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Unambiguous Evidence (unambiguous + evidence)
Selected AbstractsDual ETA/ETB vs. selective ETA endothelin receptor antagonism in patients with pulmonary hypertensionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2006C. F. Opitz Abstract Since the identification of endothelin as a key mediator in the pathogenesis of several diseases, including pulmonary arterial hypertension (PAH), the pharmacologic control of the activated endothelin system with endothelin receptor antagonists (ETRA) has been a major therapeutic achievement for the treatment of patients with PAH. To date, dual ETA/ETB and selective ETA receptor antagonists have clinically been evaluated. To answer the question of whether selective or dual ETRA is preferable in patients with PAH, experimental and clinical data with relevance to the pulmonary circulation are reviewed in this article. Whereas experimental and clinical data provide unambiguous evidence that ETA receptors mediate the detrimental effects of ET-1, such as vasoconstriction and cell proliferation, the elucidation of the role of ETB receptors has been more complex. It has been shown that there is a subpopulation of ETB receptors on smooth muscle cells and fibroblasts mediating vasoconstriction and proliferation. On the contrary, there is clear evidence that endothelial ETB receptors continue to mediate vasodilation, vasoprotection and ET-1 clearance despite the pathology associated with pulmonary hypertension. More difficult to assess is the net effect of these mechanisms in patients to be treated with ETRA. When considering the available data from controlled clinical trials, nonselectivity does not appear to carry a relevant clinical benefit for the treatment of patients with PAH when compared with selective ETA receptor antagonism. [source] Recombinant human glucose-6-phosphate dehydrogenaseFEBS JOURNAL, Issue 14 2002Evidence for a rapid-equilibrium random-order mechanism Cloning and over-expression of human glucose 6-phosphate dehydrogenase (Glc6P dehydrogenase) has for the first time allowed a detailed kinetic study of a preparation that is genetically homogeneous and in which all the protein molecules are of identical age. The steady-state kinetics of the recombinant enzyme, studied by fluorimetric initial-rate measurements, gave converging linear Lineweaver,Burk plots as expected for a ternary-complex mechanism. Patterns of product and dead-end inhibition indicated that the enzyme can bind NADP+ and Glc6P separately to form binary complexes, suggesting a random-order mechanism. The Kd value for the binding of NADP+ measured by titration of protein fluorescence is 8.0 µm, close to the value of 6.8 µm calculated from the kinetic data on the assumption of a rapid-equilibrium random-order mechanism. Strong evidence for this mechanism and against either of the compulsory-order possibilities is provided by repeating the kinetic analysis with each of the natural substrates replaced in turn by structural analogues. A full kinetic analysis was carried out with deaminoNADP+ and with deoxyglucose 6-phosphate as the alternative substrates. In each case the calculated dissociation constant upon switching a substrate in a random-order mechanism (e.g. that for NADP+ upon changing the sugar phosphate) was indeed constant within experimental error as expected. The calculated rate constants for binding of the leading substrate in a compulsory-order mechanism, however, did not remain constant when the putative second substrate was changed. Previous workers, using enzyme from pooled blood, have variously proposed either compulsory-order or random-order mechanisms. Our study appears to provide unambiguous evidence for the latter pattern of substrate binding. [source] Late Miocene fish otoliths from the Colombacci Formation (Northern Apennines, Italy): implications for the Messinian ,Lago-mare' eventGEOLOGICAL JOURNAL, Issue 5 2006Giorgio Carnevale Abstract A fish otolith assemblage from the Messinian ,Lago-mare' deposits of the Colombacci Formation cropping out in the Montecalvo in Foglia Syncline, Marche, central Italy, is described. The assemblage displays a low diversity and consists of seven taxa belonging to three families: the Gobiidae, Myctophidae and Sciaenidae. Sciaenid otoliths are the most abundant elements representing 88% of the entire assemblage. The palaeoecological analysis reveals a coastal shallow marine environment strongly influenced by continental outflow. The low diversity and high abundance of the euryecious sciaenids are indicative of a very simplified food web, which probably represented an ecological response to the fluctuating environmental parameters and available food resources. The fish remains documented here provide an unambiguous evidence that normal marine conditions were present in the Mediterranean, at least in the upper part of the ,Lago-mare' event, and unquestionably demonstrate that the marine refilling preceded the Mio-Pliocene boundary. These findings clearly demonstrate that fishes, because of their mobility and migratory behaviour, represent a useful tool for the large-scale interpretation of the environmental conditions of the Messinian Mediterranean