Control theory for principled heap sizing

We propose a new, principled approach to adaptive heap sizing based on control theory. We review current state-of-the-art heap sizing mechanisms, as deployed in Jikes RVM and HotSpot. We then formulate heap sizing as a control problem, apply and tune a standard controller algorithm, and evaluate its performance on a set of well-known benchmarks. We find our controller adapts the heap size more responsively than existing mechanisms. This responsiveness allows tighter virtual machine memory footprints while preserving target application throughput, which is ideal for both embedded and utility computing domains. In short, we argue that formal, systematic approaches to memory management should be replacing ad-hoc heuristics as the discipline matures. Control-theoretic heap sizing is one such systematic approach

The First Two Years of Electromagnetic Follow-Up with Advanced LIGO and Virgo

We anticipate the first direct detections of gravitational waves (GWs) with Advanced LIGO and Virgo later this decade. Though this groundbreaking technical achievement will be its own reward, a still greater prize could be observations of compact binary mergers in both gravitational and electromagnetic channels simultaneously. During Advanced LIGO and Virgo's first two years of operation, 2015 through 2016, we expect the global GW detector array to improve in sensitivity and livetime and expand from two to three detectors. We model the detection rate and the sky localization accuracy for binary neutron star (BNS) mergers across this transition. We have analyzed a large, astrophysically motivated source population using real-time detection and sky localization codes and higher-latency parameter estimation codes that have been expressly built for operation in the Advanced LIGO/Virgo era. We show that for most BNS events the rapid sky localization, available about a minute after a detection, is as accurate as the full parameter estimation. We demonstrate that Advanced Virgo will play an important role in sky localization, even though it is anticipated to come online with only one-third as much sensitivity as the Advanced LIGO detectors. We find that the median 90% confidence region shrinks from ~500 square degrees in 2015 to ~200 square degrees in 2016. A few distinct scenarios for the first LIGO/Virgo detections emerge from our simulations.Comment: 17 pages, 11 figures, 5 tables. For accompanying data, see http://www.ligo.org/scientists/first2year

Association of lung clearance index with survival in individuals with cystic fibrosis.

BACKGROUND The lung clearance index (LCI) assesses global ventilation inhomogeneity and is a sensitive biomarker of airway function in cystic fibrosis (CF) lung disease. OBJECTIVES We examined the association of LCI with the risk of death or lung transplantation (LTX) in individuals with CF. METHODS We performed a retrospective analysis in a cohort of individuals with CF aged≥5 years with LCI and FEV1 measurements performed between 1980 and 2006. The outcome was time until death or LTX. We used the earliest available LCI and FEV1 values in a Cox proportional hazard regression adjusted for demographic and clinical variables. For sensitivity analyses, we used the mean of the first three LCI and FEV1 measurements, stratified the cohort based on age, and investigated individuals with normal FEV1. RESULTS In total, 237 individuals with CF with a mean (range) age of 13.9 (5.6-41.0) years were included. The time-to-event analysis accrued 3813 person-years and 94 (40%) individuals died or received LTX. Crude hazard ratios [95% CI] were 1.04 [1.01-1.06] per one z-score increase in LCI and 1.25 [1.11-1.41] per one z-score decrease in FEV1. After adjusting LCI and FEV1 mutually in addition to sex, age, BMI and the number of hospitalisations, hazard ratios were 1.04 [1.01-1.07] for LCI, and 1.12 [0.95-1.33] for FEV1. Sensitivity analyses yielded similar results and using the mean LCI strengthened the associations. CONCLUSIONS Increased ventilation inhomogeneity is associated with greater risk of death or LTX. Our data support LCI as novel surrogate of survival in individuals with CF

Counterintuitive transitions in multistate curve crossing involving linear potentials

Two problems incorporating a set of horizontal linear potentials crossed by a sloped linear potential are analytically solved and compared with numerical results: (a) the case where boundary conditions are specified at the ends of a finite interval, and (b) the case where the sloped linear potential is replaced by a piecewise-linear sloped potential and the boundary conditions are specified at infinity. In the approximation of small gaps between the horizontal potentials, an approach similar to the one used for the degenerate problem (Yurovsky V A and Ben-Reuven A 1998 J. Phys. B 31,1) is applicable for both problems. The resulting scattering matrix has a form different from the semiclassical result obtained by taking the product of Landau-Zener amplitudes. Counterintuitive transitions involving a pair of successive crossings, in which the second crossing precedes the first one along the direction of motion, are allowed in both models considered here.Comment: LaTeX 2.09 using ioplppt.sty and psfig.sty, 16 pages with 5 figures. Submitted to J. Phys.

Parameter estimation on gravitational waves from neutron-star binaries with spinning components

Inspiraling binary neutron stars are expected to be one of the most significant sources of gravitational-wave signals for the new generation of advanced ground-based detectors. We investigate how well we could hope to measure properties of these binaries using the Advanced LIGO detectors, which began operation in September 2015. We study an astrophysically motivated population of sources (binary components with masses $1.2~\mathrm{M}_\odot$--$1.6~\mathrm{M}_\odot$ and spins of less than $0.05$) using the full LIGO analysis pipeline. While this simulated population covers the observed range of potential binary neutron-star sources, we do not exclude the possibility of sources with parameters outside these ranges; given the existing uncertainty in distributions of mass and spin, it is critical that analyses account for the full range of possible mass and spin configurations. We find that conservative prior assumptions on neutron-star mass and spin lead to average fractional uncertainties in component masses of $\sim 16\%$, with little constraint on spins (the median $90\%$ upper limit on the spin of the more massive component is $\sim 0.7$). Stronger prior constraints on neutron-star spins can further constrain mass estimates, but only marginally. However, we find that the sky position and luminosity distance for these sources are not influenced by the inclusion of spin; therefore, if LIGO detects a low-spin population of BNS sources, less computationally expensive results calculated neglecting spin will be sufficient for guiding electromagnetic follow-up.Comment: 10 pages, 9 figure

BrainWAVE: A flexible method for noninvasive stimulation of brain rhythms across species

Rhythmic neural activity, which coordinates brain regions and neurons to achieve multiple brain functions, is impaired in many diseases. Despite the therapeutic potential of driving brain rhythms, methods to noninvasively target deep brain regions are limited. Accordingly, we recently introduced a noninvasive stimulation approach using flickering lights and sounds ( flicker ). Flicker drives rhythmic activity in deep and superficial brain regions. Gamma flicker spurs immune function, clears pathogens, and rescues memory performance in mice with amyloid pathology. Here, we present substantial improvements to this approach that is flexible, user-friendly, and generalizable across multiple experimental settings and species. We present novel open-source methods for flicker stimulation across rodents and humans. We demonstrate rapid, cross-species induction of rhythmic activity without behavioral confounds in multiple settings from electrophysiology to neuroimaging. This flicker approach provides an exceptional opportunity to discover the therapeutic effects of brain rhythms across scales and species

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias