mannose-containing glycans from the glycocalyx covering both normal and transformed cells, and as diagnostic tools and therapeutic drugs that specifically recognize the altered high-mannose N-glycans occurring at the surface of various cancer cells. In addition to these anti-cancer properties, man-specific seaweed lectins have been widely used as potent human immunodeficiency virus (HIV-1)-inactivating proteins, due to their capacity to specifically interact with the envelope glycoprotein gp120 and prevent the virion infectivity of HIV-1 towards the host CD4+ T-lymphocyte cells in vitro

Updated review of postmortem biochemical exploration of hypothermia with a presentation of standard strategy of sampling and analyses.

Hypothermia is defined as a core body temperature below 35°C and can be caused by environmental exposure, drug intoxication, metabolic or nervous system dysfunction. This lethal pathology with medico-legal implications is complex to diagnose because macroscopic and microscopic lesions observed at the autopsy and the histological analysis are suggestive but not pathognomonic. Postmortem biochemical explorations have been progressively developed through the study of several biomarkers to improve the diagnosis decision cluster. Here, we present an updated review with novel biomarkers (such as catecholamines O-methylated metabolites, thrombomodulin and the cardiac oxyhemoglobin ratio) as well as some propositional interpretative postmortem thresholds and, to the best of our knowledge, for the first time, we present the most adapted strategy of sampling and analyses to identify biomarkers of hypothermia. For our consideration, the most relevant identified biomarkers are urinary catecholamines and their O-methylated metabolites, urinary free cortisol, blood cortisol, as well as blood, vitreous humor and pericardial fluid for ketone bodies and blood free fatty acids. These biomarkers are increased in response either to cold-mediated stress or to bioenergetics ketogenesis crisis and significantly contribute to the diagnosis by exclusion of death by hypothermia

GPU-parallelisation of Haar wavelet-based grid resolution adaptation for fast finite volume modelling: application to shallow water flows

Wavelet-based grid resolution adaptation driven by the ‘multiresolution analysis’ (MRA) of the Haar wavelet (HW) allows to devise an adaptive first-order finite volume (FV1) model (HWFV1) that can readily preserve the modelling fidelity of its reference uniform-grid FV1 counterpart. However, the MRA entails an enormous computational effort as it involves ‘encoding’ (coarsening), ‘decoding’ (refining), analysing and traversing modelled data across a deep hierarchy of nested, uniform grids. GPU-parallelisation of the MRA is needed to handle its computational effort, but its algorithmic structure (1) hinders coalesced memory access on the GPU and (2) involves an inherently sequential tree traversal problem. This work redesigns the algorithmic structure of the MRA in order to parallelise it on the GPU, addressing (1) by applying Z-order space-filling curves and (2) by adopting a parallel tree traversal algorithm. This results in a GPU-parallelised HWFV1 model (GPU-HWFV1). GPU-HWFV1 is verified against its CPU predecessor (CPU-HWFV1) and its GPU-parallelised reference uniform-grid counterpart (GPU-FV1) over five shallow water flow test cases. GPU-HWFV1 preserves the modelling fidelity of GPU-FV1 while being up to 30 times faster. Compared to CPU-HWFV1, it is up to 200 times faster, suggesting that the GPU-parallelised MRA could be used to speed up other FV1 models

Confronting the Minimal Supersymmetric Standard Model with the Study of Scalar Leptons at Future Linear e+e- Colliders

Sleptons can easily be found at future linear e+e- colliders if kinematically accessible. Measurements of their masses and decay distributions would then determine MSSM parameters. This paper presents a detailed MC study of the production and decay of the lighter scalar tau lepton, stau1. We found that mstau1 and the left-right mixing angle of stau would be measured within an error of a few percent. tanbeta is determinable in some region of the parameter space through simultaneous studies of stau1-and selectron-pair production: the polarization measurement of the tau leptons from stau1 decays and the M1, mchi1 determination using selectron pair production and decay. We also point out the possibility to determine bino-selectron-e coupling through the measurement of the angular distribution of the selectron-pair production. The error on the coupling is expected to be comparable to its typical SUSY radiative correction, which is proportional to log(msquark/mslepton). The radiative correction affects M1 and tanbeta determination, necessitating the full 1-loop radiative correction to the selectron production processes. The implication of these measurements of the MSSM parameters on selecting models of the origin of supersymmetry breaking is also discussed.Comment: 35 pages. REVTEX(gzip compressed and uuencoded). Figure are not included. Text and 15 Figures are available at http://jlcux1.kek.jp/subg/susy/index-e.html#librar

Determinants of the price response to residential water tariffs : meta-analysis and beyond

