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

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

Modeling core collapse supernovae in 2 and 3 dimensions with spectral neutrino transport

The overwhelming evidence that the core collapse supernova mechanism is inherently multidimensional, the complexity of the physical processes involved, and the increasing evidence from simulations that the explosion is marginal presents great computational challenges for the realistic modeling of this event, particularly in 3 spatial dimensions. We have developed a code which is scalable to computations in 3 dimensions which couples PPM Lagrangian with remap hydrodynamics [1], multigroup, flux-limited diffusion neutrino transport [2], with many improvements), and a nuclear network [3]. The neutrino transport is performed in a ray-by-ray plus approximation wherein all the lateral effects of neutrinos are included (e.g., pressure, velocity corrections, advection) except the transport. A moving radial grid option permits the evolution to be carried out from initial core collapse with only modest demands on the number of radial zones. The inner part of the core is evolved after collapse along with the rest of the core and mantle by subcycling the lateral evolution near the center as demanded by the small Courant times. We present results of 2-D simulations of a symmetric and an asymmetric collapse of both a 15 and an 11 M progenitor. In each of these simulations we have discovered that once the oxygen rich material reaches the shock there is a synergistic interplay between the reduced ram pressure, the energy released by the burning of the shock heated oxygen rich material, and the neutrino energy deposition which leads to a revival of the shock and an explosion.Comment: 10 pages, 3 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

Exploiting the neutronization burst of a galactic supernova

One of the robust features found in simulations of core-collapse supernovae (SNe) is the prompt neutronization burst, i.e. the first $\sim 25$ milliseconds after bounce when the SN emits with very high luminosity mainly $\nu_e$ neutrinos. We examine the dependence of this burst on variations in the input of current SN models and find that recent improvements of the electron capture rates as well as uncertainties in the nuclear equation of state or a variation of the progenitor mass have only little effect on the signature of the neutronization peak in a megaton water Cherenkov detector for different neutrino mixing schemes. We show that exploiting the time-structure of the neutronization peak allows one to identify the case of a normal mass hierarchy and large 13-mixing angle $\theta_{13}$, where the peak is absent. The robustness of the predicted total event number in the neutronization burst makes a measurement of the distance to the SN feasible with a precision of about 5%, even in the likely case that the SN is optically obscured.Comment: 14 pages, 17 eps figures, revtex4 style, minor comments adde