1,505 research outputs found
The Collaborative Development of New CFD Methods Adapted for Tilt Rotor Aircraft in the HiPerTilt Project
No abstract available
Immunodepletion in xenotransplantation
Xenograft transplantation is perhaps the most immunologically difficult problem in transplantation today. An overwhelming hyperacute rejection reaction (HAR) occurs within minutes of organ implantation. Preformed antibodies are thought to initiate this process. We used a pig-to-dog renal xenograft transplant model and investigated methods of decreasing the severity of hyperacute rejection. Female pigs weighing 15-20 kg were used as donors. Recipients were mongrel dogs weighing 15-25 kg. Experimental dogs were all given a number of treatments of IgG depletion using an antibody removal system (Dupont-Excorim). This machine immunoadsorbs plasma against a column containing immobilized staphylococcal protein A, which is known to bind the IgG Fc receptor. An 84% reduction in the IgG levels and a 71% reduction in IgM levels was achieved. Postoperative assessment was made of urine output, time to onset of HAR, and histopathological examination of the rejected kidneys. Although cross-matches between donor lymphocytes and recipient sera remained strongly positive in the treated dogs, there was a two- to fourfold reduction in the titers. The time to onset of HAR was prolonged in the experimental group, and the urine output was increased slightly. The histopathologic changes in the experimental group generally showed signs of HAR, but of less intensity than in the nonimmunodepleted control group. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted
The CRE-Like Element Inside the 5′-Upstream Region of the Rat Sodium/Iodide Symporter Gene Interacts with Diverse Classes of b-Zip Molecules that Regulate Transcriptional Activities through Strong Synergy with Pax-8
AbstractWe previously demonstrated that transcription of the rat sodium/iodide symporter (NIS) gene is regulated by NUE, an upstream enhancer located between nucleotides −2264 and −2495 of the 5′-flanking region. To elucidate the mechanism of TSH/cAMP-mediated regulation of NIS gene expression, we have characterized the putative cAMP response element (CRE)/activator protein (AP)-1 site (termed NUC) that is closely located between the two Pax-8 (paired box domain transcription factor-8) binding sites within NUE. In two different approaches using either gel supershift analyses or dominant-negative inhibitors of b-Zip molecules, we have shown that NUC can be recognized by several members of the AP-1 and CREB family transcription factors that modulate the transcriptional activity of NUE. Using tethered dimers of b-Zip molecules, we have also demonstrated that specific homo- or heterodimers of AP-1 can synergistically stimulate NUE activity in concert with Pax-8. To demonstrate further that NUC is a bona fide CRE, we made an artificial promoter with the five-time tandem repeat of this sequence (5xNUC). In comparison to the canonical CRE (5xCRE), 5xNUC manifested greater transcriptional activity and broader response to cAMP signaling. Hence, we postulate that the significance of this evolutionally conserved CRE-like site may lie in its broader cell type specificity
Small Intestinal Cannabinoid Receptor Changes Following a Single Colonic Insult with Oil of Mustard in Mice
Cannabinoids are known to be clinically beneficial for control of appetite disorders and nausea/vomiting, with emerging data that they can impact other GI disorders, such as inflammation. Post-inflammatory irritable bowel syndrome (PI-IBS) is a condition of perturbed intestinal function that occurs subsequent to earlier periods of intestinal inflammation. Cannabinoid 1 receptor (CB1R) and CB2R alterations in GI inflammation have been demonstrated in both animal models and clinically, but their continuing role in the post-inflammatory period has only been implicated to date. Therefore, to provide direct evidence for CBR involvement in altered GI functions in the absence of overt inflammation, we used a model of enhanced upper GI transit that persists for up to 4 weeks after a single insult by intracolonic 0.5% oil of mustard (OM) in mice. In mice administered OM, CB1R immunostaining in the myenteric plexus was reduced at day 7, when colonic inflammation is subsiding, and then increased at 28 days, compared to tissue from age-matched vehicle-treated mice. In the lamina propria CB2R immunostaining density was also increased at day 28. In mice tested 28 day after OM, either a