58 research outputs found

    The Role of Physical, Chemical, and Microbial Heterogeneity on the Field-Scale Transport and Attachment of Bacteria

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    A field-scale bacterial transport experiment was conducted at the Narrow Channel Focus Area of the South Oyster field site located in Oyster, Virginia. The goal of the field experiment was to determine the relative influence of subsurface heterogeneity and microbial population parameters on flow direction, velocity, and attachment of bacteria at the field scale. The field results were compared with results from laboratory-scale column experiments to develop a method for predicting field-scale bacterial transport. The field site is a shallow, sandy, unconfined, aerobic aquifer that has been characterized by geophysical, sedimentological, and hydrogeological methods. Comamonas sp. strain DA001 and a conservative tracer, bromide (Br), were injected into an area of high permeability for 12 hours. The Br and bacterial concentrations in the groundwater were monitored for 1 week at 192 sampling ports spaced over a 2-m vertical zone located from 0.5 to 7 m down-gradient of the injection well. The bacterial and Br plume was observed to move past 95 sampling ports. The densely characterized field site enabled the comparison of variations in DA001 transport to the aquifer properties. The velocity of the injected plume was correlated with geophysical estimates of hydraulic conductivity. The bacterial and Br plume appeared to follow flow paths not coincident with the hydraulic gradient but through a zone of higher permeability located off the flow axis. The amount of breakthrough of the bacteria was similar in both the high and low permeability layers with only a weak correlation between the observed hydraulic conductivity and amount of bacterial breakthrough. The uniformity in the observed attachment rates across varying grain sizes could be explained by heterogeneity of microbial properties within the single strain of injected bacteria. Application of colloid filtration theory to the field data indicated that variations in the microbial population were described by a lognormal distribution of the collision efficiency (a). Core-scale studies were used to predict the a distribution and field-scale transport distances of DA001. In sandy aquifers, physical heterogeneity may play a secondary role in controlling field-scale bacterial transport, and future research should focus on the microbial factors affecting transport

    Investigation of the Domain Wall Fermion Approach to Chiral Gauge Theories on the Lattice

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    We investigate a recent proposal to construct chiral gauge theories on the lattice using domain wall fermions. We restrict ourselves to the finite volume case, in which two domain walls are present, with modes of opposite chirality on each of them. We couple the chiral fermions on only one of the domain walls to a gauge field. In order to preserve gauge invariance, we have to add a scalar field, which gives rise to additional light mirror fermion and scalar modes. We argue that in an anomaly free model these extra modes would decouple if our model possesses a so-called strong coupling symmetric phase. However, our numerical results indicate that such a phase most probably does not exist. ---- Note: 9 Postscript figures are appended as uuencoded compressed tar file.Comment: 27p. Latex; UCSD/PTH 93-28, Wash. U. HEP/93-6

    Numerical study of wetting transitions on biomimetic surfaces using a lattice Boltzmann approach with large density ratio

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    The hydrophobicity of natural surfaces have drawn much attention of scientific communities in recent years. By mimicking natural surfaces, the manufactured biomimetic hydrophobic surfaces have been widely applied to green technologies such as self-cleaning surfaces. Although the theories for wetting and hydrophobicity have been developed, the mechanism of wetting transitions between heterogeneous wetting state and homogeneous wetting state is still not fully clarified. As understanding of wetting transitions is crucial for manufacturing a biomimetic superhydrophobic surface, more fundamental discussions in this area should be carried out. In the present work the wetting transitions are numerically studied using a phase field lattice Boltzmann approach with large density ratio, which should be helpful in understanding the mechanism of wetting transitions. The dynamic wetting transition processes between Cassie-Baxter state and Wenzel state are presented, and the energy barrier and the gravity effect on transition are discussed. It is found that the two wetting transition processes are irreversible for specific inherent contact angles and have different transition routes, the energy barrier exists on an ideally patterned surface and the gravity can be crucial to overcome the energy barrier and trigger the transition

    Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

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    Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

    The genetic architecture of type 2 diabetes

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    The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

    Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

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    The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

    Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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    Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

    Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

    Get PDF
    Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
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