337 research outputs found

    Nova light curves from the Solar Mass Ejection Imager (SMEI) - II. The extended catalogue

    Get PDF
    We present the results from observing nine Galactic novae in eruption with the Solar Mass Ejection Imager (SMEI) between 2004 and 2009. While many of these novae reached peak magnitudes that were either at or approaching the detection limits of SMEI, we were still able to produce light curves that in many cases contained more data at and around the initial rise, peak, and decline than those found in other variable star catalogs. For each nova, we obtained a peak time, maximum magnitude, and for several an estimate of the decline time (t2). Interestingly, although of lower quality than those found in Hounsell et al. (2010a), two of the light curves may indicate the presence of a pre-maximum halt. In addition the high cadence of the SMEI instrument has allowed the detection of low amplitude variations in at least one of the nova light curves

    Mechanism of primitive duct formation in the pancreas and submandibular glands: a role for SDF-1

    Get PDF
    BACKGROUND: The exocrine pancreas is composed of a branched network of ducts connected to acini. They are lined by a monolayered epithelium that derives from the endoderm and is surrounded by mesoderm-derived mesenchyme. The morphogenic mechanisms by which the ductal network is established as well as the signaling pathways involved in this process are poorly understood. RESULTS: By morphological analyzis of wild-type and mutant mouse embryos and using cultured embryonic explants we investigated how epithelial morphogenesis takes place and is regulated by chemokine signaling. Pancreas ontogenesis displayed a sequence of two opposite epithelial transitions. During the first transition, the monolayered and polarized endodermal cells give rise to tissue buds composed of a mass of non polarized epithelial cells. During the second transition the buds reorganize into branched and polarized epithelial monolayers that further differentiate into tubulo-acinar glands. We found that the second epithelial transition is controlled by the chemokine Stromal cell-Derived Factor (SDF)-1. The latter is expressed by the mesenchyme, whereas its receptor CXCR4 is expressed by the epithelium. Reorganization of cultured pancreatic buds into monolayered epithelia was blocked in the presence of AMD3100, a SDF-1 antagonist. Analyzis of sdf1 and cxcr4 knockout embryos at the stage of the second epithelial transition revealed transient defective morphogenesis of the ventral and dorsal pancreas. Reorganization of a globular mass of epithelial cells in polarized monolayers is also observed during submandibular glands development. We found that SDF-1 and CXCR4 are expressed in this organ and that AMD3100 treatment of submandibular gland explants blocks its branching morphogenesis. CONCLUSION: In conclusion, our data show that the primitive pancreatic ductal network, which is lined by a monolayered and polarized epithelium, forms by remodeling of a globular mass of non polarized epithelial cells. Our data also suggest that SDF-1 controls the branching morphogenesis of several exocrine tissues.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models

    Get PDF
    This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms. Methodology/Principal Findings: We have generated fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as confirmed by immunocytochemical analysis of cell specific markers. The three YG8R mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat stability, together with reduced expression of frataxin and reduced aconitase activity compared to control Y47R cells. Furthermore, YG8R cells also show increased sensitivity to oxidative stress and downregulation of Pgc-1α and antioxidant gene expression levels, especially Sod2. We also analysed various DNA mismatch repair (MMR) gene expression levels and found that YG8R cells displayed significant reduction in expression of several MMR genes, which may contribute to the GAA repeat stability. Conclusions/Significance: We describe the first fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be differentiated into neurons and glia. These novel FRDA mouse cell models, which exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources to further study FRDA molecular pathogenesis. They will also provide very useful tools for preclinical testing of frataxin-increasing compounds for FRDA drug therapy, for gene therapy, and as a source of cells for cell therapy testing in FRDA mice. © 2014 Sandi et al

    Untangling the Debate: The Ethics of Human Enhancement

    Get PDF
    Human enhancement, in which nanotechnology is expected to play a major role, continues to be a highly contentious ethical debate, with experts on both sides calling it the single most important issue facing science and society in this brave, new century. This paper is a broad introduction to the symposium herein that explores a range of perspectives related to that debate. We will discuss what human enhancement is and its apparent contrast to therapy; and we will begin to tease apart the myriad intertwined issues that arise in the debate: (1) freedom & autonomy, (2) health & safety, (3) fairness & equity, (4) societal disruption, and (5) human dignity

    The Effect of Auditory Distraction on the Useful Field of View in Hearing Impaired Individuals and its implications for driving

