10,351 research outputs found

    RNAseq of Deformed wing virus and other honey bee-associated viruses in eight insect taxa with or without Varroa infestation

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    The global spread of a parasitic mite (Varroa destructor) has resulted in Deformed wing virus (DWV), a previously rare pathogen, now dominating the viromes in honey bees and contributing to large-scale honey bee colony losses. DWV can be found in diverse insect taxa and has been implicated in spilling over from honey bees into associated (“apiary”) and other (“non-apiary”) insects. Here we generated next generation sequence data from 127 insect samples belonging to diverse taxa collected from Hawaiian islands with and without Varroa to identify whether the mite has indirectly affected the viral landscapes of key insect taxa across bees, wasps, flies and ants. Our data showed that, while Varroa was associated with a dramatic increase in abundance of (predominantly recombinant) DWV in honey bees (and no other honey bee-associated RNA virus), this change was not seen in any other taxa sampled. Honey bees share their environment with other insect populations and exist as a homogenous group, frequently sharing common viruses, albeit at low levels. Our data suggest that the threat of Varroa to increase viral load in an apiary does not automatically translate to an increase in virus load in other insects living in the wider community

    Mimicking exercise in three-dimensional bioengineered skeletal muscle to investigate cellular and molecular mechanisms of physiological adaptation

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    Bioengineering of skeletal muscle in vitro in order to produce highly aligned myofibres in relevant three dimensional (3D) matrices have allowed scientists to model the in vivo skeletal muscle niche. This review discusses essential experimental considerations for developing bioengineered muscle in order to investigate exercise mimicking stimuli. We identify current knowledge for the use of electrical stimulation and co-culture with motor neurons to enhance skeletal muscle maturation and contractile function in bioengineered systems in vitro. Importantly, we provide a current opinion on the use of acute and chronic exercise mimicking stimuli (electrical stimulation and mechanical overload) and the subsequent mechanisms underlying physiological adaptation in 3D bioengineered muscle. We also identify that future studies using the latest bioreactor technology, providing simultaneous electrical and mechanical loading and flow perfusion in vitro, may provide the basis for advancing knowledge in the future. We also envisage, that more studies using genetic, pharmacological, and hormonal modifications applied in human 3D bioengineered skeletal muscle may allow for an enhanced discovery of the in-depth mechanisms underlying the response to exercise in relevant human testing systems. Finally, 3D bioengineered skeletal muscle may provide an opportunity to be used as a pre-clinical in vitro test-bed to investigate the mechanisms underlying catabolic disease, while modelling disease itself via the use of cells derived from human patients without exposing animals or humans (in phase I trials) to the side effects of potential therapies

    Efficient HTTP based I/O on very large datasets for high performance computing with the libdavix library

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    Remote data access for data analysis in high performance computing is commonly done with specialized data access protocols and storage systems. These protocols are highly optimized for high throughput on very large datasets, multi-streams, high availability, low latency and efficient parallel I/O. The purpose of this paper is to describe how we have adapted a generic protocol, the Hyper Text Transport Protocol (HTTP) to make it a competitive alternative for high performance I/O and data analysis applications in a global computing grid: the Worldwide LHC Computing Grid. In this work, we first analyze the design differences between the HTTP protocol and the most common high performance I/O protocols, pointing out the main performance weaknesses of HTTP. Then, we describe in detail how we solved these issues. Our solutions have been implemented in a toolkit called davix, available through several recent Linux distributions. Finally, we describe the results of our benchmarks where we compare the performance of davix against a HPC specific protocol for a data analysis use case.Comment: Presented at: Very large Data Bases (VLDB) 2014, Hangzho

    A randomised, double blind, placebo-controlled trial of megestrol acetate or dexamethasone in treating symptomatic anorexia in people with advanced cancer

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    This multi-site, double blind, parallel arm, fixed dose, randomised placebo controlled phase III study compared megestrol acetate 480 mg/day with dexamethasone 4 mg/day for their net effects on appetite in people with cancer anorexia. Patients with advanced cancer and anorexia for ≥ 2 weeks with a score ≤ 4 (0-10 numeric rating scale (NRS) 0 = no appetite, 10 = best possible appetite) were recruited. Participants received megestrol 480 mg or dexamethasone 4 mg or placebo daily for up to 4 weeks. Primary outcomes were at day 7. Responders were defined as having a ≥ 25% improvement in NRS over baseline. There were 190 people randomised (megestrol acetate n = 61; dexamethasone n = 67, placebo n = 62). At week 1 (primary endpoint), 79·3% in the megestrol group, 65·5% in the dexamethasone group and 58·5% in the placebo group (p = 0.067) were responders. No differences in performance status or quality of life were reported. Treatment emergent adverse events were frequent (90·4% of participants), and included altered mood and insomnia. Hyperglycemia and deep vein thromboses were more frequent when on dexamethasone than the other two arms. There was no difference in groups between the three arms, with no benefit seen over placebo with anorexia improving in all arms.Trail registration: The trial was registered on 19/08/2008 with the Australian New Zealand Clinical Trials Registry (ACTRN12608000405314)

    A systematic review and meta-analysis of studies comparing burden from lung cancer and chronic obstructive pulmonary disease.

