Practical considerations of the use of cross-weld and compact tension specimens creep data

This article gives an overview of the use of cross-weld and compact tension specimen modelling and analyses data to characterise creep behaviour of the high-temperature components. Cross-weld and compact tension specimens are used to describe creep crack growth in heterogeneous material structures, such as welds, and a number of factors that affect the creep behaviour of the structure, associated with this heterogeneity, have been identified. Creep data obtained from cross-weld specimen modelling are substantially affected by the material model used (e.g. Norton power law, Liu-Murakami), stress singularities that arise at the material interfaces and in between the columnar and equiaxed zones of the weld material, residual stresses which arise through the thickness of a multi-pass weld and the extraction orientation of the specimen relative to the welding direction. Creep crack growth data obtained from compact tension specimen testing and analyses are strongly dependent on the material models used (isotropic hardening models, Norton creep law, Liu/Murakami model, etc.), the path dependence of the C*-contour integral fracture parameter for certain heterogeneous material configurations and the accurate computation of material constants for damage mechanics models and the agreement between loading state to the actual stress state of the component to which the compact tension specimen creep data are applied to. This study examines typical results and observations from cross-weld specimen and compact tension specimen creep analyses, identifying the advantages, disadvantages and limitations of each specimen procedure

A rocky planet transiting a nearby low-mass star

M-dwarf stars -- hydrogen-burning stars that are smaller than 60 per cent of the size of the Sun -- are the most common class of star in our Galaxy and outnumber Sun-like stars by a ratio of 12:1. Recent results have shown that M dwarfs host Earth-sized planets in great numbers: the average number of M-dwarf planets that are between 0.5 to 1.5 times the size of Earth is at least 1.4 per star. The nearest such planets known to transit their star are 39 parsecs away, too distant for detailed follow-up observations to measure the planetary masses or to study their atmospheres. Here we report observations of GJ 1132b, a planet with a size of 1.2 Earth radii that is transiting a small star 12 parsecs away. Our Doppler mass measurement of GJ 1132b yields a density consistent with an Earth-like bulk composition, similar to the compositions of the six known exoplanets with masses less than six times that of the Earth and precisely measured densities. Receiving 19 times more stellar radiation than the Earth, the planet is too hot to be habitable but is cool enough to support a substantial atmosphere, one that has probably been considerably depleted of hydrogen. Because the host star is nearby and only 21 per cent the radius of the Sun, existing and upcoming telescopes will be able to observe the composition and dynamics of the planetary atmosphere.Comment: Published in Nature on 12 November 2015, available at http://dx.doi.org/10.1038/nature15762. This is the authors' version of the manuscrip

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

The remnants of galaxy formation from a panoramic survey of the region around M31

In hierarchical cosmological models, galaxies grow in mass through the continual accretion of smaller ones. The tidal disruption of these systems is expected to result in loosely bound stars surrounding the galaxy, at distances that reach $10 - 100$ times the radius of the central disk. The number, luminosity and morphology of the relics of this process provide significant clues to galaxy formation history, but obtaining a comprehensive survey of these components is difficult because of their intrinsic faintness and vast extent. Here we report a panoramic survey of the Andromeda galaxy (M31). We detect stars and coherent structures that are almost certainly remnants of dwarf galaxies destroyed by the tidal field of M31. An improved census of their surviving counterparts implies that three-quarters of M31's satellites brighter than $M_V < -6$ await discovery. The brightest companion, Triangulum (M33), is surrounded by a stellar structure that provides persuasive evidence for a recent encounter with M31. This panorama of galaxy structure directly confirms the basic tenets of the hierarchical galaxy formation model and reveals the shared history of M31 and M33 in the unceasing build-up of galaxies.Comment: Published in Nature. Supplementary movie available at https://www.astrosci.ca/users/alan/PANDAS/Latest%20news%3A%20movie%20of%20orbit.htm

Phonological and orthographic influences in the bouba–kiki effect

We examine a high-profile phenomenon known as the bouba–kiki effect, in which non-word names are assigned to abstract shapes in systematic ways (e.g. rounded shapes are preferentially labelled bouba over kiki). In a detailed evaluation of the literature, we show that most accounts of the effect point to predominantly or entirely iconic cross-sensory mappings between acoustic or articulatory properties of sound and shape as the mechanism underlying the effect. However, these accounts have tended to confound the acoustic or articulatory properties of non-words with another fundamental property: their written form. We compare traditional accounts of direct audio or articulatory-visual mapping with an account in which the effect is heavily influenced by matching between the shapes of graphemes and the abstract shape targets. The results of our two studies suggest that the dominant mechanism underlying the effect for literate subjects is matching based on aligning letter curvature and shape roundedness (i.e. non-words with curved letters are matched to round shapes). We show that letter curvature is strong enough to significantly influence word–shape associations even in auditory tasks, where written word forms are never presented to participants. However, we also find an additional phonological influence in that voiced sounds are preferentially linked with rounded shapes, although this arises only in a purely auditory word–shape association task. We conclude that many previous investigations of the bouba–kiki effect may not have given appropriate consideration or weight to the influence of orthography among literate subjects

The impact of physical activity on fatigue and quality of life in lung cancer patients: a randomised controlled trial protocol

