767 research outputs found
Impingement of Droplets in 60 Deg Elbows with Potential Flow
Trajectories were determined for water droplets or other aerosol particles in air flowing through 600 elbows especially designed for two-dimensional potential motion. The elbows were established by selecting as walls of each elbow two streamlines of a flow field produced by a complex potential function that establishes a two-dimensional flow around. a 600 bend. An unlimited number of elbows with slightly different shapes can be established by selecting different pairs of streamlines as walls. Some of these have a pocket on the outside wall. The elbows produced by the complex potential function are suitable for use in aircraft air-inlet ducts and have the following characteristics: (1) The resultant velocity at any point inside the elbow is always greater than zero but never exceeds the velocity at the entrance. (2) The air flow field at the entrance and exit is almost uniform and rectilinear. (3) The elbows are symmetrical with respect to the bisector of the angle of bend. These elbows should have lower pressure losses than bends of constant cross-sectional area. The droplet impingement data derived from the trajectories are presented along with equations so that collection efficiency, area, rate, and distribution of droplet impingement can be determined for any elbow defined by any pair of streamlines within a portion of the flow field established by the complex potential function. Coordinates for some typical streamlines of the flow field and velocity components for several points along these streamlines are presented in tabular form. A comparison of the 600 elbow with previous calculations for a comparable 90 elbow indicated that the impingement characteristics of the two elbows were very similar
Overlapping and distinct expression domains of Zic2 and Zic3 during mouse gastrulation
The Zic genes are the vertebrate homologues of the Drosophila Odd-paired gene. Mutations in two of these genes are associated with human congenital genetic disorders. Mutation of human and mouse Zic2 is associated with holoprosencephaly which is caused by a defect of ventral forebrain development and mutation of human and mouse Zic3 is associated with a X-linked heterotaxy syndrome that results from a failure of left-right axis formation. The embryological role of the Zic genes in these disorders is not well understood. Here we show that both of these genes are expressed prior to and throughout gastrulation. The genes show some broad similarities in their expression domains. Both genes however are also uniquely expressed in some tissues and these unique domains correlate with regions that potentially play a role in the aetiology of the respective genetic disorders. During primitive streak stages Zic2 is expressed transiently and uniquely in the node and the head process mesendoderm. The head process is known to be required for the establishment or maintenance of the ventral forebrain, which is the region disrupted in holoprosencephaly. Zic3 is not expressed in the node during primitive streak stages but is expressed in and around the node beginning from the head fold stages of development. This expression of Zic3 correlates well with the first steps in the establishment of the left-right axis. We also examined the expression of the closely related gene, Zic1, and did not detect any transcripts in gastrulation stage embryos
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How to develop suppliers within an Extended Enterprise towards a Digital Enterprise
Complex supply chains span the world connecting a heterogeneous network of firms. Digitisation offers them the opportunity to improve by leveraging, for example: leaner interfirm workflows, swifter data sharing, smarter analytics and knowledge management, greater automation, and empowered decision-making. However, an onerous organisational development and change programme is required to adopt such innovations and move towards a digital enterprise.
Research into organisational change tends to be set within the confines of a single firm. Occasionally, it includes clusters of collaborating firms, but rarely does it cover the whole of an extended enterprise supply network. An exception is the supplier development process; yet, studies into its use for digitisation are very shallow. Moreover, research into the adoption and diffusion of enterprise-wide digital technologies has, to date, mostly had to consider them as piecemeal appendages. Suppliers will have choice and may be supportive, ambivalent, or outright hostile to the extent or pace of digital transformation. They may adopt different strategies in response to the investment, capability development, open access, and other such demands placed upon them by the focal firm. This 3-year longitudinal research programme studies Rolls-Royce and a tiered cross-section of 24 of its suppliers, in the aerospace sector, as they confront and embark upon the journey towards a digital enterprise.
Literature is synthesised to create a 9 step process, with 28 implementation guidelines, which is given the descriptive title of supplier development for digital transformation (SD/DT). The SD/DT process begins with a strategic review and ends by embedding practices into routine business. The guidelines are used to initiate action research cycles which coalesce around 21 workshops held at various international locations. A theoretical framework is established using a combination of institutional and organisational learning theories. Close to 100 interviews are conducted with buyers and suppliers. Furthermore, supplier scorecards capture quantitative data on a quarterly basis across the supply base. Data is triangulated between supplier outcomes and their relative absorptive capacity.
