Glycerol monolaurate inhibits lipase production by clinical ocular isolates without affecting bacterial cell viability

PURPOSE. We sought to determine the relative lipase production of a range of ocular bacterial isolates and to assess the efficacy of glycerol monolaurate (GML) in inhibiting this lipase production in high lipase-producing bacteria without affecting bacterial cell growth. METHODS. Staphylococcus aureus, Staphylococcus epidermidis, Propionibacterium acnes, and Corynebacterium spp. were inoculated at a density of 106/mL in varying concentrations of GML up to 25 μg/mL for 24 hours at 378C with constant shaking. Bacterial suspensions were centrifuged, bacterial cell density was determined, and production of bacterial lipase was quantified using a commercial lipase assay kit. RESULTS. Staphylococcus spp. produced high levels of lipase activity compared with P. acnes and Corynebacterium spp. GML inhibited lipase production by Staphylococcal spp. in a dosedependent manner, with S. epidermidis lipase production consistently more sensitive to GML than S. aureus. Glycerol monolaurate showed significant (P \u3c 0.05) lipase inhibition above concentrations of 15 μg /mL in S. aureus and was not cytotoxic up to 25 μg /mL. For S. epidermidis, GML showed significant (P \u3c 0.05) lipase inhibition above 7.5 μg /mL. CONCLUSIONS. Lipase activity varied between species and between strains. Staphylococcal spp. produced higher lipase activity compared with P. acnes and Corynebacterium spp. Glycerol monolaurate inhibited lipase production by S. aureus and S. epidermidis at concentrations that did not adversely affect bacterial cell growth. GML can be used to inhibit ocular bacterial lipase production without proving detrimental to commensal bacteria viability

Detection methods for non-Gaussian gravitational wave stochastic backgrounds

We address the issue of finding an optimal detection method for a discontinuous or intermittent gravitational wave stochastic background. Such a signal might sound something like popcorn popping. We derive an appropriate version of the maximum likelihood detection statistic, and compare its performance to that of the standard cross-correlation statistic both analytically and with Monte Carlo simulations. The maximum likelihood statistic performs better than the cross-correlation statistic when the background is sufficiently non-Gaussian. For both ground and space based detectors, this results in a gain factor, ranging roughly from 1 to 3, in the minimum gravitational-wave energy density necessary for detection, depending on the duty cycle of the background. Our analysis is exploratory, as we assume that the time structure of the events cannot be resolved, and we assume white, Gaussian noise in two collocated, aligned detectors. Before this detection method can be used in practice with real detector data, further work is required to generalize our analysis to accommodate separated, misaligned detectors with realistic, colored, non-Gaussian noise.Comment: 25 pages, 12 figures, submitted to physical review D, added revisions in response to reviewers comment

Hyperinsulinism-hyperammonaemia syndrome: novel mutations in the GLUD1 gene and genotype-phenotype correlations

Background: Activating mutations in the GLUD1 gene (which encodes for the intra-mitochondrial enzyme glutamate dehydrogenase, GDH) cause the hyperinsulinism–hyperammonaemia (HI/HA) syndrome. Patients present with HA and leucine-sensitive hypoglycaemia. GDH is regulated by another intra-mitochondrial enzyme sirtuin 4 (SIRT4). Sirt4 knockout mice demonstrate activation of GDH with increased amino acid-stimulated insulin secretion. Objectives: To study the genotype–phenotype correlations in patients with GLUD1 mutations. To report the phenotype and functional analysis of a novel mutation (P436L) in the GLUD1 gene associated with the absence of HA. Patients and methods: Twenty patients with HI from 16 families had mutational analysis of the GLUD1 gene in view of HA (n=19) or leucine sensitivity (n=1). Patients negative for a GLUD1 mutation had sequence analysis of the SIRT4 gene. Functional analysis of the novel P436L GLUD1 mutation was performed. Results: Heterozygous missense mutations were detected in 15 patients with HI/HA, 2 of which are novel (N410D and D451V). In addition, a patient with a normal serum ammonia concentration (21 µmol/l) was heterozygous for a novel missense mutation P436L. Functional analysis of this mutation confirms that it is associated with a loss of GTP inhibition. Seizure disorder was common (43%) in our cohort of patients with a GLUD1 mutation. No mutations in the SIRT4 gene were identified. Conclusion: Patients with HI due to mutations in the GLUD1 gene may have normal serum ammonia concentrations. Hence, GLUD1 mutational analysis may be indicated in patients with leucine sensitivity; even in the absence of HA. A high frequency of epilepsy (43%) was observed in our patients with GLUD1 mutations

