174 research outputs found

    Generalized stacking fault energy surfaces and dislocation properties of aluminum

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    We have employed the semidiscrete variational generalized Peierls-Nabarro model to study the dislocation core properties of aluminum. The generalized stacking fault energy surfaces entering the model are calculated by using first-principles Density Functional Theory (DFT) with pseudopotentials and the embedded atom method (EAM). Various core properties, including the core width, splitting behavior, energetics and Peierls stress for different dislocations have been investigated. The correlation between the core energetics and dislocation character has been explored. Our results reveal a simple relationship between the Peierls stress and the ratio between the core width and atomic spacing. The dependence of the core properties on the two methods for calculating the total energy (DFT vs. EAM) has been examined. The EAM can give gross trends for various dislocation properties but fails to predict the finer core structures, which in turn can affect the Peierls stress significantly (about one order of magnitude).Comment: 25 pages, 12 figure

    Short-Range Ising Spin Glass: Multifractal Properties

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    The multifractal properties of the Edwards-Anderson order parameter of the short-range Ising spin glass model on d=3 diamond hierarchical lattices is studied via an exact recursion procedure. The profiles of the local order parameter are calculated and analysed within a range of temperatures close to the critical point with four symmetric distributions of the coupling constants (Gaussian, Bimodal, Uniform and Exponential). Unlike the pure case, the multifractal analysis of these profiles reveals that a large spectrum of the α\alpha -H\"older exponent is required to describe the singularities of the measure defined by the normalized local order parameter, at and below the critical point. Minor changes in these spectra are observed for distinct initial distributions of coupling constants, suggesting an universal spectra behavior. For temperatures slightly above T_{c}, a dramatic change in the F(α)F(\alpha) function is found, signalizing the transition.Comment: 8 pages, LaTex, PostScript-figures included but also available upon request. To be published in Physical Review E (01/March 97

    Comprehensive Survey of SNPs in the Affymetrix Exon Array Using the 1000 Genomes Dataset

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    Microarray gene expression data has been used in genome-wide association studies to allow researchers to study gene regulation as well as other complex phenotypes including disease risks and drug response. To reach scientifically sound conclusions from these studies, however, it is necessary to get reliable summarization of gene expression intensities. Among various factors that could affect expression profiling using a microarray platform, single nucleotide polymorphisms (SNPs) in target mRNA may lead to reduced signal intensity measurements and result in spurious results. The recently released 1000 Genomes Project dataset provides an opportunity to evaluate the distribution of both known and novel SNPs in the International HapMap Project lymphoblastoid cell lines (LCLs). We mapped the 1000 Genomes Project genotypic data to the Affymetrix GeneChip Human Exon 1.0ST array (exon array), which had been used in our previous studies and for which gene expression data had been made publicly available. We also evaluated the potential impact of these SNPs on the differentially spliced probesets we had identified previously. Though the 1000 Genomes Project data allowed a comprehensive survey of the SNPs in this particular array, the same approach can certainly be applied to other microarray platforms. Furthermore, we present a detailed catalogue of SNP-containing probesets (exon-level) and transcript clusters (gene-level), which can be considered in evaluating findings using the exon array as well as benefit the design of follow-up experiments and data re-analysis

    Intestinal antibody responses to a live oral poliovirus vaccine challenge among adults previously immunized with inactivated polio vaccine in Sweden.

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    BACKGROUND: Our understanding of the acquisition of intestinal mucosal immunity and the control of poliovirus replication and transmission in later life is still emerging. METHODS: As part of a 2011 randomised, blinded, placebo-controlled clinical trial of the experimental antiviral agent pocapavir (EudraCT 2011-004804-38), Swedish adults, aged 18-50 years, who had previously received four doses of inactivated polio vaccine (IPV) in childhood were challenged with a single dose of monovalent oral polio vaccine type 1 (mOPV1). Using faecal samples collected before and serially, over the course of 45 days, after mOPV1 challenge from a subset of placebo-arm participants who did not receive pocapavir (N=12), we investigated the kinetics of the intestinal antibody response to challenge virus by measuring poliovirus type 1-specific neutralising activity and IgA concentrations. RESULTS: In faecal samples collected prior to mOPV1 challenge, we found no evidence of pre-existing intestinal neutralising antibodies to any of the three poliovirus serotypes. Despite persistent high-titered vaccine virus shedding and rising serum neutralisation responses after mOPV1 challenge, intestinal poliovirus type 1-specific neutralisation remained low with a titer of ≤18.4 across all time points and individuals. Poliovirus types 1-specific, 2-specific and 3-specific IgA remained below the limit of detection for all specimens collected postchallenge. INTERPRETATION: In contrast to recent studies demonstrating brisk intestinal antibody responses to oral polio vaccine challenge in young children previously vaccinated with IPV, this investigation finds that adults previously vaccinated with IPV have only modest intestinal poliovirus type 1-specific neutralisation and no IgA responses that are measurable in stool samples following documented mOPV1 infection

    Evolutionary Analyses of Staphylococcus aureus Identify Genetic Relationships between Nasal Carriage and Clinical Isolates

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    Nasal carriage of Staphylococcus aureus has long been hypothesized to be a major vector for the transmission of virulent strains throughout the community. To address this hypothesis, we have analyzed the relatedness between a cohort of nasal carriage strains and clinical isolates to understand better the genetic conformity therein. To assess the relatedness between nasal carriage and clinical isolates of S. aureus, a genetic association study was conducted using multilocus sequence typing (MLST) and typing of the hypervariable regions of clumping factor and fibronectin binding protein genes. At all loci analyzed, genetic associations between both nasal carriage and clinical isolates were observed. Computational analyses of MLST data indicate that nasal carriage and clinical isolates belong to the same genetic clusters (clades), despite differences in sequence type assignments. Genetic analyses of the hypervariable regions from the clumping factor and fibronectin binding protein genes revealed that not only do clinically relevant strains belong to identical genetic lineages as the nasal carriage isolates within our cohort, but they also exhibit 100% sequence similarity within these regions. The findings of this report indicate that strains of S. aureus being carried asymptomatically throughout the community via nasal colonization are genetically related to those responsible for high levels of morbidity and mortality

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Rapamycin and the transcription factor C/EBPβ as a switch in osteoclast differentiation: implications for lytic bone diseases

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    Lytic bone diseases and in particular osteoporosis are common age-related diseases characterized by enhanced bone fragility due to loss of bone density. Increasingly, osteoporosis poses a major global health-care problem due to the growth of the elderly population. Recently, it was found that the gene regulatory transcription factor CCAAT/enhancer binding protein beta (C/EBPβ) is involved in bone metabolism. C/EBPβ occurs as different protein isoforms of variable amino terminal length, and regulation of the C/EBPβ isoform ratio balance was found to represent an important factor in osteoclast differentiation and bone homeostasis. Interestingly, adjustment of the C/EBPβ isoform ratio by the process of translational control is downstream of the mammalian target of rapamycin kinase (mTOR), a sensor of the nutritional status and a target of immunosuppressive and anticancer drugs. The findings imply that modulating the process of translational control of C/EBPβ isoform expression could represent a novel therapeutic approach in osteolytic bone diseases, including cancer and infection-induced bone loss

    Differential requirements for Tousled-like kinases 1 and 2 in mammalian development

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    The regulation of chromatin structure is critical for a wide range of essential cellular processes. The Tousled-like kinases, TLK1 and TLK2, regulate ASF1, a histone H3/H4 chaperone, and likely other substrates, and their activity has been implicated in transcription, DNA replication, DNA repair, RNA interference, cell cycle progression, viral latency, chromosome segregation and mitosis. However, little is known about the functions of TLK activity in vivo or the relative functions of the highly similar TLK1 and TLK2 in any cell type. To begin to address this, we have generated Tlk1- and Tlk2-deficient mice. We found that while TLK1 was dispensable for murine viability, TLK2 loss led to late embryonic lethality because of placental failure. TLK2 was required for normal trophoblast differentiation and the phosphorylation of ASF1 was reduced in placentas lacking TLK2. Conditional bypass of the placental phenotype allowed the generation of apparently healthy Tlk2-deficient mice, while only the depletion of both TLK1 and TLK2 led to extensive genomic instability, indicating that both activities contribute to genome maintenance. Our data identifies a specific role for TLK2 in placental function during mammalian development and suggests that TLK1 and TLK2 have largely redundant roles in genome maintenance

    Effects of Mountain Pine Beetle on Fuels and Expected Fire Behavior in Lodgepole Pine Forests, Colorado, USA

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    In Colorado and southern Wyoming, mountain pine beetle (MPB) has affected over 1.6 million ha of predominantly lodgepole pine forests, raising concerns about effects of MPB-caused mortality on subsequent wildfire risk and behavior. Using empirical data we modeled potential fire behavior across a gradient of wind speeds and moisture scenarios in Green stands compared three stages since MPB attack (Red [1–3 yrs], Grey [4–10 yrs], and Old-MPB [∼30 yrs]). MPB killed 50% of the trees and 70% of the basal area in Red and Grey stages. Across moisture scenarios, canopy fuel moisture was one-third lower in Red and Grey stages compared to the Green stage, making active crown fire possible at lower wind speeds and less extreme moisture conditions. More-open canopies and high loads of large surface fuels due to treefall in Grey and Old-MPB stages significantly increased surface fireline intensities, facilitating active crown fire at lower wind speeds (>30–55 km/hr) across all moisture scenarios. Not accounting for low foliar moistures in Red and Grey stages, and large surface fuels in Grey and Old-MPB stages, underestimates the occurrence of active crown fire. Under extreme burning conditions, minimum wind speeds for active crown fire were 25–35 km/hr lower for Red, Grey and Old-MPB stands compared to Green. However, if transition to crown fire occurs (outside the stand, or within the stand via ladder fuels or wind gusts >65 km/hr), active crown fire would be sustained at similar wind speeds, suggesting observed fire behavior may not be qualitatively different among MPB stages under extreme burning conditions. Overall, the risk (probability) of active crown fire appears elevated in MPB-affected stands, but the predominant fire hazard (crown fire) is similar across MPB stages and is characteristic of lodgepole pine forests where extremely dry, gusty weather conditions are key factors in determining fire behavior
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