A test of general relativity from the three-dimensional orbital geometry of a binary pulsar

Binary pulsars provide an excellent system for testing general relativity because of their intrinsic rotational stability and the precision with which radio observations can be used to determine their orbital dynamics. Measurements of the rate of orbital decay of two pulsars have been shown to be consistent with the emission of gravitational waves as predicted by general relativity, providing the most convincing evidence for the self-consistency of the theory to date. However, independent verification of the orbital geometry in these systems was not possible. Such verification may be obtained by determining the orientation of a binary pulsar system using only classical geometric constraints, permitting an independent prediction of general relativistic effects. Here we report high-precision timing of the nearby binary millisecond pulsar PSR J0437-4715, which establish the three-dimensional structure of its orbit. We see the expected retardation of the pulse signal arising from the curvature of space-time in the vicinity of the companion object (the `Shapiro delay'), and we determine the mass of the pulsar and its white dwarf companion. Such mass determinations contribute to our understanding of the origin and evolution of neutron stars.Comment: 5 pages, 2 figure

Planetary science and exploration in the deep subsurface: results from the MINAR Program, Boulby Mine, UK

The subsurface exploration of other planetary bodies can be used to unravel their geological history and assess their habitability. On Mars in particular, present-day habitable conditions may be restricted to the subsurface. Using a deep subsurface mine, we carried out a program of extraterrestrial analog research – MINe Analog Research (MINAR). MINAR aims to carry out the scientific study of the deep subsurface and test instrumentation designed for planetary surface exploration by investigating deep subsurface geology, whilst establishing the potential this technology has to be transferred into the mining industry. An integrated multi-instrument suite was used to investigate samples of representative evaporite minerals from a subsurface Permian evaporite sequence, in particular to assess mineral and elemental variations which provide small-scale regions of enhanced habitability. The instruments used were the Panoramic Camera emulator, Close-Up Imager, Raman spectrometer, Small Planetary Linear Impulse Tool, Ultrasonic drill and handheld X-ray diffraction (XRD). We present science results from the analog research and show that these instruments can be used to investigate in situ the geological context and mineralogical variations of a deep subsurface environment, and thus habitability, from millimetre to metre scales. We also show that these instruments are complementary. For example, the identification of primary evaporite minerals such as NaCl and KCl, which are difficult to detect by portable Raman spectrometers, can be accomplished with XRD. By contrast, Raman is highly effective at locating and detecting mineral inclusions in primary evaporite minerals. MINAR demonstrates the effective use of a deep subsurface environment for planetary instrument development, understanding the habitability of extreme deep subsurface environments on Earth and other planetary bodies, and advancing the use of space technology in economic mining

Influence of a montmorency cherry juice blend on indices of exercise-induced stress and upper respiratory tract symptoms following marathon running—a pilot investigation

Background: Prolonged exercise, such as marathon running, has been associated with an increase in respiratory mucosal inflammation. The aim of this pilot study was to examine the effects of Montmorency cherry juice on markers of stress, immunity and inflammation following a Marathon. Methods: Twenty recreational Marathon runners consumed either cherry juice (CJ) or placebo (PL) before and after a Marathon race. Markers of mucosal immunity secretory immunoglobulin A (sIgA), immunoglobulin G (IgG), salivary cortisol, inflammation (CRP) and self-reported incidence and severity of upper respiratory tract symptoms (URTS) were measured before and following the race. Results: All variables except secretory IgA and IgG concentrations in saliva showed a significant time effect (P < 0.01). Serum CRP showed a significant interaction and treatment effect (P < 0.01). The CRP increase at 24 and 48 h post-Marathon was lower (P < 0.01) in the CJ group compared to PL group. Mucosal immunity and salivary cortisol showed no interaction effect or treatment effect. The incidence and severity of URTS was significantly greater than baseline at 24 h and 48 h following the race in the PL group and was also greater than the CJ group (P < 0.05). No URTS were reported in the CJ group whereas 50 % of runners in the PL group reported URTS at 24 h and 48 h post-Marathon. Conclusions: This is the first study that provides encouraging evidence of the potential role of Montmorency cherries in reducing the development of URTS post-Marathon possibly caused by exercise-induced hyperventilation trauma, and/or other infectious and non-infectious factors

Mind your step: the effects of mobile phone use on gaze behavior in stair climbing

Stair walking is a hazardous activity and a common cause of fatal and non-fatal falls. Previous studies have assessed the role of eye movements in stair walking by asking people to repeatedly go up and down stairs in quiet and controlled conditions, while the role of peripheral vision was examined by giving participants specific fixation instructions or working memory tasks. We here extend this research to stair walking in a natural environment with other people present on the stairs and a now common secondary task: Using one's mobile phone. Results show that using the mobile phone strongly draws one's attention away from the stairs, but that the distribution of gaze locations away from the phone is little influenced by using one's phone. Phone use also increased the time needed to walk the stairs, but handrail use remained low. These results indicate that limited foveal vision suffices for adequate stair walking in normal environments, but that mobile phone use has a strong influence on attention, which may pose problems when unexpected obstacles are encountered

Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression

Over the past decade, it has become clear that mammalian genomes encode thousands of long non-coding RNAs (lncRNAs), many of which are now implicated in diverse biological processes. Recent work studying the molecular mechanisms of several key examples — including Xist, which orchestrates X chromosome inactivation — has provided new insights into how lncRNAs can control cellular functions by acting in the nucleus. Here we discuss emerging mechanistic insights into how lncRNAs can regulate gene expression by coordinating regulatory proteins, localizing to target loci and shaping three-dimensional (3D) nuclear organization. We explore these principles to highlight biological challenges in gene regulation, in which lncRNAs are well-suited to perform roles that cannot be carried out by DNA elements or protein regulators alone, such as acting as spatial amplifiers of regulatory signals in the nucleus

CIP2A expression predicts recurrences of tamoxifen-treated breast cancer

CIP2A is emerging as an oncoprotein overexpressed commonly across many tumours and generally correlated with higher tumour grade and therapeutic resistance. CIP2A drives an oncogenic potential through inhibiting protein phosphatase 2A, stabilizing MYC, and promoting epithelial-to-mesenchymal transition, although further biological mechanisms for CIP2A are yet to be defined. CIP2A protein expression was studied by immunohistochemistry in oestrogen receptor–positive primary breast cancers (n = 250) obtained from the Leeds Tissue Bank. In total, 51 cases presented with a relapse or metastasis during adjuvant treatment with tamoxifen and were regarded as tamoxifen resistant. CIP2A expression was scored separately for cytoplasmic, nuclear, or membranous staining, and scores were tested for statistically significant relationships with clinicopathological features. Membranous CIP2A was preferentially expressed in cases who experienced a recurrence during tamoxifen treatment thus predicting a worse overall survival (log rank = 8.357, p = 0.004) and disease-free survival (log rank = 21.766, p < 0.001). Cox multivariate analysis indicates that it is an independent prognostic indicator for overall survival (hazard ratio = 4.310, p = 0.013) and disease-free survival (hazard ratio = 5.449, p = 0.002). In this study, we propose the assessment of membranous CIP2A expression as a potential novel prognostic and predictive indicator for tamoxifen resistance and recurrence within oestrogen receptor–positive breast cancer

A novel outbred mouse model of 2009 pandemic influenza and bacterial co-infection severity

Influenza viruses pose a significant health risk and annually impose a great cost to patients and the health care system. The molecular determinants of influenza severity, often exacerbated by secondary bacterial infection, are largely unclear. We generated a novel outbred mouse model of influenza virus, Staphylococcus aureus, and coinfection utilizing influenza A/CA/07/2009 virus and S. aureus (USA300). Outbred mice displayed a wide range of pathologic phenotypes following influenza virus or co-infection ranging broadly in severity. Influenza viral burden positively correlated with weight loss although lung histopathology did not. Inflammatory cytokines including IL-6, TNF-α, G-CSF, and CXCL10 positively correlated with both weight loss and viral burden. In S. aureus infection, IL-1β, G-CSF, TNF-α, and IL-6 positively correlated with weight loss and bacterial burden. In co-infection, IL-1β production correlated with decreased weight loss suggesting a protective role. The data demonstrate an approach to identify biomarkers of severe disease and to understand pathogenic mechanisms in pneumonia. © 2013 McHugh et al

Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Harvest: an open-source tool for the validation and improvement of peptide identification metrics and fragmentation exploration

<p>Abstract</p> <p>Background</p> <p>Protein identification using mass spectrometry is an important tool in many areas of the life sciences, and in proteomics research in particular. Increasing the number of proteins correctly identified is dependent on the ability to include new knowledge about the mass spectrometry fragmentation process, into computational algorithms designed to separate true matches of peptides to unidentified mass spectra from spurious matches. This discrimination is achieved by computing a function of the various features of the potential match between the observed and theoretical spectra to give a numerical approximation of their similarity. It is these underlying "metrics" that determine the ability of a protein identification package to maximise correct identifications while limiting false discovery rates. There is currently no software available specifically for the simple implementation and analysis of arbitrary novel metrics for peptide matching and for the exploration of fragmentation patterns for a given dataset.</p> <p>Results</p> <p>We present Harvest: an open source software tool for analysing fragmentation patterns and assessing the power of a new piece of information about the MS/MS fragmentation process to more clearly differentiate between correct and random peptide assignments. We demonstrate this functionality using data metrics derived from the properties of individual datasets in a peptide identification context. Using Harvest, we demonstrate how the development of such metrics may improve correct peptide assignment confidence in the context of a high-throughput proteomics experiment and characterise properties of peptide fragmentation.</p> <p>Conclusions</p> <p>Harvest provides a simple framework in C++ for analysing and prototyping metrics for peptide matching, the core of the protein identification problem. It is not a protein identification package and answers a different research question to packages such as Sequest, Mascot, X!Tandem, and other protein identification packages. It does not aim to maximise the number of assigned peptides from a set of unknown spectra, but instead provides a method by which researchers can explore fragmentation properties and assess the power of novel metrics for peptide matching in the context of a given experiment. Metrics developed using Harvest may then become candidates for later integration into protein identification packages.</p