167 research outputs found
Study of hadron interactions in a lead-emulsion target
Topological and kinematical characteristics of hadron interactions have been
studied using a lead-emulsion target exposed to 2, 4 and 10 GeV/c hadron beams.
A total length of 60 m tracks was followed using a high speed automated
emulsion scanning system. A total of 318 hadron interaction vertices and their
secondary charged particle tracks were reconstructed. Measurement results of
interaction lengths, charged particle multiplicity, emission angles and momenta
of secondary charged particles are compared with a Monte Carlo simulation and
appear to be consistent. Nuclear fragments emitted from interaction vertices
were also detected by a newly developed emulsion scanning system with
wide-angle acceptance. Their emission angle distributions are in good agreement
with the simulated distributions. Probabilities of an event being associated
with at least one fragment track are found to be greater than 50% for beam
momentum GeV/c and are well reproduced by the simulation. These
experimental results validate estimation of the background due to hadron
interactions in the sample of decay candidates in the OPERA oscillation experiment.Comment: 14 pages, 11 figure
Relationship between chronotropic incompetence and β-blockers based on changes in chronotropic response during cardiopulmonary exercise testing
AbstractBackgroundChronotropic incompetence (CI), an attenuated heart rate (HR) response to exercise, is common in patients with cardiovascular disease. The aim of this study was to assess changes in the chronotropic response (CR) during cardiopulmonary exercise testing (CPET) in patients undergoing cardiac rehabilitation and investigate the effects of β-blockers.MethodsPatients undergoing cardiac rehabilitation performed CPET. Failure to achieve 80% of the age-predicted maximal HR (APMHR) defined CI. Values of the metabolic chronotropic relationship (MCR) were calculated from the ratio of the HR reserve to metabolic reserve at 4 stages, warm-up (MCR-Wu), anaerobic threshold (MCR-AT), respiratory compensation (MCR-Rc), and peak point (MCR-Pk), using the Wilkoff model. In patients who showed an increase in MCR at âĽ3 of the 4 exercise stages, CR was considered to have improved.ResultsPatients with high BNP levels (âĽ80pg/ml) had a lower MCR at all stages compared with those with low BNP levels (<80pg/ml). Of the 80 patients, 47 showed an increase in both peak VO2 and AT, and of these 31 (66.0%) were taking β-blockers. Improvement in CR was observed in 30 of 47 patients with CI, and 70% of these were taking β-blockers. In patients not taking β-blockers, MCR-AT was lower than MCR-Rc, whereas in those taking β-blockers MCR-AT was higher than MCR-Rc.ConclusionsAn attenuated HR response may occur during the early stages of exercise. The HR response according to the presence or absence of β-blockers is clearly identifiable by comparing MCR-AT and MCR-Rc using the Wilkoff model
Myosin motor Myo1c and its receptor NEMO/IKK-Îł promote TNF-Îąâinduced serine307 phosphorylation of IRS-1
Tumor necrosis factor-Îą (TNF-Îą) signaling through the IÎşB kinase (IKK) complex attenuates insulin action via the phosphorylation of insulin receptor substrate 1 (IRS-1) at Ser307. However, the precise molecular mechanism by which the IKK complex phosphorylates IRS-1 is unknown. In this study, we report nuclear factor ÎşB essential modulator (NEMO)/IKK-Îł subunit accumulation in membrane ruffles followed by an interaction with IRS-1. This intracellular trafficking of NEMO requires insulin, an intact actin cytoskeletal network, and the motor protein Myo1c. Increased Myo1c expression enhanced the NEMOâIRS-1 interaction, which is essential for TNF-Îąâ induced phosphorylation of Ser307âIRS-1. In contrast, dominant inhibitory Myo1c cargo domain expression diminished this interaction and inhibited IRS-1 phosphorylation. NEMO expression also enhanced TNF-Îąâinduced Ser307âIRS-1 phosphorylation and inhibited glucose uptake. In contrast, a deletion mutant of NEMO lacking the IKK-βâbinding domain or silencing NEMO blocked the TNF-Îą signal. Thus, motor protein Myo1c and its receptor protein NEMO act cooperatively to form the IKKâIRS-1 complex and function in TNF-Îąâinduced insulin resistance
High-precision mapping of proteinâprotein interfaces: an integrated genetic strategy combining en masse mutagenesis and DNA-level parallel analysis on a yeast two-hybrid platform
