347 research outputs found
Switched-capacitor networks for image processing : analysis, synthesis, response bounding, and implementation
Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1994.Includes bibliographical references (p. 279-284).by Mark N. Seidel.Sc.D
Implementing an apparent-horizon finder in three dimensions
Locating apparent horizons is not only important for a complete understanding
of numerically generated spacetimes, but it may also be a crucial component of
the technique for evolving black-hole spacetimes accurately. A scheme proposed
by Libson et al., based on expanding the location of the apparent horizon in
terms of symmetric trace-free tensors, seems very promising for use with
three-dimensional numerical data sets. In this paper, we generalize this scheme
and perform a number of code tests to fully calibrate its behavior in
black-hole spacetimes similar to those we expect to encounter in solving the
binary black-hole coalescence problem. An important aspect of the
generalization is that we can compute the symmetric trace-free tensor expansion
to any order. This enables us to determine how far we must carry the expansion
to achieve results of a desired accuracy. To accomplish this generalization, we
describe a new and very convenient set of recurrence relations which apply to
symmetric trace-free tensors.Comment: 14 pages (RevTeX 3.0 with 3 figures
Identification of an amino-terminus determinant critical for ryanodine receptor/Ca2+ release channel function
Aims
The cardiac ryanodine receptor (RyR2), which mediates intracellular Ca2+ release to trigger cardiomyocyte contraction, participates in development of acquired and inherited arrhythmogenic cardiac disease. This study was undertaken to characterize the network of inter- and intra-subunit interactions regulating the activity of the RyR2 homotetramer.
Methods and Results
We use mutational investigations combined with biochemical assays to identify the peptide sequence bridging the β8 with β9 strand as the primary determinant mediating RyR2 N-terminus self-association. The negatively-charged side chains of two aspartate residues (D179 and D180) within the β8-β9 loop are crucial for the N-terminal inter-subunit interaction. We also show that the RyR2 N-terminus domain interacts with the C-terminal channel pore region in a Ca2+-independent manner. The β8-β9 loop is required for efficient RyR2 subunit oligomerization but it is dispensable for N-terminus interaction with C-terminus. Deletion of the β8-β9 sequence produces unstable tetrameric channels with subdued intracellular Ca2+ mobilization implicating a role for this domain in channel opening. The arrhythmia-linked R176Q mutation within the β8-β9 loop decreases N-terminus tetramerization but does not affect RyR2 subunit tetramerization or the N-terminus interaction with C-terminus. RyR2R176Q is a characteristic hypersensitive channel displaying enhanced intracellular Ca2+ mobilization suggesting an additional role for the β8-β9 domain in channel closing.
Conclusions
These results suggest that efficient N-terminus inter-subunit communication mediated by the β8-β9 loop may constitute a primary regulatory mechanism for both RyR2 channel activation and suppression.
Translational Potential
Our findings that the RyR2 β8-β9 loop is involved in both Ca2+ release channel opening and closing have important clinical implications. This RyR2 domain is a known “hot-spot” for mutations associated with arrhythmogenic cardiac disease, which could produce hypersensitive as well as hyposensitive channels. Therapeutic strategies currently focus on gain-of-function RyR2 channels to suppress sarcoplasmic reticulum Ca2+ release either indirectly with class I/II anti-arrhythmic drugs, or by directly targeting RyR2 to inhibit channel activity. These strategies may not only be ineffective, but they may exacerbate the malignant phenotype in the case of loss-of-function RyR2 mutations
Three-dimensional general relativistic hydrodynamics II: long-term dynamics of single relativistic stars
This is the second in a series of papers on the construction and validation
of a three-dimensional code for the solution of the coupled system of the
Einstein equations and of the general relativistic hydrodynamic equations, and
on the application of this code to problems in general relativistic
astrophysics. In particular, we report on the accuracy of our code in the
long-term dynamical evolution of relativistic stars and on some new physics
results obtained in the process of code testing. The tests involve single
non-rotating stars in stable equilibrium, non-rotating stars undergoing radial
and quadrupolar oscillations, non-rotating stars on the unstable branch of the
equilibrium configurations migrating to the stable branch, non-rotating stars
undergoing gravitational collapse to a black hole, and rapidly rotating stars
in stable equilibrium and undergoing quasi-radial oscillations. The numerical
evolutions have been carried out in full general relativity using different
types of polytropic equations of state using either the rest-mass density only,
or the rest-mass density and the internal energy as independent variables. New
variants of the spacetime evolution and new high resolution shock capturing
(HRSC) treatments based on Riemann solvers and slope limiters have been
implemented and the results compared with those obtained from previous methods.
