Non-linear multiparameter eigenvalue problems for ordinary differential equations

AbstractIn this paper we consider the non-linear multiparameter eigenvalue problem in ordinary differential equations: y″r(xr) + qr(xr)yr(xr) + Mr(yr) + ∑s = 1n μs(ars(xr + Prs) yr(xr) = 0, r = 1,…, n, where the non-linear functions Mrand Prs will be required to satisfy certain Fréchet differentiability conditions. We study bifurcation from the simple eigenvalues of the corresponding linear problem and state a completeness theorem for the eigenfunctions of these systems

Background Studies for the Neutral Current Detector Array in the Sudbury Neutrino Observatory

An array of 3He-filled proportional counters will be used in the Sudbury Neutrino Observatory to measure the neutral-current interaction of neutrinos and deuterium. We describe the backgrounds to this detection method.Comment: Accepted for publication in the proceedings of TAUP99. 2 page

Physical activity patterns in a nationally representative sample of adults in Ireland

Original article can be found at: http://journals.cambridge.org/ Copyright - the authors. DOI: 10.1079/PHN2001192Objective To evaluate habitual levels of physical activity in a nationally representative sample of adults in Ireland. Design Cross-sectional survey using a self-administered questionnaire. Usual levels of work, recreational and household activities were evaluated in relation to anthropometric, demographic and socio-economic characteristics. The amount and intensity of all activities were quantified by assigning metabolic equivalents (METS) to each activity. Setting Republic of Ireland and Northern Ireland, 1997–1999. Subjects Random sample of 1379 adults aged 18–64 years. Results Men were approximately twice as active in work and recreational activity (139.7 ± 83.9 METS) as women (68.5 ± 49.8 METS; P 28kg m−2) or obese (BMI > 30kg m−2). Fewer obese subjects reported higher levels of work and leisure activities. However, a higher percentage of obese women reported participation in the higher levels of household activities. Participation rates in recreational activities were low. Walking was the most important leisure activity of both men (41%) and women (60%). In terms of hours per week spent in vigorous physical activity, men were more active than women, professional and skilled non-manual women were more active than women in other social classes, and younger subjects (aged 18–35 years) were more active than older subjects. Conclusions The holistic approach used in the assessment of physical activity in this study has revealed important and subtle differences in the activity patterns of men and women. Failure to fully characterise the respective activity patterns of men and women could lead to ill-informed public health policy aimed at promoting and sustaining lifetime habits of physical activity. The results suggest that simple population-focused programmes to promote physical activity are unlikely to offer the same chance of long-term success as more sensitive and individualised strategies.Peer reviewe

Design and use of the MATLAB Parallel Processing Gateway

This report describes a collection of software utilities that together form a "parallel processing gateway" for the computer aided control system design software package,MATLAB. These utilities allow control engineers to configure and boot processes on the parallel computer and concurrent and parallel routines transparently from the MATLAB command line. Here, the requirements of such a gateway, its design, implementation and use and features that enable the control engineer to readily exploit a parallel computer are described and discussed. In addition, the performance of the gateway is assessed in terms of the communications achievable between MATLAB and the parallel computer

Efficient scheme for one-way quantum computing in thermal cavities

We propose a practical scheme for one-way quantum computing based on efficient generation of 2D cluster state in thermal cavities. We achieve a controlled-phase gate that is neither sensitive to cavity decay nor to thermal field by adding a strong classical field to the two-level atoms. We show that a 2D cluster state can be generated directly by making every two atoms collide in an array of cavities, with numerically calculated parameters and appropriate operation sequence that can be easily achieved in practical Cavity QED experiments. Based on a generated cluster state in Box$^{(4)}$ configuration, we then implement Grover's search algorithm for four database elements in a very simple way as an example of one-way quantum computing.Comment: 6 pages, 3 figure

Study protocol; thyroid hormone replacement for untreated older adults with subclinical hypothyroidism - a randomised placebo controlled trial (TRUST)

Background: Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Methods: Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects <50Kg body weight or known coronary heart disease) with titration of dose in the active treatment group according to TSH level, and a mock titration in the placebo group. The primary outcomes are changes in two domains (hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. Discussion: This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Trial registration: Clinicaltrials.gov NCT01660126; registered 8th June 2012