Understanding networks of proteinâprotein interactions constitutes an essential component on a path towards comprehensive description of cell function. Whereas efficient techniques are readily available for the initial identification of interacting protein partners, practical strategies are lacking for the subsequent high-resolution mapping of regions involved in proteinâprotein interfaces. We present here a genetic strategy to accurately map interacting protein regions at amino acid precision. The system is based on parallel construction, sampling and analysis of a comprehensive insertion mutant library. The methodology integrates Mu in vitro transposition-based random pentapeptide mutagenesis of proteins, yeast two-hybrid screening and high-resolution genetic footprinting. The strategy is general and applicable to any interacting protein pair. We demonstrate the feasibility of the methodology by mapping the region in human JFC1 that interacts with Rab8A, and we show that the association is mediated by the Slp homology domain 1
Ectopic fat deposition and global cardiometabolic risk : New paradigm in cardiovascular medicine
The obesity epidemic is a global public health concern that increases the likelihood of morbidity and mortality of metabolic and cardiovascular disease (CVD) and threatens to reduce life expectancy around the world. The concept of the metabolic syndrome (MetS) takes into account that visceral fat plays an essential role in the development of metabolic and cardiovascular diseases. However, MetS cannot be used to assess global CVD risk but is at best one more modifiable CVD risk factor. Thus, global cardiometabolic risk (the global risk of cardiovascular disease resulting from traditional risk factors combined with the additional contribution of the metabolic syndrome and/or insulin resistance) should be considered individually. There is solid evidence supporting the notion that excess abdominal fat is predictive of insulin resistance and the presence of related metabolic abnormalities currently referred to as MetS. Despite the fact that abdominal obesity is a highly prevalent feature of MetS, the mechanisms by which abdominal obesity is causally related to MetS are not fully elucidated. Besides visceral fat accumulation, ectopic lipid deposition, especially in liver and skeletal muscle, has been implicated in the pathophysiology of diabetes, insulin resistance and obesity-related disorders. Also, ectopic fat deposition could be deteriorated in the heart components such as (1) circulatory and locally recruited fat, (2) intra- and extra-myocellular fat, (3) perivascular fat, and (4) pericardial fat. In this review, the contribution of ectopic lipid deposition to global cardiometabolic risk is reviewed and also discussed are potential underlying mechanisms including adipocytokine, insulin resistance and lipotoxicity
ă¤ăˇă§ăťă¤ ăˇă㌠ă 2ăŹăż ăăŚăă§ăŚăă§ăŚ ăˇăłăžăŚ ăąăăŤăłăă§ăŚ
There is evidence supporting the notion that excess abdominal fat is predictive of insulin resistance and the presence of related metabolic abnormalities currently referred to as the metabolic syndrome (MetS). Despite the fact that abdominal obesity is a highly prevalent feature of MetS, the mechanisms by which abdominal obesity is causally related to MetS are not fully elucidated. Besides visceral fat accumulation, ectopic lipid deposition, especially in the liver and skeletal muscle, has been implicated in the pathophysiology of diabetes, insulin resistance and obesity-related disorders. In addition, ectopic fat deposition play a critical role in the heart components such as (1) circulatory and locally recruited fat, (2) intra-and extra-myocellular fat, (3) perivascular fat, and (4) pericardial fat. In this review, the contribution of ectopic lipid deposition to global cardiometabolic risk is discussed via possible mechanisms including adipocytokine, insulin resistance and lipotoxicity
Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release
Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed
Emulsion sheet doublets as interface trackers for the OPERA experiment
New methods for efficient and unambiguous interconnection between electronic
counters and target units based on nuclear photographic emulsion films have
been developed. The application to the OPERA experiment, that aims at detecting
oscillations between mu neutrino and tau neutrino in the CNGS neutrino beam, is
reported in this paper. In order to reduce background due to latent tracks
collected before installation in the detector, on-site large-scale treatments
of the emulsions ("refreshing") have been applied. Changeable Sheet (CSd)
packages, each made of a doublet of emulsion films, have been designed,
assembled and coupled to the OPERA target units ("ECC bricks"). A device has
been built to print X-ray spots for accurate interconnection both within the
CSd and between the CSd and the related ECC brick. Sample emulsion films have
been extensively scanned with state-of-the-art automated optical microscopes.
Efficient track-matching and powerful background rejection have been achieved
in tests with electronically tagged penetrating muons. Further improvement of
in-doublet film alignment was obtained by matching the pattern of low-energy
electron tracks. The commissioning of the overall OPERA alignment procedure is
in progress.Comment: 19 pages, 19 figure
- âŚ