Generic tests of the existence of the gravitational dipole radiation and the variation of the gravitational constant

We present results from the high precision timing analysis of the pulsar-white dwarf (WD) binary PSR J1012+5307 using 15 years of multi-telescope data. Observations were performed regularly by the European Pulsar Timing Array (EPTA) network, consisting of Effelsberg, Jodrell Bank, Westerbork and Nan\c{c}ay. All the timing parameters have been improved from the previously published values, most by an order of magnitude. In addition, a parallax measurement of $\pi = 1.2(3)$ mas is obtained for the first time for PSR J1012+5307, being consistent with the optical estimation from the WD companion. Combining improved 3D velocity information and models for the Galactic potential the complete evolutionary Galactic path of the system is obtained. A new intrinsic eccentricity upper limit of $e<8.4\times 10^{-7}$ is acquired, one of the smallest calculated for a binary system and a measurement of the variation of the projected semi-major axis also constrains the system's orbital orientation for the first time. It is shown that PSR J1012+5307 is an ideal laboratory for testing alternative theories of gravity. The measurement of the change of the orbital period of the system of $\dot{P}_{b} = 5(1)\times 10^{-14}$ is used to set an upper limit on the dipole gravitational wave emission that is valid for a wide class of alternative theories of gravity. Moreover, it is shown that in combination with other binary pulsars PSR J1012+5307 is an ideal system to provide self-consistent, generic limits, based only on millisecond pulsar data, for the dipole radiation and the variation of the gravitational constant $\dot{G}$.Comment: accepted for publication in MNRAS, 11 pages, 5 figures, 2 table

A geometric analysis of hallux valgus: correlation with clinical assessment of severity

<p>Abstract</p> <p>Background</p> <p>Application of plane geometry to the study of bunion deformity may represent an interesting and novel approach in the research field of hallux valgus. For the purpose of contributing to development of a different perspective in the assessment of hallux valgus, this study was conducted with three objectives: a) to determine the position on the intersection point of the perpendicular bisectors of the longitudinal axes of the first metatarsal and proximal phalanx (IP), b) to correlate the location of this point with hallux valgus deformity according to angular measurements and according to visual assessment of the severity carried out by three independent observers, and c) to assess whether this IP correlated with the radius of the first metatarsophalangeal arc circumference.</p> <p>Methods</p> <p>Measurements evaluated were intermetatarsal angle (IMA), hallux valgus angle (HVA), and proximal phalangeal articular angle (PPAA). The Autocad^®program computed the location of the IP inside or outside of the foot. Three independent observers rated the severity of hallux valgus in photographs using a 100-mm visual analogue scale (VAS).</p> <p>Results</p> <p>Measurements of all angles except PPAA showed significantly lower values when the IP was located out of the foot more distantly and vice versa, significantly higher values for severe deformities in which the IP was found inside the foot (<it>p </it>< 0.001). The IP correlated significantly with VAS scores and with the length of the radius of the circle that included the first metatarsophalangeal arc circumference (<it>p </it>< 0.001)</p> <p>Conclusion</p> <p>The IP is a useful indicator of hallux valgus deformity because correlated significantly with IMA and HVA measurements, VAS scores obtained by visual inspection of the degree of deformity, and location of the center of the first metatarsophalangeal arc circumference.</p

Asymptomatic Carriage of Plasmodium in Urban Dakar: The Risk of Malaria Should Not Be Underestimated

Introduction: The objective of this study was to measure the rate of asymptomatic carriage of plasmodium in the Dakar region two years after the implementation of new strategies in clinical malaria management. Methodology: Between October and December 2008, 2952 households selected in 50 sites of Dakar area, were visited for interviews and blood sampling. Giemsa-stained thick blood smears (TBS) were performed for microscopy in asymptomatic adult women and children aged 2 to 10 years. To ensure the quality of the microscopy, we performed a polymerase chai

Effects of Protein Deficiency on Perinatal and Postnatal Health Outcomes

There are a variety of environmental insults that can occur during pregnancy which cause low birth weight and poor fetal health outcomes. One such insult is maternal malnutrition, which can be further narrowed down to a low protein diet during gestation. Studies show that perinatal protein deficiencies can impair proper organ growth and development, leading to long-term metabolic dysfunction. Understanding the molecular mechanisms that underlie how this deficiency leads to adverse developmental outcomes is essential for establishing better therapeuticstrategies that may alleviate or prevent diseases in later life. This chapter reviews how perinatal protein restriction in humans and animals leads to metabolic disease, and it identifies the mechanisms that have been elucidated, to date. These include alterations in transcriptional and epigenetic mechanisms, as well as indirect means such as endoplasmic reticulum (ER) stress and oxidative stress. Furthermore, nutritional and pharmaceutical interventions are highlighted to illustrate that the plasticity of the underdeveloped organs during perinatal life can be exploited to prevent onset of long-term metabolic disease

Diversity in sound pressure levels and estimated active space of resident killer whale vocalizations

