7,051 research outputs found
Reduced mechanical efficiency in left-ventricular trabeculae of the spontaneously hypertensive rat.
Long-term systemic arterial hypertension, and its associated compensatory response of left-ventricular hypertrophy, is fatal. This disease leads to cardiac failure and culminates in death. The spontaneously hypertensive rat (SHR) is an excellent animal model for studying this pathology, suffering from ventricular failure beginning at about 18 months of age. In this study, we isolated left-ventricular trabeculae from SHR-F hearts and contrasted their mechanoenergetic performance with those from nonfailing SHR (SHR-NF) and normotensive Wistar rats. Our results show that, whereas the performance of the SHR-F differed little from that of the SHR-NF, both SHR groups performed less stress-length work than that of Wistar trabeculae. Their lower work output arose from reduced ability to produce sufficient force and shortening. Neither their heat production nor their enthalpy output (the sum of work and heat), particularly the energy cost of Ca(2+) cycling, differed from that of the Wistar controls. Consequently, mechanical efficiency (the ratio of work to change of enthalpy) of both SHR groups was lower than that of the Wistar trabeculae. Our data suggest that in hypertension-induced left-ventricular hypertrophy, the mechanical performance of the tissue is compromised such that myocardial efficiency is reduced
Measurement properties of the Musculoskeletal Health Questionnaire (MSK-HQ): a between country comparison.
Background: The Musculoskeletal Health Questionnaire (MSK-HQ) has been developed to measure musculoskeletal health status across musculoskeletal conditions and settings. However, the MSK-HQ needs to be further evaluated across settings and different languages. Objective: The objective of the study was to evaluate and compare measurement properties of the MSK-HQ across Danish (DK) and English (UK) cohorts of patients from primary care physiotherapy services with musculoskeletal pain
Physical realization of coupled Hilbert-space mirrors for quantum-state engineering
Manipulation of superpositions of discrete quantum states has a mathematical
counterpart in the motion of a unit-length statevector in an N-dimensional
Hilbert space. Any such statevector motion can be regarded as a succession of
two-dimensional rotations. But the desired statevector change can also be
treated as a succession of reflections, the generalization of Householder
transformations. In multidimensional Hilbert space such reflection sequences
offer more efficient procedures for statevector manipulation than do sequences
of rotations. We here show how such reflections can be designed for a system
with two degenerate levels - a generalization of the traditional two-state atom
- that allows the construction of propagators for angular momentum states. We
use the Morris-Shore transformation to express the propagator in terms of
Morris-Shore basis states and Cayley-Klein parameters, which allows us to
connect properties of laser pulses to Hilbert-space motion. Under suitable
conditions on the couplings and the common detuning, the propagators within
each set of degenerate states represent products of generalized Householder
reflections, with orthogonal vectors. We propose physical realizations of this
novel geometrical object with resonant, near-resonant and far-off-resonant
laser pulses. We give several examples of implementations in real atoms or
molecules.Comment: 15 pages, 6 figure
Correlation between nucleotide composition and folding energy of coding sequences with special attention to wobble bases
Background: The secondary structure and complexity of mRNA influences its
accessibility to regulatory molecules (proteins, micro-RNAs), its stability and
its level of expression. The mobile elements of the RNA sequence, the wobble
bases, are expected to regulate the formation of structures encompassing coding
sequences.
Results: The sequence/folding energy (FE) relationship was studied by
statistical, bioinformatic methods in 90 CDS containing 26,370 codons. I found
that the FE (dG) associated with coding sequences is significant and negative
(407 kcal/1000 bases, mean +/- S.E.M.) indicating that these sequences are able
to form structures. However, the FE has only a small free component, less than
10% of the total. The contribution of the 1st and 3rd codon bases to the FE is
larger than the contribution of the 2nd (central) bases. It is possible to
achieve a ~ 4-fold change in FE by altering the wobble bases in synonymous
codons. The sequence/FE relationship can be described with a simple algorithm,
and the total FE can be predicted solely from the sequence composition of the
nucleic acid. The contributions of different synonymous codons to the FE are
additive and one codon cannot replace another. The accumulated contributions of
synonymous codons of an amino acid to the total folding energy of an mRNA is
strongly correlated to the relative amount of that amino acid in the translated
protein.
