127 research outputs found
Role of adenylate cyclase 9 in the pharmacogenomic response to dalcetrapib clinical paradigm and molecular mechanisms in precision cardiovascular medicine
Following the neutral results of the dal-OUTCOMES trial, a genome-wide study identified the rs1967309 variant in the adenylate cyclase type 9 (ADCY9) gene on chromosome 16 as being associated with the risk of future cardiovascular events only in subjects taking dalcetrapib, a CETP (cholesterol ester transfer protein) modulator. Homozygotes for the minor A allele (AA) were protected from recurrent cardiovascular events when treated with dalcetrapib, while homozygotes for the major G allele (GG) had increased risk. Here, we present the current state of knowledge regarding the impact of rs1967309 in ADCY9 on clinical observations and biomarkers in dalcetrapib trials and the effects of mouse ADCY9 gene inactivation on cardiovascular physiology. Finally, we present our current model of the interaction between dalcetrapib and ADCY9 gene variants in the arterial wall macrophage, based on the intracellular role of CETP in the transfer of complex lipids from endoplasmic reticulum membranes to lipid droplets. Briefly, the concept is that dalcetrapib would inhibit CETP-mediated transfer of cholesteryl esters, resulting in a progressive inhibition of cholesteryl ester synthesis and free cholesterol accumulation in the endoplasmic reticulum. Reduced ADCY9 activity, by paradoxically leading to higher cyclic AMP levels and in turn increased cellular cholesterol efflux, could impart cardiovascular protection in rs1967309 AA patients. The ongoing dal-GenE trial recruited 6145 patients with the protective AA genotype and will provide a definitive answer to whether dalcetrapib will be protective in this population.Cardiolog
Observation of Scaling Violations in Scaled Momentum Distributions at HERA
Charged particle production has been measured in deep inelastic scattering
(DIS) events over a large range of and using the ZEUS detector. The
evolution of the scaled momentum, , with in the range 10 to 1280
, has been investigated in the current fragmentation region of the Breit
frame. The results show clear evidence, in a single experiment, for scaling
violations in scaled momenta as a function of .Comment: 21 pages including 4 figures, to be published in Physics Letters B.
Two references adde
D* Production in Deep Inelastic Scattering at HERA
This paper presents measurements of D^{*\pm} production in deep inelastic
scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The
data have been taken with the ZEUS detector at HERA. The decay channel
(+ c.c.) has been used in the study. The
cross section for inclusive D^{*\pm} production with
and is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region
{ GeV and }. Differential cross
sections as functions of p_T(D^{*\pm}), and are
compared with next-to-leading order QCD calculations based on the photon-gluon
fusion production mechanism. After an extrapolation of the cross section to the
full kinematic region in p_T(D^{*\pm}) and (D^{*\pm}), the charm
contribution to the proton structure function is
determined for Bjorken between 2 10 and 5 10.Comment: 17 pages including 4 figure
Prospects for Studies of Stellar Evolution and Stellar Death in the JWST Era
I review the prospects for studies of the advanced evolutionary stages of
low-, intermediate- and high-mass stars by the JWST and concurrent facilities,
with particular emphasis on how they may help elucidate the dominant
contributors to the interstellar dust component of galaxies. Observations
extending from the mid-infrared to the submillimeter can help quantify the
heavy element and dust species inputs to galaxies from AGB stars. JWST's MIRI
mid-infrared instrument will be so sensitive that observations of the dust
emission from individual intergalactic AGB stars and planetary nebulae in the
Virgo Cluster will be feasible. The Herschel Space Observatory will enable the
last largely unexplored spectral region, the far-IR to the submillimeter, to be
surveyed for new lines and dust features, while SOFIA will cover the wavelength
gap between JWST and Herschel, a spectral region containing important fine
structure lines, together with key water-ice and crystalline silicate bands.
Spitzer has significantly increased the number of Type II supernovae that have
been surveyed for early-epoch dust formation but reliable quantification of the
dust contributions from massive star supernovae of Type II, Type Ib and Type Ic
to low- and high-redshift galaxies should come from JWST MIRI observations,
which will be able to probe a volume over 1000 times larger than Spitzer.Comment: 24 pages, 19 figures. To appear in `Astrophysics in the Next Decade:
JWST and Concurrent Facilities' (JWST Conference Proceedings), edited by H.
A. Thronson, M. Stiavelli and A. G. G. M. Tielens; Springer Series:
Astrophysics and Space Science Proceeding
Observation of Events with an Energetic Forward Neutron in Deep Inelastic Scattering at HERA
In deep inelastic neutral current scattering of positrons and protons at the center of mass energy of 300 GeV, we observe, with the ZEUS detector, events with a high energy neutron produced at very small scattering angles with respect to the proton direction. The events constitute a fixed fraction of the deep inelastic, neutral current event sample independent of Bjorken x and Q2 in the range 3 · 10-4 \u3c xBJ \u3c 6 · 10-3 and 10 \u3c Q2 \u3c 100 GeV2
Sudden death in two patients with variant angina and apparently minimal fixed coronary stenoses
This report deals with two patients suffering from typical variant angina in whom sudden death occurred 13 and 7 months respectively after coronary angiograms which demonstrated apparently minimal coronary stenoses. These cases illustrate possible mechanisms of sudden death in such patients including high degree AV block and ventricular tachyarrhythmias
Trace metal residues in soil as markers of ancient site occupance in Greece
Wetensch. publicatieFaculty of Archeolog
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