Meta-analyses synthesise available data on a phenomenon to get a broader understanding of its determinants. This work proposes a two-step methodology. 1) Based on a broad dataset of residential water demand studies, it builds a meta-regression model to estimate mean and standard deviation of price elasticity of residential water demand. 2) The resulting meta-model serves as a basis for implementing an approach that directly simulates the range of price elasticities resulting from policy-relevant combinations of its determinants. This simulation approach is validated using the available dataset. Despite evidence of low average price elasticity, the scenarios simulated using our meta-regression estimates show that increasing block rate tariffs are associated with higher price elasticity, and stresses the importance of using state-of-the-art methodologies when evaluating the price response. This completes other methodological insights obtained from the meta-analysis itself. Policy implications on the use of pricing to bring about water savings are discussed

Examen médical des personnes victimes de violence : fréquence des facteurs aggravants au sens du Code pénal, hétérogénéité des pratiques

Objectifs En cas de violences volontaires, le Code pénal reconnaît l’existence de facteurs aggravants. Aucune donnée n’est disponible sur la fréquence des facteurs aggravants lors des situations de violence. L’objectif principal était de déterminer cette fréquence. L’objectif secondaire était de préciser les résultats de la détermination d’incapacité totale de travail (ITT) dans plusieurs consultations médico-judiciaires en France. Méthodes Le recueil de données prospectif porte sur six centres et 300 situations de violence. Les éléments recueillis concernaient l’existence de facteurs aggravants, les caractéristiques de la victime et des violences, les résultats de l’examen médical et les facteurs intervenus dans la détermination de l’ITT. Résultats Il existait un facteur aggravant dans 232 cas sur 300, 77 %. La durée médiane d’ITT était de deux jours (extrêmes : 0–60). La fréquence des cas sans ITT était comprise entre 0 et 56 % selon les centres (Chi2, p < 0,0001). Les médecins examinateurs considéraient ne pas avoir évalué l’état psychique dans 63 cas (21 %), d’importantes différences étant observées selon les centres (p < 0,0001). L’ITT était surtout fondée sur des éléments lésionnels dans 45 % des cas et sur des éléments fonctionnels dans 55 % des cas, cette répartition variant selon les centres (p = 0,01). L’état psychique était prépondérant dans la détermination de l’ITT dans 0 à 23 % des cas selon les centres (p = 0,009)

Polarization of τ\tau lepton from scalar tau decay as a probe of neutralino mixing

The $\tau$ lepton arising from the scalar tau (\st) decay is naturally polarized. \ptau depends on the left--right mixing of the \st and the gaugino--higgsino mixing of the neutralino. The polarization \ptau could be measured from the energy distribution of the decay products of $\tau$ at future \epem colliders. A measurement of \ptauand of the \st production cross section allows to determine both these mixing angles.Comment: 20 pages Latex, 5 figures(not included). compressed ps file of the figures available at ftp://ftp.kek.jp/kek/preprints/TH/TH-425/fig.ps.g

Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab.

Cluster of differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and autoimmune disorders but whose structure and function are unknown. Rituximab (RTX) has been in clinical use for two decades, but how it activates complement to kill B cells remains poorly understood. We obtained a structure of CD20 in complex with RTX, revealing CD20 as a compact double-barrel dimer bound by two RTX antigen-binding fragments (Fabs), each of which engages a composite epitope and an extensive homotypic Fab:Fab interface. Our data suggest that RTX cross-links CD20 into circular assemblies and lead to a structural model for complement recruitment. Our results further highlight the potential relevance of homotypic Fab:Fab interactions in targeting oligomeric cell-surface markers

Structural basis for HCMV Pentamer receptor recognition and antibody neutralization

Human cytomegalovirus (HCMV) represents the viral leading cause of congenital birth defects and uses the gH/ gL/UL128-130-131A complex (Pentamer) to enter different cell types, including epithelial and endothelial cells. Upon infection, Pentamer elicits the most potent neutralizing response against HCMV, representing a key vaccine candidate. Despite its relevance, the structural basis for Pentamer receptor recognition and antibody neutralization is largely unknown. Here, we determine the structures of Pentamer bound to neuropilin 2 (NRP2) and a set of potent neutralizing antibodies against HCMV. Moreover, we identify thrombomodulin (THBD) as a functional HCMV receptor and determine the structures of the Pentamer-THBD complex. Unexpectedly, both NRP2 and THBD also promote dimerization of Pentamer. Our results provide a framework for understanding HCMV receptor engagement, cell entry, antibody neutralization, and outline strategies for antiviral therapies against HCMV