267 research outputs found
Accelerated expansion from ghost-free bigravity: a statistical analysis with improved generality
We study the background cosmology of the ghost-free, bimetric theory of
gravity. We perform an extensive statistical analysis of the model using both
frequentist and Bayesian frameworks and employ the constraints on the expansion
history of the Universe from the observations of supernovae, the cosmic
microwave background and the large scale structure to estimate the model's
parameters and test the goodness of the fits. We explore the parameter space of
the model with nested sampling to find the best-fit chi-square, obtain the
Bayesian evidence, and compute the marginalized posteriors and mean
likelihoods. We mainly focus on a class of sub-models with no explicit
cosmological constant (or vacuum energy) term to assess the ability of the
theory to dynamically cause a late-time accelerated expansion. The model
behaves as standard gravity without a cosmological constant at early times,
with an emergent extra contribution to the energy density that converges to a
cosmological constant in the far future. The model can in most cases yield very
good fits and is in perfect agreement with the data. This is because many
points in the parameter space of the model exist that give rise to
time-evolution equations that are effectively very similar to those of the
CDM. This similarity makes the model compatible with observations as
in the CDM case, at least at the background level. Even though our
results indicate a slightly better fit for the CDM concordance model
in terms of the -value and evidence, none of the models is statistically
preferred to the other. However, the parameters of the bigravity model are in
general degenerate. A similar but perturbative analysis of the model as well as
more data will be required to break the degeneracies and constrain the
parameters, in case the model will still be viable compared to the
CDM.Comment: 42 pages, 9 figures; typos corrected in equations (2.12), (2.13),
(3.7), (3.8) and (3.9); more discussions added (footnotes 5, 8, 10 and 13)
and abstract, sections 4.2, 4.3 and 5 (conclusions) modified in response to
referee's comments; references added; acknowledgements modified; all results
completely unchanged; matches version accepted for publication in JHE
Diffusion of electrons in random magnetic fields,
Diffusion of electrons in a two-dimensional system in static random magnetic
fields is studied by solving the time-dependent Schr\"{o}dinger equation
numerically. The asymptotic behaviors of the second moment of the wave packets
and the temporal auto-correlation function in such systems are investigated. It
is shown that, in the region away from the band edge, the growth of the
variance of the wave packets turns out to be diffusive, whereas the exponents
for the power-law decay of the temporal auto- correlation function suggest a
kind of fractal structure in the energy spectrum and in the wave functions. The
present results are consistent with the interpretation that the states away
from the band edge region are critical.Comment: 22 pages (8 figures will be mailed if requested), LaTeX, to appear in
Phys. Rev.
Towards a Resolution of the Cosmological Singularity in Non-local Higher Derivative Theories of Gravity
One of the greatest problems of standard cosmology is the Big Bang
singularity. Previously it has been shown that non-local ghostfree
higher-derivative modifications of Einstein gravity in the ultra-violet regime
can admit non-singular bouncing solutions. In this paper we study in more
details the dynamical properties of the equations of motion for these theories
of gravity in presence of positive and negative cosmological constants and
radiation. We find stable inflationary attractor solutions in the presence of a
positive cosmological constant which renders inflation {\it geodesically
complete}, while in the presence of a negative cosmological constant a cyclic
universe emerges. We also provide an algorithm for tracking the super-Hubble
perturbations during the bounce and show that the bouncing solutions are free
from any perturbative instability.Comment: 38 pages, 6 figures. V2: Added: a word to the title, clarifications,
an appendix, many references. To appear in JCA
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe
The Extragalactic Background Light (EBL) includes photons with wavelengths
from ultraviolet to infrared, which are effective at attenuating gamma rays
with energy above ~10 GeV during propagation from sources at cosmological
distances. This results in a redshift- and energy-dependent attenuation of the
gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts
(GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray
blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using
photons above 10 GeV collected by Fermi over more than one year of observations
for these sources, we investigate the effect of gamma-ray flux attenuation by
the EBL. We place upper limits on the gamma-ray opacity of the Universe at
various energies and redshifts, and compare this with predictions from
well-known EBL models. We find that an EBL intensity in the optical-ultraviolet
wavelengths as great as predicted by the "baseline" model of Stecker et al.
(2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication
in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A.
