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Analysis of random oracle instantiation scenarios for OAEP and other practical schemes
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Requests for Abortion in Latin America Related to Concern about Zika Virus Exposure.
This is the final version of the article. It first appeared from the Massachusetts Medical Society via http://dx.doi.org/10.1056/NEJMc160538
Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein
Infections with human respiratory syncytial virus (HRSV) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of HRSV, reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of FcRI and FcRIII. Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. HRSV-infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SHe-based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SHe. Using SHe as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T-cell responses could be complemented with a SHe-based antigen to further improve immune protection
Therapy: Metformin takes a new route to clinical efficacy.
International audienceMetformin is currently the first-line treatment option for patients with type 2 diabetes mellitus, yet its mechanism of action remains uncertain. A new study reveals the important role for the activation of a duodenal AMPK-dependent neuronal pathway in the acute antihyperglycaemic effect of metformin and the inhibition of hepatic glucose production
The Cosmic Microwave Background and Particle Physics
In forthcoming years, connections between cosmology and particle physics will
be made increasingly important with the advent of a new generation of cosmic
microwave background (CMB) experiments. Here, we review a number of these
links. Our primary focus is on new CMB tests of inflation. We explain how the
inflationary predictions for the geometry of the Universe and primordial
density perturbations will be tested by CMB temperature fluctuations, and how
the gravitational waves predicted by inflation can be pursued with the CMB
polarization. The CMB signatures of topological defects and primordial magnetic
fields from cosmological phase transitions are also discussed. Furthermore, we
review current and future CMB constraints on various types of dark matter (e.g.
massive neutrinos, weakly interacting massive particles, axions, vacuum
energy), decaying particles, the baryon asymmetry of the Universe,
ultra-high-energy cosmic rays, exotic cosmological topologies, and other new
physics.Comment: 43 pages. To appear in Annual Reviews of Nuclear and Particle Scienc
Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells
The anti-diabetic drug metformin regulates T-cell responses to immune activation and is proposed to function by regulating the energy-stress-sensing adenosine-monophosphate-activated protein kinase (AMPK). However, the molecular details of how metformin controls T cell immune responses have not been studied nor is there any direct evidence that metformin acts on T cells via AMPK. Here, we report that metformin regulates cell growth and proliferation of antigen-activated T cells by modulating the metabolic reprogramming that is required for effector T cell differentiation. Metformin thus inhibits the mammalian target of rapamycin complex I signalling pathway and prevents the expression of the transcription factors c-Myc and hypoxia-inducible factor 1 alpha. However, the inhibitory effects of metformin on T cells did not depend on the expression of AMPK in T cells. Accordingly, experiments with metformin inform about the importance of metabolic reprogramming for T cell immune responses but do not inform about the importance of AMPK
Spectral quantification of nonlinear behaviour of the nearshore seabed and correlations with potential forcings at Duck, N.C., U.S.A
Local bathymetric quasi-periodic patterns of oscillation are identified from
monthly profile surveys taken at two shore-perpendicular transects at the USACE
field research facility in Duck, North Carolina, USA, spanning 24.5 years and
covering the swash and surf zones. The chosen transects are the two furthest
(north and south) from the pier located at the study site. Research at Duck has
traditionally focused on one or more of these transects as the effects of the
pier are least at these locations. The patterns are identified using singular
spectrum analysis (SSA). Possible correlations with potential forcing
mechanisms are discussed by 1) doing an SSA with same parameter settings to
independently identify the quasi-periodic cycles embedded within three
potentially linked sequences: monthly wave heights (MWH), monthly mean water
levels (MWL) and the large scale atmospheric index known as the North Atlantic
Oscillation (NAO) and 2) comparing the patterns within MWH, MWL and NAO to the
local bathymetric patterns. The results agree well with previous patterns
identified using wavelets and confirm the highly nonstationary behaviour of
beach levels at Duck; the discussion of potential correlations with
hydrodynamic and atmospheric phenomena is a new contribution. The study is then
extended to all measured bathymetric profiles, covering an area of 1100m
(alongshore) by 440m (cross-shore), to 1) analyse linear correlations between
the bathymetry and the potential forcings using multivariate empirical
orthogonal functions (MEOF) and linear correlation analysis and 2) identify
which collective quasi-periodic bathymetric patterns are correlated with those
within MWH, MWL or NAO, based on a (nonlinear) multichannel singular spectrum
analysis (MSSA). (...continued in submitted paper)Comment: 50 pages, 3 tables, 8 figure
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