RNA denaturation: excluded volume, pseudoknots and transition scenarios

A lattice model of RNA denaturation which fully accounts for the excluded volume effects among nucleotides is proposed. A numerical study shows that interactions forming pseudoknots must be included in order to get a sharp continuous transition. Otherwise a smooth crossover occurs from the swollen linear polymer behavior to highly ramified, almost compact conformations with secondary structures. In the latter scenario, which is appropriate when these structures are much more stable than pseudoknot links, probability distributions for the lengths of both loops and main branches obey scaling with nonclassical exponents.Comment: 4 pages 3 figure

Discovery of a new Transient X-ray Pulsar in the Small Magellanic Cloud

Rossi X-Ray Timing Explorer observations of the Small Magellanic Cloud have revealed a previously unknown transient X-ray pulsar with a pulse period of 95s. Provisionally designated XTE SMC95, the pulsar was detected in three Proportional Counter Array observations during an outburst spanning 4 weeks in March/April 1999. The pulse profile is double peaked reaching a pulse fraction \~0.8. The source is proposed as a Be/neutron star system on the basis of its pulsations, transient nature and characteristically hard X-ray spectrum. The 2-10 keV X-ray luminosity implied by our observations is > 2x10^37 erg/s which is consistent with that of normal outbursts seen in Galactic systems. This discovery adds to the emerging picture of the SMC as containing an extremely dense population of transient high mass X-ray binaries.Comment: Accepted by A&A. 7 pages, 6 figure

The variable X-ray light curve of GRB 050713A: the case of refreshed shocks

We present a detailed study of the spectral and temporal properties of the X-ray and optical emission of GRB050713a up to 0.5 day after the main GRB event. The X-ray light curve exhibits large amplitude variations with several rebrightenings superposed on the underlying three-segment broken powerlaw that is often seen in Swift GRBs. Our time-resolved spectral analysis supports the interpretation of a long-lived central engine, with rebrightenings consistent with energy injection in refreshed shocks as slower shells generated in the central engine prompt phase catch up with the afterglow shock at later times. Our sparsely-sampled light curve of the optical afterglow can be fitted with a single power law without large flares. The optical decay index appears flatter than the X-ray one, especially at later times.Comment: few changes, to be published in A&

XMM-Newton observations of IGRJ18410-0535: The ingestion of a clump by a supergiant fast X-ray transient

IGRJ18410-0535 is a supergiant fast X-ray transients. This subclass of supergiant X-ray binaries typically undergoes few- hour-long outbursts reaching luminosities of 10^(36)-10^(37) erg/s, the occurrence of which has been ascribed to the combined effect of the intense magnetic field and rotation of the compact object hosted in them and/or the presence of dense structures ("clumps") in the wind of their supergiant companion. IGR J18410-0535 was observed for 45 ks by XMM-Newton as part of a program designed to study the quiescent emission of supergiant fast X-ray transients and clarify the origin of their peculiar X-ray variability. We carried out an in-depth spectral and timing analysis of these XMM-Newton data. IGR J18410-0535 underwent a bright X-ray flare that started about 5 ks after the beginning of the observation and lasted for \sim15 ks. Thanks to the capabilities of the instruments on-board XMM-Newton, the whole event could be followed in great detail. The results of our analysis provide strong convincing evidence that the flare was produced by the accretion of matter from a massive clump onto the compact object hosted in this system. By assuming that the clump is spherical and moves at the same velocity as the homogeneous stellar wind, we estimate a mass and radius of Mcl \simeq1.4\times10^(22) g and Rcl \simeq8\times10^(11) cm. These are in qualitative agreement with values expected from theoretical calculations. We found no evidence of pulsations at \sim4.7 s after investigating coherent modulations in the range 3.5 ms-100 s. A reanalysis of the archival ASCA and Swift data of IGR J18410-0535, for which these pulsations were previously detected, revealed that they were likely to be due to a statistical fluctuation and an instrumental effect, respectively.Comment: Accepted for publication on A&A. V2: Inserted correct version of Fig.1

Drug-gene interactions of antihypertensive medications and risk of incident cardiovascular disease: a pharmacogenomics study from the CHARGE consortium

Background Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals. Methods Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases). Results Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10−8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ≥ 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD

The VLT-FLAMES Tarantula survey XX. The nature of the X-ray bright emission-line star VFTS 399

