76 research outputs found
An Impedance Investigation of the Mechanism of Pure Magnesium Corrosion in Sodium Sulfate Solutions
The corrosion behavior of pure magnesium in sodium sulfate solutions was investigated using voltammetry and electrochemical impedance spectroscopy with a rotating disk electrode. The analysis of impedance data obtained at the corrosion potential was consistent with the hypothesis that Mg corrosion is controlled by the presence of a very thin oxide film, probably MgO, and that the dissolution occurs at film-free spots only. This hypothesis was substantiated both by the superposition of the EIS diagrams, obtained for different immersion times and for two Na2SO4 concentrations once normalized, and by use of scanning electrochemical microscopy in the ac mode to sense the local conductivity of the material. On the basis of the electrochemical results, a model was proposed to describe magnesium corrosion at the open-circuit potential. Simulation of the impedance diagrams was in good agreement with the experimental results
CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor–β–dependent manner
Tumor growth promotes the expansion of CD4+CD25+ regulatory T (T reg) cells that counteract T cell–mediated immune responses. An inverse correlation between natural killer (NK) cell activation and T reg cell expansion in tumor-bearing patients, shown here, prompted us to address the role of T reg cells in controlling innate antitumor immunity. Our experiments indicate that human T reg cells expressed membrane-bound transforming growth factor (TGF)–β, which directly inhibited NK cell effector functions and down-regulated NKG2D receptors on the NK cell surface. Adoptive transfer of wild-type T reg cells but not TGF-β−/− T reg cells into nude mice suppressed NK cell–mediated cytotoxicity, reduced NKG2D receptor expression, and accelerated the growth of tumors that are normally controlled by NK cells. Conversely, the depletion of mouse T reg cells exacerbated NK cell proliferation and cytotoxicity in vivo. Human NK cell–mediated tumor recognition could also be restored by depletion of T reg cells from tumor-infiltrating lymphocytes. These findings support a role for T reg cells in blunting the NK cell arm of the innate immune system
Influence of the meridional shifts of the Kuroshio and the Oyashio Extensions on the atmospheric circulation
Author Posting. © American Meteorological Society, 2011. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 24 (2011): 762-777, doi:10.1175/2010JCLI3731.1.The meridional shifts of the Oyashio Extension (OE) and of the Kuroshio Extension (KE), as derived from high-resolution monthly sea surface temperature (SST) anomalies in 1982–2008 and historical temperature profiles in 1979–2007, respectively, are shown based on lagged regression analysis to significantly influence the large-scale atmospheric circulation. The signals are independent from the ENSO teleconnections, which were removed by seasonally varying, asymmetric regression onto the first three principal components of the tropical Pacific SST anomalies. The response to the meridional shifts of the OE front is equivalent barotropic and broadly resembles the North Pacific Oscillation/western Pacific pattern in a positive phase for a northward frontal displacement. The response may reach 35 m at 250 hPa for a typical OE shift, a strong sensitivity since the associated SST anomaly is 0.5 K. However, the amplitude, but not the pattern or statistical significance, strongly depends on the lag and an assumed 2-month atmospheric response time. The response is stronger during fall and winter and when the front is displaced southward. The response to the northward KE shifts primarily consists of a high centered in the northwestern North Pacific and hemispheric teleconnections. The response is also equivalent barotropic, except near Kamchatka, where it tilts slightly westward with height. The typical amplitude is half as large as that associated with OE shifts.This
work was supported in part by the L’Institut universitaire
de France (CF), the WHOI Heyman fellowship, and the
NASAGrant withAwardNNX09AF35G(Y.-O. K), and
grants through NOAA’s Climate Variability and Predictability
Program (MAA)
Association of Killer Cell Immunoglobulin-Like Receptor Genes with Hodgkin's Lymphoma in a Familial Study
