Statistical properties of driven Magnetohydrodynamic turbulence in three dimensions: Novel universality

We analyse the universal properties of nonequilibrium steady states of driven Magnetohydrodynamic (MHD) turbulence in three dimensions (3d). We elucidate the dependence of various phenomenologically important dimensionless constants on the symmetries of the two-point correlation functions. We, for the first time, also suggest the intriguing possibility of multiscaling universality class varying continuously with certain dimensionless parameters. The experimental and theoretical implications of our results are discussed.Comment: To appear in Europhys. Lett. (2004

Photometric Monitoring of Open Clusters I. The Survey

Open clusters, which have age, abundance, and extinction information from studies of main-sequence turn off stars, are the ideal location in which to determine the mass-luminosity-radius relation for low-mass stars. We have undertaken a photometric monitoring survey of open clusters in the Galaxy designed to detect low-mass eclipsing binary systems through variations in their relative light curves. Our aim is to provide an improved calibration of the mass-luminosity-radius relation for low-mass stars and brown dwarfs, to test stellar structure and evolution models, and to help quantify the contribution of low-mass stars to the global mass census in the Galaxy. In this paper we present our survey, describing the data and outlining the analysis techniques. We study six nearby open clusters, with a range of ages from $\sim 0.2$ to 4 Gyr and metallicities from approximately solar to -0.2dex. We monitor a field-of-view of > 1 square degree per target cluster, well beyond the characteristic cluster radius, over timescales of hours, days, and months with a sampling rate optimised for the detection of eclipsing binaries with periods of hours to days. Our survey depth is designed to detect eclipse events in a binary with a primary star of \lesssim 0.3~M_{\sun}. Our data have a photometric precision of $\sim 3$ mmag at $I\approx 16$.Comment: 50 pages, 18 figures, accepted for publication in A

Iron Age and Anglo-Saxon genomes from East England reveal British migration history

British population history has been shaped by a series of immigrations, including the early Anglo-Saxon migrations after 400 CE. It remains an open question how these events affected the genetic composition of the current British population. Here, we present whole-genome sequences from 10 individuals excavated close to Cambridge in the East of England, ranging from the late Iron Age to the middle Anglo-Saxon period. By analysing shared rare variants with hundreds of modern samples from Britain and Europe, we estimate that on average the contemporary East English population derives 38% of its ancestry from Anglo-Saxon migrations. We gain further insight with a new method, rarecoal, which infers population history and identifies fine-scale genetic ancestry from rare variants. Using rarecoal we find that the Anglo-Saxon samples are closely related to modern Dutch and Danish populations, while the Iron Age samples share ancestors with multiple Northern European populations including Britain

Comparative Performance of Single Nucleotide Polymorphism and Microsatellite Markers for Population Genetic Analysis

Microsatellite loci are standard genetic markers for population genetic analysis, whereas single nucleotide polymorphisms (SNPs) are more recent tools that require assessment of neutrality and appropriate use in population genetics. Twelve SNP markers were used to describe the genetic structure of Diabrotica virgifera virgifera (LeConte; Coleoptera: Chrysomelidae) in the United States of America and revealed a high mean observed heterozygosity (0.40 ± 0.059) and low global FST (0.029). Pairwise FST estimates ranged from 0.007 to 0.045, and all but 2 populations showed significant levels of genetic differentiation (P ≤ 0.008). Population parameters and conclusions based on SNP markers were analogous to that obtained by use of microsatellite markers from the identical population samples. SNP-based FST estimates were 3-fold higher than corresponding estimates from microsatellites, wherein lower microsatellite FST estimates likely resulted from an overestimate of migration rates between subpopulations due to convergence of allele size (homoplasy). No significant difference was observed in the proportion of SNP or microsatellite markers loci that were nonneutral within populations. SNP markers provided estimates of population genetic parameters consistent with those from microsatellite data, and their low back mutation rates may result in reduced propensity for error in estimation of population parameters

Biological, clinical and population relevance of 95 loci for blood lipids.

