179 research outputs found

    Scale-down studies for assessing the impact of different stress parameters on growth and product quality during animal cell culture

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    Two series of reproducible fed-batch bench scale cultures have been undertaken, one series simulating the impact of spatial variations in pH and nutrients as found at commercial scale on performance, the other, the impact of fluid dynamic stresses associated with agitation. The first was unsuccessful because, somewhat surprisingly, the use of a peristaltic pump to circulate cells and medium through different spatial environments always led to a similar reduction in culture time and resulting product titre compared to uncirculated controls. This fall was sufficient to essentially mask other effects. In the second, even at maximum specific energy dissipation rates up to ~160 times > with laminar extensional flow and ~25 times > with turbulent flow compared to typical commercial conditions, no significant effects were observed on cell growth and viability. Most importantly, in all of the cases studied, product quality was unaffected compared to controls. In addition, it is suggested that because of the possibility of cell line specific behaviour and the relationship between damage to entities and the Kolmogorov scale of turbulence, sensitivity to fluid dynamic stresses is best studied in turbulent bench scale bioreactors. © 2013 The Institution of Chemical Engineers

    Ocean Modeling on a Mesh With Resolution Following the Local Rossby Radius

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    We discuss the performance of the Finite Element Ocean Model (FESOM) on locally eddy-resolving global unstructured meshes. In particular, the utility of the mesh design approach whereby mesh horizontal resolution is varied as half the Rossby radius in most of the model domain is explored. Model simulations on such a mesh (FESOM-XR) are compared with FESOM simulations on a smaller-size mesh, where refinement depends only on the pattern of observed variability (FESOM-HR). We also compare FESOM results to a simulation of the ocean model of the Max Planck Institute for Meteorology (MPIOM) on a tripolar regular grid with refinement toward the poles, which uses a number of degrees of freedom similar to FESOM-XR. The mesh design strategy, which relies on the Rossby radius and/or the observed variability pattern, tends to coarsen the resolution in tropical and partly subtropical latitudes compared to the regular MPIOM grid. Excessive variations of mesh resolution are found to affect the performance in other nearby areas, presumably through dissipation that increases if resolution is coarsened. The largest improvement shown by FESOM-XR is a reduction of the surface temperature bias in the so-called North-West corner of the North Atlantic Ocean where horizontal resolution was increased dramatically. However, other biases in FESOM-XR remain largely unchanged compared to FESOM-HR. We conclude that resolving the Rossby radius alone (with two points per Rossby radius) is insufficient, and that careful use of a priori information on eddy dynamics is required to exploit the full potential of ocean models on unstructured meshes

    Low-NO atmospheric oxidation pathways in a polluted megacity

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    The impact of emissions of volatile organic compounds (VOCs) to the atmosphere on the production of secondary pollutants, such as ozone and secondary organic aerosol (SOA), is mediated by the concentration of nitric oxide (NO). Polluted urban atmospheres are typically considered to be “high-NO” environments, while remote regions such as rainforests, with minimal anthropogenic influences, are considered to be “low NO”. However, our observations from central Beijing show that this simplistic separation of regimes is flawed. Despite being in one of the largest megacities in the world, we observe formation of gas- and aerosol-phase oxidation products usually associated with low-NO “rainforest-like” atmospheric oxidation pathways during the afternoon, caused by extreme suppression of NO concentrations at this time. Box model calculations suggest that during the morning high-NO chemistry predominates (95 %) but in the afternoon low-NO chemistry plays a greater role (30 %). Current emissions inventories are applied in the GEOS-Chem model which shows that such models, when run at the regional scale, fail to accurately predict such an extreme diurnal cycle in the NO concentration. With increasing global emphasis on reducing air pollution, it is crucial for the modelling tools used to develop urban air quality policy to be able to accurately represent such extreme diurnal variations in NO to accurately predict the formation of pollutants such as SOA and ozone

    Phylogeographic Study of Apodemus ilex (Rodentia: Muridae) in Southwest China

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    BACKGROUND: The Mountains of southwest China have complex river systems and a profoundly complex topography and are among the most important biodiversity hotspots in the world. However, only a few studies have shed light on how the mountains and river valleys promote genetic diversity. Apodemus ilex is a fine model for investigating this subject. METHODOLOGY/PRINCIPAL FINDINGS: To assess the genetic diversity and biogeographic patterns of Apodemus ilex, the complete cytochrome b gene sequences (1,140 bp) were determined from 203 samples of A. draco/ilex that were collected from southwest China. The results obtained suggested that A. ilex and A. draco are sistergroups and diverged from each other approximately 2.25 million years ago. A. ilex could be divided into Eastern and Western phylogroups, each containing two sub-groups and being widespread in different geographical regions of the southern Hengduan Mountains and the western Yunnan - Guizhou Plateau. The population expansions of A. ilex were roughly from 0.089 Mya to 0.023 Mya. CONCLUSIONS: Our result suggested that A. ilex is a valid species rather than synonym of A. draco. As a middle-high elevation inhabitant, the phylogenetic pattern of A. ilex was strongly related to the complex geographical structures in southwest China, particularly the existence of deep river valley systems, such as the Mekong and Salween rivers. Also, it appears that the evolutionary history of A. ilex, such as lineage divergences and population expansions were strongly affected by climate fluctuation in the Late Pleistocene

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    How should beta-diversity inform biodiversity conservation?