Finally, we have obtained the first eigenfrequencies of rotating stars in full
general relativity and rapid rotation. A long standing problem, such
frequencies have not been obtained by other methods. Overall, and to the best
of our knowledge, the results presented in this paper represent the most
accurate long-term three-dimensional evolutions of relativistic stars available
to date.Comment: 19 pages, 17 figure
Scientific Potential of Einstein Telescope
Einstein gravitational-wave Telescope (ET) is a design study funded by the
European Commission to explore the technological challenges of and scientific
benefits from building a third generation gravitational wave detector. The
three-year study, which concluded earlier this year, has formulated the
conceptual design of an observatory that can support the implementation of new
technology for the next two to three decades. The goal of this talk is to
introduce the audience to the overall aims and objectives of the project and to
enumerate ET's potential to influence our understanding of fundamental physics,
astrophysics and cosmology.Comment: Conforms to conference proceedings, several author names correcte
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
The epidemic of bovine spongiform encephalopathy (BSE) has led to a world-wide drop in the market for beef by-products, such as Meat-and-Bone Meal (MBM), a fat-containing but mainly proteinaceaous product traditionally used as an animal feed supplement. While normal rendering is insufficient, the production of biodiesel from MBM has been suggested to destroy infectivity from transmissible spongiform encephalopathies (TSEs). In addition to producing fuel, this method simultaneously generates a nutritious solid residue. In our study we produced biodiesel from MBM under defined conditions using a modified form of alkaline methanolysis. We evaluated the presence of prion in the three resulting phases of the biodiesel reaction (Biodiesel, Glycerol and Solid Residue) in vitro and in vivo. Analysis of the reaction products from 263K scrapie infected MBM led to no detectable immunoreactivity by Western Blot. Importantly, and in contrast to the biochemical results the solid MBM residue from the reaction retained infectivity when tested in an animal bioassay. Histochemical analysis of hamster brains inoculated with the solid residue showed typical spongiform degeneration and vacuolation. Re-inoculation of these brains into a new cohort of hamsters led to onset of clinical scrapie symptoms within 75 days, suggesting that the specific infectivity of the prion protein was not changed during the biodiesel process. The biodiesel reaction cannot be considered a viable prion decontamination method for MBM, although we observed increased survival time of hamsters and reduced infectivity greater than 6 log orders in the solid MBM residue. Furthermore, results from our study compare for the first time prion detection by Western Blot versus an infectivity bioassay for analysis of biodiesel reaction products. We could show that biochemical analysis alone is insufficient for detection of prion infectivity after a biodiesel process
Scientific Objectives of Einstein Telescope
The advanced interferometer network will herald a new era in observational
astronomy. There is a very strong science case to go beyond the advanced
detector network and build detectors that operate in a frequency range from 1
Hz-10 kHz, with sensitivity a factor ten better in amplitude. Such detectors
will be able to probe a range of topics in nuclear physics, astronomy,
cosmology and fundamental physics, providing insights into many unsolved
problems in these areas.Comment: 18 pages, 4 figures, Plenary talk given at Amaldi Meeting, July 201
Testing gravitational-wave searches with numerical relativity waveforms: Results from the first Numerical INJection Analysis (NINJA) project
The Numerical INJection Analysis (NINJA) project is a collaborative effort
between members of the numerical relativity and gravitational-wave data
analysis communities. The purpose of NINJA is to study the sensitivity of
existing gravitational-wave search algorithms using numerically generated
waveforms and to foster closer collaboration between the numerical relativity
and data analysis communities. We describe the results of the first NINJA
analysis which focused on gravitational waveforms from binary black hole
coalescence. Ten numerical relativity groups contributed numerical data which
were used to generate a set of gravitational-wave signals. These signals were
injected into a simulated data set, designed to mimic the response of the
Initial LIGO and Virgo gravitational-wave detectors. Nine groups analysed this
data using search and parameter-estimation pipelines. Matched filter
algorithms, un-modelled-burst searches and Bayesian parameter-estimation and
model-selection algorithms were applied to the data. We report the efficiency
of these search methods in detecting the numerical waveforms and measuring
their parameters. We describe preliminary comparisons between the different
search methods and suggest improvements for future NINJA analyses.Comment: 56 pages, 25 figures; various clarifications; accepted to CQ
Dental cell type atlas reveals stem and differentiated cell types in mouse and human teeth
Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation. Unlike human teeth, mouse incisors grow throughout life, based on stem and progenitor cell activity. Here the authors generate single cell RNA-seq comparative maps of continuously-growing mouse incisor, non-growing mouse molar and human teeth, combined with lineage tracing to reveal dental cell complexity.Peer reviewe
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