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD

Deployment of ACT antimalarials for treatment of malaria: challenges and opportunities

Following a long period when the effectiveness of existing mono-therapies for antimalarials was steadily declining with no clear alternative, most malaria-endemic countries in Africa and Asia have adopted artemisinin combination therapy (ACT) as antimalarial drug policy. Several ACT drugs exist and others are in the pipeline. If properly targeted, they have the potential to reduce mortality from malaria substantially. The major challenge now is to get the drugs to the right people. Current evidence suggests that most of those who need the drugs do not get them. Simultaneously, a high proportion of those who are given antimalarials do not in fact have malaria. Financial and other barriers mean that, in many settings, the majority of those with malaria, particularly the poorest, do not access formal healthcare, so the provision of free antimalarials via this route has only limited impact. The higher cost of ACT creates a market for fake drugs. Addressing these problems is now a priority. This review outlines current evidence, possible solutions and research priorities

Acute weight gain, gender, and therapeutic response to antipsychotics in the treatment of patients with schizophrenia

BACKGROUND: Previous research indicated that women are more vulnerable than men to adverse psychological consequences of weight gain. Other research has suggested that weight gain experienced during antipsychotic therapy may also psychologically impact women more negatively. This study assessed the impact of acute treatment-emergent weight gain on clinical and functional outcomes of patients with schizophrenia by patient gender and antipsychotic treatment (olanzapine or haloperidol). METHODS: Data were drawn from the acute phase (first 6-weeks) of a double-blind randomized clinical trial of olanzapine versus haloperidol in the treatment of 1296 men and 700 women with schizophrenia-spectrum disorders. The associations between weight change and change in core schizophrenia symptoms, depressive symptoms, and functional status were examined post-hoc for men and women and for each medication group. Core schizophrenia symptoms (positive and negative) were measured with the Brief Psychiatric Rating Scale (BPRS), depressive symptoms with the BPRS Anxiety/Depression Scale and the Montgomery-Asberg Depression Rating Scale, and functional status with the mental and physical component scores on the Medical Outcome Survey-Short Form 36. Statistical analysis included methods that controlled for treatment duration. RESULTS: Weight gain during 6-week treatment with olanzapine and haloperidol was significantly associated with improvements in core schizophrenia symptoms, depressive symptoms, mental functioning, and physical functioning for men and women alike. The conditional probability of clinical response (20% reduction in core schizophrenia symptom), given a clinically significant weight gain (at least 7% of baseline weight), showed that about half of the patients who lost weight responded to treatment, whereas three-quarters of the patients who had a clinically significant weight gain responded to treatment. The positive associations between therapeutic response and weight gain were similar for the olanzapine and haloperidol treatment groups. Improved outcomes were, however, more pronounced for the olanzapine-treated patients, and more olanzapine-treated patients gained weight. CONCLUSIONS: The findings of significant relationships between treatment-emergent weight gain and improvements in clinical and functional status at 6-weeks suggest that patients who have greater treatment-emergent weight gain are more likely to benefit from treatment with olanzapine or haloperidol regardless of gender

Crystal Structure and Size-Dependent Neutralization Properties of HK20, a Human Monoclonal Antibody Binding to the Highly Conserved Heptad Repeat 1 of gp41

The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 Å resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a conserved hydrophobic HR1 pocket that is occupied by HR2 residues in the gp41 post fusion conformation. Compared to the previously described HR1-specific mAb D5, HK20 approaches its epitope with a different angle which might favor epitope access and thus contribute to its higher neutralization breadth and potency. Comparison of the neutralization activities of HK20 IgG, Fab and scFv employing both single cycle and multiple cycle neutralization assays revealed much higher potencies for the smaller Fab and scFv over IgG, implying that the target site is difficult to access for complete antibodies. Nevertheless, two thirds of sera from HIV-1 infected individuals contain significant titers of HK20-inhibiting antibodies. The breadth of neutralization of primary isolates across all clades, the higher potencies for C-clade viruses and the targeting of a distinct site as compared to the fusion inhibitor T-20 demonstrate the potential of HK20 scFv as a therapeutic tool