1,034 research outputs found
Metabolomic Profiling of Statin Use and Genetic Inhibition of HMG-CoA Reductase
Background Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain incompletely characterized. Objectives This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways. Methods Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.5 to 23.0 years of follow-up). Concentration changes in 80 lipid and metabolite measures during follow-up were compared between 716 individuals who started statin therapy and 4,874 persistent nonusers. To further understand the pharmacological effects of statins, we used Mendelian randomization to assess associations of a genetic variant known to mimic inhibition of HMG-CoA reductase (the intended drug target) with the same lipids and metabolites for 27,914 individuals from 8 population-based cohorts. Results Starting statin therapy was associated with numerous lipoprotein and fatty acid changes, including substantial lowering of remnant cholesterol (80% relative to low-density lipoprotein cholesterol [LDL-C]), but only modest lowering of triglycerides (25% relative to LDL-C). Among fatty acids, omega-6 levels decreased the most (68% relative to LDL-C); other fatty acids were only modestly affected. No robust changes were observed for circulating amino acids, ketones, or glycolysis-related metabolites. The intricate metabolic changes associated with statin use closely matched the association pattern with rs12916 in the HMGCR gene (R2 = 0.94, slope 1.00 ± 0.03). Conclusions Statin use leads to extensive lipid changes beyond LDL-C and appears efficacious for lowering remnant cholesterol. Metabolomic profiling, however, suggested minimal effects on amino acids. The results exemplify how detailed metabolic characterization of genetic proxies for drug targets can inform indications, pleiotropic effects, and pharmacological mechanisms
Experimental investigation of the edge states structure at fractional filling factors
We experimentally study electron transport between edge states in the
fractional quantum Hall effect regime. We find an anomalous increase of the
transport across the 2/3 incompressible fractional stripe in comparison with
theoretical predictions for the smooth edge potential profile. We interpret our
results as a first experimental demonstration of the intrinsic structure of the
incompressible stripes arising at the sample edge in the fractional quantum
Hall effect regime.Comment: 5 pages, 5 figures included. Submitted to JETP Letter
Concave Plasmonic Particles: Broad-Band Geometrical Tunability in the Near Infra-Red
Optical resonances spanning the Near and Short Infra-Red spectral regime were
exhibited experimentally by arrays of plasmonic nano-particles with concave
cross-section. The concavity of the particle was shown to be the key ingredient
for enabling the broad band tunability of the resonance frequency, even for
particles with dimensional aspect ratios of order unity. The atypical
flexibility of setting the resonance wavelength is shown to stem from a unique
interplay of local geometry with surface charge distributions
Microwave Assisted Synthesis of Py-Im Polyamides
Microwave synthesis was utilized to rapidly build Py-Im polyamides in high yields and purity using Boc-protection chemistry on Kaiser oxime resin. A representative polyamide targeting the 5′-WGWWCW-3′ (W = A or T) subset of the consensus Androgen and Glucocorticoid Response Elements was synthesized in 56% yield after 20 linear steps and HPLC purification. It was confirmed by Mosher amide derivatization of the polyamide that a chiral α-amino acid does not racemize after several additional coupling steps
A Very Intense Neutrino Super Beam Experiment for Leptonic CP Violation Discovery based on the European Spallation Source Linac: A Snowmass 2013 White Paper
Very intense neutrino beams and large neutrino detectors will be needed in
order to enable the discovery of CP violation in the leptonic sector. We
propose to use the proton linac of the European Spallation Source currently
under construction in Lund, Sweden to deliver, in parallel with the spallation
neutron production, a very intense, cost effective and high performance
neutrino beam. The baseline program for the European Spallation Source linac is
that it will be fully operational at 5 MW average power by 2022, producing 2
GeV 2.86 ms long proton pulses at a rate of 14 Hz. Our proposal is to upgrade
the linac to 10 MW average power and 28 Hz, producing 14 pulses/s for neutron
production and 14 pulses/s for neutrino production. Furthermore, because of the
high current required in the pulsed neutrino horn, the length of the pulses
used for neutrino production needs to be compressed to a few s with the
aid of an accumulator ring. A long baseline experiment using this Super Beam
and a megaton underground Water Cherenkov detector located in existing mines
300-600 km from Lund will make it possible to discover leptonic CP violation at
5 significance level in up to 50% of the leptonic Dirac CP-violating
phase range. This experiment could also determine the neutrino mass hierarchy
at a significance level of more than 3 if this issue will not already
have been settled by other experiments by then. The mass hierarchy performance
could be increased by combining the neutrino beam results with those obtained
from atmospheric neutrinos detected by the same large volume detector. This
detector will also be used to measure the proton lifetime, detect cosmological
neutrinos and neutrinos from supernova explosions. Results on the sensitivity
to leptonic CP violation and the neutrino mass hierarchy are presented.Comment: 28 page
The OPERA experiment Target Tracker
The main task of the Target Tracker detector of the long baseline neutrino
oscillation OPERA experiment is to locate in which of the target elementary
constituents, the lead/emulsion bricks, the neutrino interactions have occurred
and also to give calorimetric information about each event. The technology used
consists in walls of two planes of plastic scintillator strips, one per
transverse direction. Wavelength shifting fibres collect the light signal
emitted by the scintillator strips and guide it to both ends where it is read
by multi-anode photomultiplier tubes. All the elements used in the construction
of this detector and its main characteristics are described.Comment: 25 pages, submitted to Nuclear Instrument and Method
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