799 research outputs found
Evidence for a Positive Cosmological Constant from Flows of Galaxies and Distant Supernovae
Recent observations of high-redshift supernovae seem to suggest that the
global geometry of the Universe may be affected by a `cosmological constant',
which acts to accelerate the expansion rate with time. But these data by
themselves still permit an open universe of low mass density and no
cosmological constant. Here we derive an independent constraint on the lower
bound to the mass density, based on deviations of galaxy velocities from a
smooth universal expansion. This constraint rules out a low-density open
universe with a vanishing cosmological constant, and together the two favour a
nearly flat universe in which the contributions from mass density and the
cosmological constant are comparable. This type of universe, however, seems to
require a degree of fine tuning of the initial conditions that is in apparent
conflict with `common wisdom'.Comment: 8 pages, 1 figure. Slightly revised version. Letter to Natur
Trends and variation in mild disability and functional limitations among older adults in Norway, 1986–2008
An increase in the number of older adults may raise the demand for health and care services, whereas decreasing prevalence of disability and functional limitations among them might counteract this demographic effect. However, the trends in health are inconsistent between studies and countries. In this article, we estimated the trends in mild disability and functional limitations among older Norwegians and analyzed whether they differ between socio-demographic groups. Data were obtained from repeated cross-sectional surveys conducted in 1987, 1991, 1995, 2002, 2005, and 2008, in total 4,036 non-institutionalized persons aged 67 years or older. We analyzed trends using multivariate logistic regression. On average, the age-adjusted trend in functional limitations was −3.3% per year, and in disability 3.4% per year. The risk for functional limitations or disability was elevated for women compared to men, for married compared to non-married, and was inversely associated with educational level The trends were significantly weaker with increasing age for disabilities, whereas none of the trends differed significantly between subgroups of sexes, educational level or marital status. Both functional limitations free and disability-free life expectancy appeared to have increased more than total life expectancy at age 67 during this period. The analysis suggests downward trends in the prevalence of mild disability and functional limitations among older Norwegians between 1987 and 2008 and a compression of lifetime in such health states. The reduced numbers of older people with disability and functional limitations may have restrained the demand for health and care services caused by the increase in the number of older adults
Charting the landscape of N=4 flux compactifications
We analyse the vacuum structure of isotropic Z_2 x Z_2 flux
compactifications, allowing for a single set of sources. Combining algebraic
geometry with supergravity techniques, we are able to classify all vacua for
both type IIA and IIB backgrounds with arbitrary gauge and geometric fluxes.
Surprisingly, geometric IIA compactifications lead to a unique theory with four
different vacua. In this case we also perform the general analysis allowing for
sources compatible with minimal supersymmetry. Moreover, some relevant examples
of type IIB non-geometric compactifications are studied. The computation of the
full N=4 mass spectrum reveals the presence of a number of non-supersymmetric
and nevertheless stable AdS_4 vacua. In addition we find a novel dS_4 solution
based on a non-semisimple gauging.Comment: Minor corrections and references added. Version published in JHE
Genetic, environmental and stochastic factors in monozygotic twin discordance with a focus on epigenetic differences
PMCID: PMC3566971This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease
Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al
Spin-2 spectrum of defect theories
We study spin-2 excitations in the background of the recently-discovered
type-IIB solutions of D'Hoker et al. These are holographically-dual to defect
conformal field theories, and they are also of interest in the context of the
Karch-Randall proposal for a string-theory embedding of localized gravity. We
first generalize an argument by Csaki et al to show that for any solution with
four-dimensional anti-de Sitter, Poincare or de Sitter invariance the spin-2
excitations obey the massless scalar wave equation in ten dimensions. For the
interface solutions at hand this reduces to a Laplace-Beltrami equation on a
Riemann surface with disk topology, and in the simplest case of the
supersymmetric Janus solution it further reduces to an ordinary differential
equation known as Heun's equation. We solve this equation numerically, and
exhibit the spectrum as a function of the dilaton-jump parameter .