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    BACKGROUND:Chronic obstructive pulmonary disease and lung cancer are both life-limiting diseases that confer burden in the form of symptoms and affect functioning and quality of life. Comparing burden between these diseases is of interest to determine whether people with chronic obstructive pulmonary disease require improved access to Specialist Palliative Care. Access should be based on needs rather than diagnosis or prognosis but is limited for people with chronic obstructive pulmonary disease compared to lung cancer. AIM:The aim of this study was to synthesise research comparing burden from chronic obstructive pulmonary disease and lung cancer to estimate relative need for Specialist Palliative Care. DESIGN:A systematic review was conducted of observational quantitative studies published in English peer-reviewed journals comparing burden from chronic obstructive pulmonary disease and lung cancer (PROSPERO CRD42018108819). No limits were placed on disease stage. Meta-analyses were performed where studies used the same measure; otherwise, synthesis used a narrative approach. Risk of bias was assessed using the Agency for Healthcare Research and Quality tool. DATA SOURCES:Electronic databases were searched in September 2019. RESULTS:Of 790 articles returned, 13 were included, reporting 11 studies. Risk of bias was generally moderate. Except for pain, burden tended to be at least as substantial from chronic obstructive pulmonary disease as from lung cancer, with breathlessness and impacts on functioning being significantly worse. Longitudinal studies suggest that people with chronic obstructive pulmonary disease live with burden for longer. CONCLUSION:Efforts should be made to ensure that access to Specialist Palliative Care is commensurate with chronic obstructive pulmonary disease's substantial and long-lasting burden. Future research should clarify whether managing burden in chronic obstructive pulmonary disease and lung cancer requires different approaches

    Forces between clustered stereocilia minimize friction in the ear on a subnanometre scale

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    The detection of sound begins when energy derived from acoustic stimuli deflects the hair bundles atop hair cells. As hair bundles move, the viscous friction between stereocilia and the surrounding liquid poses a fundamental challenge to the ear's high sensitivity and sharp frequency selectivity. Part of the solution to this problem lies in the active process that uses energy for frequency-selective sound amplification. Here we demonstrate that a complementary part involves the fluid-structure interaction between the liquid within the hair bundle and the stereocilia. Using force measurement on a dynamically scaled model, finite-element analysis, analytical estimation of hydrodynamic forces, stochastic simulation and high-resolution interferometric measurement of hair bundles, we characterize the origin and magnitude of the forces between individual stereocilia during small hair-bundle deflections. We find that the close apposition of stereocilia effectively immobilizes the liquid between them, which reduces the drag and suppresses the relative squeezing but not the sliding mode of stereociliary motion. The obliquely oriented tip links couple the mechanotransduction channels to this least dissipative coherent mode, whereas the elastic horizontal top connectors stabilize the structure, further reducing the drag. As measured from the distortion products associated with channel gating at physiological stimulation amplitudes of tens of nanometres, the balance of forces in a hair bundle permits a relative mode of motion between adjacent stereocilia that encompasses only a fraction of a nanometre. A combination of high-resolution experiments and detailed numerical modelling of fluid-structure interactions reveals the physical principles behind the basic structural features of hair bundles and shows quantitatively how these organelles are adapted to the needs of sensitive mechanotransduction.Comment: 21 pages, including 3 figures. For supplementary information, please see the online version of the article at http://www.nature.com/natur

    Electrical detection of 31P spin quantum states

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    In recent years, a variety of solid-state qubits has been realized, including quantum dots, superconducting tunnel junctions and point defects. Due to its potential compatibility with existing microelectronics, the proposal by Kane based on phosphorus donors in Si has also been pursued intensively. A key issue of this concept is the readout of the P quantum state. While electrical measurements of magnetic resonance have been performed on single spins, the statistical nature of these experiments based on random telegraph noise measurements has impeded the readout of single spin states. In this letter, we demonstrate the measurement of the spin state of P donor electrons in silicon and the observation of Rabi flops by purely electric means, accomplished by coherent manipulation of spin-dependent charge carrier recombination between the P donor and paramagnetic localized states at the Si/SiO2 interface via pulsed electrically detected magnetic resonance. The electron spin information is shown to be coupled through the hyperfine interaction with the P nucleus, which demonstrates the feasibility of a recombination-based readout of nuclear spins
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