543 research outputs found
Moduli-Induced Vacuum Destabilisation
We look for ways to destabilise the vacuum. We describe how dense matter
environments source a contribution to moduli potentials and analyse the
conditions required to initiate either decompactification or a local shift in
moduli vevs. We consider astrophysical objects such as neutron stars as well as
cosmological and black hole singularities. Regrettably neutron stars cannot
destabilise realistic Planck coupled moduli, which would require objects many
orders of magnitude denser. However gravitational collapse, either in
matter-dominated universes or in black hole formation, inevitably leads to a
destabilisation of the compact volume causing a super-inflationary expansion of
the extra dimensions.Comment: 21 pages, 12 figure
IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection
Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD
A population-specific reference panel empowers genetic studies of Anabaptist populations
Genotype imputation is a powerful strategy for achieving the large sample sizes required for identification of variants underlying complex phenotypes, but imputation of rare variants remains problematic. Genetically isolated populations offer one solution, however population-specific reference panels are needed to assure optimal imputation accuracy and allele frequency estimation. Here we report the Anabaptist Genome Reference Panel (AGRP), the first whole-genome catalogue of variants and phased haplotypes in people of Amish and Mennonite ancestry. Based on high-depth whole-genome sequence (WGS) from 265 individuals, the AGRP contains >12 M high-confidence single nucleotide variants and short indels, of which ~12.5% are novel. These Anabaptist-specific variants were more deleterious than variants with comparable frequencies observed in the 1000 Genomes panel. About 43,000 variants showed enriched allele frequencies in AGRP, consistent with drift. When combined with the 1000 Genomes Project reference panel, the AGRP substantially improved imputation, especially for rarer variants. The AGRP is freely available to researchers through an imputation server
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
Tests of chameleon gravity
Theories of modified gravity, where light scalars with non-trivial self-interactions and non-minimal couplings to matter—chameleon and symmetron theories—dynamically suppress deviations from general relativity in the solar system. On other scales, the environmental nature of the screening means that such scalars may be relevant. The highly-nonlinear nature of screening mechanisms means that they evade classical fifth-force searches, and there has been an intense effort towards designing new and novel tests to probe them, both in the laboratory and using astrophysical objects, and by reinterpreting existing datasets. The results of these searches are often presented using different parametrizations, which can make it difficult to compare constraints coming from different probes. The purpose of this review is to summarize the present state-of-the-art searches for screened scalars coupled to matter, and to translate the current bounds into a single parametrization to survey the state of the models. Presently, commonly studied chameleon models are well-constrained but less commonly studied models have large regions of parameter space that are still viable. Symmetron models are constrained well by astrophysical and laboratory tests, but there is a desert separating the two scales where the model is unconstrained. The coupling of chameleons to photons is tightly constrained but the symmetron coupling has yet to be explored. We also summarize the current bounds on f(R) models that exhibit the chameleon mechanism (Hu and Sawicki models). The simplest of these are well constrained by astrophysical probes, but there are currently few reported bounds for theories with higher powers of R. The review ends by discussing the future prospects for constraining screened modified gravity models further using upcoming and planned experiments
Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease
Background
1Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes.
Methodology
We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.
Principal Findings
We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD.
Significance
Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches
Biomedical informatics and translational medicine
Biomedical informatics involves a core set of methodologies that can provide a foundation for crossing the "translational barriers" associated with translational medicine. To this end, the fundamental aspects of biomedical informatics (e.g., bioinformatics, imaging informatics, clinical informatics, and public health informatics) may be essential in helping improve the ability to bring basic research findings to the bedside, evaluate the efficacy of interventions across communities, and enable the assessment of the eventual impact of translational medicine innovations on health policies. Here, a brief description is provided for a selection of key biomedical informatics topics (Decision Support, Natural Language Processing, Standards, Information Retrieval, and Electronic Health Records) and their relevance to translational medicine. Based on contributions and advancements in each of these topic areas, the article proposes that biomedical informatics practitioners ("biomedical informaticians") can be essential members of translational medicine teams
Varying constants, Gravitation and Cosmology
Fundamental constants are a cornerstone of our physical laws. Any constant
varying in space and/or time would reflect the existence of an almost massless
field that couples to matter. This will induce a violation of the universality
of free fall. It is thus of utmost importance for our understanding of gravity
and of the domain of validity of general relativity to test for their
constancy. We thus detail the relations between the constants, the tests of the
local position invariance and of the universality of free fall. We then review
the main experimental and observational constraints that have been obtained
from atomic clocks, the Oklo phenomenon, Solar system observations, meteorites
dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic
microwave background and big bang nucleosynthesis. At each step we describe the
basics of each system, its dependence with respect to the constants, the known
systematic effects and the most recent constraints that have been obtained. We
then describe the main theoretical frameworks in which the low-energy constants
may actually be varying and we focus on the unification mechanisms and the
relations between the variation of different constants. To finish, we discuss
the more speculative possibility of understanding their numerical values and
the apparent fine-tuning that they confront us with.Comment: 145 pages, 10 figures, Review for Living Reviews in Relativit
- …