163 research outputs found
Lessons from the decoupling limit of Horava gravity
We consider the so-called "healthy" extension of Horava gravity in the limit
where the Stuckelberg field decouples from the graviton. We verify the alleged
strong coupling problem in this limit, under the assumption that no large
dimensionless parameters are put in by hand. This follows from the fact that
the dispersion relation for the Stuckelberg field does not have the desired z =
3 anisotropic scaling in the UV. To get the desired scaling and avoid strong
coupling one has to introduce a low scale of Lorentz violation and retain some
coupling between the graviton and the Stuckelberg field. We also make use of
the foliation preserving symmetry to show how the Stuckelberg field couples to
some violation of energy conservation. We source the Stuckelberg field using a
point particle with a slowly varying mass and show that two such particles feel
a constant attractive force. In this particular example, we see no Vainshtein
effect, and violations of the Equivalence Principle. The latter is probably
generic to other types of source and could potentially be used to place lower
bounds on the scale of Lorentz violation.Comment: 18 pages, 1 figure. Version to appear in JHEP. Conclusions with
respect to strong coupling modified - our strong coupling analysis does not
apply to a low scale of Lorentz violation. Expanded Equivalence Principle
violation discussion, noting it presents a challenge to low scale Lorentz
violation, exactly the scenario designed to cure strong coupling. Other minor
corrections and references adde
Identification of Heterozygous Single- and Multi-exon Deletions in IL7R by Whole Exome Sequencing
PURPOSE: We aimed to achieve a retrospective molecular diagnosis by applying state-of-the-art genomic sequencing methods to past patients with T-B+NK+ severe combined immunodeficiency (SCID). We included identification of copy number variations (CNVs) by whole exome sequencing (WES) using the CNV calling method ExomeDepth to detect gene alterations for which routine Sanger sequencing analysis is not suitable, such as large heterozygous deletions. METHODS: Of a total of 12 undiagnosed patients with T-B+NK+ SCID, we analyzed eight probands by WES, using GATK to detect single nucleotide variants (SNVs) and small insertions and deletions (INDELs) and ExomeDepth to detect CNVs. RESULTS: We found heterozygous single- or multi-exon deletions in IL7R, a known disease gene for autosomal recessive T-B+NK+ SCID, in four families (seven patients). In three families (five patients), these deletions coexisted with a heterozygous splice site or nonsense mutation elsewhere in the same gene, consistent with compound heterozygosity. In our cohort, about a quarter of T-B+NK+ SCID patients (26%) had such compound heterozygous IL7R deletions. CONCLUSIONS: We show that heterozygous IL7R exon deletions are common in T-B+NK+ SCID and are detectable by WES. They should be considered if Sanger sequencing fails to detect homozygous or compound heterozygous IL7R SNVs or INDELs
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First measurement of neutrino oscillation parameters using neutrinos and antineutrinos by NOvA.