Digital minimum standards are created which provide a shared vision, common vocabulary, and framework for heterogeneous change management. Two interim waypoints are set on the journey towards a digital enterprise and progress is measured for the 24 suppliers in the cohort. Overall, an encouraging success rate is achieved. Also, the use of supplier scorecards to operationalise and measure relative absorptive capacity shows promise. There are only 3 suppliers for whom the results do not triangulate. Transferability is explored together with recommendations for further work.This research was funded by Rolls-Royce. The thesis has been cleared by Rolls-Royce for release on an open-access basis
Endothelial Cell-Specific Deletion of P2Y2 Receptor Promotes Plaque Stability in Atherosclerosis-Susceptible ApoE-Null Mice
OBJECTIVE:
Nucleotide P2Y2 receptor (P2Y2R) contributes to vascular inflammation by increasing vascular cell adhesion molecule-1 expression in endothelial cells (EC), and global P2Y2R deficiency prevents fatty streak formation in apolipoprotein E null (ApoE-/-) mice. Because P2Y2R is ubiquitously expressed in vascular cells, we investigated the contribution of endothelial P2Y2R in the pathogenesis of atherosclerosis.
APPROACH AND RESULTS:
EC-specific P2Y2R-deficient mice were generated by breeding VEcadherin5-Cre mice with the P2Y2R floxed mice. Endothelial P2Y2R deficiency reduced endothelial nitric oxide synthase activity and significantly altered ATP- and UTP (uridine 5'-triphosphate)-induced vasorelaxation without affecting vasodilatory responses to acetylcholine. Telemetric blood pressure and echocardiography measurements indicated that EC-specific P2Y2R-deficient mice did not develop hypertension. We investigated the role of endothelial P2Y2R in the development of atherosclerotic lesions by crossing the EC-specific P2Y2R knockout mice onto an ApoE-/- background and evaluated lesion development after feeding a standard chow diet for 25 weeks. Histopathologic examination demonstrated reduced atherosclerotic lesions in the aortic sinus and entire aorta, decreased macrophage infiltration, and increased smooth muscle cell and collagen content, leading to the formation of a subendothelial fibrous cap in EC-specific P2Y2R-deficient ApoE-/- mice. Expression and proteolytic activity of matrix metalloproteinase-2 was significantly reduced in atherosclerotic lesions from EC-specific P2Y2R-deficient ApoE-/- mice. Furthermore, EC-specific P2Y2R deficiency inhibited nitric oxide production, leading to significant increase in smooth muscle cell migration out of aortic explants.
CONCLUSIONS:
EC-specific P2Y2R deficiency reduces atherosclerotic burden and promotes plaque stability in ApoE-/- mice through impaired macrophage infiltration acting together with reduced matrix metalloproteinase-2 activity and increased smooth muscle cell migration
Peptidyl-prolyl cis-trans isomerases (immunophilins) and their roles in parasite biochemistry, host-parasite interaction and antiparasitic drug action.
