Predicting the effectiveness of hepatitis C virus neutralizing antibodies by bioinformatic analysis of conserved epitope residues using public sequence data

Hepatitis C virus (HCV) is a global health issue. Although direct-acting antivirals are available to target HCV, there is currently no vaccine. The diversity of the virus is a major obstacle to HCV vaccine development. One approach toward a vaccine is to utilize a strategy to elicit broadly neutralizing antibodies (bNAbs) that target highly-conserved epitopes. The conserved epitopes of bNAbs have been mapped almost exclusively to the E2 glycoprotein. In this study, we have used HCV-GLUE, a bioinformatics resource for HCV sequence data, to investigate the major epitopes targeted by well-characterized bNAbs. Here, we analyze the level of conservation of each epitope by genotype and subtype and consider the most promising bNAbs identified to date for further study as potential vaccine leads. For the most conserved epitopes, we also identify the most prevalent sequence variants in the circulating HCV population. We examine the distribution of E2 sequence data from across the globe and highlight regions with no coverage. Genotype 1 is the most prevalent genotype worldwide, but in many regions, it is not the dominant genotype. We find that the sequence conservation data is very encouraging; several bNAbs have a high level of conservation across all genotypes suggesting that it may be unnecessary to tailor vaccines according to the geographical distribution of genotypes

Scaffold searching: automated identification of similar ring systems for the design of combinatorial libraries

Rigid ring systems can be used to position receptor-binding functional groups in 3D space and they thus play an increasingly important role in the design of combinatorial libraries. This paper discusses the use of shape-similarity methods to identify ring systems that are structurally similar to, and aligned with, a user-defined target ring system. These systems can be used as alternative scaffolds for the construction of a combinatorial library

Tracking system study

A digital computer program was generated which mathematically describes an optimal estimator-controller technique as applied to the control of antenna tracking systems used by NASA. Simulation studies utilizing this program were conducted using the IBM 360/91 computer. The basic ideas of applying optimal estimator-controller techniques to antenna tracking systems are discussed. A survey of existing tracking methods is given along with shortcomings and inherent errors. It is explained how these errors can be considerably reduced if optimal estimation and control are used. The modified programs generated in this project are described and the simulation results are summarized. The new algorithms for direct synthesis and stabilization of the systems including nonlinearities, are presented

Australian health policy on access to medical care for refugees and asylum seekers

Since the tightening of Australian policy for protection visa applicants began in the 1990s, access to health care has been increasingly restricted to asylum seekers on a range of different visa types. This paper summarises those legislative changes and discusses their implications for health policy relating to refugees and asylum seekers in Australia. Of particular concern are asylum seekers on Bridging Visas with no work rights and no access to Medicare. The paper examines several key questions: What is the current state of play, in terms of health screening and medical care policies, for asylum seekers and refugees? Relatedly, how has current policy changed from that of the past? How does Australia compare with other countries in relation to health policy for asylum seekers and refugees? These questions are addressed with the aim of providing a clear description of the current situation concerning Australian health policy on access to medical care for asylum seekers and refugees. Issues concerning lack of access to appropriate health care and related services are raised, ethical and practical issues are explored, and current policy gaps are investigated

FOOD HABITS OF COYOTES (CANIS LATRANS) IN THE VALLES CALDERA NATIONAL PRESERVE, NEW MEXICO

Wildlife managers needed to understand coyote (Canis latrans) ecology in order to develop management plans on the nascent Valles Caldera National Preserve in northern New Mexico. Managers concerned about low elk (Cervus elaphus) recruitment had observed an increase in sightings of coyotes and observations of coyote predation on elk calves. Our objective was to identify and quantify coyote diet, and assess the temporal variation in coyote diet on the Valles Caldera National Preserve, particularly as related to elk calf consumption. We examined coyote food habits using 1,385 scats analyzed monthly from May 2005 to November 2008. The most frequent taxa were rodents (predominantly voles from the genus Microtus, and northern pocket gophers, Thomomys talpoides), elk, insects from the orders Orthoptera (grasshoppers and crickets) and Coleoptera (beetles), mountain cottontail rabbit (Sylvilagus nuttallii), and plant material (mainly grass). We detected rodent and elk in scats during all months of the study and were each present in 54% of scats overall. We identified elk remains in 43% of spring scats, 72% of winter scats, and 56% of fall scats. During summers, we could distinguish calf from adult elk hair: 8% of summer the scats contained adult elk hair and 39% contained calf elk hair. The frequency of prey items varied significantly over most seasons and years, with notable exceptions being that elk did not vary among summers and winters, and rabbits were a consistent diet item through all seasons. The high frequency of elk in the coyote diet bears further study on the density of elk calves, the vulnerability of elk to predation, the nutritional impacts from the quality of forage available to elk, and the role of hunting and other mammalian predators in providing carcasses