First upper limit analysis and results from LIGO science data: stochastic background

I describe analysis of correlations in the outputs of the three LIGO interferometers from LIGO's first science run, held over 17 days in August and September of 2002, and the resulting upper limit set on a stochastic background of gravitational waves. By searching for cross-correlations between the LIGO detectors in Livingston, LA and Hanford, WA, we are able to set a 90% confidence level upper limit of h_{100}^2 Omega_0 < 23 +/- 4.6.Comment: 7 pages; 1 eps figures; proceeding from 2003 Edoardo Amaldi Meeting on Gravitational Wave

Detecting gravitational waves from precessing binaries of spinning compact objects: Adiabatic limit

Black-hole (BH) binaries with single-BH masses m=5--20 Msun, moving on quasicircular orbits, are among the most promising sources for first-generation ground-based gravitational-wave (GW) detectors. Until now, the development of data-analysis techniques to detect GWs from these sources has been focused mostly on nonspinning BHs. The data-analysis problem for the spinning case is complicated by the necessity to model the precession-induced modulations of the GW signal, and by the large number of parameters needed to characterize the system, including the initial directions of the spins, and the position and orientation of the binary with respect to the GW detector. In this paper we consider binaries of maximally spinning BHs, and we work in the adiabatic-inspiral regime to build families of modulated detection templates that (i) are functions of very few physical and phenomenological parameters, (ii) model remarkably well the dynamical and precessional effects on the GW signal, with fitting factors on average >~ 0.97, but (iii) might require increasing the detection thresholds, offsetting at least partially the gains in the fitting factors. Our detection-template families are quite promising also for the case of neutron-star--black-hole binaries, with fitting factors on average ~ 0.93. For these binaries we also suggest (but do not test) a further template family, which would produce essentially exact waveforms written directly in terms of the physical spin parameters.Comment: 38 pages, 16 figures, RevTeX4. Final PRD version. Lingering typos corrected. Small corrections to GW flux terms as per Blanchet et al., PRD 71, 129902(E)-129904(E) (2005

Measuring gravitational waves from binary black hole coalescences: II. the waves' information and its extraction, with and without templates

We discuss the extraction of information from detected binary black hole (BBH) coalescence gravitational waves, focusing on the merger phase that occurs after the gradual inspiral and before the ringdown. Our results are: (1) If numerical relativity simulations have not produced template merger waveforms before BBH detections by LIGO/VIRGO, one can band-pass filter the merger waves. For BBHs smaller than about 40 solar masses detected via their inspiral waves, the band pass filtering signal to noise ratio indicates that the merger waves should typically be just barely visible in the noise for initial and advanced LIGO interferometers. (2) We derive an optimized (maximum likelihood) method for extracting a best-fit merger waveform from the noisy detector output; one "perpendicularly projects" this output onto a function space (specified using wavelets) that incorporates our prior knowledge of the waveforms. An extension of the method allows one to extract the BBH's two independent waveforms from outputs of several interferometers. (3) If numerical relativists produce codes for generating merger templates but running the codes is too expensive to allow an extensive survey of the merger parameter space, then a coarse survey of this parameter space, to determine the ranges of the several key parameters and to explore several qualitative issues which we describe, would be useful for data analysis purposes. (4) A complete set of templates could be used to test the nonlinear dynamics of general relativity and to measure some of the binary parameters. We estimate the number of bits of information obtainable from the merger waves (about 10 to 60 for LIGO/VIRGO, up to 200 for LISA), estimate the information loss due to template numerical errors or sparseness in the template grid, and infer approximate requirements on template accuracy and spacing.Comment: 33 pages, Rextex 3.1 macros, no figures, submitted to Phys Rev

Facilitators and Barriers to Prescribing PreExposure Prophylaxis (PrEP) for the Prevention of HIV