Author Posting. © The Author, 2005. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Comparative Physiology A: Sensory, Neural, and Behavioral Physiology 192 (2006): 449-459, doi:10.1007/s00359-005-0085-2.Signal source intensity and detection range, which integrates source intensity with propagation loss, background noise and receiver hearing abilities, are important characteristics of communication signals. Apparent source levels were calculated for 819 pulsed calls and 24 whistles produced by free-ranging resident killer whales by triangulating the angles-of-arrival of sounds on two beamforming arrays towed in series. Levels in the 1-20 kHz band ranged from 131-168 dB re 1μPa @1m, with differences in the means of different sound classes (whistles: 140.2 ± 4.1 dB; variable calls: 146.6 ± 6.6 dB; stereotyped calls: 152.6 ± 5.9 dB), and among stereotyped call types. Repertoire diversity carried through to estimates of active space, with “long-range” stereotyped calls all containing overlapping, independently-modulated high-frequency components (mean estimated active space of 10-16km in sea state zero) and “short-range” sounds (5-9 km) included all stereotyped calls without a high-frequency component, whistles, and variable calls. Short-range sounds are reported to be more common during social and resting behaviors, while long-range stereotyped calls predominate in dispersed travel and foraging behaviors. These results suggest that variability in sound pressure levels may reflect diverse social and ecological functions of the acoustic repertoire of killer whales.Funding was provided by WHOI’s Ocean Ventures Fund and Rinehart Coastal Research Center and a Royal Society fellowship

Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer

Tamoxifen is the standard-of-care treatment for estrogen receptor-positive premenopausal breast cancer. We examined tamoxifen metabolism via blood metabolite concentrations and germline variations of CYP3A5, CYP2C9, CYP2C19 and CYP2D6 in 587 premenopausal patients (Asians, Middle Eastern Arabs, Caucasian-UK; median age 39 years) and clinical outcome in 306 patients. N-desmethyltamoxifen (DM-Tam)/(Z)-endoxifen and CYP2D6 phenotype significantly correlated across ethnicities (R2: 53%, P&lt;10?77). CYP2C19 and CYP2C9 correlated with norendoxifen and (Z)-4-hydroxytamoxifen concentrations, respectively (P&lt;0.001). DM-Tam was influenced by body mass index (P&lt;0.001). Improved distant relapse-free survival (DRFS) was associated with decreasing DM-Tam/(Z)-endoxifen (P=0.036) and increasing CYP2D6 activity score (hazard ratio (HR)=0.62; 95% confidence interval (CI), 0.43–0.91; P=0.013). Low (&lt;14?nM) compared with high (&gt;35?nM) endoxifen concentrations were associated with shorter DRFS (univariate P=0.03; multivariate HR=1.94; 95% CI, 1.04–4.14; P=0.064). Our data indicate that endoxifen formation in premenopausal women depends on CYP2D6 irrespective of ethnicity. Low endoxifen concentration/formation and decreased CYP2D6 activity predict shorter DRFS

Reconstruction of metabolic pathways for the cattle genome

<p>Abstract</p> <p>Background</p> <p>Metabolic reconstruction of microbial, plant and animal genomes is a necessary step toward understanding the evolutionary origins of metabolism and species-specific adaptive traits. The aims of this study were to reconstruct conserved metabolic pathways in the cattle genome and to identify metabolic pathways with missing genes and proteins. The MetaCyc database and PathwayTools software suite were chosen for this work because they are widely used and easy to implement.</p> <p>Results</p> <p>An amalgamated cattle genome database was created using the NCBI and Ensembl cattle genome databases (based on build 3.1) as data sources. PathwayTools was used to create a cattle-specific pathway genome database, which was followed by comprehensive manual curation for the reconstruction of metabolic pathways. The curated database, CattleCyc 1.0, consists of 217 metabolic pathways. A total of 64 mammalian-specific metabolic pathways were modified from the reference pathways in MetaCyc, and two pathways previously identified but missing from MetaCyc were added. Comparative analysis of metabolic pathways revealed the absence of mammalian genes for 22 metabolic enzymes whose activity was reported in the literature. We also identified six human metabolic protein-coding genes for which the cattle ortholog is missing from the sequence assembly.</p> <p>Conclusion</p> <p>CattleCyc is a powerful tool for understanding the biology of ruminants and other cetartiodactyl species. In addition, the approach used to develop CattleCyc provides a framework for the metabolic reconstruction of other newly sequenced mammalian genomes. It is clear that metabolic pathway analysis strongly reflects the quality of the underlying genome annotations. Thus, having well-annotated genomes from many mammalian species hosted in BioCyc will facilitate the comparative analysis of metabolic pathways among different species and a systems approach to comparative physiology.</p

Illuminating the life of GPCRs

The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented

Variability in the analysis of a single neuroimaging dataset by many teams

Data analysis workflows in many scientific domains have become increasingly complex and flexible. To assess the impact of this flexibility on functional magnetic resonance imaging (fMRI) results, the same dataset was independently analyzed by 70 teams, testing nine ex-ante hypotheses. The flexibility of analytic approaches is exemplified by the fact that no two teams chose identical workflows to analyze the data. This flexibility resulted in sizeable variation in hypothesis test results, even for teams whose statistical maps were highly correlated at intermediate stages of their analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Importantly, meta-analytic approaches that aggregated information across teams yielded significant consensus in activated regions across teams. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset. Our findings show that analytic flexibility can have substantial effects on scientific conclusions, and demonstrate factors related to variability in fMRI. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for multiple analyses of the same data. Potential approaches to mitigate issues related to analytical variability are discussed