Dynamic model of spherical perturbations in the Friedman universe. III. Automodel solutions

A class of exact spherically symmetric perturbations of retarding automodel solutions linearized around Friedman background of Einstein equations for an ideal fluid with an arbitrary barotrope value is obtained and investigated.Comment: 12 pages, 4 figures, 8 reference

Expression of human adenosine deaminase in nonhuman primates after retrovirus-mediated gene transfer.

Primate bone marrow cells were infected with a retroviral vector carrying the genes for human adenosine deaminase (h-ADA) and bacterial neomycin resistance (neor). The infected cells were infused back into the lethally irradiated donor animals. Several monkeys fully reconstituted and were shown to express the h-ADA and neor genes at low levels in their recirculating hematopoietic cells for short periods of time

Investigation of Non-Stable Processes in Close Binary Ry Scuti

We present results of reanalysis of old electrophotometric data of early type close binary system RY Scuti obtained at the Abastumani Astrophysical Observatory, Georgia, during 1972-1990 years and at the Maidanak Observatory, Uzbekistan, during 1979-1991 years. It is revealed non-stable processes in RY Sct from period to period, from month to month and from year to year. This variation consists from the hundredths up to the tenths of a magnitude. Furthermore, periodical changes in the system's light are displayed near the first maximum on timescales of a few years. That is of great interest with regard to some similar variations seen in luminous blue variable (LBV) stars. This also could be closely related to the question of why RY Sct ejected its nebula.Comment: 11 pages, 6 figures, 2 table

Synchronized Optical and Electronic Detection of Biomolecules Using a Low Noise Nanopore Platform

In the past two decades there has been a tremendous amount of research into the use of nanopores as single molecule sensors, which has been inspired by the Coulter counter and molecular transport across biological pores. Recently, the desire to increase structural resolution and analytical throughput has led to the integration of additional detection methods such as fluorescence spectroscopy. For structural information to be probed electronically high bandwidth measurements are crucial due to the high translocation velocity of molecules. The most commonly used solid-state nanopore sensors consist of a silicon nitride membrane and bulk silicon substrate. Unfortunately, the photoinduced noise associated with illumination of these platforms limits their applicability to high-bandwidth, high-laser-power synchronized optical and electronic measurements. Here we present a unique low-noise nanopore platform, composed of a predominately Pyrex substrate and silicon nitride membrane, for synchronized optical and electronic detection of biomolecules. Proof of principle experiments are conducted showing that the Pyrex substrates have substantially lowers ionic current noise arising from both laser illumination and platform capacitance. Furthermore, using confocal microscopy and a partially metallic pore we demonstrate high signal-to-noise synchronized optical and electronic detection of dsDNA

Skyrmion Hall Effect Revealed by Direct Time-Resolved X-Ray Microscopy

Magnetic skyrmions are highly promising candidates for future spintronic applications such as skyrmion racetrack memories and logic devices. They exhibit exotic and complex dynamics governed by topology and are less influenced by defects, such as edge roughness, than conventionally used domain walls. In particular, their finite topological charge leads to a predicted "skyrmion Hall effect", in which current-driven skyrmions acquire a transverse velocity component analogous to charged particles in the conventional Hall effect. Here, we present nanoscale pump-probe imaging that for the first time reveals the real-time dynamics of skyrmions driven by current-induced spin orbit torque (SOT). We find that skyrmions move at a well-defined angle {\Theta}_{SH} that can exceed 30{\deg} with respect to the current flow, but in contrast to theoretical expectations, {\Theta}_{SH} increases linearly with velocity up to at least 100 m/s. We explain our observation based on internal mode excitations in combination with a field-like SOT, showing that one must go beyond the usual rigid skyrmion description to unravel the dynamics.Comment: pdf document arxiv_v1.1. 24 pages (incl. 9 figures and supplementary information

Protective Effects of Non-Anticoagulant Activated Protein C Variant (D36A/L38D/A39V) in a Murine Model of Ischaemic Stroke