Conclusion: Synonymous codons are not interchangable with regard to their
role in determining the mRNA FE and the relative amounts of amino acids in the
translated protein, even if they are indistinguishable in respect of amino acid
coding.Comment: 14 pages including 6 figures and 1 tabl
Risk of complications following external cardioversion in cardiovascular implantable electronic devices with and without generator replacement
Targeted temperature management after out-of-hospital cardiac arrest: certainties and uncertainties
NADPH oxidase, NOX1, mediates vascular injury in ischemic retinopathy
<b>Aims:</b> Ischemic retinal diseases such as retinopathy of prematurity are major causes of blindness due to damage to the retinal microvasculature. Despite this clinical situation, retinopathy of prematurity is mechanistically poorly understood. Therefore, effective preventative therapies are not available. However, hypoxic-induced increases in reactive oxygen species (ROS) have been suggested to be involved with NADPH oxidases (NOX), the only known dedicated enzymatic source of ROS. Our major aim was to determine the contribution of NOX isoforms (1, 2, and 4) to a rodent model of retinopathy of prematurity. <b>Results:</b> Using a genetic approach, we determined that only mice with a deletion of NOX1, but not NOX2 or NOX4, were protected from retinal neovascularization and vaso-obliteration, adhesion of leukocytes, microglial accumulation, and the increased generation of proangiogenic and proinflammatory factors and ROS. We complemented these studies by showing that the specific NOX inhibitor, GKT137831, reduced vasculopathy and ROS levels in retina. The source of NOX isoforms was evaluated in retinal vascular cells and neuro-glial elements. Microglia, the immune cells of the retina, expressed NOX1, 2, and 4 and responded to hypoxia with increased ROS formation, which was reduced by GKT137831. <b>Innovation:</b> Our studies are the first to identify the NOX1 isoform as having an important role in the pathogenesis of retinopathy of prematurity. <b>Conclusions:</b> Our findings suggest that strategies targeting NOX1 have the potential to be effective treatments for a range of ischemic retinopathie
On the Trace Anomaly and the Anomaly Puzzle in N=1 Pure Yang-Mills
The trace anomaly of the energy-momentum tensor is usually quoted in the form
which is proportional to the beta function of the theory. However, there are in
general many definitions of gauge couplings depending on renormalization
schemes, and hence many beta functions. In particular, N=1 supersymmetric pure
Yang-Mills has the holomorphic gauge coupling whose beta function is one-loop
exact, and the canonical gauge coupling whose beta function is given by the
Novikov-Shifman-Vainshtein-Zakharov beta function. In this paper, we study
which beta function should appear in the trace anomaly in N=1 pure Yang-Mills.
We calculate the trace anomaly by employing the N=4 regularization of N=1 pure
Yang-Mills. It is shown that the trace anomaly is given by one-loop exact form
if the composite operator appearing in the trace anomaly is renormalized in a
preferred way. This result gives the simplest resolution to the anomaly puzzle
in N=1 pure Yang-Mills. The most important point is to examine in which scheme
the quantum action principle is valid, which is crucial in the derivation of
the trace anomaly.Comment: 25 pages, 1 figure; v2:slight correction in sec.5, minor addition in
appendi
Symbolic Partial-Order Execution for Testing Multi-Threaded Programs
We describe a technique for systematic testing of multi-threaded programs. We
combine Quasi-Optimal Partial-Order Reduction, a state-of-the-art technique
that tackles path explosion due to interleaving non-determinism, with symbolic
execution to handle data non-determinism. Our technique iteratively and
exhaustively finds all executions of the program. It represents program
executions using partial orders and finds the next execution using an
underlying unfolding semantics. We avoid the exploration of redundant program
traces using cutoff events. We implemented our technique as an extension of
KLEE and evaluated it on a set of large multi-threaded C programs. Our
experiments found several previously undiscovered bugs and undefined behaviors
in memcached and GNU sort, showing that the new method is capable of finding
bugs in industrial-size benchmarks.Comment: Extended version of a paper presented at CAV'2
Individual variation in levels of haptoglobin-related protein in children from Gabon
Background: Haptoglobin related protein (Hpr) is a key component of trypanosome lytic factors (TLF), a subset of highdensity lipoproteins (HDL) that form the first line of human defence against African trypanosomes. Hpr, like haptoglobin (Hp) can bind to hemoglobin (Hb) and it is the Hpr-Hb complexes which bind to these parasites allowing uptake of TLF. This unique form of innate immunity is primate-specific. To date, there have been no population studies of plasma levels of Hpr, particularly in relation to hemolysis and a high prevalence of ahaptoglobinemia as found in malaria endemic areas. Methods and Principal Findings: We developed a specific enzyme-linked immunosorbent assay to measure levels of plasma Hpr in Gabonese children sampled during a period of seasonal malaria transmission when acute phase responses (APR), malaria infection and associated hemolysis were prevalent. Median Hpr concentration was 0.28 mg/ml (range 0.03-1.1). This was 5-fold higher than that found in Caucasian children (0.049 mg/ml, range 0.002-0.26) with no evidence of an APR. A general linear model was used to investigate associations between Hpr levels, host polymorphisms, parasitological factors and the acute phase proteins, Hp, C-reactive protein (CRP) and albumin. Levels of Hpr were associated with Hp genotype, decreased with age and were higher in females. Hpr concentration was strongly correlated with that of Hp, but not CRP
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