37 research outputs found

    The wall shear stress produced by the normal impingement of a jet on a flat surface

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    A method for the theoretical determination of the wall shear stress under impinging jets of various congurations is presented. Axisymmetric and two-dimensional incompressible jets of a wide range of Reynolds numbers and jet heights are considered. Theoretical predictions from this approach are compared with available wall shear stress measurements. These data are critically evaluated based on the method of measurement and its applicability to the boundary layer under consideration. It was found that impingement-region wall shear stress measurements using the electrochemical method in submerged impinging liquid jets provide the greatest accuracy of any indirect method. A unique wall shear stress measurement technique, based on observing the removal of monosized spheres from well-characterized surfaces, was used to conrm the impinging jet analysis presented for gas jets. The technique was also used to determine an empirical relation describing the rise in wall shear stress due to compressibility eects in impinging high-velocity jets

    Molecular Characterization of Podoviral Bacteriophages Virulent for Clostridium perfringens and Their Comparison with Members of the Picovirinae

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    Clostridium perfringens is a Gram-positive, spore-forming anaerobic bacterium responsible for human food-borne disease as well as non-food-borne human, animal and poultry diseases. Because bacteriophages or their gene products could be applied to control bacterial diseases in a species-specific manner, they are potential important alternatives to antibiotics. Consequently, poultry intestinal material, soil, sewage and poultry processing drainage water were screened for virulent bacteriophages that lysed C. perfringens. Two bacteriophages, designated ΊCPV4 and ΊZP2, were isolated in the Moscow Region of the Russian Federation while another closely related virus, named ΊCP7R, was isolated in the southeastern USA. The viruses were identified as members of the order Caudovirales in the family Podoviridae with short, non-contractile tails of the C1 morphotype. The genomes of the three bacteriophages were 17.972, 18.078 and 18.397 kbp respectively; encoding twenty-six to twenty-eight ORF's with inverted terminal repeats and an average GC content of 34.6%. Structural proteins identified by mass spectrometry in the purified ΊCP7R virion included a pre-neck/appendage with putative lyase activity, major head, tail, connector/upper collar, lower collar and a structural protein with putative lysozyme-peptidase activity. All three podoviral bacteriophage genomes encoded a predicted N-acetylmuramoyl-L-alanine amidase and a putative stage V sporulation protein. Each putative amidase contained a predicted bacterial SH3 domain at the C-terminal end of the protein, presumably involved with binding the C. perfringens cell wall. The predicted DNA polymerase type B protein sequences were closely related to other members of the Podoviridae including Bacillus phage Ί29. Whole-genome comparisons supported this relationship, but also indicated that the Russian and USA viruses may be unique members of the sub-family Picovirinae

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∌99% of the euchromatic genome and is accurate to an error rate of ∌1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    A refractive tilting-plate technique for measurement of dynamic contact angles

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    The contact angle is a critical parameter in liquid interface dynamics ranging from liquid spreading on a solid surface on earth to liquid motion in partially filled containers in space. A refractive tilting-plate technique employing a scanning laser beam is developed to conduct an experimental study of a moving contact line, with the intention of making accurate measurements of the contact angle. The technique shows promise as an accurate and potentially fully automated means to determine the velocity dependence of the contact angle at the intersection of the interface between two transparent fluids with a transparent solid surface. Ray tracing calculations are included to reinforce the measurement concept. The principal experiments were conducted at speeds ranging from 0.05 to 1.00 mm/s, both advancing and receding, using an immiscible liquid pair (nonane/formamide) in contact with glass. The contact angle was found to depend for practical purposes only on the sign of the velocity and not on its magnitude for the range of velocities studied. Other observations revealed a bimodal behavior of the contact line that depends on which liquid first contacts the glass, with resulting drift in the dynamic contact angle with time

    Effect of particle size and material properties on aerodynamic resuspension from surfaces

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    An experimental study of the aerodynamic entrainment of monodisperse spheres from glass substrates is presented. The spheres were made of ammonium fluorescein and polystyrene standards (M_W=3700, 18,700, and 114,200 amu). The use of monosized particles with carefully controlled properties leads to a narrow distribution of sphere-surface adhesion forces, facilitating the determination of the particle entrainment threshold. The spheres were exposed to well-characterized shear stresses in two different flows, (i) laminar channel flow; and (ii) a normally impinging gas jet. Threshold shear stresses were found to be more sensitive to particle size than predicted by the existing resuspension theories, which are based on equilibrium adhesion models. Furthermore, resuspension was also found to be sensitive to the duration of the applied shear stress. This sensitivity depends upon the particle size and material properties. A kinetic model of particle detachment is presented to account for these observed trends
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