A model for the accidental catalysis of protein unfolding in vivo

Activated processes such as protein unfolding are highly sensitive to heterogeneity in the environment. We study a highly simplified model of a protein in a random heterogeneous environment, a model of the in vivo environment. It is found that if the heterogeneity is sufficiently large the total rate of the process is essentially a random variable; this may be the cause of the species-to-species variability in the rate of prion protein conversion found by Deleault et al. [Nature, 425 (2003) 717].Comment: 5 pages, 2 figure

Conserved masses in GHS Einstein and string black holes

We analyze the relationship between quasilocal masses calculated for solutions of conformally related theories. We show that the ADM mass of a static, spherically symmetric solution is conformally invariant (up to a constant factor) only if the background action functional is conformally invariant. Thus, the requirement of conformal invariance places restrictions on the choice of reference spacetimes. We calculate the mass of the black hole solutions obtained by Garfinkle, Horowitz, and Strominger (GHS) for both the string and the Einstein metrics. In addition, the quasilocal thermodynamic quantities in the string metrics are computed and discussed.Comment: 16 pages REVTeX with packages amsfonts and amssym

Learning about compact binary merger: the interplay between numerical relativity and gravitational-wave astronomy

Activities in data analysis and numerical simulation of gravitational waves have to date largely proceeded independently. In this work we study how waveforms obtained from numerical simulations could be effectively used within the data analysis effort to search for gravitational waves from black hole binaries. We propose measures to quantify the accuracy of numerical waveforms for the purpose of data analysis and study how sensitive the analysis is to errors in the waveforms. We estimate that ~100 templates (and ~10 simulations with different mass ratios) are needed to detect waves from non-spinning binary black holes with total masses in the range 100 Msun < M < 400 Msun using initial LIGO. Of course, many more simulation runs will be needed to confirm that the correct physics is captured in the numerical evolutions. From this perspective, we also discuss sources of systematic errors in numerical waveform extraction and provide order of magnitude estimates for the computational cost of simulations that could be used to estimate the cost of parameter space surveys. Finally, we discuss what information from near-future numerical simulations of compact binary systems would be most useful for enhancing the detectability of such events with contemporary gravitational wave detectors and emphasize the role of numerical simulations for the interpretation of eventual gravitational-wave observations.Comment: 19 pages, 12 figure

Initial medical management of rotator cuff tears: a demographic analysis of surgical and nonsurgical treatment in the United States Medicare population

BACKGROUND: Rotator cuff tears have a lifetime incidence between 25% and 40% in the United States, but optimum treatment strategies and protocol have not yet been widely accepted. This study evaluated the proportions of patients treated with nonoperative and operative modalities and how this proportion has changed during an 8-year period (2005-2012) among patients with Medicare. METHODS: Using the PearlDiver patient record database, we identified Medicare patients having been diagnosed with a rotator cuff tear. These patients were then stratified on the basis of treatment with physical therapy, subacromial/glenohumeral injection, or rotator cuff repair. We analyzed the data in regard to standard demographic information, comorbidities, and the Charlson Comorbidity Index. RESULTS: During the study period, 878,049 patients were identified and 397,116 patients had rotator cuff repair. The proportion of patients treated initially with physical therapy dropped from 30.0% in 2005 to 13.2% in 2012, and the subacromial/glenohumeral injection proportion decreased from 6.00% to 4.19% (P &lt; .001). The proportion of patients who had rotator cuff repair increased from 33.8% to 40.4% from 2005 to 2012 (P &lt; .001). Charlson Comorbidity Indexes were significantly lower in operative patients compared with each nonoperative treatment examined. DISCUSSION: This analysis demonstrates a significant decrease in the initial trial of nonoperative treatment and an increase in the rate of surgery. Patients undergoing rotator cuff repair had fewer comorbidities than those undergoing nonoperative treatments. It also demonstrates that patients who had a trial of injection had a higher incidence of eventual rotator cuff repair compared with the patients with an initial trial of physical therapy

Entropy of Constant Curvature Black Holes in General Relativity

We consider the thermodynamic properties of the constant curvature black hole solution recently found by Banados. We show that it is possible to compute the entropy and the quasilocal thermodynamics of the spacetime using the Einstein-Hilbert action of General Relativity. The constant curvature black hole has some unusual properties which have not been seen in other black hole spacetimes. The entropy of the black hole is not associated with the event horizon; rather it is associated with the region between the event horizon and the observer. Further, surfaces of constant internal energy are not isotherms so the first law of thermodynamics exists only in an integral form. These properties arise from the unusual topology of the Euclidean black hole instanton.Comment: 4 pages LaTeX2e (RevTeX), 2 PostScript figures. Small corrections in the text and the reference

