4,922 research outputs found

    TAIR: A transonic airfoil analysis computer code

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    The operation of the TAIR (Transonic AIRfoil) computer code, which uses a fast, fully implicit algorithm to solve the conservative full-potential equation for transonic flow fields about arbitrary airfoils, is described on two levels of sophistication: simplified operation and detailed operation. The program organization and theory are elaborated to simplify modification of TAIR for new applications. Examples with input and output are given for a wide range of cases, including incompressible, subcritical compressible, and transonic calculations

    Identification of a quorum sensing-dependent communication pathway mediating bacteria-gut-brain cross talk

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    Despite recently established contributions of the intestinal microbiome to human health and disease, our understanding of bacteria-host communication pathways with regard to the gut-brain axis remains limited. Here we provide evidence that intestinal neurons are able to “sense” bacteria independently of the host immune system. Using supernatants from cultures of the opportunistic pathogen Staphylococcus aureus (S. aureus) we demonstrate the release of mediators with neuromodulatory properties at high population density. These mediators induced a biphasic response in extrinsic sensory afferent nerves, increased membrane permeability in cultured sensory neurons, and altered intestinal motility and secretion. Genetic manipulation of S. aureus revealed two key quorum sensing-regulated classes of pore forming toxins that mediate excitation and inhibition of extrinsic sensory nerves, respectively. As such, bacterial mediators have the potential to directly modulate gut-brain communication to influence intestinal symptoms and reflex function in vivo, contributing to homeostatic, behavioral, and sensory consequences of infection

    Liver Transplantation to Provide Low-Density-Lipoprotein Receptors and Lower Plasma Cholesterol in a Child with Homozygous Familial Hypercholesterolemia

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    A six-year-old girl with severe hypercholesterolemia and atherosclerosis had two defective genes at the low-density-lipoprotein (LDL) receptor locus, as determined by biochemical studies of cultured fibroblasts. One gene, inherited from the mother, produced no LDL receptors; the other gene, inherited from the father, produced a receptor precursor that was not transported to the cell surface and was unable to bind LDL. The patient degraded intravenously administered 125I-LDL at an extremely low rate, indicating that her high plasma LDL-cholesterol level was caused by defective receptor-mediated removal of LDL from plasma. After transplantation of a liver and a heart from a normal donor, the patient's plasma LDL-cholesterol level declined by 81 per cent, from 988 to 184 mg per deciliter. The fractional catabolic rate for intravenously administered 125I-LDL, a measure of functional LDL receptors in vivo, increased by 2.5-fold. Thus, the transplanted liver, with its normal complement of LDL receptors, was able to remove LDL cholesterol from plasma at a nearly normal rate. We conclude that a genetically determined deficiency of LDL receptors can be largely reversed by liver transplantation. These data underscore the importance of hepatic LDL receptors in controlling the plasma level of LDL cholesterol in human beings. (N Engl J Med 1984; 311: 1658–64.). © 1984, Massachusetts Medical Society. All rights reserved

    The Albedo, Size, and Density of Binary Kuiper Belt Object (47171) 1999 TC36

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    We measured the system-integrated thermal emission of the binary Kuiper Belt Object 1999 TC36 at wavelengths near 24 and 70 microns using the Spitzer space telescope. We fit these data and the visual magnitude using both the Standard Thermal Model and thermophysical models. We find that the effective diameter of the binary is 405 km, with a range of 350 -- 470 km, and the effective visible geometric albedo for the system is 0.079 with a range of 0.055 -- 0.11. The binary orbit, magnitude contrast between the components, and system mass have been determined from HST data (Margot et al., 2004; 2005a; 2005b). Our effective diameter, combined with that system mass, indicate an average density for the objects of 0.5 g/cm3, with a range 0.3 -- 0.8 g/cm3. This density is low compared to that of materials expected to be abundant in solid bodies in the trans-Neptunian region, requiring 50 -- 75% of the interior of 1999 TC36 be taken up by void space. This conclusion is not greatly affected if 1999 TC36 is ``differentiated'' (in the sense of having either a rocky or just a non-porous core). If the primary is itself a binary, the average density of that (hypothetical) triple system would be in the range 0.4 -- 1.1 g/cm3, with a porosity in the range 15 -- 70%.Comment: ApJ, in press (May, 2006