Context. The stellar population of the 30 Doradus star-forming region in the Large Magellanic Cloud contains a subset of apparently single, rapidly rotating O-type stars. The physical processes leading to the formation of this cohort are currently uncertain. Aims. One member of this group, the late O-type star VFTS 399, is found to be unexpectedly X-ray bright for its bolometric luminosity − in this study we aim to determine its physical nature and the cause of this behaviour. Methods. To accomplish this we performed a time-resolved analysis of optical, infrared and X-ray observations. Results. We found VFTS 399 to be an aperiodic photometric variable with an apparent near-IR excess. Its optical spectrum demonstrates complex emission profiles in the lower Balmer series and select He i lines − taken together these suggest an OeBe classification. The highly variable X-ray luminosity is too great to be produced by a single star, while the hard, non-thermal nature suggests the presence of an accreting relativistic companion. Finally, the detection of periodic modulation of the X-ray lightcurve is most naturally explained under the assumption that the accretor is a neutron star. Conclusions. VFTS 399 appears to be the first high-mass X-ray binary identified within 30 Dor, sharing many observational characteristics with classical Be X-ray binaries. Comparison of the current properties of VFTS 399 to binary-evolution models suggests a progenitor mass ≳25 M⊙ for the putative neutron star, which may host a magnetic field comparable in strength to those of magnetars. VFTS 399 is now the second member of the cohort of rapidly rotating “single” O-type stars in 30 Dor to show evidence of binary interaction resulting in spin-up, suggesting that this may be a viable evolutionary pathway for the formation of a subset of this stellar population

Long-term spectral and timing properties of the soft gamma-ray repeater SGR 1833-0832 and detection of extended X-ray emission around the radio pulsar PSR B1830-08

SGR 1833-0832 was discovered on 2010 March 19 thanks to the Swift detection of a short hard X-ray burst and follow-up X-ray observations. Since then, it was repeatedly observed with Swift, Rossi X-ray Timing Explorer, and XMM-Newton. Using these data, which span about 225 days, we studied the long-term spectral and timing characteristics of SGR 1833-0832. We found evidence for diffuse emission surrounding SGR 1833-0832, which is most likely a halo produced by the scattering of the point source X-ray radiation by dust along the line of sight, and we show that the source X-ray spectrum is well described by an absorbed blackbody, with temperature kT=1.2 keV and absorbing column nH=(10.4+/-0.2)E22 cm^-2, while different or more complex models are disfavoured. The source persistent X-ray emission remained fairly constant at about 3.7E-12 erg/cm^2/s for the first 20 days after the onset of the bursting episode, then it faded by a factor 40 in the subsequent 140 days, following a power-law trend with index alpha=-0.5. We obtained a phase-coherent timing solution with the longest baseline (225 days) to date for this source which, besides period P=7.5654084(4) s and period derivative dP/dt=3.5(3)E-12 s/s, includes higher order period derivatives. We also report on our search of the counterpart to the SGR at radio frequencies using the Australia Telescope Compact Array and the Parkes radio telescope. No evidence for radio emission was found, down to flux densities of 0.9 mJy (at 1.5 GHz) and 0.09 mJy (at 1.4 GHz) for the continuum and pulsed emissions, respectively, consistently with other observations at different epochs.Comment: 12 pages, 7 colour figures and 3 tables, accepted for publication in MNRAS. Figure 6 in reduced quality and abstract abridged for astro-ph submissio

Kant, race, and natural history

This article presents a new argument concerning the relation between Kant’s theory of race and aspects of the critical philosophy. It argues that Kant’s treatment of the problem of the systematic unity of nature and knowledge in the Critique of Pure Reason and the Critique of the Power of Judgment can be traced back a methodological problem in the natural history of the period – that of the possibility of a natural system of nature. Kant’s transformation of the methodological problem from natural history into a set of philosophical (and specifically epistemological) problems proceeds by way of the working out of his own problem in natural history – the problem of the natural history of the human races – and specifically the problem of the unity in diversity of the human species, in response to which he develops a theory of race. This theory of race is, further, the first developed model of the use of teleological judgment in Kant’s work. The article thus argues that Kant’s philosophical position on the systematic unity of nature and of knowledge in the first and third Critiques, and his account and defense of teleological judgment, are developed out of problems first articulated in his solution to the problem of the unity in diversity of the human species – that is, in his theory of race. The article does not seek to establish that these aspects of the critical philosophy are therefore racialised. But it does demonstrate, against those who deny its salience to his philosophy, how the problem of the unity in diversity of the human species and Kant’s theory of race is significant for the development of aspects of the critical philosophy and thus contributes to their philosophical problematics

Polymorphisms of an Innate Immune Gene, Toll-Like Receptor 4, and Aggressive Prostate Cancer Risk: A Systematic Review and Meta-Analysis

Background: Toll-like receptor 4 (TLR4) is one of the best known TLR members expressed on the surface of several leukocytes and tissue cells and has a key function in detecting pathogen and danger-associated molecular patterns. The role of TLR4 in the pathophysiology of several age-related diseases is also well recognized, such as prostate cancer (PCa). TLR4 polymorphisms have been related to PCa risk, but the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews. Methods: We performed a systematic review and meta-analysis of candidate-gene and genome-wide association studies analyzing this relationship and included only white population. Considering appropriate criteria, only nine studies were analyzed in the meta-analysis, including 3,937 aggressive PCa and 7,382 controls. Results: Using random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973). Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). Meta-regression revealed that study type was not a significant source of between-study heterogeneity. Conclusions: TLR4 polymorphisms were not significantly associated with the risk of aggressive PCa

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels