489 research outputs found

    Orbiter/payload proximity operations: Lateral approach technique

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    The lateral approach is presented for proximity operations associated with the retrieval of free flying payloads. An out of plane final approach emphasizing onboard software support is recommended for all except the latter segment of the final approach in which manual control is considered mandatory. An overall assessment of various candidate proximity operations techniques are made

    Orbit targeting specialist function: Level C formulation requirements

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    A definition of the level C requirements for onboard maneuver targeting software is provided. Included are revisions of the level C software requirements delineated in JSC IN 78-FM-27, Proximity Operations Software; Level C Requirements, dated May 1978. The software supports the terminal phase midcourse (TPM) maneuver, braking and close-in operations as well as supporting computation of the rendezvous corrective combination maneuver (NCC), and the terminal phase initiation (TPI). Specific formulation is contained here for the orbit targeting specialist function including the processing logic, linkage, and data base definitions for all modules. The crew interface with the software is through the keyboard and the ORBIT-TGT display

    Mean Dynamic Topography of the Arctic Ocean

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    ICESat and Envisat altimetry data provide measurements of the instantaneous sea surface height (SSH) across the Arctic Ocean, using lead and open water elevation within the sea ice pack. First, these data were used to derive two independent mean sea surface (MSS) models by stacking and averaging along-track SSH profiles gathered between 2003 and 2009. The ICESat and Envisat MSS data were combined to construct the high-resolution ICEn MSS. Second, we estimate the 5.5-year mean dynamic topography (MDT) of the Arctic Ocean by differencing the ICEn MSS with the new GOCO02S geoid model, derived from GRACE and GOCE gravity. Using these satellite-only data we map the major features of Arctic Ocean dynamical height that are consistent with in situ observations, including the topographical highs and lows of the Beaufort and Greenland Gyres, respectively. Smaller-scale MDT structures remain largely unresolved due to uncertainties in the geoid at short wavelengths

    A case series of patients with isolated IgG4-related hypophysitis treated with rituximab

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    Context The acute presentation of Immunoglobulin G4 (IgG4)-related hypophysitis can be indistinguishable from other forms of acute hypophysitis and histology remains the diagnostic gold standard. The high recurrence rate necessitates long term immunosuppressive therapy. Rituximab (RTX) has been shown to be effective in systemic IgG4-related disease (IgG4-RD), but experience with isolated pituitary involvement remains limited. Case description We report three female patients with MRI findings suggestive of hypophysitis. All patients underwent transsphenoidal biopsy and fulfilled diagnostic criteria for IgG4-related hypophysitis. Treatment with GCs (GC) resulted in good therapeutic response in patients 1 and 2, but the disease recurred on tapering doses of GCs. GC treatment led to emotional lability in Patient 3 necessitating dose reduction. All three patients received RTX and Patients 2 and 3 received further courses when symptoms returned and B-cells repopulated. Patient 3 did not receive RTX until 12 months from onset of symptoms. Patient 1 was not able to have further RTX treatments due to an allergic reaction when receiving the second dose. RTX treatment resulted in sustained remission and full recovery of anterior pituitary function in Patients 1 and 2 with complete resolution of pituitary enlargement. By contrast, Patient 3 only showed symptomatic response following RTX treatment, but pituitary enlargement and hypofunction persisted. Conclusion RTX treatment for IgG4-related hypophysitis resulted in sustained remission in two patients treated early in the disease process, but only achieved partial response in a patient with chronic disease suggesting that early therapeutic intervention may be crucial to avoid irreversible changes

    Glomerulonephritis and autoimmune vasculitis are independent of P2RX7 but may depend on alternative inflammasome pathways

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    P2RX7, an ionotropic receptor for extracellular ATP, is expressed on immune cells, including macrophages, monocytes and dendritic cells and is up-regulated on non-immune cells following injury. P2RX7 plays a role in many biological processes, including production of pro-inflammatory cytokines such as IL-1β via the canonical inflammasome pathway. P2RX7 has been shown to be important in inflammation and fibrosis and may also play a role in autoimmunity. We have developed and phenotyped a novel P2RX7 knock-out (KO) inbred rat strain and taking advantage of the human-resembling unique histopathological features of rat models of glomerulonephritis, we induced three models of disease: nephrotoxic nephritis, experimental autoimmune glomerulonephritis, and experimental autoimmune vasculitis. We found that deletion of P2RX7 does not protect rats from models of experimental glomerulonephritis or the development of autoimmunity. Notably, treatment with A-438079, a P2RX7 antagonist, was equally protective in WKY WT and P2RX7 KO rats, revealing its 'off-target' properties. We identify a novel ATP/P2RX7/K+ efflux-independent and caspase-1/8-dependent pathway for production of IL-1β in rat dendritic cells, which was absent in macrophages. Taken together, these results comprehensively establish that inflammation and autoimmunity in glomerulonephritis is independent of P2RX7 and reveals the off-target properties of drugs previously known as selective P2RX7 antagonists. Rat mononuclear phagocytes may be able to utilise an 'alternative inflammasome' pathway to produce IL-1β independently of P2RX7, which may account for the susceptibility of P2RX7 KO rats to inflammation and autoimmunity in glomerulonephritis. This article is protected by copyright. All rights reserved