In the limit of large a nearly-flat linear-dilaton dimension grows
large, and the Janus geometry becomes effectively five-dimensional. We also
discuss the difficulties of localizing four-dimensional gravity in the more
general backgrounds with NS5-brane or D5-brane charge, which will be analyzed
in detail in a companion paper.Comment: 41 pages, 6 figure
Comparison of Population-Based Association Study Methods Correcting for Population Stratification
Population stratification can cause spurious associations in population–based association studies. Several statistical methods have been proposed to reduce the impact of population stratification on population–based association studies. We simulated a set of stratified populations based on the real haplotype data from the HapMap ENCODE project, and compared the relative power, type I error rates, accuracy and positive prediction value of four prevailing population–based association study methods: traditional case-control tests, structured association (SA), genomic control (GC) and principal components analysis (PCA) under various population stratification levels. Additionally, we evaluated the effects of sample sizes and frequencies of disease susceptible allele on the performance of the four analytical methods in the presence of population stratification. We found that the performance of PCA was very stable under various scenarios. Our comparison results suggest that SA and PCA have comparable performance, if sufficient ancestral informative markers are used in SA analysis. GC appeared to be strongly conservative in significantly stratified populations. It may be better to apply GC in the stratified populations with low stratification level. Our study intends to provide a practical guideline for researchers to select proper study methods and make appropriate inference of the results in population-based association studies
Serum 25-Hydroxyvitamin D and Risk of Lung Cancer in Male Smokers: A Nested Case-Control Study
A role for vitamin D in cancer risk reduction has been hypothesized, but few data exist for lung cancer. We investigated the relationship between vitamin D status, using circulating 25-hydroxyvitamin D [25(OH)D], and lung cancer risk in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers.Lung cancer cases (n = 500) were randomly selected based on month of blood collection, and 500 controls were matched to them based on age and blood collection date. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate-adjusted conditional logistic regression. To account for seasonal variation in 25(OH)D concentrations, season-specific and season-standardized quintiles of 25(OH)D were examined, and models were also stratified on season of blood collection (darker season = November-April and sunnier season = May-October). Pre-determined, clinically-defined cutpoints for 25(OH)D and 25(OH)D as a continuous measure were also examined.Overall, 25(OH)D was not associated with lung cancer. Risks were 1.08 (95% CI 0.67-1.75) and 0.83 (95% CI 0.53-1.31) in the highest vs. lowest season-specific and season-standardized quintiles of 25(OH)D, respectively, and 0.91 (95% CI 0.48-1.72) for the ≥75 vs. <25 nmol/L clinical categories. Inverse associations were, however, suggested for subjects with blood collections from November-April, with ORs of 0.77 (95% CI 0.41-1.45, p-trend = 0.05) and 0.65 (95% CI 0.37-1.14, p-trend = 0.07) in the highest vs. lowest season-specific and season-standardized quintiles of 25(OH)D, respectively, and 0.61 (95% CI 0.24-1.52, p-trend = 0.01) for ≥75 vs. <25 nmol/L. We also found 11% lower risk for a 10 nmol/L increase in 25(OH)D in the darker season based on the continuous measure (OR = 0.89, 95% CI 0.81-0.98, p = 0.02).In this prospective study of male smokers, circulating 25(OH)D was not associated with lung cancer risk overall, although inverse associations were suggested among those whose blood was drawn during darker months
Early- and advanced non-enzymatic glycation in diabetic vascular complications: the search for therapeutics
Cardiovascular disease is a common complication of diabetes and the leading cause of death among people with diabetes. Because of the huge premature morbidity and mortality associated with diabetes, prevention of vascular complications is a key issue. Although the exact mechanism by which vascular damage occurs in diabetes in not fully understood, numerous studies support the hypothesis of a causal relationship of non-enzymatic glycation with vascular complications. In this review, data which point to an important role of Amadori-modified glycated proteins and advanced glycation endproducts in vascular disease are surveyed. Because of the potential role of early- and advanced non-enzymatic glycation in vascular complications, we also described recent developments of pharmacological inhibitors that inhibit the formation of these glycated products or the biological consequences of glycation and thereby retard the development of vascular complications in diabetes
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