A modular CRISPR screen identifies individual and combination pathways contributing to HIV-1 latency

Transcriptional silencing of latent HIV-1 proviruses entails complex and overlapping mechanisms that pose a major barrier to in vivo elimination of HIV-1. We developed a new latency CRISPR screening strategy, called Latency HIV-CRISPR which uses the packaging of guideRNA-encoding lentiviral vector genomes into the supernatant of budding virions as a direct readout of factors involved in the maintenance of HIV-1 latency. We developed a custom guideRNA library targeting epigenetic regulatory genes and paired the screen with and without a latency reversal agent-AZD5582, an activator of the non-canonical NFκB pathway-to examine a combination of mechanisms controlling HIV-1 latency. A component of the Nucleosome Acetyltransferase of H4 histone acetylation (NuA4 HAT) complex, ING3, acts in concert with AZD5582 to activate proviruses in J-Lat cell lines and in a primary CD4+ T cell model of HIV-1 latency. We found that the knockout of ING3 reduces acetylation of the H4 histone tail and BRD4 occupancy on the HIV-1 LTR. However, the combination of ING3 knockout accompanied with the activation of the non-canonical NFκB pathway via AZD5582 resulted in a dramatic increase in initiation and elongation of RNA Polymerase II on the HIV-1 provirus in a manner that is nearly unique among all cellular promoters

Epigenome-wide SRC-1 mediated gene silencing represses cellular differentiation in advanced breast cancer

Abstract Purpose: Despite the clinical utility of endocrine therapies for estrogen receptor–positive (ER) breast cancer, up to 40% of patients eventually develop resistance, leading to disease progression. The molecular determinants that drive this adaptation to treatment remain poorly understood. Methylome aberrations drive cancer growth yet the functional role and mechanism of these epimutations in drug resistance are poorly elucidated. Experimental Design: Genome-wide multi-omics sequencing approach identified a differentially methylated hub of prodifferentiation genes in endocrine resistant breast cancer patients and cell models. Clinical relevance of the functionally validated methyl-targets was assessed in a cohort of endocrine-treated human breast cancers and patient-derived ex vivo metastatic tumors. Results: Enhanced global hypermethylation was observed in endocrine treatment resistant cells and patient metastasis relative to sensitive parent cells and matched primary breast tumor, respectively. Using paired methylation and transcriptional profiles, we found that SRC-1–dependent alterations in endocrine resistance lead to aberrant hypermethylation that resulted in reduced expression of a set of differentiation genes. Analysis of ER-positive endocrine-treated human breast tumors (n = 669) demonstrated that low expression of this prodifferentiation gene set significantly associated with poor clinical outcome (P = 0.00009). We demonstrate that the reactivation of these genes in vitro and ex vivo reverses the aggressive phenotype. Conclusions: Our work demonstrates that SRC-1-dependent epigenetic remodeling is a ’high level’ regulator of the poorly differentiated state in ER-positive breast cancer. Collectively these data revealed an epigenetic reprograming pathway, whereby concerted differential DNA methylation is potentiated by SRC-1 in the endocrine resistant setting. Clin Cancer Res; 24(15); 3692–703. ©2018 AACR.</jats:p

Measurement of key resonance states for the 40P(p,g)31S reaction rate, and the production of intermediate-mass elements in nova explosions

We report the first experimental constraints on spectroscopic factors and strengths of key resonances in the 30P(p, γ)31Sreaction critical for determining the production of intermediate-mass elements up to Ca in nova ejecta. The 30P(d, n)31Sreaction was studied in inverse kinematics using the GRETINA γ-ray array to measure the angle-integrated cross-sections of states above the proton threshold. In general, negative-parity states are found to be most strongly produced but the absolute values of spectroscopic factors are typically an order of magnitude lower than predicted by the shell-model calculations employing WBP Hamiltonian for the negative-parity states. The results clearly indicate the dominance of a single 3/2−resonance state at 196 keV in the region of nova burning T≈0.10–0.17GK, well within the region of interest for nova nucleosynthesis. Hydrodynamic simulations of nova explosions have been performed to demonstrate the effect on the composition of nova ejecta.Postprint (published version