1,783 research outputs found

    Microbubbly drag reduction in Taylor-Couette flow in the wavy vortex regime

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    We investigate the effect of microbubbles on Taylor-Couette flow by means of direct numerical simulations. We employ an Eulerian-Lagrangian approach with a gas-fluid coupling based on the point-force approximation. Added mass, drag, lift, and gravity are taken into account in the modeling of the motion of the individual bubble. We find that very dilute suspensions of small non-deformable bubbles (volume void fraction below 1%, zero Weber number and bubble Reynolds number <10) induce a robust statistically steady drag reduction (up to 20%) in the so called wavy vortex flow regime (Re = 600-2500). The Reynolds number dependence of the normalized torque (the so-called Torque Reduction Ratio (TRR) which corresponds to the drag reduction) is consistent with a recent series of experimental measurements performed by Murai et al. (J. Phys. 14, 143 (2005)). Our analysis suggests that the physical mechanism for the torque reduction in this regime is due to the local axial forcing, induced by rising bubbles, that is able to break the highly dissipative Taylor wavy vortices in the system. We finally show that the lift force acting on the bubble is crucial in this process. When neglecting it, the bubbles preferentially accumulate near the inner cylinder and the bulk flow is less efficiently modified.Comment: 21 pages, 13 figures, extended and revised versio

    Funding Translational Medicine via Public Markets: The Business Development Company

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    A business development company (BDC) is a type of closed-end investment fund with certain relaxed requirements that allow it to raise money in the public equity and debt markets, and can be used to fund multiple early-stage biomedical ventures, using financial diversification to de-risk translational medicine. By electing to be a “Regulated Investment Company” for tax purposes, a BDC can avoid double taxation on income and net capital gains distributed to its shareholders. BDCs are ideally suited for long-term investors in biomedical innovation, including: (i) investors with biomedical expertise who understand the risks of the FDA approval process, (ii) “banking entities,” now prohibited from investing in hedge funds and private equity funds by the Volcker Rule, but who are permitted to invest in BDCs, subject to certain restrictions, and (iii) retail investors, who traditionally have had to invest in large pharmaceutical companies to gain exposure to similar assets. We describe the history of BDCs, summarize the requirements for creating and managing them, and conclude with a discussion of the advantages and disadvantages of the BDC structure for funding biomedical innovatio

    Environmental limits of Rift Valley fever revealed using ecoepidemiological mechanistic models.

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    Vector-borne diseases (VBDs) of humans and domestic animals are a significant component of the global burden of disease and a key driver of poverty. The transmission cycles of VBDs are often strongly mediated by the ecological requirements of the vectors, resulting in complex transmission dynamics, including intermittent epidemics and an unclear link between environmental conditions and disease persistence. An important broader concern is the extent to which theoretical models are reliable at forecasting VBDs; infection dynamics can be complex, and the resulting systems are highly unstable. Here, we examine these problems in detail using a case study of Rift Valley fever (RVF), a high-burden disease endemic to Africa. We develop an ecoepidemiological, compartmental, mathematical model coupled to the dynamics of ambient temperature and water availability and apply it to a realistic setting using empirical environmental data from Kenya. Importantly, we identify the range of seasonally varying ambient temperatures and water-body availability that leads to either the extinction of mosquito populations and/or RVF (nonpersistent regimens) or the establishment of long-term mosquito populations and consequently, the endemicity of the RVF infection (persistent regimens). Instabilities arise when the range of the environmental variables overlaps with the threshold of persistence. The model captures the intermittent nature of RVF occurrence, which is explained as low-level circulation under the threshold of detection, with intermittent emergence sometimes after long periods. Using the approach developed here opens up the ability to improve predictions of the emergence and behaviors of epidemics of many other important VBDs.The work was partially supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Environmental Change and Health at the London School of Hygiene and Tropical Medicine in partnership with Public Health England (PHE) and in collaboration with the University of Exeter, University College London, and the Met Office. European Union FP7 Project ANTIGONE (Contract 278976). Royal Society Wolfson Research Merit Award. The Alborada Trust

    A Decline in Walking Speed is Associated with Incident Knee Replacement in Adults with and at Risk for Knee Osteoarthritis

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    OBJECTIVE: To determine if a one-year change in walking speed is associated with receiving an incident knee replacement during the following year in adults with and at risk for knee osteoarthritis (OA). METHODS: Using data from the Osteoarthritis Initiative, we determined a one-year change in 20- meter walk speed from three observation periods (i.e., 0-12, 12-24, and 24-36 month). We operationally defined one-year change in walking speed as either: 1) decline: \u3c -0.1 m/s change, 2) no change: between -0.1 and 0.1 m/s change, 3) increase: \u3e 0.1 m/s change. Incident knee replacement was defined using each subsequent one-year period (i.e., 12-24, 24- 36, and 36-48 month). Combining data from the three observation periods, we performed a Poisson regression with robust error variance to determine the relative risk between a change in walking speed (exposure) and incident knee replacement over the following year (outcome). RESULTS: Of the 4,264 participants included within this analysis (11,311 total person visits), 115 (3%) adults received a knee replacement. Decline in walking speed was associated with a 104% increase in risk [adjusted relative risk (RR)=2.04; 95% confidence interval (CI)= 1.40-2.98], while an increase in walking speed associated with a 55% decrease in risk (RR=0.45; 95% CI=0.22-0.93) of incident knee replacement in the following year compared to a person with no change in walking speed. CONCLUSION: A one-year decline in walking speed is associated with an increased risk, while one-year increase in walking speed is associated with a decreased risk of future incident knee replacement

