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- Coustenis, A., et al.
(författare)
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TandEM : Titan and Enceladus mission
- 2009
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 23:3, s. 893-946
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Tidskriftsartikel (refereegranskat)abstract
- TandEM was proposed as an L-class (large) mission in response to ESA's Cosmic Vision 2015-2025 Call, and accepted for further studies, with the goal of exploring Titan and Enceladus. The mission concept is to perform in situ investigations of two worlds tied together by location and properties, whose remarkable natures have been partly revealed by the ongoing Cassini-Huygens mission. These bodies still hold mysteries requiring a complete exploration using a variety of vehicles and instruments. TandEM is an ambitious mission because its targets are two of the most exciting and challenging bodies in the Solar System. It is designed to build on but exceed the scientific and technological accomplishments of the Cassini-Huygens mission, exploring Titan and Enceladus in ways that are not currently possible (full close-up and in situ coverage over long periods of time). In the current mission architecture, TandEM proposes to deliver two medium-sized spacecraft to the Saturnian system. One spacecraft would be an orbiter with a large host of instruments which would perform several Enceladus flybys and deliver penetrators to its surface before going into a dedicated orbit around Titan alone, while the other spacecraft would carry the Titan in situ investigation components, i.e. a hot-air balloon (MontgolfiSre) and possibly several landing probes to be delivered through the atmosphere.
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- Crowley, S. D., et al.
(författare)
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Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis
- 2009
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Ingår i: J Clin Invest. - 1558-8238 .- 1558-8238 .- 0021-9738. ; 119:4, s. 943-53
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Tidskriftsartikel (refereegranskat)abstract
- Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin (AT1) receptors in glomerular inflammation associated with autoimmune disease, we generated MRL-Faslpr/lpr (lpr) mice lacking the major murine type 1 angiotensin receptor (AT1A); lpr mice develop a generalized autoimmune disease with glomerulonephritis that resembles SLE. Surprisingly, AT1A deficiency was not protective against disease but instead substantially accelerated mortality, proteinuria, and kidney pathology. Increased disease severity was not a direct effect of immune cells, since transplantation of AT1A-deficient bone marrow did not affect survival. Moreover, autoimmune injury in extrarenal tissues, including skin, heart, and joints, was unaffected by AT1A deficiency. In murine systems, there is a second type 1 angiotensin receptor isoform, AT1B, and its expression is especially prominent in the renal glomerulus within podocytes. Further, expression of renin was enhanced in kidneys of AT1A-deficient lpr mice, and they showed evidence of exaggerated AT1B receptor activation, including substantially increased podocyte injury and expression of inflammatory mediators. Administration of losartan, which blocks all type 1 angiotensin receptors, reduced markers of kidney disease, including proteinuria, glomerular pathology, and cytokine mRNA expression. Since AT1A-deficient lpr mice had low blood pressure, these findings suggest that activation of type 1 angiotensin receptors in the glomerulus is sufficient to accelerate renal injury and inflammation in the absence of hypertension.
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| 3. |
- Slanger, Tom G., et al.
(författare)
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Variability of the mesospheric nightglow sodium D2/D1 ratio
- 2005
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 110:23, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of the intensity ratio of the 589.0/589.6 nm sodium doublet in the terrestrial nightglow over an 8-year period, involving >300 separate determinations, have established that it is variable, the value RD = I(D2)/I(D1) lying between 1.2 and 1.8. Sky spectra from the Keck I telescope with the High-Resolution Echelle Spectrometer (HIRES) échelle spectrograph and the Keck II telescope with the Échellette Spectrograph and Imager (ESI) échelle spectrograph were used in this analysis. The result contrasts with the accepted view, from earlier measurements at midlatitude, that the ratio is 2.0, as expected on statistical grounds. The lack of dependence of the ratio on viewing elevation angle, and hence Na slant column, allows self-absorption to be ruled out as a cause of the variability. The data suggest a semiannual oscillation in the ratio, maximum at the equinoxes and minimum at the solstices. Airborne measurements over the North Atlantic (40°-50°N) in 2002 show an even larger range in the nightglow ratio and no correlation with the upper mesospheric temperature determined from the OH 6-2 bands. A laboratory study confirms that the ratio does not depend on temperature; however, it is shown to be sensitive to the [O]/[O2] ratio. It is therefore postulated that the variable ratio arises from a competition between O reacting with NaO(A3∑+), produced from the reaction of Na with O3, to yield D-line emission with a D2/D1 ratio greater than about 2.0, and quenching by O2 to produce NaO(X2II), possibly with vibrational excitation, which then reacts with O to produce emission with a ratio of less than 1.3. Copyright 2005 by the American Geophysical Union.
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| 7. |
- Harrington, Robert A., et al.
(författare)
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The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA.CER) trial : study design and rationale
- 2009
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 158:3, s. 327-334
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Tidskriftsartikel (refereegranskat)abstract
- Background The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA.CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. Trial design TRA.CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least I year. The TRA.CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. Conclusion TRA.CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies.
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