The NOvA experiment has seen a 4.4σ signal of ν[over ¯]_{e} appearance in a 2 GeV ν[over ¯]_{μ} beam at a distance of 810 km. Using 12.33×10^{20} protons on target delivered to the Fermilab NuMI neutrino beamline, the experiment recorded 27 ν[over ¯]_{μ}→ν[over ¯]_{e} candidates with a background of 10.3 and 102 ν[over ¯]_{μ}→ν[over ¯]_{μ} candidates. This new antineutrino data are combined with neutrino data to measure the parameters |Δm_{32}^{2}|=2.48_{-0.06}^{+0.11}×10^{-3} eV^{2}/c^{4} and sin^{2}θ_{23} in the ranges from (0.53-0.60) and (0.45-0.48) in the normal neutrino mass hierarchy. The data exclude most values near δ_{CP}=π/2 for the inverted mass hierarchy by more than 3σ and favor the normal neutrino mass hierarchy by 1.9σ and θ_{23} values in the upper octant by 1.6σ
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Observation of seasonal variation of atmospheric multiple-muon events in the NOvA Near Detector
Using two years of data from the NOvA Near Detector at Fermilab, we report a seasonal variation of cosmic ray induced multiple-muon (Nμ≥2) event rates which has an opposite phase to the seasonal variation in the atmospheric temperature. The strength of the seasonal multiple-muon variation is shown to increase as a function of the muon multiplicity. However, no significant dependence of the strength of the seasonal variation of the multiple-muon variation is seen as a function of the muon zenith angle, or the spatial or angular separation between the correlated muons
Exposure to Uteroplacental Insufficiency Reduces the Expression of Signal Transducer and Activator of Transcription 3 and Proopiomelanocortin in the Hypothalamus of Newborn Rats
IUGR has been linked to the development of type 2 diabetes. Recent data suggest that some of the molecular defects underlying type 2 diabetes reside in the CNS. Disruption of the signal transducer and activator of transcription 3 (STAT3) in the hypothalamic neurons expressing leptin receptor, results in severe obesity, hyperglycaemia, and hyperinsulinemia. Our aim was to investigate the expression of STAT3 and its downstream effector proopiomelanocortin (POMC) in IUGR rats obtained by uterine artery ligation. On day 19 of gestation, time-dated Sprague-Dawley pregnant rats were anesthetized, and both the uterine arteries were ligated. At birth, hypothalamus was dissected and processed to evaluate the expression of STAT3, its phosphorylated form, and POMC. STAT3 mRNA, STAT3 protein, phosphorylated STAT3, POW mRNA, and POMC protein were significantly reduced in IUGR versus sham animals (p < 0.0001. p < 0.05 and p < 0.001, p < 0.01, p < 0.01 respectively). No significant differences either in serum leptin concentrations or in hypothalamic leptin receptor expression were observed. Our results suggest that an abnormal intrauterine milieu call affect the hypothalamic expression of STAT3 and POW at birth. altering the hypothalamic signaling pathways that regulate the energy homeostasis. (Pediatr Res 66: 208-211, 2009
A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279
It is widely accepted that strong and variable radiation detected over all
accessible energy bands in a number of active galaxies arises from a
relativistic, Doppler-boosted jet pointing close to our line of sight. The size
of the emitting zone and the location of this region relative to the central
supermassive black hole are, however, poorly known, with estimates ranging from
light-hours to a light-year or more. Here we report the coincidence of a
gamma-ray flare with a dramatic change of optical polarization angle. This
provides evidence for co-spatiality of optical and gamma-ray emission regions
and indicates a highly ordered jet magnetic field. The results also require a
non-axisymmetric structure of the emission zone, implying a curved trajectory
for the emitting material within the jet, with the dissipation region located
at a considerable distance from the black hole, at about 10^5 gravitational
radii.Comment: Published in Nature issued on 18 February 2010. Corresponding
authors: Masaaki Hayashida and Greg Madejsk
Modified Gravity and Cosmology
In this review we present a thoroughly comprehensive survey of recent work on
modified theories of gravity and their cosmological consequences. Amongst other
things, we cover General Relativity, Scalar-Tensor, Einstein-Aether, and
Bimetric theories, as well as TeVeS, f(R), general higher-order theories,
Horava-Lifschitz gravity, Galileons, Ghost Condensates, and models of extra
dimensions including Kaluza-Klein, Randall-Sundrum, DGP, and higher
co-dimension braneworlds. We also review attempts to construct a Parameterised
Post-Friedmannian formalism, that can be used to constrain deviations from
General Relativity in cosmology, and that is suitable for comparison with data
on the largest scales. These subjects have been intensively studied over the
past decade, largely motivated by rapid progress in the field of observational
cosmology that now allows, for the first time, precision tests of fundamental