    The Mucosae-Associated Epithelial Chemokine (MEC/CCL28) Modulates Immunity in HIV Infection

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    BACKGROUND. CCL28 (MEC) binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASC) in the mucosal lamina propria (MLP). Mucosal HIV-specific IgA are detected in HIV-infection and exposure. The CCL28 circuit was analyzed in HIV-infected and-exposed individuals and in HIV-unexposed controls; the effect of CCL28 administration on gastrointestinal MLP IgA-ASC was verified in a mouse model. METHODOLOGY/FINDINGS. CCL28 was augmented in breast milk (BM) plasma and saliva of HIV-infected and –exposed individuals; CCR3+ and CCR10+ B lymphocytes were increased in these same individuals. Additionally: 1) CCL28 concentration in BM was associated with longer survival in HIV vertically-infected children; and 2) gastro-intestinal mucosal IgA-ASC were significantly increased in VSV-immunized mice receiving CCL28. CONCLUSIONS. CCL28 mediates mucosal immunity in HIV exposure and infection. CCL28-including constructs should be considered in mucosal vaccines to prevent HIV infection of the gastro-intestinal MLP via modulation of IgA-ASC.Istituto Superiore di Sanita' "Programma Nazionale di Ricerca sull' AIDS"; DG Right to Health and Solidarity Policy; EMPRO and AVIP EC WP6 Projects; Japan Health Science Foundation; National Institutes of Child Health and Human Development (HD 39611, HD 40777

    Pattern of joint damage in persons with knee osteoarthritis and concomitant ACL tears.

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    OBJECTIVE: The aim of this study was to evaluate the morphological changes of the lateral meniscus in end-stage lateral compartment osteoarthritis (OA) of the knee. METHODS: One hundred fifty-eight knee joints from 133 patients that subsequently underwent total knee joint arthroplasty from January 2008 to December 2009 were enrolled. There were 26 men and 107 women. Their ages ranged from 56 to 81 (mean 67.4 + 6.5 years). All study participants had complete obliteration of the lateral joint space identified by weight-bearing radiography. Meniscal position was assessed by measuring meniscal subluxation and meniscal height. The meniscal morphology was assessed using a modification of the whole-organ magnetic resonance imaging score (WORMS). The frequency of different meniscal morphology and their respective positions was calculated. RESULTS: The predominant type (42.4%, 53.8% and 52.5% in the anterior horn, mid-body and posterior horn, respectively) of abnormal meniscal morphology was a complete maceration/destruction or complete resection. The anterior horn of non-macerated lateral meniscus was more subluxed than that of the non-macerated medial meniscus in patients with lateral OA. CONCLUSION: This study suggests that the lateral meniscus in persons with end-stage lateral OA are mostly macerated or destroyed. Also, unlike isolated end-staged medial compartment OA, the anterior horn of the lateral meniscus in isolated end-stage lateral OA is commonly affected. Copyright 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved

    Integrated dopaminergic neuronal model with reduced intracellular processes and inhibitory autoreceptors

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    Dopamine (DA) is an important neurotransmitter for multiple brain functions, and dysfunctions of the dopaminergic system are implicated in neurological and neuropsychiatric disorders. Although the dopaminergic system has been studied at multiple levels, an integrated and efficient computational model that bridges from molecular to neuronal circuit level is still lacking. In this study, the authors aim to develop a realistic yet efficient computational model of a dopaminergic pre‐synaptic terminal. They first systematically perturb the variables/substrates of an established computational model of DA synthesis, release and uptake, and based on their relative dynamical timescales and steady‐state changes, approximate and reduce the model into two versions: one for simulating hourly timescale, and another for millisecond timescale. They show that the original and reduced models exhibit rather similar steady and perturbed states, whereas the reduced models are more computationally efficient and illuminate the underlying key mechanisms. They then incorporate the reduced fast model into a spiking neuronal model that can realistically simulate the spiking behaviour of dopaminergic neurons. In addition, they successfully include autoreceptor‐mediated inhibitory current explicitly in the neuronal model. This integrated computational model provides the first step toward an efficient computational platform for realistic multiscale simulation of dopaminergic systems in in silico neuropharmacology

    Construction of a BAC library and mapping BAC clones to the linkage map of Barramundi, Lates calcarifer

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    <p>Abstract</p> <p>Background</p> <p>Barramundi (<it>Lates calcarifer</it>) is an important farmed marine food fish species. Its first generation linkage map has been applied to map QTL for growth traits. To identify genes located in QTL responsible for specific traits, genomic large insert libraries are of crucial importance. We reported herein a bacterial artificial chromosome (BAC) library and the mapping of BAC clones to the linkage map.</p> <p>Results</p> <p>This BAC library consisted of 49,152 clones with an average insert size of 98 kb, representing 6.9-fold haploid genome coverage. Screening the library with 24 microsatellites and 15 ESTs/genes demonstrated that the library had good genome coverage. In addition, 62 novel microsatellites each isolated from 62 BAC clones were mapped onto the first generation linkage map. A total of 86 BAC clones were anchored on the linkage map with at least one BAC clone on each linkage group.</p> <p>Conclusion</p> <p>We have constructed the first BAC library for <it>L. calcarifer </it>and mapped 86 BAC clones to the first generation linkage map. This BAC library and the improved linkage map with 302 DNA markers not only supply an indispensable tool to the integration of physical and linkage maps, the fine mapping of QTL and map based cloning genes located in QTL of commercial importance, but also contribute to comparative genomic studies and eventually whole genome sequencing.</p
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