    Experimental crescentic glomerulonephritis:a new bicongenic rat model

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    SUMMARY Crescentic glomerulonephritis (CRGN) is a major cause of human kidney failure, but the underlying mechanisms are not fully understood. Wistar Kyoto (WKY) rats are uniquely susceptible to CRGN following injection of nephrotoxic serum, whereas Lewis (LEW) rats are resistant. Our previous genetic studies of nephrotoxic nephritis (NTN), a form of CRGN induced by nephrotoxic serum, identified Fcgr3 and Jund as WKY genes underlying the two strongest quantitative trait loci for NTN phenotypes: Crgn1 and Crgn2, respectively. We also showed that introgression of WKY Crgn1 or Crgn2 individually into a LEW background did not lead to the formation of glomerular crescents. We have now generated a bicongenic strain, LEW.WCrgn1,2, in which WKY Crgn1 and Crgn2 are both introgressed into the LEW genetic background. These rats show development of NTN phenotypes, including glomerular crescents. Furthermore, we characterised macrophage function and glomerular cytokine profiles in this new strain. Additionally, we show that LEW.WCrgn1,2 rats are resistant to the development of glomerular crescents that is usually induced following immunisation with recombinant rat α3(IV)NC1, the specific Goodpasture autoantigen located in the glomerular basement membrane against which the immune response is directed in experimental autoimmune glomerulonephritis. Our results show that the new bicongenic strain responds differently to two distinct experimental triggers of CRGN. This is the first time that CRGN has been induced on a normally resistant rat genetic background and identifies the LEW.WCrgn1,2 strain as a new, potentially valuable model of macrophage-dependent glomerulonephritis

    Efficacy of sub-Tenon's block using an equal volume of local anaesthetic administered either as a single or as divided doses. A randomised clinical trial

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    <p>Abstract</p> <p>Background</p> <p>Sub-Tenon's anaesthetic is effective and reliable in producing both akinesia and anaesthesia for cataract surgery. Our clinical experience indicates that it is sometimes necessary when absolute akinesia is required during surgery to augment the block with 1–2 ml of local anaesthetic. Hypothesis was that after first injection some of the volume injected may spill out and before second injection the effect of hyaluronidase has taken place and second volume injectate will have desired effect.</p> <p>Methods</p> <p>A prospective, randomised, control trial in which patients were randomly allocated to one of two groups. In group 1, single injection of 5 ml of local anaesthetic was injected. In group 2, 3 ml of the same anaesthetic solution was injected followed by application of gentle orbital pressure for 2 minutes. A further 2 ml of the same anaesthetic solution was injected through the same conjunctival incision. Measurement of movement in four quadrants of eye was done by the surgeon at 3 and 6 minutes. Intraocular pressure, chemosis, and subconjuctival haemorrhage were also measured.</p> <p>Results</p> <p>Significant differences at 3 minutes between groups for overall movement, medial, superior, and lateral quadrants occurred. At 6 minutes no significant group differences emerged for the overall movement or for any of four quadrants.</p> <p>Conclusion</p> <p>Single injection of local anaesthesia for sub-Tenon's block with mixture of lignocaine with adrenaline, bupivacaine and hyaluronidase was found to be superior to provide akinesia of ocular muscles compared to divided dose given by two injections. No difference in groups in terms of haemorrhage, chemosis, patient's satisfaction and intraocular pressure was found.</p> <p>Trial registration</p> <p>Trial registration no-ISRCTN73431052</p

    A simple and efficient GIS tool for volume calculations of submarine landslides

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    A numeric tool is presented for calculating volumes of topographic voids such as slump scars of landslides, canyons or craters (negative/concave morphology), or alternatively, bumps and hills (positive/convex morphology) by means of digital elevation models embedded within a geographical information system (GIS). In this study, it has been used to calculate landslide volumes. The basic idea is that a (singular) event (landslide, meteorite impact, volcanic eruption) has disturbed an intact surface such that it is still possible to distinguish between the former (undisturbed) landscape and the disturbance (crater, slide scar, debris avalanche). In such cases, it is possible to reconstruct the paleo-surface and to calculate the volume difference between both surfaces, thereby approximating the volume gain or loss caused by the event. I tested the approach using synthetically generated land surfaces that were created on the basis of Shuttle Radar Topography Mission data. Also, I show the application to two real cases, (1) the calculation of the volume of the Masaya Slide, a submarine landslide on the Pacific continental slope of Nicaragua, and (2) the calculation of the void of a segment of the Fish River Canyon, Namibia. The tool is provided as a script file for the free GIS GRASS. It performs with little effort, and offers a range of interpolation parameters. Testing with different sets of interpolation parameters results in a small range of uncertainty. This tool should prove useful in surface studies not exclusively on earth
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