physics on the scale of the observable Universe. The purpose of this review is
to provide a reference tool for researchers and students in cosmology and
gravitational physics, as well as a self-contained, comprehensive and
up-to-date introduction to the subject as a whole.Comment: 312 pages, 15 figure
Cardiogenic Induction of Pluripotent Stem Cells Streamlined Through a Conserved SDF-1/VEGF/BMP2 Integrated Network
BACKGROUND: Pluripotent stem cells produce tissue-specific lineages through programmed acquisition of sequential gene expression patterns that function as a blueprint for organ formation. As embryonic stem cells respond concomitantly to diverse signaling pathways during differentiation, extraction of a pro-cardiogenic network would offer a roadmap to streamline cardiac progenitor output. METHODS AND RESULTS: To resolve gene ontology priorities within precursor transcriptomes, cardiogenic subpopulations were here generated according to either growth factor guidance or stage-specific biomarker sorting. Innate expression profiles were independently delineated through unbiased systems biology mapping, and cross-referenced to filter transcriptional noise unmasking a conserved progenitor motif (55 up- and 233 down-regulated genes). The streamlined pool of 288 genes organized into a core biological network that prioritized the "Cardiovascular Development" function. Recursive in silico deconvolution of the cardiogenic neighborhood and associated canonical signaling pathways identified a combination of integrated axes, CXCR4/SDF-1, Flk-1/VEGF and BMP2r/BMP2, predicted to synchronize cardiac specification. In vitro targeting of the resolved triad in embryoid bodies accelerated expression of Nkx2.5, Mef2C and cardiac-MHC, enhanced beating activity, and augmented cardiogenic yield. CONCLUSIONS: Transcriptome-wide dissection of a conserved progenitor profile thus revealed functional highways that coordinate cardiogenic maturation from a pluripotent ground state. Validating the bioinformatics algorithm established a strategy to rationally modulate cell fate, and optimize stem cell-derived cardiogenesis
Etiology of Diarrhea in Older Children, Adolescents and Adults: A Systematic Review
Diarrhea is an important cause of illness and death around the world and among people of all ages, but unfortunately we often do not know what specific bacterium or virus causes the illness. We conducted a review of the scientific literature with the goal of finding published studies that identified bacteria and viruses among patients with diarrhea in the community and in hospital settings. We initially found nearly 26,000 papers on this topic but narrowed the list to 22 studies that met all of our specific criteria for inclusion in our review. Among patients hospitalized for diarrhea, E coli and Vibrio cholerae were found in more than 49% of people living in middle income and poor countries. Among patients who sought care from their doctor on an outpatient basis, Salmonella spp., Shigella spp., and E. histolytica were most often found. In our review we focused on the differences in the distribution of pathogens between patients in inpatient vs. outpatient settings because these estimates may best approximate what we would expect to see if the distribution were applied to global estimates of diarrhea deaths vs. uncomplicated illnesses
miR-135A Regulates Preimplantation Embryo Development through Down-Regulation of E3 Ubiquitin Ligase Seven in Absentia Homolog 1A (SIAH1A) Expression
Background: MicroRNAs (miRNAs) are small non-coding RNA molecules capable of regulating transcription and translation. Previously, a cluster of miRNAs that are specifically expressed in mouse zygotes but not in oocytes or other preimplantation stages embryos are identified by multiplex real-time polymerase chain reaction-based miRNA profiling. The functional role of one of these zygote-specific miRNAs, miR-135a, in preimplantation embryo development was investigated. Methodology/Principal Findings: Microinjection of miR-135a inhibitor suppressed first cell cleavage in more than 30% of the zygotes. Bioinformatics analysis identified E3 Ubiquitin Ligase Seven In Absentia Homolog 1A (Siah1a) as a predicted target of miR-135a. Western blotting and 3′UTR luciferase functional assays demonstrated that miR-135a down-regulated the expression of Siah1 in HeLa cells and in mouse zygotes. Siah1a was expressed in preimplantation embryos and its expression pattern negatively correlated with that of miR-135a. Co-injection of Siah1a-specific antibody with miR-135a inhibitor partially nullified the effect of miR-135a inhibition. Proteasome inhibition by MG-132 revealed that miR-135a regulated proteasomal degradation and potentially controlled the expression of chemokinesin DNA binding protein (Kid). Conclusions/Significance: The present study demonstrated for the first time that zygotic specific miRNA modulates the first cell cleavage through regulating expression of Siah1a. © 2011 Pang et al.published_or_final_versio
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