C-Terminus of Progranulin Interacts with the Beta-Propeller Region of Sortilin to Regulate Progranulin Trafficking

Progranulin haplo-insufficiency is a main cause of frontotemporal lobar degeneration (FTLD) with TDP-43 aggregates. Previous studies have shown that sortilin regulates progranulin trafficking and is a main determinant of progranulin level in the brain. In this study, we mapped the binding site between progranulin and sortilin. Progranulin binds to the beta-propeller region of sortilin through its C-terminal tail. The C-terminal progranulin fragment is fully sufficient for sortilin binding and progranulin C-terminal peptide displaces progranulin binding to sortilin. Deletion of the last 3 residues of progranulin (QLL) abolishes its binding to sortilin and also sortilin dependent regulation of progranulin trafficking. Since progranulin haplo-insufficiency results in FTLD, these results may provide important insights into future studies of progranulin trafficking and signaling and progranulin based therapy for FTLD

Searching for Gravitational Waves from the Inspiral of Precessing Binary Systems: New Hierarchical Scheme using "Spiky" Templates

In a recent investigation of the effects of precession on the anticipated detection of gravitational-wave inspiral signals from compact object binaries with moderate total masses, we found that (i) if precession is ignored, the inspiral detection rate can decrease by almost a factor of 10, and (ii) previously proposed ``mimic'' templates cannot improve the detection rate significantly (by more than a factor of 2). In this paper we propose a new family of templates that can improve the detection rate by factors of 5--6 in cases where precession is most important. Our proposed method for these new ``mimic'' templates involves a hierarchical scheme of efficient, two-parameter template searches that can account for a sequence of spikes that appear in the residual inspiral phase, after one corrects for the any oscillatory modification in the phase. We present our results for two cases of compact object masses (10 and 1.4 solar masses and 7 and 3 solar masses) as a function of spin properties. Although further work is needed to fully assess the computational efficiency of this newly proposed template family, we conclude that these ``spiky templates'' are good candidates for a family of precession templates used in realistic searches, that can improve detection rates of inspiral events.Comment: 17 pages, 22 figures, version accepted by PRD. Minor revision

Data analysis of gravitational-wave signals from spinning neutron stars. IV. An all-sky search

We develop a set of data analysis tools for a realistic all-sky search for continuous gravitational-wave signals. The methods that we present apply to data from both the resonant bar detectors that are currently in operation and the laser interferometric detectors that are in the final stages of construction and commissioning. We show that with our techniques we shall be able to perform an all-sky 2-day long coherent search of the narrow-band data from the resonant bar EXPLORER with no loss of signals with the dimensionless amplitude greater than $2.8\times10^{-23}$.Comment: REVTeX, 26 pages, 1 figure, submitted to Phys. Rev.

Matching of the continuous gravitational wave in an all sky search

We investigate the matching of continuous gravitational wave (CGW) signals in an all sky search with reference to Earth based laser interferometric detectors. We consider the source location as the parameters of the signal manifold and templates corresponding to different source locations. It has been found that the matching of signals from locations in the sky that differ in their co-latitude and longitude by $\pi$ radians decreases with source frequency. We have also made an analysis with the other parameters affecting the symmetries. We observe that it may not be relevant to take care of the symmetries in the sky locations for the search of CGW from the output of LIGO-I, GEO600 and TAMA detectors.Comment: 16 pages, 7 figures, 3 Tables, To appear in Int. J. Mod. Phys.