Optimal shapes of compact strings

Optimal geometrical arrangements, such as the stacking of atoms, are of relevance in diverse disciplines. A classic problem is the determination of the optimal arrangement of spheres in three dimensions in order to achieve the highest packing fraction; only recently has it been proved that the answer for infinite systems is a face-centred-cubic lattice. This simply stated problem has had a profound impact in many areas, ranging from the crystallization and melting of atomic systems, to optimal packing of objects and subdivision of space. Here we study an analogous problem--that of determining the optimal shapes of closely packed compact strings. This problem is a mathematical idealization of situations commonly encountered in biology, chemistry and physics, involving the optimal structure of folded polymeric chains. We find that, in cases where boundary effects are not dominant, helices with a particular pitch-radius ratio are selected. Interestingly, the same geometry is observed in helices in naturally-occurring proteins.Comment: 8 pages, 3 composite ps figure

Deriving amino acid contact potentials from their frequencies of occurence in proteins: a lattice model study

The possibility of deriving the contact potentials between amino acids from their frequencies of occurence in proteins is discussed in evolutionary terms. This approach allows the use of traditional thermodynamics to describe such frequencies and, consequently, to develop a strategy to include in the calculations correlations due to the spatial proximity of the amino acids and to their overall tendency of being conserved in proteins. Making use of a lattice model to describe protein chains and defining a "true" potential, we test these strategies by selecting a database of folding model sequences, deriving the contact potentials from such sequences and comparing them with the "true" potential. Taking into account correlations allows for a markedly better prediction of the interaction potentials

Searching for periodic sources with LIGO

We investigate the computational requirements for all-sky, all-frequency searches for gravitational waves from spinning neutron stars, using archived data from interferometric gravitational wave detectors such as LIGO. These sources are expected to be weak, so the optimal strategy involves coherent accumulaton of signal-to-noise using Fourier transforms of long stretches of data (months to years). Earth-motion-induced Doppler shifts, and intrinsic pulsar spindown, will reduce the narrow-band signal-to-noise by spreading power across many frequency bins; therefore, it is necessary to correct for these effects before performing the Fourier transform. The corrections can be implemented by a parametrized model, in which one does a search over a discrete set of parameter values. We define a metric on this parameter space, which can be used to determine the optimal spacing between points in a search; the metric is used to compute the number of independent parameter-space points Np that must be searched, as a function of observation time T. The number Np(T) depends on the maximum gravitational wave frequency and the minimum spindown age tau=f/(df/dt) that the search can detect. The signal-to-noise ratio required, in order to have 99% confidence of a detection, also depends on Np(T). We find that for an all-sky, all-frequency search lasting T=10^7 s, this detection threshhold is at a level of 4 to 5 times h(3/yr), where h(3/yr) is the corresponding 99% confidence threshhold if one knows in advance the pulsar position and spin period.Comment: 18 pages, LaTeX, 12 PostScript figures included using psfig. Submitted to Phys. Rev.

Seismic topographic scattering in the context of GW detector site selection

In this paper, we present a calculation of seismic scattering from irregular surface topography in the Born approximation. Based on US-wide topographic data, we investigate topographic scattering at specific sites to demonstrate its impact on Newtonian-noise estimation and subtraction for future gravitational-wave detectors. We find that topographic scattering at a comparatively flat site in Oregon would not pose any problems, whereas scattering at a second site in Montana leads to significant broadening of wave amplitudes in wavenumber space that would make Newtonian-noise subtraction very challenging. Therefore, it is shown that topographic scattering should be included as criterion in the site-selection process of future low-frequency gravitational-wave detectors.Comment: 16 pages, 7 figure

An excess power statistic for detection of burst sources of gravitational radiation

We examine the properties of an excess power method to detect gravitational waves in interferometric detector data. This method is designed to detect short-duration (< 0.5 s) burst signals of unknown waveform, such as those from supernovae or black hole mergers. If only the bursts' duration and frequency band are known, the method is an optimal detection strategy in both Bayesian and frequentist senses. It consists of summing the data power over the known time interval and frequency band of the burst. If the detector noise is stationary and Gaussian, this sum is distributed as a chi-squared (non-central chi-squared) deviate in the absence (presence) of a signal. One can use these distributions to compute frequentist detection thresholds for the measured power. We derive the method from Bayesian analyses and show how to compute Bayesian thresholds. More generically, when only upper and/or lower bounds on the bursts duration and frequency band are known, one must search for excess power in all concordant durations and bands. Two search schemes are presented and their computational efficiencies are compared. We find that given reasonable constraints on the effective duration and bandwidth of signals, the excess power search can be performed on a single workstation. Furthermore, the method can be almost as efficient as matched filtering when a large template bank is required. Finally, we derive generalizations of the method to a network of several interferometers under the assumption of Gaussian noise.Comment: 22 pages, 6 figure