1,802 research outputs found
Investigations into the Sarcomeric Protein and Ca2+-Regulation Abnormalities Underlying Hypertrophic Cardiomyopathy in Cats (Felix catus).
Hypertrophic cardiomyopathy (HCM) is the most common single gene inherited cardiomyopathy. In cats (Felix catus) HCM is even more prevalent and affects 16% of the outbred population and up to 26% in pedigree breeds such as Maine Coon and Ragdoll. Homozygous MYBPC3 mutations have been identified in these breeds but the mutations in other cats are unknown. At the clinical and physiological level feline HCM is closely analogous to human HCM but little is known about the primary causative mechanism. Most identified HCM causing mutations are in the genes coding for proteins of the sarcomere. We therefore investigated contractile and regulatory proteins in left ventricular tissue from 25 cats, 18 diagnosed with HCM, including a Ragdoll cat with a homozygous MYBPC3 R820W, and 7 non-HCM cats in comparison with human HCM (from septal myectomy) and donor heart tissue. Myofibrillar protein expression was normal except that we observed 20–44% MyBP-C haploinsufficiency in 5 of the HCM cats. Troponin extracted from 8 HCM and 5 non-HCM cat hearts was incorporated into thin filaments and studied by in vitro motility assay. All HCM cat hearts had a higher (2.06 ± 0.13 fold) Ca2+-sensitivity than non-HCM cats and, in all the HCM cats, Ca2+-sensitivity was not modulated by troponin I phosphorylation. We were able to restore modulation of Ca2+-sensitivity by replacing troponin T with wild-type protein or by adding 100 μM Epigallocatechin 3-gallate (EGCG). These fundamental regulatory characteristics closely mimic those seen in human HCM indicating a common molecular mechanism that is independent of the causative mutation. Thus, the HCM cat is a potentially useful large animal model
Ascertaining the Core Collapse Supernova Mechanism: An Emerging Picture?
Here we present the results from two sets of simulations, in two and three
spatial dimensions. In two dimensions, the simulations include multifrequency
flux-limited diffusion neutrino transport in the "ray-by-ray-plus"
approximation, two-dimensional self gravity in the Newtonian limit, and nuclear
burning through a 14-isotope alpha network. The three-dimensional simulations
are model simulations constructed to reflect the post stellar core bounce
conditions during neutrino shock reheating at the onset of explosion. They are
hydrodynamics-only models that focus on critical aspects of the shock stability
and dynamics and their impact on the supernova mechanism and explosion. In two
dimensions, we obtain explosions (although in one case weak) for two
progenitors (11 and 15 Solar mass models). Moreover, in both cases the
explosion is initiated when the inner edge of the oxygen layer accretes through
the shock. Thus, the shock is not revived while in the iron core, as previously
discussed in the literature. The three-dimensional studies of the development
of the stationary accretion shock instability (SASI) demonstrate the
fundamentally new dynamics allowed when simulations are performed in three
spatial dimensions. The predominant l=1 SASI mode gives way to a stable m=1
mode, which in turn has significant ramifications for the distribution of
angular momentum in the region between the shock and proto-neutron star and,
ultimately, for the spin of the remnant neutron star. Moreover, the
three-dimensional simulations make clear, given the increased number of degrees
of freedom, that two-dimensional models are severely limited by artificially
imposed symmetries.Comment: 9 pages, 3 figure
Neutrino-driven supernovae: Boltzmann neutrino transport and the explosion mechanism
Core-collapse supernovae are, despite their spectacular visual display,
neutrino events. Virtually all of the 10^53 ergs of gravitational binding
energy released in the formation of the nascent neutron star is carried away in
the form of neutrinos and antineutrinos of all three flavors, and these
neutrinos are primarily responsible for powering the explosion. This mechanism
depends sensitively on the neutrino transport between the neutrinospheres and
the shock. In light of this, we have performed a comparison of multigroup
Boltzmann neutrino transport (MGBT) and multigroup flux-limited diffusion
(MGFLD) in post-core bounce environments. Differences in the mean inverse flux
factors, luminosities, and RMS energies translate to heating rates that are up
to 2 times larger for Boltzmann transport, with net cooling rates below the
gain radius that are typically 0.8 times the MGFLD rates. These differences are
greatest at earlier postbounce times for a given progenitor mass, and for a
given postbounce time, greater for greater progenitor mass. The increased
differences with increased progenitor mass suggest that the net heating
enhancement from MGBT is potentially robust and self-regulated.Comment: 7 pages, 2 figures, 1 table; LaTex using iopconf.sty; To appear in:
Proceedings of The Second Oak Ridge Symposium on Atomic & Nuclear