FAR and NEAR Target Dynamic Visual Acuity: A Functional Assessment of Canal and Otolith Performance

Upon their return to earth, astronauts experience the effects of vestibular adaptation to microgravity. The postflight changes in vestibular information processing can affect postural and locomotor stability and may lead to oscillopsia during activities of daily living. However, it is likely that time spent in microgravity affects canal and otolith function differently. As a result, the isolated rotational stimuli used in traditional tests of canal function may fail to identify vestibular deficits after spaceflight. Also, the functional consequences of deficits that are identified often remain unknown. In a gaze control task, the relative contributions of the canal and otolith organs are modulated with viewing distance. The ability to stabilize gaze during a perturbation, on visual targets placed at different distances from the head may therefore provide independent insight into the function of this systems. Our goal was to develop a functional measure of gaze control that can also offer independent information about the function of the canal and otolith organs

Data analysis of gravitational-wave signals from spinning neutron stars. III. Detection statistics and computational requirements

We develop the analytic and numerical tools for data analysis of the gravitational-wave signals from spinning neutron stars for ground-based laser interferometric detectors. We study in detail the statistical properties of the optimum functional that need to be calculated in order to detect the gravitational-wave signal from a spinning neutron star and estimate its parameters. We derive formulae for false alarm and detection probabilities both for the optimal and the suboptimal filters. We assess the computational requirements needed to do the signal search. We compare a number of criteria to build sufficiently accurate templates for our data analysis scheme. We verify the validity of our concepts and formulae by means of the Monte Carlo simulations. We present algorithms by which one can estimate the parameters of the continuous signals accurately.Comment: LaTeX, 45 pages, 13 figures, submitted to Phys. Rev.

Searching for Gravitational Waves from Binary Inspirals with LIGO

We describe the current status of the search for gravitational waves from inspiralling compact binary systems in LIGO data. We review the result from the first scientific run of LIGO (S1). We present the goals of the search of data taken in the second scientific run (S2) and describe the differences between the methods used in S1 and S2.Comment: 9 pages, 2 figures. Published in proceedings of the 8th Gravitational Wave Data Analysis Workshop, Milwaukee, WI, USA, 17-20 December 200

Searching for periodic sources with LIGO. II: Hierarchical searches

The detection of quasi-periodic sources of gravitational waves requires the accumulation of signal-to-noise over long observation times. If not removed, Earth-motion induced Doppler modulations, and intrinsic variations of the gravitational-wave frequency make the signals impossible to detect. These effects can be corrected (removed) using a parameterized model for the frequency evolution. We compute the number of independent corrections $N_p(\Delta T,N)$ required for incoherent search strategies which use stacked power spectra---a demodulated time series is divided into $N$ segments of length $\Delta T$, each segment is FFTed, the power is computed, and the $N$ spectra are summed up. We estimate that the sensitivity of an all-sky search that uses incoherent stacks is a factor of 2--4 better than would be achieved using coherent Fourier transforms; incoherent methods are computationally efficient at exploring large parameter spaces. A two-stage hierarchical search which yields another 20--60% improvement in sensitivity in all-sky searches for old (>= 1000 yr) slow (= 40 yr) fast (<= 1000 Hz) pulsars. Assuming 10^{12} flops of effective computing power for data analysis, enhanced LIGO interferometers should be sensitive to: (i) Galactic core pulsars with gravitational ellipticities of \epsilon\agt5\times 10^{-6} at 200 Hz, (ii) Gravitational waves emitted by the unstable r-modes of newborn neutron stars out to distances of ~8 Mpc, and (iii) neutron stars in LMXB's with x-ray fluxes which exceed $2 \times 10^{-8} erg/(cm^2 s)$. Moreover, gravitational waves from the neutron star in Sco X-1 should be detectable is the interferometer is operated in a signal-recycled, narrow-band configuration.Comment: 22 Pages, 13 Figure

Observational Limit on Gravitational Waves from Binary Neutron Stars in the Galaxy

Using optimal matched filtering, we search 25 hours of data from the LIGO 40-meter prototype laser interferometric gravitational-wave detector for gravitational-wave chirps emitted by coalescing binary systems within our Galaxy. This is the first test of this filtering technique on real interferometric data. An upper limit on the rate R of neutron star binary inspirals in our Galaxy is obtained: with 90% confidence, R< 0.5/hour. Similar experiments with LIGO interferometers will provide constraints on the population of tight binary neutron star systems in the Universe.Comment: RevTeX, minor revisions, exactly as published in PRL 83 (1999) p1498, 4 pages, 2 figures include