289 research outputs found
Electrophysiological features of atrial flutter in cardiac sarcoidosis: a report of two cases
We report two cases of systemic sarcoidosis with atrial flutter as the clinical manifestation. In one patient, who had symptoms of shorter duration, the arrhythmia was no longer inducible after a course of glucocorticoid therapy. Electroanatomical mapping in the other case revealed patchy fibrosis of the left atrial myocardium and multiple macro-reentrant circuits. Sinus rhythm could be restored with ablation of these reentrant circuits. To our knowledge, this is the first report on the demonstration of atrial scarring in a patient with sarcoidosis using 3-D electroanatomical mapping. These two cases illustrate that the inflammation of atrial myocardium is the primary mechanism of atrial arrhythmias in patients with cardiac sarcoidosis.Narayanan Namboodiri, Martin K Stiles, Glenn D Young, Prashanthan Sander
The Multifragmentation Freeze--Out Volume in Heavy Ion Collisions
The reduced velocity correlation function for fragments from the reaction Fe
+ Au at 100 A~MeV bombarding energy is investigated using the
dynamical--statistical approach QMD+SMM and compared to experimental data to
extract the Freeze--Out volume assuming simultaneous multifragmentation.Comment: 8 pages; 3 uuencoded figures available with figures command, LateX,
UCRL-J-1157
Antiproton Production in Collisions at AGS Energies
Inclusive and semi-inclusive measurements are presented for antiproton
() production in proton-nucleus collisions at the AGS. The inclusive
yields per event increase strongly with increasing beam energy and decrease
slightly with increasing target mass. The yield in 17.5 GeV/c p+Au
collisions decreases with grey track multiplicity, , for ,
consistent with annihilation within the target nucleus. The relationship
between and the number of scatterings of the proton in the nucleus is
used to estimate the annihilation cross section in the nuclear
medium. The resulting cross section is at least a factor of five smaller than
the free annihilation cross section when assuming a small or
negligible formation time. Only with a long formation time can the data be
described with the free annihilation cross section.Comment: 8 pages, 6 figure
Semi-Inclusive Lambda and Kshort Production in p-Au Collisions at 17.5 GeV/c
The first detailed measurements of the centrality dependence of strangeness
production in p-A collisions are presented. Lambda and Kshort dn/dy
distributions from 17.5 GeV/c p-Au collisions are shown as a function of "grey"
track multiplicity and the estimated number of collisions, nu, made by the
proton. The nu dependence of the Lambda yield deviates from a scaling of p-p
data by the number of participants, increasing faster than this scaling for
nu<=5 and saturating for larger nu. A slower growth in Kshort multiplicity with
nu is observed, consistent with a weaker nu dependence of K-Kbar production
than Y-K production.Comment: 5 pages, 3 figures, formatted with RevTex, current version has
enlarged figure catpion
Strangeness Enhancement in and Interactions at SPS Energies
The systematics of strangeness enhancement is calculated using the HIJING and
VENUS models and compared to recent data on , and
collisions at CERN/SPS energies (). The HIJING model is used to
perform a {\em linear} extrapolation from to . VENUS is used to
estimate the effects of final state cascading and possible non-conventional
production mechanisms. This comparison shows that the large enhancement of
strangeness observed in collisions, interpreted previously as possible
evidence for quark-gluon plasma formation, has its origins in non-equilibrium
dynamics of few nucleon systems. % Strangeness enhancement %is therefore traced
back to the change in the production dynamics %from to minimum bias
and central collisions. A factor of two enhancement of at
mid-rapidity is indicated by recent data, where on the average {\em one}
projectile nucleon interacts with only {\em two} target nucleons. There appears
to be another factor of two enhancement in the light ion reaction relative
to , when on the average only two projectile nucleons interact with two
target ones.Comment: 29 pages, 8 figures in uuencoded postscript fil
A Computational Approach to Finding Novel Targets for Existing Drugs
Repositioning existing drugs for new therapeutic uses is an efficient approach to drug discovery. We have developed a computational drug repositioning pipeline to perform large-scale molecular docking of small molecule drugs against protein drug targets, in order to map the drug-target interaction space and find novel interactions. Our method emphasizes removing false positive interaction predictions using criteria from known interaction docking, consensus scoring, and specificity. In all, our database contains 252 human protein drug targets that we classify as reliable-for-docking as well as 4621 approved and experimental small molecule drugs from DrugBank. These were cross-docked, then filtered through stringent scoring criteria to select top drug-target interactions. In particular, we used MAPK14 and the kinase inhibitor BIM-8 as examples where our stringent thresholds enriched the predicted drug-target interactions with known interactions up to 20 times compared to standard score thresholds. We validated nilotinib as a potent MAPK14 inhibitor in vitro (IC50 40 nM), suggesting a potential use for this drug in treating inflammatory diseases. The published literature indicated experimental evidence for 31 of the top predicted interactions, highlighting the promising nature of our approach. Novel interactions discovered may lead to the drug being repositioned as a therapeutic treatment for its off-target's associated disease, added insight into the drug's mechanism of action, and added insight into the drug's side effects
Metabolic acetate therapy improves phenotype in the tremor rat model of Canavan disease
Genetic mutations that severely diminish the activity of aspartoacylase (ASPA) result in the fatal brain dysmyelinating disorder, Canavan disease. There is no effective treatment. ASPA produces free acetate from the concentrated brain metabolite, N-acetylaspartate (NAA). Because acetyl coenzyme A is a key building block for lipid synthesis, we postulated that the inability to catabolize NAA leads to a brain acetate deficiency during a critical period of CNS development, impairing myelination and possibly other aspects of brain development. We tested the hypothesis that acetate supplementation during postnatal myelination would ameliorate the severe phenotype associated with ASPA deficiency using the tremor rat model of Canavan disease. Glyceryltriacetate (GTA) was administered orally to tremor rats starting 7Â days after birth, and was continued in food and water after weaning. Motor function, myelin lipids, and brain vacuolation were analyzed in GTA-treated and untreated tremor rats. Significant improvements were observed in motor performance and myelin galactocerebroside content in tremor rats treated with GTA. Further, brain vacuolation was modestly reduced, and these reductions were positively correlated with improved motor performance. We also examined the expression of the acetyl coenzyme A synthesizing enzyme acetyl coenzyme A synthase 1 and found upregulation of expression in tremor rats, with a return to near normal expression levels in GTA-treated tremor rats. These results confirm the critical role played by NAA-derived acetate in brain myelination and development, and demonstrate the potential usefulness of acetate therapy for the treatment of Canavan disease
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