    Get PDF
    This study assessed whether the increased demand of listening in hearing impaired individuals exacerbates the detrimental impact of auditory distraction on a visual task (useful field of view test), relative to normally hearing listeners. Auditory distraction negatively affects this visual task, which is linked with various driving performance outcomes. Hearing impaired and normally hearing participants performed useful field of view testing with and without a simultaneous listening task. They also undertook a cognitive test battery. For all participants, performing the visual and auditory tasks together reduced performance on each respective test. For a number of subtests, hearing impaired participants showed poorer visual task performance, though not to a statistically significant extent. Hearing impaired participants were significantly poorer at a reading span task than normally hearing participants and tended to score lower on the most visually complex subtest of the visual task in the absence of auditory task engagement. Useful field of view performance is negatively affected by auditory distraction, and hearing loss may present further problems, given the reductions in visual and cognitive task performance suggested in this study. Suggestions are made for future work to extend this study, given the practical importance of the findings

    Action Without Awareness: Reaching to an Object You Do Not Remember Seeing

    Get PDF
    BACKGROUND: Previous work by our group has shown that the scaling of reach trajectories to target size is independent of obligatory awareness of that target property and that "action without awareness" can persist for up to 2000 ms of visual delay. In the present investigation we sought to determine if the ability to scale reaching trajectories to target size following a delay is related to the pre-computing of movement parameters during initial stimulus presentation or the maintenance of a sensory (i.e., visual) representation for on-demand response parameterization. METHODOLOGY/PRINCIPAL FINDINGS: Participants completed immediate or delayed (i.e., 2000 ms) perceptual reports and reaching responses to different sized targets under non-masked and masked target conditions. For the reaching task, the limb associated with a trial (i.e., left or right) was not specified until the time of response cuing: a manipulation that prevented participants from pre-computing the effector-related parameters of their response. In terms of the immediate and delayed perceptual tasks, target size was accurately reported during non-masked trials; however, for masked trials only a chance level of accuracy was observed. For the immediate and delayed reaching tasks, movement time as well as other temporal kinematic measures (e.g., times to peak acceleration, velocity and deceleration) increased in relation to decreasing target size across non-masked and masked trials. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that speed-accuracy relations were observed regardless of whether participants were aware (i.e., non-masked trials) or unaware (i.e., masked trials) of target size. Moreover, the equivalent scaling of immediate and delayed reaches during masked trials indicates that a persistent sensory-based representation supports the unconscious and metrical scaling of memory-guided reaching

    Dying well with reduced agency: a scoping review and thematic synthesis of the decision-making process in dementia, traumatic brain injury and frailty

    Get PDF
    Background In most Anglophone nations, policy and law increasingly foster an autonomy-based model, raising issues for large numbers of people who fail to fit the paradigm, and indicating problems in translating practical and theoretical understandings of ‘good death’ to policy. Three exemplar populations are frail older people, people with dementia and people with severe traumatic brain injury. We hypothesise that these groups face some over-lapping challenges in securing good end-of-life care linked to their limited agency. To better understand these challenges, we conducted a scoping review and thematic synthesis. Methods To capture a range of literature, we followed established scoping review methods. We then used thematic synthesis to describe the broad themes emerging from this literature. Results Initial searches generated 22,375 references, and screening yielded 49, highly heterogeneous, studies that met inclusion criteria, encompassing 12 countries and a variety of settings. The thematic synthesis identified three themes: the first concerned the processes of end-of-life decision-making, highlighting the ambiguity of the dominant shared decision-making process, wherein decisions are determined by families or doctors, sometimes explicitly marginalising the antecedent decisions of patients. Despite this marginalisation, however, the patient does play a role both as a social presence and as an active agent, by whose actions the decisions of those with authority are influenced. The second theme examined the tension between predominant notions of a good death as ‘natural’ and the drive to medicalise death through the lens of the experiences and actions of those faced with the actuality of death. The final theme considered the concept of antecedent end-of-life decision-making (in all its forms), its influence on policy and decision-making, and some caveats that arise from the studies. Conclusions Together these three themes indicate a number of directions for future research, which are likely to be applicable to other conditions that result in reduced agency. Above all, this review emphasises the need for new concepts and fresh approaches to end of life decision-making that address the needs of the growing population of frail older people, people with dementia and those with severe traumatic brain injury
    • …
    corecore