Reimer, L.C. Reye
Transforming matters: sustaining gold lifeways in artisanal and small-scale mining
Growth strategies in mining regions promote gold extraction basedonindustrial mining, associating Artisanal and Small-scale Gold Mining (ASGM) with persistent informality. Against this background, we consider how to approach transformations to sustainability in ASGM. Acknowledging how problematic this topic is for sustainability debates,given howASGM is associated with a host of environmental and social problems,we argue that a justice lens demands we confront such challenges within the global politics of sustainability. This leads us to review advances inthe study of ASGM, linked to debates on extractivism, resource materialities, and informality. We use the notion of gold lifeways to capture how the matter of mining shapes different worlds of extraction. We argue that consideration of the potential for transformations to sustainability needs to be grounded within the realities of ASGM. This necessitates giving value to miners’ knowledge(s), perspectives and interests, while recognising the plurality of mining futures. Nevertheless, we conclude that between the immediacy of precarious work and the structural barriers to change in ASGM, the challenges for transformation cannot be underestimated.NWOGlobal Challenges (FSW
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Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies
Funder: Dutch Scientific OrganizationFunder: Foundation Plan AlzheimerFunder: Icelandic Heart AssociationFunder: Academy of FinlandFunder: VicHealth and Cancer Council VictoriaFunder: Juselius FoundationFunder: Uppsala University Hospital and the Swedish Research Council for Health, Working Life and WelfareFunder: the Institut National de la Sante et de la Recherche MedicaleFunder: , the University Bordeaux 2 Victor SegalenFunder: Sanofi; funder-id: http://dx.doi.org/10.13039/100004339Funder: Fondation pour la Recherche Medicale, the Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sante, MGEN, Institut de la Longevite, Conseils Regionaux d’Aquitaine et Bourgogne, Fondation de France, Ministry of Research–Institut National de la Sante and de la Recherche Medicale Programme CohortesFunder: Caisse Nationale pour la Solidarite et l’AutonomieFunder: Swedish Research Council for Health, Working Life and Welfare, Uppsala City Council, Swedish Research Council, and Swedish Diabetes FoundationBackground: De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D). Methods and findings: Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970–1973 to 2006–2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3–75.5 years; % women = 20.4%–62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41–1.66; p < 0.001) for 16:0, 1.40 (1.33–1.48; p < 0.001) for 16:1n-7, 1.14 (1.05–1.22; p = 0.001) for 18:0, and 1.16 (1.07–1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%–73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94–1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors. Conclusions: Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D
Shedding Light on The Role of Keratinocyte-Derived Extracellular Vesicles on Skin-Homing Cells
Extracellular vesicles (EVs) are secretory lipid membranes with the ability to regulate cellular functions by exchanging biological components between different cells. Resident skin cells such as keratinocytes, fibroblasts, melanocytes, and inflammatory cells can secrete different types of EVs depending on their biological state. These vesicles can influence the physiological properties and pathological processes of skin, such as pigmentation, cutaneous immunity, and wound healing. Since keratinocytes constitute the majority of skin cells, secreted EVs from these cells may alter the pathophysiological behavior of other skin cells. This paper reviews the contents of keratinocyte-derived EVs and their impact on fibroblasts, melanocytes, and immune cells to provide an insight for better understanding of the pathophysiological mechanisms of skin disorders and their use in related therapeutic approaches
Monoallelic Variation in DHX9, the Gene Encoding the Dexh-Box Helicase DHX9, Underlies Neurodevelopment Disorders and Charcot-Marie-Tooth Disease
DExD/H-box RNA helicases (DDX/DHX) are encoded by a large paralogous gene family; in a subset of these human helicase genes, pathogenic variation causes neurodevelopmental disorder (NDD) traits and cancer. DHX9 encodes a BRCA1-interacting nuclear helicase regulating transcription, R-loops, and homologous recombination and exhibits the highest mutational constraint of all DDX/DHX paralogs but remains unassociated with disease traits in OMIM. Using exome sequencing and family-based rare-variant analyses, we identified 20 individuals with de novo, ultra-rare, heterozygous missense or loss-of-function (LoF) DHX9 variant alleles. Phenotypes ranged from NDDs to the distal symmetric polyneuropathy axonal Charcot-Marie-Tooth disease (CMT2). Quantitative Human Phenotype Ontology (HPO) analysis demonstrated genotype-phenotype correlations with LoF variants causing mild NDD phenotypes and nuclear localization signal (NLS) missense variants causing severe NDD. We investigated DHX9 variant-associated cellular phenotypes in human cell lines. Whereas wild-type DHX9 was restricted to the nucleus, NLS missense variants abnormally accumulated in the cytoplasm. Fibroblasts from an individual with an NLS variant also showed abnormal cytoplasmic DHX9 accumulation. CMT2-associated missense variants caused aberrant nucleolar DHX9 accumulation, a phenomenon previously associated with cellular stress. Two NDD-associated variants, p.Gly411Glu and p.Arg761Gln, altered DHX9 ATPase activity. The severe NDD-associated variant p.Arg141Gln did not affect DHX9 localization but instead increased R-loop levels and double-stranded DNA breaks. Dhx
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