Astrophysic
Measurement of the two-photon absorption cross-section of liquid argon with a time projection chamber
This paper reports on laser-induced multiphoton ionization at 266 nm of
liquid argon in a time projection chamber (LAr TPC) detector. The electron
signal produced by the laser beam is a formidable tool for the calibration and
monitoring of next-generation large-mass LAr TPCs. The detector that we
designed and tested allowed us to measure the two-photon absorption
cross-section of LAr with unprecedented accuracy and precision:
sigma_ex=(1.24\pm 0.10stat \pm 0.30syst) 10^{-56} cm^4s{-1}.Comment: 15 pages, 9 figure
2D and 3D Core-Collapse Supernovae Simulation Results Obtained with the CHIMERA Code
Much progress in realistic modeling of core-collapse supernovae has occurred
recently through the availability of multi-teraflop machines and the increasing
sophistication of supernova codes. These improvements are enabling simulations
with enough realism that the explosion mechanism, long a mystery, may soon be
delineated. We briefly describe the CHIMERA code, a supernova code we have
developed to simulate core-collapse supernovae in 1, 2, and 3 spatial
dimensions. We then describe the results of an ongoing suite of 2D simulations
initiated from a 12, 15, 20, and 25 solar mass progenitor. These have all
exhibited explosions and are currently in the expanding phase with the shock at
between 5,000 and 20,000 km. We also briefly describe an ongoing simulation in
3 spatial dimensions initiated from the 15 solar mass progenitor.Comment: 5 pages, 3 figure
Gravitational Waves from Core Collapse Supernovae
We present the gravitational wave signatures for a suite of axisymmetric core
collapse supernova models with progenitors masses between 12 and 25 solar
masses. These models are distinguished by the fact they explode and contain
essential physics (in particular, multi-frequency neutrino transport and
general relativity) needed for a more realistic description. Thus, we are able
to compute complete waveforms (i.e., through explosion) based on
non-parameterized, first-principles models. This is essential if the waveform
amplitudes and time scales are to be computed more precisely. Fourier
decomposition shows that the gravitational wave signals we predict should be
observable by AdvLIGO across the range of progenitors considered here. The
fundamental limitation of these models is in their imposition of axisymmetry.
Further progress will require counterpart three-dimensional models.Comment: 10 pages, 5 figure
Evaluating ‘enhancing pragmatic language skills for young children with social communication impairments’ (E-PLAYS): protocol for a feasibility randomised controlled trial study
Background: A number of children experience difficulties with social communication and this has long-term deleterious effects on their mental health, social development and education. The proposal presented in this article describes a feasibility study for a trial to test an intervention (‘E-PLAYS’) aimed at supporting children with social communication impairments. E-PLAYS harnesses technology in the form of a novel computer game in order to develop collaborative and communication skills. Preliminary studies by the authors show that when E-PLAYS was administered by the research team, children with social communication impairments showed improvements on communication test scores and on observed collaborative behaviours. The study described here is a pragmatic trial to test the application of E-PLAYS delivered by NHS speech and language therapists together with schools.
Methods: This protocol outlines a two-arm feasibility cluster-randomised controlled trial of the E-PLAYS intervention with treatment as usual control arm, with randomisation at the level of the speech and language therapist. The aim of this study is to ascertain whether it will be feasible to progress to running a full-scale definitive trial to test the effectiveness of E-PLAYS in an NHS setting. Data relating to recruitment and retention, the appropriateness of outcomes and the acceptability of E-PLAYS to participants will be collected.
Speech and language therapists will select suitable children (ages 4–7 years old) from their caseloads and deliver either the E-PLAYS intervention (experimental group) or treatment as usual (control group). Assessments will include blinded language measures and observations, non-blinded teacher-reported measures of peer relations and classroom behaviour and parent-reported use of resources and quality of life. There will also be a qualitative process evaluation.
Discussion: The findings of this study will inform the decision as to whether to progress to a full-scale definitive randomised controlled trial to test the effectiveness of E-PLAYS when delivered by speech and language therapists and teaching assistants within schools. The use of technology in game form is a novel approach in an area where there are currently few available interventions
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