1,402 research outputs found
In silico prediction of the granzyme B degradome
10.1186/1471-2164-12-S3-S1110th Int. Conference on Bioinformatics - 1st ISCB Asia Joint Conference 2011, InCoB 2011/ISCB-Asia 2011: Computational Biology - Proceedings from Asia Pacific Bioinformatics Network (APBioNet)12SUPPL. 3S1
Introduction of article-processing charges for Population Health Metrics
Population Health Metrics is an open-access online electronic journal published by BioMed Central – it is universally and freely available online to everyone, its authors retain copyright, and it is archived in at least one internationally recognised free repository. To fund this, from November 1 2003, authors of articles accepted for publication will be asked to pay an article-processing charge of US$500. This editorial outlines the reasons for the introduction of article-processing charges and the way in which this policy will work. Waiver requests will be considered on a case-by-case basis, by the Editor-in-Chief. Article-processing charges will not apply to authors whose institutions are 'members' of BioMed Central. Current members include NHS England, the World Health Organization, the US National Institutes of Health, Harvard, Princeton and Yale universities, and all UK universities. No charge is made for articles that are rejected after peer review. Many funding agencies have also realized the importance of open access publishing and have specified that their grants may be used directly to pay APCs
Non-Perturbative Superpotentials in F-theory and String Duality
We use open-closed string duality between F-theory on K3xK3 and type II
strings on CY manifolds without branes to study non-perturbative
superpotentials in generalized flux compactifications. On the F-theory side we
obtain the full flux potential including D3-instanton contributions and show
that it leads to an explicit and simple realization of the three ingredients of
the KKLT model for stringy dS vacua. The D3-instanton contribution is highly
non-trivial, can be systematically computed including the determinant factors
and demonstrates that a particular flux lifts very effectively zero modes on
the instanton. On the closed string side, we propose a generalization of the
Gukov-Vafa-Witten superpotential for type II strings on generalized CY
manifolds, depending on all moduli multiplets.Comment: 49 pages, harvmac, 1 figure; references & figures adde
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Modelling the potential non-breeding distribution of Spoon-billed Sandpiper Calidris pygmaea
SummaryThe Spoon-billed Sandpiper Calidris pygmaea is a ‘Critically Endangered’ migratory shorebird. The species faces an array of threats in its non-breeding range, making conservation intervention essential. However, conservation efforts are reliant on identifying the species’ key stopover and wintering sites. Using Maximum Entropy models, we predicted Spoon-billed Sandpiper distribution across the non-breeding range, using data from recent field surveys and satellite tracking. Model outputs suggest only a limited number of stopover sites are suitable for migrating birds, with sites in the Yellow Sea and on the Jiangsu coast in China highlighted as particularly important. All the previously known core wintering sites were identified by the model including the Ganges-Brahmaputra Delta, Nan Thar Island and the Gulf of Mottama. In addition, the model highlighted sites subsequently found to be occupied, and pinpointed potential new sites meriting investigation, notably on Borneo and Sulawesi, and in parts of India and the Philippines. A comparison between the areas identified as most likely to be occupied and protected areas showed that very few locations are covered by conservation designations. Known sites must be managed for conservation as a priority, and potential new sites should be surveyed as soon as is feasible to assess occupancy status. Site protection should take place in concert with conservation interventions including habitat management, discouraging hunting, and fostering alternative livelihoods.Field surveys in Russian non-breeding grounds were supported by RSPB, MHS and NABU. Field surveys in Gulf of Mottama partly supported by BBC Wildlife Fund. Satellite tagging data collection partly supported by The Biodiversity Investigation, Observation and Assessment Program (2019 - 2023) of the Ministry of Ecology and Environment of China, RSPB and a private donor. Bangladesh Spoon-billed Sandpiper Conservation Project’s fieldwork in Meghna Estuary (2015 - 2016) supported by RSPB. Data collection by EL partly supported by Basic research program (budgetary funds), projects number АААА-А19-119022190168-8 and АААА-А19-119021990093-8). PT supported by Moscow State University Grant for Leading Scientific Schools "Depository of the Living Systems" in the MSU Development Program framework. TBL was funded by the Natural Environment Research Council UK, and the IAPETUS Doctoral Training Partnership
Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study.
Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD
Mendelian randomization evaluation of causal effects of fibrinogen on incident coronary heart disease
Background
Fibrinogen is an essential hemostatic factor and cardiovascular disease risk factor. Early
attempts at evaluating the causal effect of fibrinogen on coronary heart disease (CHD) and
myocardial infraction (MI) using Mendelian randomization (MR) used single variant
approaches, and did not take advantage of recent genome-wide association studies
(GWAS) or multi-variant, pleiotropy robust MR methodologies.
Methods and findings
We evaluated evidence for a causal effect of fibrinogen on both CHD and MI using MR. We
used both an allele score approach and pleiotropy robust MR models. The allele score was
composed of 38 fibrinogen-associated variants from recent GWAS. Initial analyses using
the allele score used a meta-analysis of 11 European-ancestry prospective cohorts, free of
CHD and MI at baseline, to examine incidence CHD and MI. We also applied 2 sample MR
methods with data from a prevalent CHD and MI GWAS. Results are given in terms of the
hazard ratio (HR) or odds ratio (OR), depending on the study design, and associated 95%
confidence interval (CI).
In single variant analyses no causal effect of fibrinogen on CHD or MI was observed. In
multi-variant analyses using incidence CHD cases and the allele score approach, the estimated causal effect (HR) of a 1 g/L higher fibrinogen concentration was 1.62 (CI = 1.12,
2.36) when using incident cases and the allele score approach. In 2 sample MR analyses
that accounted for pleiotropy, the causal estimate (OR) was reduced to 1.18 (CI = 0.98, 1.42) and 1.09 (CI = 0.89, 1.33) in the 2 most precise (smallest CI) models, out of 4 models
evaluated. In the 2 sample MR analyses for MI, there was only very weak evidence of a
causal effect in only 1 out of 4 models.
Conclusions
A small causal effect of fibrinogen on CHD is observed using multi-variant MR approaches
which account for pleiotropy, but not single variant MR approaches. Taken together, results
indicate that even with large sample sizes and multi-variant approaches MR analyses still
cannot exclude the null when estimating the causal effect of fibrinogen on CHD, but that any
potential causal effect is likely to be much smaller than observed in epidemiological studies
Enhancement of outflow facility in the murine eye by targeting selected tight-junctions of Schlemm's canal endothelia
The juxtacanalicular connective tissue of the trabecular meshwork together with inner wall endothelium of Schlemm’s canal (SC) provide the bulk of resistance to aqueous outflow from the anterior chamber. Endothelial cells lining SC elaborate tight junctions (TJs), down-regulation of which may widen paracellular spaces between cells, allowing greater fluid outflow. We observed significant increase in paracellular permeability following siRNA-mediated suppression of TJ transcripts, claudin-11, zonula-occludens-1 (ZO-1) and tricellulin in human SC endothelial monolayers. In mice claudin-11 was not detected, but intracameral injection of siRNAs targeting ZO-1 and tricellulin increased outflow facility significantly. Structural qualitative and quantitative analysis of SC inner wall by transmission electron microscopy revealed significantly more open clefts between endothelial cells treated with targeting, as opposed to non-targeting siRNA. These data substantiate the concept that the continuity of SC endothelium is an important determinant of outflow resistance, and suggest that SC endothelial TJs represent a specific target for enhancement of aqueous movement through the conventional outflow system
Computational Cancer Biology: An Evolutionary Perspective
ISSN:1553-734XISSN:1553-735
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