56 research outputs found
Sequential bottlenecks drive viral evolution in early acute Hepatitis C virus infection
Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection
Grain Surface Models and Data for Astrochemistry
AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of âŒ25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions
The Origin of the Pseudogap in Underdoped HTSC
Here the Origin of the pseudogap in HTSC is attributed to the modulated
antiferromagnetic (AFM) phase, whose preliminary version has been sketched
recently by the present author [1](arXiv:0901.3896v2 (cond.-mat.sup-con)).
Starting from the t-J Hamiltonian, I show that the formal failure of the
perturbation theory leads to a transformation to the pseudogap phase. This
phase is characterized by the aggregation of the holes into rows and columns,
which in turn results in two internal fields. The first is the modulated AFM
field, whose main evidence comes from Neutron scattering experiments. The
second internal field is made up by the checkerboard charge density waves that
have been observed by Scanning Tunneling Measurements. The present paper deals
mainly with the internal field of the first type, and discusses the second type
only tentatively. Formalism is derived that yields the ground state, the
internal field, the Hamiltonian, and the propagators of the condensed phase.
Our results resolve the presumably inherent self contradictory concept of
pseudogap. It is shown that the excitation energy spectrum is gapless despite
the order parameter that is inherent to the condensed system. In addition, it
is shown qualitatively that our model predicts "Fermi surface" that is in
agreement with experiment
Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder
This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of MĂŒnster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de EconomĂa, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch
TolerĂąncia e potencial fitorremediador de Stizolobium aterrimum associada ao fungo micorrĂzico arbuscular Glomus etunicatum em solo contaminado por chumbo
Auroral Processes at the Giant Planets: Energy Deposition, Emission Mechanisms, Morphology and Spectra
Simulation support for the formulation of domestic sector upgrading strategies
This paper describes the application of a building simulation program to construct a decision-support tool for use by policy makers addressing the needs of the Scottish domestic housing sector. The process of tool formulation is described and an example given of its use to identify best-value retrofit options while taking factors such as future climate change and improved standard of living into consideration. It is argued that the process of tool formation renders it applicable to the cumulative roll-out of upgrade measures in the long term, both within and outwith the UK
THE IMPACT OF INTRA HOUSEHOLD BALANCE OF POWER ON EXPENDITURE PATTERN: THE AUSTRALIAN EVIDENCE*
Intra-Household Resource Allocation, Consumer Preferences and Commodity Tax Reforms: Australian Evidence
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