Ischaemic stroke is caused by occlusive thrombi in the cerebral vasculature. Although tissue-plasminogen activator (tPA) can be administered as thrombolytic therapy, it has major limitations, which include disruption of the blood-brain barrier and an increased risk of bleeding. Treatments that prevent or limit such deleterious effects could be of major clinical importance. Activated protein C (APC) is a natural anticoagulant that regulates thrombin generation, but also confers endothelial cytoprotective effects and improved endothelial barrier function mediated through its cell signalling properties. In murine models of stroke, although APC can limit the deleterious effects of tPA due to its cell signalling function, its anticoagulant actions can further elevate the risk of bleeding. Thus, APC variants such as APC(5A), APC(Ca-ins) and APC(36-39) with reduced anticoagulant, but normal signalling function may have therapeutic benefit. Human and murine protein C (5A), (Ca-ins) and (36-39) variants were expressed and characterised. All protein C variants were secreted normally, but 5-20% of the protein C (Ca-ins) variants were secreted as disulphide-linked dimers. Thrombin generation assays suggested reductions in anticoagulant function of 50- to 57-fold for APC(36-39), 22- to 27-fold for APC(Ca-ins) and 14- to 17-fold for APC(5A). Interestingly, whereas human wt APC, APC(36-39) and APC(Ca-ins) were inhibited similarly by protein C inhibitor (t½ - 33 to 39 mins), APC(5A) was inactivated ~9-fold faster (t½ - 4 mins). Using the murine middle cerebral artery occlusion ischaemia/repurfusion injury model, in combination with tPA, APC(36-39), which cannot be enhanced by its cofactor protein S, significantly improved neurological scores, reduced cerebral infarct area by ~50% and reduced oedema ratio. APC(36-39) also significantly reduced bleeding in the brain induced by administration of tPA, whereas wt APC did not. If our data can be extrapolated to clinical settings, then APC(36-39) could represent a feasible adjunctive therapy for ischaemic stroke

Human preferences for sexually dimorphic faces may be evolutionarily novel

This article has been made available through the Brunel Open Access Publishing Fund.A large literature proposes that preferences for exaggerated sex typicality in human faces (masculinity/femininity) reflect a long evolutionary history of sexual and social selection. This proposal implies that dimorphism was important to judgments of attractiveness and personality in ancestral environments. It is difficult to evaluate, however, because most available data come from largescale, industrialized, urban populations. Here, we report the results for 12 populations with very diverse levels of economic development. Surprisingly, preferences for exaggerated sex-specific traits are only found in the novel, highly developed environments. Similarly, perceptions that masculine males look aggressive increase strongly with development, specifically, urbanization. These data challenge the hypothesis that facial dimorphism was an important ancestral signal of heritable mate value. One possibility is that highly developed environments provide novel opportunities to discern relationships between facial traits and behavior by exposing individuals to large numbers of unfamiliar faces, revealing patterns too subtle to detect with smaller samples

Flavor conversion of cosmic neutrinos from hidden jets

High energy cosmic neutrino fluxes can be produced inside relativistic jets under the envelopes of collapsing stars. In the energy range E ~ (0.3 - 1e5) GeV, flavor conversion of these neutrinos is modified by various matter effects inside the star and the Earth. We present a comprehensive (both analytic and numerical) description of the flavor conversion of these neutrinos which includes: (i) oscillations inside jets, (ii) flavor-to-mass state transitions in an envelope, (iii) loss of coherence on the way to observer, and (iv) oscillations of the mass states inside the Earth. We show that conversion has several new features which are not realized in other objects, in particular interference effects ("L- and H- wiggles") induced by the adiabaticity violation. The neutrino-neutrino scattering inside jet and inelastic neutrino interactions in the envelope may produce some additional features at E > 1e4 GeV. We study dependence of the probabilities and flavor ratios in the matter-affected region on angles theta13 and theta23, on the CP-phase delta, as well as on the initial flavor content and density profile of the star. We show that measurements of the energy dependence of the flavor ratios will, in principle, allow to determine independently the neutrino and astrophysical parameters.Comment: 56 pages, 19 figures. Minor changes. Accepted by JHEP

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer