133 research outputs found

    The influence of föhn winds on annual and seasonal surface melt on the Larsen C Ice Shelf, Antarctica

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    Abstract. Warm, dry föhn winds are observed over the Larsen C Ice Shelf year-round and are thought to contribute to the continuing weakening and collapse of ice shelves on the eastern Antarctic Peninsula (AP). We use a surface energy balance (SEB) model, driven by observations from two locations on the Larsen C Ice Shelf and one on the remnants of Larsen B, in combination with output from the Antarctic Mesoscale Prediction System (AMPS), to investigate the year-round impact of föhn winds on the SEB and melt from 2009 to 2012. Föhn winds have an impact on the individual components of the surface energy balance in all seasons and lead to an increase in surface melt in spring, summer and autumn up to 100 km away from the foot of the AP. When föhn winds occur in spring they increase surface melt, extend the melt season and increase the number of melt days within a year. Whilst AMPS is able to simulate the percentage of melt days associated with föhn with high skill, it overestimates the total amount of melting during föhn events and non-föhn events. This study extends previous attempts to quantify the impact of föhn on the Larsen C Ice Shelf by including a 4-year study period and a wider area of interest and provides evidence for föhn-related melting on both the Larsen C and Larsen B ice shelves. </jats:p

    The HLA class II allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis

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    Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients. Methods/Principal Findings: HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3-2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DLCO) compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036). Conclusions/Significance: DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease

    Alzheimer's disease polygenic risk score as a predictor of conversion from mild-cognitive impairment

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    Mild-cognitive impairment (MCI) occurs in up to one-fifth of individuals over the age of 65, with approximately a third of MCI individuals converting to dementia in later life. There is a growing necessity for early identification for those at risk of dementia as pathological processes begin decades before onset of symptoms. A cohort of 122 individuals diagnosed with MCI and followed up for a 36-month period for conversion to late-onset Alzheimer’s disease (LOAD) were genotyped on the NeuroChip array along with pathologically confirmed cases of LOAD and cognitively normal controls. Polygenic risk scores (PRS) for each individual were generated using PRSice-2, derived from summary statistics produced from the International Genomics of Alzheimer’s Disease Project (IGAP) genome-wide association study. Predictability models for LOAD were developed incorporating the PRS with APOE SNPs (rs7412 and rs429358), age and gender. This model was subsequently applied to the MCI cohort to determine whether it could be used to predict conversion from MCI to LOAD. The PRS model for LOAD using area under the precision-recall curve (AUPRC) calculated a predictability for LOAD of 82.5%. When applied to the MCI cohort predictability for conversion from MCI to LOAD was 61.0%. Increases in average PRS scores across diagnosis group were observed with one-way ANOVA suggesting significant differences in PRS between the groups (p < 0.0001). This analysis suggests that the PRS model for LOAD can be used to identify individuals with MCI at risk of conversion to LOAD

    Application of Graphene within Optoelectronic Devices and Transistors

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    Scientists are always yearning for new and exciting ways to unlock graphene's true potential. However, recent reports suggest this two-dimensional material may harbor some unique properties, making it a viable candidate for use in optoelectronic and semiconducting devices. Whereas on one hand, graphene is highly transparent due to its atomic thickness, the material does exhibit a strong interaction with photons. This has clear advantages over existing materials used in photonic devices such as Indium-based compounds. Moreover, the material can be used to 'trap' light and alter the incident wavelength, forming the basis of the plasmonic devices. We also highlight upon graphene's nonlinear optical response to an applied electric field, and the phenomenon of saturable absorption. Within the context of logical devices, graphene has no discernible band-gap. Therefore, generating one will be of utmost importance. Amongst many others, some existing methods to open this band-gap include chemical doping, deformation of the honeycomb structure, or the use of carbon nanotubes (CNTs). We shall also discuss various designs of transistors, including those which incorporate CNTs, and others which exploit the idea of quantum tunneling. A key advantage of the CNT transistor is that ballistic transport occurs throughout the CNT channel, with short channel effects being minimized. We shall also discuss recent developments of the graphene tunneling transistor, with emphasis being placed upon its operational mechanism. Finally, we provide perspective for incorporating graphene within high frequency devices, which do not require a pre-defined band-gap.Comment: Due to be published in "Current Topics in Applied Spectroscopy and the Science of Nanomaterials" - Springer (Fall 2014). (17 pages, 19 figures

    Psychological and social consequences among mothers suffering from perinatal loss: perspective from a low income country

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    <p>Abstract</p> <p>Background</p> <p>In developed countries, perinatal death is known to cause major emotional and social effects on mothers. However, little is known about these effects in low income countries which bear the brunt of perinatal mortality burden. This paper reports the impact of perinatal death on psychological status and social consequences among mothers in a rural area of Bangladesh.</p> <p>Methods</p> <p>A total of 476 women including 122 women with perinatal deaths were assessed with the Edinburgh Postnatal Depression Scale (EPDS-B) at 6 weeks and 6 months postpartum, and followed up for negative social consequences at 6 months postpartum. Trained female interviewers carried out structured interviews at women's home.</p> <p>Results</p> <p>Overall 43% (95% CI: 33.7-51.8%) of women with a perinatal loss at 6 weeks postpartum were depressed compared to 17% (95% CI: 13.7-21.9%) with healthy babies (p = < 0.001). Depression status were significantly associated with women reporting negative life changes such as worse relationships with their husband (adjusted OR = 3.89, 95% CI: 1.37-11.04) and feeling guilty (adjusted OR = 2.61, 95% CI: 1.22-5.63) following the results of their last pregnancy outcome after 6 months of childbirth.</p> <p>Conclusions</p> <p>This study highlights the greatly increased vulnerability of women with perinatal death to experience negative psychological and social consequences. There is an urgent need to develop appropriate mental health care services for mothers with perinatal deaths in Bangladesh, including interventions to develop positive family support.</p

    Microbiological profiles of sputum and gastric juice aspirates in Cystic Fibrosis patients.

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    Gastro-Oesophageal Reflux (GOR) is a key problem in Cystic Fibrosis (CF), but the relationship between lung and gastric microbiomes is not well understood. We hypothesised that CF gastric and lung microbiomes are related. Gastric and sputum cultures were obtained from fifteen CF patients receiving percutaneous endoscopic gastrostomy feeding. Non-CF gastric juice data was obtained through endoscopy from 14 patients without lung disease. Bacterial and fungal isolates were identified by culture. Molecular bacterial profiling used next generation sequencing (NGS) of the 16S rRNA gene. Cultures grew bacteria and/or fungi in all CF gastric juice and sputa and in 9/14 non-CF gastric juices. Pseudomonas aeruginosa(Pa) was present in CF sputum in 11 patients, 4 had identical Pa strains in the stomach. NGS data from non-CF gastric juice samples were significantly more diverse compared to CF samples. NGS showed CF gastric juice had markedly lower abundance of normal gut bacteria; Bacteroides and Faecalibacterium, but increased Pseudomonas compared with non-CF. Multivariate partial least squares discriminant analysis demonstrated similar bacterial profiles of CF sputum and gastric juice samples, which were distinct from non-CF gastric juice. We provide novel evidence suggesting the existence of an aerodigestive microbiome in CF, which may have clinical relevance

    Iterative Structure-Based Peptide-Like Inhibitor Design against the Botulinum Neurotoxin Serotype A

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    The botulinum neurotoxin serotype A light chain (BoNT/A LC) protease is the catalytic component responsible for the neuroparalysis that is characteristic of the disease state botulism. Three related peptide-like molecules (PLMs) were designed using previous information from co-crystal structures, synthesized, and assayed for in vitro inhibition against BoNT/A LC. Our results indicate these PLMS are competitive inhibitors of the BoNT/A LC protease and their Ki values are in the nM-range. A co-crystal structure for one of these inhibitors was determined and reveals that the PLM, in accord with the goals of our design strategy, simultaneously involves both ionic interactions via its P1 residue and hydrophobic contacts by means of an aromatic group in the P2′ position. The PLM adopts a helical conformation similar to previously determined co-crystal structures of PLMs, although there are also major differences to these other structures such as contacts with specific BoNT/A LC residues. Our structure further demonstrates the remarkable plasticity of the substrate binding cleft of the BoNT/A LC protease and provides a paradigm for iterative structure-based design and development of BoNT/A LC inhibitors

    The Population Structure of Acinetobacter baumannii: Expanding Multiresistant Clones from an Ancestral Susceptible Genetic Pool

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    Outbreaks of hospital infections caused by multidrug resistant Acinetobacter baumannii strains are of increasing concern worldwide. Although it has been reported that particular outbreak strains are geographically widespread, little is known about the diversity and phylogenetic relatedness of A. baumannii clonal groups. Sequencing of internal portions of seven housekeeping genes (total 2,976 nt) was performed in 154 A. baumannii strains covering the breadth of known diversity and including representatives of previously recognized international clones, and in 19 representatives of other Acinetobacter species. Restricted amounts of diversity and a star-like phylogeny reveal that A. baumannii is a genetically compact species that suffered a severe bottleneck in the recent past, possibly linked to a restricted ecological niche. A. baumannii is neatly demarcated from its closest relative (genomic species 13TU) and other Acinetobacter species. Multilocus sequence typing analysis demonstrated that the previously recognized international clones I to III correspond to three clonal complexes, each made of a central, predominant genotype and few single locus variants, a hallmark of recent clonal expansion. Whereas antimicrobial resistance was almost universal among isolates of these and a novel international clone (ST15), isolates of the other genotypes were mostly susceptible. This dichotomy indicates that antimicrobial resistance is a major selective advantage that drives the ongoing rapid clonal expansion of these highly problematic agents of nosocomial infections
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