Background: People with lung cancer have substantial symptom burden and more unmet needs than the general cancer population. Physical activity (PA) has been shown to positively influence quality of life (QOL), fatigue and daily functioning in the curative treatment of people with breast and colorectal cancers and lung diseases, as well as in palliative settings. A randomised controlled trial (RCT) is needed to determine if lung cancer patients benefit from structured PA intervention. The Physical Activity in Lung Cancer (PAL) trial is designed to evaluate the impact of a 2-month PA intervention on fatigue and QOL in patients with non-resectable lung cancer. Biological mechanisms will also be studied.Methods/design: A multi-centre RCT with patients randomised to usual care or a 2-month PA programme, involving supervised PA sessions including a behavioural change component and home-based PA. QOL questionnaires, disease and functional status and body composition will be assessed at baseline, 2, 4 and 6 months follow-up. The primary endpoint is comparative levels of fatigue between the 2 arms. Secondary endpoints include: QOL, functional abilities and physical function. Exploratory endpoints include: anxiety, depression, distress, dyspnoea, PA behaviour, fitness, hospitalisations, survival, cytokines and insulin-like growth factor levels.Discussion: This study will provide high-level evidence of the effect of PA programmes on cancer-related fatigue and QOL in patients with advanced lung cancer. If positive, the study has the potential to change care for people with cancer using a simple, inexpensive intervention to improve their QOL and help them maintain independent function for as long as possible.Trial registration: Australian New Zealand Clinical Trials Registry No. ACTRN12609000971235. © 2012 Dhillon et al.; licensee BioMed Central Ltd

Aquaporins: important but elusive drug targets.

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators

Enabling large-scale design, synthesis and validation of small molecule protein-protein antagonists

Although there is no shortage of potential drug targets, there are only a handful known low-molecular-weight inhibitors of protein-protein interactions (PPIs). One problem is that current efforts are dominated by low-yield high-throughput screening, whose rigid framework is not suitable for the diverse chemotypes present in PPIs. Here, we developed a novel pharmacophore-based interactive screening technology that builds on the role anchor residues, or deeply buried hot spots, have in PPIs, and redesigns these entry points with anchor-biased virtual multicomponent reactions, delivering tens of millions of readily synthesizable novel compounds. Application of this approach to the MDM2/p53 cancer target led to high hit rates, resulting in a large and diverse set of confirmed inhibitors, and co-crystal structures validate the designed compounds. Our unique open-access technology promises to expand chemical space and the exploration of the human interactome by leveraging in-house small-scale assays and user-friendly chemistry to rationally design ligands for PPIs with known structure. © 2012 Koes et al

Kinematics of the Tucana Dwarf Galaxy: an unusually dense dwarf in the Local Group

We present new FLAMES+GIRAFFE spectroscopy of 36 member stars in the isolated Local Group dwarf spheroidal galaxy Tucana. We measure a systemic velocity for the system of $v_{Tuc}$=216.7$^{+2.9}_{−2.8}$ km s$^{−1}$, and a velocity dispersion of σ$_{v,Tuc}$=14.4$^{+2.8}_{−2.3}$ km s$^{−1}$. We also detect a rotation gradient of $\frac{dvr}{dχ}$=7.6$^{+4.2}_{−4.3}$ km s$^{−1}$ kpc$^{−1}$, which reduces the systemic velocity to $v_{Tuc}$=215.2$^{+2.8}_{−2.7}$ km s$^{−1}$ and the velocity dispersion to σ$_{v,Tuc}$=13.3$^{+2.7}_{−2.3}$ km s$^{−1}$. We perform Jeans modelling of the density profile of Tucana, using the line-of-sight velocities of the member stars. We find that it favours a high central density consistent with ‘pristine’ subhaloes in Λ cold dark matter, and a massive dark matter halo (~10$^{10}$ M$_\odot$) consistent with expectations from abundance matching. Tucana appears to be significantly more centrally dense than other isolated Local Group dwarfs, making it an ideal laboratory for testing dark matter models

Cerebrospinal fluid biomarker panel of synaptic dysfunction in Alzheimer's disease and other neurodegenerative disorders

Introduction: Synaptic degeneration is a key part of the pathophysiology of neurodegenerative diseases, and biomarkers reflecting the pathological alterations are greatly needed. Method: Seventeen synaptic proteins were quantified in a pathology-confirmed cerebrospinal fluid cohort of patients with Alzheimer's disease (AD; n = 63), frontotemporal lobar degeneration (FTLD; n = 53), and Lewy body spectrum of disorders (LBD; n = 21), as well as healthy controls (HC; n = 48). Results: Comparisons revealed four distinct patterns: markers decreased across all neurodegenerative conditions compared to HC (the neuronal pentraxins), markers increased across all neurodegenerative conditions (14-3-3 zeta/delta), markers selectively increased in AD compared to other neurodegenerative conditions (neurogranin and beta-synuclein), and markers selectively decreased in LBD and FTLD compared to HC and AD (AP2B1 and syntaxin-1B). Discussion: Several of the synaptic proteins may serve as biomarkers for synaptic dysfunction in AD, LBD, and FTLD. Additionally, differential patterns of synaptic protein alterations seem to be present across neurodegenerative diseases. Highlights: A panel of synaptic proteins were quantified in the cerebrospinal fluid using mass spectrometry. We compared Alzheimer's disease, frontotemporal degeneration, and Lewy body spectrum of disorders. Pathology was confirmed by autopsy or familial mutations. We discovered synaptic biomarkers for synaptic degeneration and cognitive decline. We found differential patterns of synaptic proteins across neurodegenerative diseases