Background: What is PrEP and who gets it? PrEP is the use of medication by individuals to prevent HIV contraction, approved in 2012 after demonstrating safety and efficacy in the iPrEx study and Partners PrEP2 trials. HIV infection risk is 92% lower in patients using PrEP. Truvada®, a combination of tenofovir and emtricitabine taken orally daily, is the only approved PrEP regimen and is intended to compliment other prevention strategies such as condoms. HIV negative-individuals at risk for exposure to HIV have been identified as men who have sex with men (MSM), IV drug users, heterosexuals who have unprotected sex with partners of unknown HIV status, and those in serodiscordant relationships. Barriers to PrEP Implementation PrEP is effective when patients adhere; however, both the medical community and some high-risk populations have been slow to adopt it as an HIV prevention strategy. Surveys have shown clinicians perceived barriers to PrEP such as adverse side effects, viral drug resistance, increased high-risk behavior, cost, and training. HIV in Vermont New diagnoses of HIV among Vermont residents has remained relatively stable over the last twenty years. Vermont CARES, a non-profit, offers free and anonymous HIV tests and in-person risk-reduction counseling. Clients are increasingly asking about PrEP as a prevention strategy, but the response from the medical community is difficult to ascertain.https://scholarworks.uvm.edu/comphp_gallery/1235/thumbnail.jp

Stochastic Background Search Correlating ALLEGRO with LIGO Engineering Data

We describe the role of correlation measurements between the LIGO interferometer in Livingston, LA, and the ALLEGRO resonant bar detector in Baton Rouge, LA, in searches for a stochastic background of gravitational waves. Such measurements provide a valuable complement to correlations between interferometers at the two LIGO sites, since they are sensitive in a different, higher, frequency band. Additionally, the variable orientation of the ALLEGRO detector provides a means to distinguish gravitational wave correlations from correlated environmental noise. We describe the analysis underway to set a limit on the strength of a stochastic background at frequencies near 900 Hz using ALLEGRO data and data from LIGO's E7 Engineering Run.Comment: 8 pages, 2 encapsulated PostScript figures, uses IOP class files, submitted to the proceedings of the 7th Gravitational Wave Data Analysis Workshop (which will be published in Classical and Quantum Gravity

A Comparison of search templates for gravitational waves from binary inspiral

We compare the performances of the templates defined by three different types of approaches: traditional post-Newtonian templates (Taylor-approximants), ``resummed'' post-Newtonian templates assuming the adiabatic approximation and stopping before the plunge (P-approximants), and further ``resummed'' post-Newtonian templates going beyond the adiabatic approximation and incorporating the plunge with its transition from the inspiral (Effective-one-body approximants). The signal to noise ratio is significantly enhanced (mainly because of the inclusion of the plunge signal) by using these new effective-one-body templates relative to the usual post-Newtonian ones for binary masses greater than $30 M_\odot$, the most likely sources for initial laser interferometers. Independently of the question of the plunge signal, the comparison of the various templates confirms the usefulness of using resummation methods. The paper also summarizes the key elements of the construction of various templates and thus can serve as a resource for those involved in writing inspiral search software.Comment: eta-dependent tail terms corrected after related errata by Blanchet (2005

Avalanche dynamics of radio pulsar glitches

We test statistically the hypothesis that radio pulsar glitches result from an avalanche process, in which angular momentum is transferred erratically from the flywheel-like superfluid in the star to the slowly decelerating, solid crust via spatially connected chains of local, impulsive, threshold-activated events, so that the system fluctuates around a self-organised critical state. Analysis of the glitch population (currently 285 events from 101 pulsars) demonstrates that the size distribution in individual pulsars is consistent with being scale invariant, as expected for an avalanche process. The waiting-time distribution is consistent with being exponential in seven out of nine pulsars where it can be measured reliably, after adjusting for observational limits on the minimum waiting time, as for a constant-rate Poisson process. PSR J0537$-$6910 and PSR J0835$-$4510 are the exceptions; their waiting-time distributions show evidence of quasiperiodicity. In each object, stationarity requires that the rate $\lambda$ equals $- \epsilon \dot{\nu} /$, where $\dot{\nu}$ is the angular acceleration of the crust, $$ is the mean glitch size, and $\epsilon\dot{\nu}$ is the relative angular acceleration of the crust and superfluid. There is no evidence that $\lambda$ changes monotonically with spin-down age. The rate distribution itself is fitted reasonably well by an exponential for $\lambda \geq 0.25 {\rm yr^{-1}}$. For $\lambda < 0.25 {\rm yr^{-1}}$, its exact form is unknown; the exponential overestimates the number of glitching pulsars observed at low $\lambda$, where the limited total observation time exercises a selection bias.Comment: Accepted for publication in the Astrophysical Journa