399 research outputs found
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 âmultiresolution analysisâ (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 âencodingâ (coarsening), âdecodingâ (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
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
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
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 pĂ©nal reconnaĂźt lâexistence de facteurs aggravants. Aucune donnĂ©e nâest disponible sur la frĂ©quence des facteurs aggravants lors des situations de violence. Lâobjectif principal Ă©tait de dĂ©terminer cette frĂ©quence. Lâobjectif secondaire Ă©tait de prĂ©ciser les rĂ©sultats de la dĂ©termination dâincapacitĂ© totale de travail (ITT) dans plusieurs consultations mĂ©dico-judiciaires en France.
MĂ©thodes
Le recueil de donnĂ©es prospectif porte sur six centres et 300 situations de violence. Les Ă©lĂ©ments recueillis concernaient lâexistence de facteurs aggravants, les caractĂ©ristiques de la victime et des violences, les rĂ©sultats de lâexamen mĂ©dical et les facteurs intervenus dans la dĂ©termination de lâITT.
RĂ©sultats
Il existait un facteur aggravant dans 232 cas sur 300, 77 %. La durĂ©e mĂ©diane dâITT Ă©tait de deux jours (extrĂȘmes : 0â60). La frĂ©quence des cas sans ITT Ă©tait comprise entre 0 et 56 % selon les centres (Chi2, p < 0,0001). Les mĂ©decins examinateurs considĂ©raient ne pas avoir Ă©valuĂ© lâĂ©tat psychique dans 63 cas (21 %), dâimportantes diffĂ©rences Ă©tant observĂ©es selon les centres (p < 0,0001). LâITT Ă©tait surtout fondĂ©e sur des Ă©lĂ©ments lĂ©sionnels dans 45 % des cas et sur des Ă©lĂ©ments fonctionnels dans 55 % des cas, cette rĂ©partition variant selon les centres (p = 0,01). LâĂ©tat psychique Ă©tait prĂ©pondĂ©rant dans la dĂ©termination de lâITT dans 0 à 23 % des cas selon les centres (p = 0,009)
Polarization of lepton from scalar tau decay as a probe of neutralino mixing
The 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 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
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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
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