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    To design robust protected area networks, accurately measure species losses, or understand the processes that maintain species diversity, conservation science must consider the organization of biodiversity in space. Central is beta-diversity - the component of regional diversity that accumulates from compositional differences between local species assemblages. We review how beta-diversity is impacted by human activities, including farming, selective logging, urbanization, species invasions, overhunting, and climate change. Beta-diversity increases, decreases, or remains unchanged by these impacts, depending on the balance of processes that cause species composition to become more different (biotic heterogenization) or more similar (biotic homogenization) between sites. While maintaining high beta-diversity is not always a desirable conservation outcome, understanding beta-diversity is essential for protecting regional diversity and can directly assist conservation planning. Beta-diversity reveals the spatial scaling of diversity loss.Beta-diversity illuminates mechanisms of regional diversity maintenance.Human activities cause beta-diversity to increase, decrease, or remain unchanged.Conservation significance of beta-diversity shift depends on local diversity dynamics

    Gabapentin for chronic pelvic pain in women (GaPP2):a multicentre, randomised, double-blind, placebo-controlled trial

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    BackgroundChronic pelvic pain affects 2–24% of women worldwide and evidence for medical treatments is scarce. Gabapentin is effective in treating some chronic pain conditions. We aimed to measure the efficacy and safety of gabapentin in women with chronic pelvic pain and no obvious pelvic pathology.MethodsWe performed a multicentre, randomised, double-blind, placebo-controlled randomised trial in 39 UK hospital centres. Eligible participants were women with chronic pelvic pain (with or without dysmenorrhoea or dyspareunia) of at least 3 months duration. Inclusion criteria were 18–50 years of age, use or willingness to use contraception to avoid pregnancy, and no obvious pelvic pathology at laparoscopy, which must have taken place at least 2 weeks before consent but less than 36 months previously. Participants were randomly assigned in a 1:1 ratio to receive gabapentin (titrated to a maximum dose of 2700 mg daily) or matching placebo for 16 weeks. The online randomisation system minimised allocations by presence or absence of dysmenorrhoea, psychological distress, current use of hormonal contraceptives, and hospital centre. The appearance, route, and administration of the assigned intervention were identical in both groups. Patients, clinicians, and research staff were unaware of the trial group assignments throughout the trial. Participants were unmasked once they had provided all outcome data at week 16–17, or sooner if a serious adverse event requiring knowledge of the study drug occurred. The dual primary outcome measures were worst and average pain scores assessed separately on a numerical rating scale in weeks 13–16 after randomisation, in the intention-to-treat population. Self-reported adverse events were assessed according to intention-to-treat principles. This trial is registered with the ISRCTN registry, ISCRTN77451762.FindingsParticipants were screened between Nov 30, 2015, and March 6, 2019, and 306 were randomly assigned (153 to gabapentin and 153 to placebo). There were no significant between-group differences in both worst and average numerical rating scale (NRS) pain scores at 13–16 weeks after randomisation. The mean worst NRS pain score was 7·1 (standard deviation [SD] 2·6) in the gabapentin group and 7·4 (SD 2·2) in the placebo group. Mean change from baseline was −1·4 (SD 2·3) in the gabapentin group and −1·2 (SD 2·1) in the placebo group (adjusted mean difference −0·20 [97·5% CI −0·81 to 0·42]; p=0·47). The mean average NRS pain score was 4·3 (SD 2·3) in the gabapentin group and 4·5 (SD 2·2) in the placebo group. Mean change from baseline was −1·1 (SD 2·0) in the gabapentin group and −0·9 (SD 1·8) in the placebo group (adjusted mean difference −0·18 [97·5% CI −0·71 to 0·35]; p=0·45). More women had a serious adverse event in the gabapentin group than in the placebo group (10 [7%] of 153 in the gabapentin group compared with 3 [2%] of 153 in the placebo group; p=0·04). Dizziness, drowsiness, and visual disturbances were more common in the gabapentin group.InterpretationThis study was adequately powered, but treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo. Given the increasing reports of abuse and evidence of potential harms associated with gabapentin use, it is important that clinicians consider alternative treatment options to off-label gabapentin for the management of chronic pelvic pain and no obvious pelvic pathology.FundingNational Institute for Health Research
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