13,802 research outputs found
Metabolism of ticagrelor in patients with acute coronary syndromes.
© The Author(s) 2018Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.Peer reviewedFinal Published versio
Suzaku Observations of Local Ultraluminous Infrared Galaxies
We report the results from our analysis of {\it Suzaku} XIS (0.5-10 keV) and
HXD/PIN (15-40 keV) observations of five well-known local ULIRGs: {\em IRAS}
F05189-2524, {\em IRAS} F08572+3915, Mrk 273, PKS 1345+12, and Arp 220. The XIS
observations of F05189-2524 and Mrk 273 reveal strong iron lines consistent
with Fe K and changes in spectral shapes with respect to previous {\it
Chandra} and {\it XMM-Newton} observations. Mrk 273 is also detected by the
HXD/PIN at 1.8-. For F05189-2524, modeling of the data from the
different epochs suggests that the change in spectral shape is likely due to
the central source switching off, leaving behind a residual reflection
spectrum, or an increase in the absorbing column. An increase in the covering
fraction of the absorber can describe the spectral variations seen in Mrk 273,
although a reduction in the intrinsic AGN luminosity cannot be formally ruled
out. The {\it Suzaku} spectra of Mrk 273 are well fit by a ~94% covering
fraction model with a column density of cm. The
absorption-corrected log[ / ] ratio is consistent
with those found in PG Quasars. The 0.5-10 keV spectrum of PKS 1345+12 and Arp
220 seem unchanged from previous observations and their hard X-ray emission is
not convincingly detected by the HXD/PIN. The large column density derived from
CO observations and the large equivalent width of an ionized Fe line in Arp 220
can be reconciled by an ionized reflection model. F08572+3915 is undetected in
both the XIS and HXD/PIN, but the analysis of unpublished {\em Chandra} data
provides a new measurement at low energies.Comment: 37 pages including 4 tables and 10 figures. Accepted for publication
in ApJ. It is tentatively scheduled to appear in the January 20, 2009 issue
of Ap
Influence of aggregation and linker proteins on chromophore structure in allophycocyanin (Mastigocladus laminosus).
Exploring the Dust Content of Galactic Winds with Herschel. I. NGC 4631
We present a detailed analysis of deep far-infrared observations of the
nearby edge-on star-forming galaxy NGC 4631 obtained with the Herschel Space
Observatory. Our PACS images at 70 and 160 um show a rich complex of filaments
and chimney-like features that extends up to a projected distance of 6 kpc
above the plane of the galaxy. The PACS features often match extraplanar
Halpha, radio-continuum, and soft X-ray features observed in this galaxy,
pointing to a tight disk-halo connection regulated by star formation. On the
other hand, the morphology of the colder dust component detected on larger
scale in the SPIRE 250, 350, and 500 um data matches the extraplanar H~I
streams previously reported in NGC 4631 and suggests a tidal origin. The PACS
70/160 ratios are elevated in the central ~3.0 kpc region above the nucleus of
this galaxy (the "superbubble"). A pixel-by-pixel analysis shows that dust in
this region has a higher temperature and/or an emissivity with a steeper
spectral index (beta > 2) than the dust in the disk, possibly the result of the
harsher environment in the superbubble. Star formation in the disk seems
energetically insufficient to lift the material out of the disk, unless it was
more active in the past or the dust-to-gas ratio in the superbubble region is
higher than the Galactic value. Some of the dust in the halo may also have been
tidally stripped from nearby companions or lifted from the disk by galaxy
interactions.Comment: Accepted for publication in The Astrophysical Journa
Search for the Lepton-Number-Violating Decay
A sensitive search for the lepton-number-violating decay has been performed using a sample of hyperons
produced in 800 GeV/ -Cu collisions. We obtain at 90% confidence, improving on the best
previous limit by four orders of magnitude.Comment: 9 pages, 5 figures, to be published in Phys. Rev. Let
delta S = 2 nonleptonic hyperon decays
A sensitive search for the rare decays \Omega^- \to \Lambda \pi^- and \Xi^0
\to p \pi^- has been performed using data from the 1997 run of the HyperCP
(Fermilab E871) experiment. Limits on other such processes do not exclude the
possibility of observable rates for |\Delta S| = 2 nonleptonic hyperon decays,
provided the decays occur through parity-odd operators. We obtain the
branching-fraction limits B(\Omega^- \to \Lambda \pi^-)< 2.9 x 10^{-6} and
B(\Xi^0 \to p \pi^-)< 8.2 x 10^{-6}, both at 90% confidence level.Comment: 4 pages, 5 figures, PRL pape
Broadband spin-controlled focusing via logarithmic-spiral nanoslits of varying width
This work presents analytical, numerical and experimental demonstrations of light diffracted through a logarithmic spiral (LS) nanoslit, which forms a type of switchable and focus-tunable structure. Owing to a strong dependence on the incident photon spin, the proposed LS-nanoslit converges incoming light of opposite handedness (to that of the LS-nanoslit) into a confined subwavelength spot, while it shapes light with similar chirality into a donut-like intensity profile. Benefitting from the varying width of the LS-nanoslit, different incident wavelengths interfere constructively at different positions, i.e., the focal length shifts from 7.5 μm (at λ = 632.8 nm) to 10 μm (at λ = 488 nm), which opens up new opportunities for tuning and spatially separating broadband light at the micrometer scale
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Role of biomechanical forces in the natural history of coronary atherosclerosis.
Atherosclerosis remains a major cause of morbidity and mortality worldwide, and a thorough understanding of the underlying pathophysiological mechanisms is crucial for the development of new therapeutic strategies. Although atherosclerosis is a systemic inflammatory disease, coronary atherosclerotic plaques are not uniformly distributed in the vascular tree. Experimental and clinical data highlight that biomechanical forces, including wall shear stress (WSS) and plaque structural stress (PSS), have an important role in the natural history of coronary atherosclerosis. Endothelial cell function is heavily influenced by changes in WSS, and longitudinal animal and human studies have shown that coronary regions with low WSS undergo increased plaque growth compared with high WSS regions. Local alterations in WSS might also promote transformation of stable to unstable plaque subtypes. Plaque rupture is determined by the balance between PSS and material strength, with plaque composition having a profound effect on PSS. Prospective clinical studies are required to ascertain whether integrating mechanical parameters with medical imaging can improve our ability to identify patients at highest risk of rapid disease progression or sudden cardiac events.This work was supported by the British Heart Foundation (FS/13/33/30168), Heart Research UK (RG2638/14/16), the Cambridge NIHR Biomedical Research Centre, and the BHF Cambridge Centre for Research Excellence.This is the author accepted manuscript. The final version is available from Nature Publishing Group at http://dx.doi.org/10.1038/nrcardio.2015.203
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