An Evidence Based Search Method For Gravitational Waves From Neutron Star Ring-downs

The excitation of quadrupolar quasi-normal modes in a neutron star leads to the emission of a short, distinctive, burst of gravitational radiation in the form of a decaying sinusoid or `ring-down'. We present a Bayesian analysis method which incorporates relevant prior information about the source and known instrumental artifacts to conduct a robust search for the gravitational wave emission associated with pulsar glitches and soft $\gamma$-ray repeater flares. Instrumental transients are modelled as sine-Gaussian and their evidence, or marginal likelihood, is compared with that of Gaussian white noise and ring-downs via the `odds-ratio'. Tests using simulated data with a noise spectral density similar to the LIGO interferometer around 1 kHz yield 50% detection efficiency and 1% false alarm probability for ring-down signals with signal-to-noise ratio $\rho=5.2$. For a source at 15 kpc this requires an energy of 1.3\times 10^{-5}M_{\astrosun}c^2 to be emitted as gravitational waves.Comment: 14 pages, 12 figure

A closer look at ARSA activity in a patient with metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease mainly caused by a deficiency of arylsulfatase A activity. The typical clinical course of patients with the late infantile form includes a regression in motor skills with progression to dysphagia, seizures, hypotonia and death. We present a case of a 4-year-old female with rapidly progressive developmental regression with loss of motor milestones, spasticity and dysphagia. MRI showed volume loss and markedly abnormal deep white matter. Enzymatic testing in one laboratory showed arylsulfatase A activity in their normal range. However, extraction of urine showed a large increase in sulfatide excretion in a second laboratory. Measurement of arylsulfatase A in that laboratory showed a partial decrease in arylsulfatase A activity measured under typical conditions (about 37% of the normal mean). When the concentration of substrate in the assay was lowered to one quarter of that normally used, this individual had activity \u3c10% of controls. The patient was found to be homozygous for an unusual missense mutation in the arylsulfatase A gene confirming the diagnosis of MLD. This case illustrates the importance of careful biochemical and molecular testing for MLD if there is suspicion of this diagnosis

Synthetic and Evolutionary Construction of a Chlorate-Reducing Shewanella oneidensis MR-1.

UnlabelledDespite evidence for the prevalence of horizontal gene transfer of respiratory genes, little is known about how pathways functionally integrate within new hosts. One example of a mobile respiratory metabolism is bacterial chlorate reduction, which is frequently encoded on composite transposons. This implies that the essential components of the metabolism are encoded on these mobile elements. To test this, we heterologously expressed genes for chlorate reduction from Shewanella algae ACDC in the non-chlorate-reducing Shewanella oneidensis MR-1. The construct that ultimately endowed robust growth on chlorate included cld, a cytochrome c gene, clrABDC, and two genes of unknown function. Although strain MR-1 was unable to grow on chlorate after initial insertion of these genes into the chromosome, 11 derived strains capable of chlorate respiration were obtained through adaptive evolution. Genome resequencing indicated that all of the evolved chlorate-reducing strains replicated a large genomic region containing chlorate reduction genes. Contraction in copy number and loss of the ability to reduce chlorate were also observed, indicating that this phenomenon was extremely dynamic. Although most strains contained more than six copies of the replicated region, a single strain with less duplication also grew rapidly. This strain contained three additional mutations that we hypothesized compensated for the low copy number. We remade the mutations combinatorially in the unevolved strain and determined that a single nucleotide polymorphism (SNP) upstream of cld enabled growth on chlorate and was epistatic to a second base pair change in the NarP binding sequence between narQP and nrfA that enhanced growth.ImportanceThe ability of chlorate reduction composite transposons to form functional metabolisms after transfer to a new host is an important part of their propagation. To study this phenomenon, we engineered Shewanella oneidensis MR-1 into a chlorate reducer. We defined a set of genes sufficient to endow growth on chlorate from a plasmid, but found that chromosomal insertion of these genes was nonfunctional. Evolution of this inoperative strain into a chlorate reducer showed that tandem duplication was a dominant mechanism of activation. While copy number changes are a relatively rapid way of increasing gene dosage, replicating almost 1 megabase of extra DNA is costly. Mutations that alleviate the need for high copy number are expected to arise and eventually predominate, and we identified a single nucleotide polymorphism (SNP) that relieved the copy number requirement. This study uses both rational and evolutionary approaches to gain insight into the evolution of a fascinating respiratory metabolism

Subdomain-based test data generation

Abstract Considerable effort is required to test software thoroughly. Even with automated test data generation tools, it is still necessary to evaluate the output of each test case and identify unexpected results. Manual effort can be reduced by restricting the range of inputs testers need to consider to regions that are more likely to reveal faults, thus reducing the number of test cases overall, and therefore reducing the effort needed to create oracles. This article describes and evaluates search-based techniques, using evolution strategies and subset selection, for identifying regions of the input domain (known as subdomains) such that test cases sampled at random from within these regions can be used efficiently to find faults. The fault finding capability of each subdomain is evaluated using mutation analysis, a technique that is based on faults programmers are likely to make. The resulting subdomains kill more mutants than random testing (up to six times as many in one case) with the same number or fewer test cases. Optimised subdomains can be used as a starting point for program analysis and regression testing. They can easily be comprehended by a human test engineer, so may be used to provide information about the software under test and design further highly efficient test suites