Immunophilin is the collective name given to the cyclophilin and FK506-binding protein (FKBP) families. As the name suggests, these include the major binding proteins of certain immunosuppressive drugs: cyclophilins for the cyclic peptide cyclosporin A and FKBPs for the macrolactones FK506 and rapamycin. Both families, although dissimilar in sequence, possess peptidyl-prolyl <i>cis-trans</i> isomerase activity in vitro and can play roles in protein folding and transport, RNA splicing and the regulation of multiprotein complexes in cells. In addition to enzymic activity, many immunophilins act as molecular chaperones. This property may be conferred by the isomerase domain and/or by additional domains. Recent years have seen a great increase in the number of known immunophilin genes in parasitic protozoa and helminths and in many cases their products have been characterized biochemically and their temporal and spatial expression patterns have been examined. Some of these genes represent novel types: one
example is a <i>Toxoplasma gondii</i> gene encoding a protein with both cyclophilin and FKBP domains. Likely roles in protein folding and oligomerisation, RNA splicing and sexual differentiation have been suggested for parasite immunophilins. In addition, unexpected roles in parasite virulence (Mip FKBP of <i>Trypanosoma cruzi</i>) and host immuno-modulation (e.g. 18-kDa cyclophilin of <i>Toxoplasma gondii</i>) have been established. Furthermore, in view of the potent antiparasitic activities of cyclosporins, macrolactones and nonimmunosuppressive derivatives of these compounds, immunophilins may mediate drug action and/or may themselves represent potential drug targets. Investigation of the mechanisms of action of these agents may lead to the design of potent and selective antimalarial and other antiparasitic drugs. This review discusses the properties of immunophilins in parasites and the 'animal model' <i>Caenorhabditis elegans</i> and relates these to our understanding of the roles of these proteins in cellular biochemistry, host-parasite interaction and the antiparasitic mechanisms of the drugs that bind to them
Studien zum Realismus I. S. Turgenevs
Beobachtung seiner Umwelt war für Turgenev, die Quelle seiner dichterischen Inspiration. Der eigentliche Gegenstand des Turgenevschen Schaffens ist das Russland seiner Zeit; die Darstellung des russischen Menschen fasste der Dichter als seine Aufgabe auf. </P
Using routine data to monitor inequalities in an acute trust: a retrospective study
<p><b>Abstract</b></p> <p><b>Background</b></p> <p>Reducing inequalities is one of the priorities of the National Health Service. However, there is no standard system for monitoring inequalities in the care provided by acute trusts. We explore the feasibility of monitoring inequalities within an acute trust using routine data.</p> <p><b>Methods</b></p> <p>A retrospective study of hospital episode statistics from one acute trust in London over three years (2007 to 2010). Waiting times, length of stay and readmission rates were described for seven common surgical procedures. Inequalities by age, sex, ethnicity and social deprivation were examined using multiple logistic regression, adjusting for the other socio-demographic variables and comorbidities. Sample size calculations were computed to estimate how many years of data would be ideal for this analysis.</p> <p><b>Results</b></p> <p>This study found that even in a large acute trust, there was not enough power to detect differences between subgroups. There was little evidence of inequalities for the outcome and process measures examined, statistically significant differences by age, sex, ethnicity or deprivation were only found in 11 out of 80 analyses. Bariatric surgery patients who were black African or Caribbean were more likely than white patients to experience a prolonged wait (longer than 64 days, aOR = 2.47, 95% CI: 1.36-4.49). Following a coronary angioplasty, patients from more deprived areas were more likely to have had a prolonged length of stay (aOR = 1.66, 95% CI: 1.25-2.20).</p> <p><b>Conclusions</b></p> <p>This study found difficulties in using routine data to identify inequalities on a trust level. Little evidence of inequalities in waiting time, length of stay or readmission rates by sex, ethnicity or social deprivation were identified although some differences were identified which warrant further investigation. Even with three years of data from a large trust there was little power to detect inequalities by procedure. Data will therefore need to be pooled from multiple trusts to detect inequalities.</p
Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8α+ conventional dendritic cells
Although CD103-expressing dendritic cells (DCs) are widely present in nonlymphoid tissues, the transcription factors controlling their development and their relationship to other DC subsets remain unclear. Mice lacking the transcription factor Batf3 have a defect in the development of CD8α(+) conventional DCs (cDCs) within lymphoid tissues. We demonstrate that Batf3(−/−) mice also lack CD103(+)CD11b(−) DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes. Notably, Batf3(−/−) mice displayed reduced priming of CD8 T cells after pulmonary Sendai virus infection, with increased pulmonary inflammation. In the MLNs and intestine, Batf3 deficiency resulted in the specific lack of CD103(+)CD11b(−) DCs, with the population of CD103(+)CD11b(+) DCs remaining intact. Batf3(−/−) mice showed no evidence of spontaneous gastrointestinal inflammation and had a normal contact hypersensitivity (CHS) response, despite previous suggestions that CD103(+) DCs were required for immune homeostasis in the gut and CHS. The relationship between CD8α(+) cDCs and nonlymphoid CD103(+) DCs implied by their shared dependence on Batf3 was further supported by similar patterns of gene expression and their shared developmental dependence on the transcription factor Irf8. These data provide evidence for a developmental relationship between lymphoid organ–resident CD8α(+) cDCs and nonlymphoid CD103(+) DCs
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