Space use and social ecology of coyotes (\u3ci\u3eCanis latrans\u3c/i\u3e) in a high-elevation ecosystem: relative stability in a changing environment

Coyote (Canis latrans) spatial and social ecology are variable, but have been little studied in high-elevation environments. In these temperate ecosystems, large ungulates are prevalent and coyote pack size may be large in order for them to scavenge and defend ungulate carcasses from conspecifics in neighboring packs. We initiated a study to understand the spatial and social ecology of coyotes on the Valles Caldera National Preserve, a high-elevation (2450–3400 m) protected area in northern New Mexico. Our objectives were to (1) describe the home range size and habitat use of coyotes in the preserve, (2) describe coyote movements within and outside of packs, and (3) to evaluate the relationship between coyote social cohesion and the amount of elk (Cervus elaphus) in the coyote diet. We acquired global positioning system and telemetry locations from 33 coyotes from August 2005 to July 2009. We classified 23 coyotes (70 % of individuals) as residents (i.e., territorial) during at least part of the study and ten coyotes (30 %) as transients. Overall mean home range size of resident packs was 10.6 ± 2.2 (SD) km2. Home range size varied between packs, but did not vary by season or year. Coyotes used dry and wet meadow habitats as expected based on availability; coyotes used riparian habitat more than expected, and forests less than expected. Social cohesion did not vary among biological seasons. Alpha coyotes were more socially cohesive with each other than with other pack members, and a transient exhibited temporal–spatial avoidance of pack members while inside the pack’s territory followed by integration into the pack. Contrary to expectations, we found no relationship between coyote social cohesion and the proportion of elk in coyote diets. We concluded that coyote space use and sociality on the preserve were relatively stable year-round despite changes in biological needs, snow depth, and utilization of variously sized prey

Comparative analysis reveals the long-term co-evolutionary history of parvoviruses and vertebrates [preprint]

Parvoviruses (family Parvoviridae) are small, non-enveloped DNA viruses that infect a broad range of animal species. Comparative studies, supported by experimental evidence, show that many vertebrate species contain sequences derived from ancient parvoviruses embedded in their genomes. These ‘endogenous parvoviral elements’ (EPVs), which arose via recombination-based mechanisms in infected germline cells of ancestral organisms, constitute a form of ‘molecular fossil record’ that can be used to investigate the origin and evolution of the parvovirus family. Here, we use comparative approaches to investigate 198 EPV loci, represented by 470 EPV sequences identified in a comprehensive in silico screen of 752 published vertebrate genomes. We investigated EPV loci by constructing an open resource that contains all of the data items required for comparative sequence analysis of parvoviruses and uses a relational database to represent the complex semantic relationships between them. We used this standardised framework to implement reproducible comparative phylogenetic analysis of combined EPV and virus data. Our analysis reveals that viruses closely related to contemporary parvoviruses have circulated among vertebrates since the Late Cretaceous epoch (100-66 million years ago). We present evidence that the subfamily Parvovirinae, which includes ten vertebrate-specific genera, has evolved in broad congruence with the emergence and diversification of major vertebrate groups. Furthermore, we infer defining aspects of evolution within individual parvovirus genera - mammalian vicariance for protoparvoviruses (genus Protoparvovirus), and inter-class transmission for dependoparvoviruses (genus Dependoparvovirus) - thereby establishing an ecological and evolutionary perspective through which to approach analysis of these virus groups. We also identify evidence of EPV expression at RNA level and show that EPV coding sequences have frequently been maintained during evolution, adding to a growing body of evidence that EPV loci have been co-opted or exapted by vertebrate species, and especially by mammals. Our findings offer fundamental insights into parvovirus evolution. In addition, we establish novel genomic resources that can advance the development of parvovirus-related research - including both therapeutics and disease prevention efforts - by enabling more efficient dissemination and utilisation of relevant, evolution-related domain knowledge

Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome

Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P = .041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis

Core handling and processing for the WAIS Divide ice-core project

On 1 December 2011 the West Antarctic Ice Sheet (WAIS) Divide ice-core project reached its final depth of 3405 m. The WAIS Divide ice core is not only the longest US ice core to date, but is also the highest-quality deep ice core, including ice from the brittle ice zone, that the US has ever recovered. The methods used at WAIS Divide to handle and log the drilled ice, the procedures used to safely retrograde the ice back to the US National Ice Core Laboratory (NICL) and the methods used to process and sample the ice at the NICL are described and discussed

The 4-H Dairy Club

June, 1939."Prepared by M. J. Regan and Warren Gifford, Extension Dairyman, in collaboration with T. T. Martin and E . T. Itschner, State Club Agents. Acknowledgment is made of material used from Mo. Exp. Sta. Bul. 377, 'Raising the Dairy Calf,' by A. H. A. Herman."Cover title.I. Calf -- II. Heifer -- III. Cow -- IV. Cow testing