    Serotonin exerts a direct modulatory role on bladder afferent firing in mice

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    Serotonin (5-HT) is an excitatory mediator, which in the gastrointestinal (GI) tract, plays a physiological role in gut-brain signaling and which is dysregulated in functional GI disorders such as irritable bowel syndrome (IBS). Patients suffering from IBS frequently suffer from urological symptoms characteristic of interstitial cystitis/painful bladder syndrome, which manifests due to cross-sensitization of shared innervation pathways between the bladder and colon. However, a direct modulatory role of 5-HT in bladder afferent signaling and its role in colon-bladder neuronal crosstalk remain elusive. The aim of this study was to investigate the action of 5-HT on bladder afferent signaling in normal mice and mice with chronic visceral hypersensitivity (CVH) following trinitrobenzenesulfonic acid (TNBS) induced colitis. Bladder afferent activity was recorded directly using ex vivo afferent nerve recordings. Expression of 14 5-HT receptor subtypes, the serotonin transporter (SERT) and 5-HT producing enzymes were determined in the urothelium using RT-PCR. Retrograde labelling of bladder projecting dorsal root ganglion (DRG) neurons was used to investigate expression of 5-HT3 receptors using single cell RT-PCR, while sensory neuronal and urothelial responses to 5-HT were determined by live cell calcium imaging. 5-HT elicited bladder afferent firing predominantly via 5-HT3 receptors expressed on afferent terminals. CVH animals showed a downregulation of SERT mRNA expression in urothelium, suggesting increased 5-HT bioavailability. Granisetron, a 5-HT3 antagonist, reversed bladder afferent hypersensitivity in CVH mice. These data suggest 5-HT exerts a direct effect on bladder afferents to enhance signaling. 5-HT3 antagonists could therefore be a potential therapeutic target to treat functional bladder and bowel disorders

    Assessing the number of users who are excluded by domestic heating controls

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    This is the pre-print version of the Article. This Article is also referred to as: "Assessing the 'Design Exclusion' of Heating Controls at a Low-Cost, Low-Carbon Housing Development". - Copyright @ 2011 Taylor & FrancisSpace heating accounts for almost 60% of the energy delivered to housing which in turn accounts for nearly 27% of the total UK's carbon emissions. This study was conducted to investigate the influence of heating control design on the degree of ‘user exclusion’. This was calculated using the Design Exclusion Calculator, developed by the Engineering Design Centre at the University of Cambridge. To elucidate the capability requirements of the system, a detailed hierarchical task analysis was produced, due to the complexity of the overall task. The Exclusion Calculation found that the current design placed excessive demands upon the capabilities of at least 9.5% of the UK population over 16 years old, particularly in terms of ‘vision’, ‘thinking’ and ‘dexterity’ requirements. This increased to 20.7% for users over 60 years old. The method does not account for the level of numeracy and literacy and so the true exclusion may be higher. Usability testing was conducted to help validate the results which indicated that 66% of users at a low-carbon housing development could not programme their controls as desired. Therefore, more detailed analysis of the cognitive demands placed upon the users is required to understand where problems within the programming process occur. Further research focusing on this cognitive interaction will work towards a solution that may allow users to behave easily in a more sustainable manner

    Serotonin exerts a direct modulatory role on bladder afferent firing in mice

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    Key points Functional disorders (i.e., interstitial cystitis/painful bladder syndrome and irritable bowel syndrome) are associated with hyperexcitability of afferent nerves innervating the urinary tract and the bowel respectively. Various non‐5‐HT3 receptor mRNA transcripts are expressed in mouse urothelium and exert functional responses to 5‐HT. Whilst 5‐HT3 receptors were not detected in mouse urothelium, 5‐HT3 receptors expressed on bladder sensory neurons plays a role in bladder afferent excitability under both normal conditions and in a mouse model of chronic visceral hypersensitivity (CVH). These data suggest that the role 5‐HT3 receptors play in bladder afferent signaling warrants further study as a potential therapeutic target for functional bladder disorders. Abstract Serotonin (5‐HT) is an excitatory mediator, which in the gastrointestinal (GI) tract, plays a physiological role in gut‐brain signaling and which is dysregulated in functional GI disorders such as irritable bowel syndrome (IBS). Patients suffering from IBS frequently suffer from urological symptoms characteristic of interstitial cystitis/painful bladder syndrome, which manifests due to cross‐sensitization of shared innervation pathways between the bladder and colon. However, a direct modulatory role of 5‐HT in bladder afferent signaling and its role in colon‐bladder neuronal crosstalk remain elusive. The aim of this study was to investigate the action of 5‐HT on bladder afferent signaling in normal mice and mice with chronic visceral hypersensitivity (CVH) following trinitrobenzenesulfonic acid (TNBS) induced colitis. Bladder afferent activity was recorded directly using ex vivo afferent nerve recordings. Expression of 14 5‐HT receptor subtypes, the serotonin transporter (SERT) and 5‐HT producing enzymes were determined in the urothelium using RT‐PCR. Retrograde labelling of bladder projecting dorsal root ganglion (DRG) neurons was used to investigate expression of 5‐HT3 receptors using single cell RT‐PCR, while sensory neuronal and urothelial responses to 5‐HT were determined by live cell calcium imaging. 5‐HT elicited bladder afferent firing predominantly via 5‐HT3 receptors expressed on afferent terminals. CVH animals showed a downregulation of SERT mRNA expression in urothelium, suggesting increased 5‐HT bioavailability. Granisetron, a 5‐HT3 antagonist, reversed bladder afferent hypersensitivity in CVH mice. These data suggest 5‐HT exerts a direct effect on bladder afferents to enhance signaling.5‐HT3 antagonists could therefore be a potential therapeutic target to treat functional bladder and bowel disorders
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