BACKGROUND: Epstein-Barr virus (EBV) is the major environmental factor associated with Hodgkin's lymphoma (HL), a common lymphoma in young adults. Natural killer (NK) cells are key actors of the innate immune response against viruses. The regulation of NK cell function involves activating and inhibitory Killer cell Immunoglobulin-like receptors (KIRs), which are expressed in variable numbers on NK cells. Various viral and virus-related malignant disorders have been associated with the presence/absence of certain KIR genes in case/control studies. We investigated the role of the KIR cluster in HL in a family-based association study. METHODOLOGY: We included 90 families with 90 HL index cases (age 16–35 years) and 255 first-degree relatives (parents and siblings). We developed a procedure for reconstructing full genotypic information (number of gene copies) at each KIR locus from the standard KIR gene content. Out of the 90 collected families, 84 were informative and suitable for further analysis. An association study was then carried out with specific family-based analysis methods on these 84 families. PRINCIPAL FINDINGS: Five KIR genes in strong linkage disequilibrium were found significantly associated with HL. Refined haplotype analysis showed that the association was supported by a dominant protective effect of KIR3DS1 and/or KIR2DS1, both of which are activating receptors. The odds ratios for developing HL in subjects with at least one copy of KIR3DS1 or KIR2DS1 with respect to subjects with neither of these genes were 0.44[95% confidence interval 0.23–0.85] and 0.42[0.21–0.85], respectively. No significant association was found in a tentative replication case/control study of 68 HL cases (age 18–71 years). In the familial study, the protective effect of KIR3DS1/KIR2DS1 tended to be stronger in HL patients with detectable EBV in blood or tumour cells. CONCLUSIONS: This work defines a template for family-based association studies based on full genotypic information for the KIR cluster, and provides the first evidence that activating KIRs can have a protective role in HL
Role of the Gulf Stream and Kuroshio–Oyashio systems in large-scale atmosphere–ocean interaction : a review
Author Posting. © American Meteorological Society, 2010. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 23 (2010): 3249-3281, doi:10.1175/2010JCLI3343.1.Ocean–atmosphere interaction over the Northern Hemisphere western boundary current (WBC) regions (i.e., the Gulf Stream, Kuroshio, Oyashio, and their extensions) is reviewed with an emphasis on their role in basin-scale climate variability. SST anomalies exhibit considerable variance on interannual to decadal time scales in these regions. Low-frequency SST variability is primarily driven by basin-scale wind stress curl variability via the oceanic Rossby wave adjustment of the gyre-scale circulation that modulates the latitude and strength of the WBC-related oceanic fronts. Rectification of the variability by mesoscale eddies, reemergence of the anomalies from the preceding winter, and tropical remote forcing also play important roles in driving and maintaining the low-frequency variability in these regions. In the Gulf Stream region, interaction with the deep western boundary current also likely influences the low-frequency variability. Surface heat fluxes damp the low-frequency SST anomalies over the WBC regions; thus, heat fluxes originate with heat anomalies in the ocean and have the potential to drive the overlying atmospheric circulation. While recent observational studies demonstrate a local atmospheric boundary layer response to WBC changes, the latter’s influence on the large-scale atmospheric circulation is still unclear. Nevertheless, heat and moisture fluxes from the WBCs into the atmosphere influence the mean state of the atmospheric circulation, including anchoring the latitude of the storm tracks to the WBCs. Furthermore, many climate models suggest that the large-scale atmospheric response to SST anomalies driven by ocean dynamics in WBC regions can be important in generating decadal climate variability. As a step toward bridging climate model results and observations, the degree of realism of the WBC in current climate model simulations is assessed. Finally, outstanding issues concerning ocean–atmosphere interaction in WBC regions and its impact on climate variability are discussed.Funding for LT was
provided by the NASA-sponsored Ocean Surface Topography
Science Team, under Contract 1267196 with
the University of Washington, administered by the Jet
Propulsion Laboratory. HN was supported in part by the
Grant-in-Aid 18204044 by the Japan Society for Promotion
for Science (JSPS) and the Global Environment
Research Fund (S-5) of the Japanese Ministry of Environment.
YK was supported by the Kerr Endowed Fund
and Penzance Endowed Fund
Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.
RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)
The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases
The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Les écrits de Claude Vivier
Le plus gros du présent numéro rassemble une collection de soixante-deux textes, pour la plupart inédits. Ils sont présentés et annotés par Véronique Robert.The greater part of this issue brings together a collection of sixty two texts, most of them unpublished, presented and annotated by Véronique Robert
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