water body. The necessity of a new scenario of palaeoenvironmental evolution for the post-evaporitic Messinian of the Mediterranean is also discussed. Copyright © 2006 John Wiley & Sons, Ltd. [source] The impact of lunchtime closure on market behaviour: evidence from the Sydney Futures ExchangeACCOUNTING & FINANCE, Issue 1-2 2001Alex Frino This paper examines the impact of lunchtime closure on market behaviour. Between May and September, 1994 the Sydney Futures Exchange trialed lunchtime trading. The trial provides a unique natural laboratory experiment for examining the impact of lunchtime closure. The analysis reported in this paper documents abnormally high bid ask spreads, price volatility and trading volume on re-opening of the market following lunchtime closure. These results confirm that closure has an impact on trading activity, and are consistent with the effects of strategic informed trading, a loss in price discovery and/or trading associated with risk transfer. An abnormal increase in trading volume prior to lunchtime closure is also documented, providing unambiguous evidence of trading activity motivated by risk transfer. Overall these results imply that lunchtime closure disrupts trading activity and reduces market quality by imposing additional costs on market participants. [source] Two decapitations from Roman TowcesterINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 6 2001T. Anderson Abstract Two young adult males from a Roman cemetery at Towcester show unambiguous evidence of decapitation In one, the skull had been placed over the lower legs, and in the other, the skull was in its correct anatomical position. The significance of this variation and the reasons for decapitation are discussed. Copyright © 2001 John Wiley & Sons, Ltd. [source] Shocked quartz grains in the polymict breccia of the Granby structure, Sweden,-Verification of an impactMETEORITICS & PLANETARY SCIENCE, Issue 8 2009Carl Alwmark In this study, drill core samples of a sedimentary breccia from the Granby structure have been investigated for microscopic shock metamorphic evidence in an attempt to verify the impact genesis of the structure. The finding of multiple sets of decorated planar deformation features (PDFs) in quartz grains in these samples provides unambiguous evidence that the structure is impact derived. Furthermore, the orientation of the PDFs, e.g., , {101}, , {101} and r, z {101}, is characteristic for impact deformation. The fact that a majority of the PDFs are decorated implies a water-bearing target. The shocked quartz grains can be divided into two groups; rounded grains found in the breccia matrix likely originated from mature sandstone, and angular grains in fragments from crystalline target rocks. The absence of melt particles provides an estimated maximum shock pressure for the sedimentary derived quartz of 15,20 GPa and the frequency distribution of PDF orientations in the bedrock quartz implies pressures of the order of 10 GPa. [source] The X-ray spectra of Compton-thick Seyfert 2 galaxies as seen by BeppoSAXMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2000G. Matt Results from BeppoSAX observations of Compton-thick Seyfert 2 galaxies are summarized and reviewed, and their general properties derived and discussed. In five out of the seven observed sources, the nucleus is directly visible at high X-ray energies, where the photons penetrate absorbers with column densities in the range 1.1,4.3×1024 cm,2 (in the other two sources, NGC 1068 and NGC 7674, the nucleus is instead totally obscured at all energies, implying even larger column densities). In most sources there is unambiguous evidence of a reflection component from optically thick, cold matter, while in two (or maybe four) cases there is also evidence of reflection from ionized matter. For the sources with a measured X-ray luminosity, a comparison with the infrared luminosity is made; while in two cases (the Circinus galaxy and NGC 4945) the IR emission appears to be dominated by starburst activity, in the other three sources (NGC 6240, Mrk 3 and TOL 0109-383) it is likely to be dominated by reprocessing of the UV and X-ray photons emitted by an active galactic nucleus. [source] Magnetoresistivity model and ionization-energy approximation for ferromagnetsPHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 5 2009Andrew Das Arulsamy Abstract The evolution of resistivity versus temperature (, (T)) curve for different doping elements, and in the presence of various defects and clustering are explained for both diluted magnetic semiconductors (DMS) and manganites. Here, we provide unambiguous evidence that the concept of ionization energy (EI) which is explicitly associated with the atomic energy levels, can be related quantitatively to transport measurements. The proposed ionization energy model is used to understand how the valence states of ions affect the evolution of , (T) curves for different doping elements. We also explain how the , (T) curves evolve in the presence of, and in the absence of defects and clustering. The model also complements the results obtained from first-principles calculations. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] | |||||||||||||