CB1R-selective agonist, ACEA (1 and 3 mg/kg, s.c.) or a CB2R-selective agonist, JWH-133 (3 and 10 mg/kg, s.c.) reduced the enhanced small intestinal transit in a dose-related manner. Doses of ACEA and JWH-133 (1 mg/kg), alone or combined, reduced small intestinal transit of OM-treated mice to a greater extent than control mice. Thus, in this post-colonic inflammation model, both CBR subtypes are up-regulated and there is increased efficacy of both CB1R and CB2R agonists. We conclude that CBR remodeling occurs not only during GI inflammation but continues during the recovery phase. Thus, either CB1R- or CB2-selective agonists could be efficacious for modulating GI motility in individuals experiencing diarrhea-predominant PI-IBS
Liver Cirrhosis Patients Homozygous for MTHFR C677T Develop Portal Vein Thrombosis 8 Years Earlier Than Wild Type
Background and Aim Age at portal vein thrombosis (PVT) in liver cirrhosis (LC) carriers of the methylene tetrahydrofolate reductase (MTHFR) rs1801133 (C -> T667 transition) polymorphism has never been addressed; we compared age at PVT in LC patients genotyped for the MTHFR and explored the interrelated clinical and laboratory factors predicting age at PVT. Approach and Results Retrospective cross-sectional cohort study. PVT participants: MTHFR CC n = 36, MTHFR CT n = 53, MTHFR TT n = 19; age, sex, age at PVT, Child-Pugh score, rs1799963 PT polymorphisms (G -> A 20,210 transition), plasma HC and natural anticoagulants available for all participants. Age at PVT was lower in MTHFR TT than CT and CC (56 +/- 13 vs. 57 +/- 13 vs. 64 +/- 9 years, p = 0.001); median (IQR) plasma HC was higher in MTHFR TT than in the other groups [(17 (9.4, 23.3) vs 13 (8,14.7) vs 11 (8.9, 12.7) mu mol/l, p = 0.03)]. MTHFR TT, male gender and protein C predicted age at PVT (p = 0.02, p = 0.04 and p = 0.08); MTHFR TT and Child-Pugh score predicted plasma HC (p = 0.005 and p = 0.01) as well as low plasma protein C (p < 0.0001 and p = 0.0002). Plasma HC inversely related to protein C in the MTHFR TT group (p < 0.0001). Compound MTHFR TT with PT GA had lower age at PVT compared to MTHFR TT alone (49 +/- 18 vs 58 +/- 12 years). Conclusions MTHFR TT anticipates PVT associated with LC by an average of 8 years; MTHFR TT associates with severity of liver disease and to high plasma HC; the latter may contribute to the prematurity of PVT by interfering with the anticoagulant activity of protein C
Comparison of relativity theories with observer-independent scales of both velocity and length/mass
We consider the two most studied proposals of relativity theories with
observer-independent scales of both velocity and length/mass: the one discussed
by Amelino-Camelia as illustrative example for the original proposal
(gr-qc/0012051) of theories with two relativistic invariants, and an
alternative more recently proposed by Magueijo and Smolin (hep-th/0112090). We
show that these two relativistic theories are much more closely connected than
it would appear on the basis of a naive analysis of their original
formulations. In particular, in spite of adopting a rather different formal
description of the deformed boost generators, they end up assigning the same
dependence of momentum on rapidity, which can be described as the core feature
of these relativistic theories. We show that this observation can be used to
clarify the concepts of particle mass, particle velocity, and
energy-momentum-conservation rules in these theories with two relativistic
invariants.Comment: 21 pages, LaTex. v2: Andrea Procaccini (contributing some results
from hia Laurea thesis) is added to the list of authors and the paper
provides further elements of comparison between DSR1 and DSR2, including the
observation that both lead to the same formula for the dependence of momentum
on rapidit
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Correlations between FEV1 and patient-reported outcomes: A pooled analysis of 23 clinical trials in patients with chronic obstructive pulmonary disease.
BACKGROUND: In clinical trials of inhaled bronchodilators, chronic obstructive pulmonary disease (COPD) guidelines recommend that patient-reported outcomes (PROs) are assessed alongside lung function. How these endpoints are related is unclear. METHODS: Pooled longitudinal data from 23 randomised controlled COPD studies were analyzed (N = 23,213). Treatments included long-acting β2 agonists, long-acting muscarinic antagonists (LABAs or LAMAs) and the LABA/LAMA combination QVA149. Outcome measures were Transition Dyspnoea Index (TDI) and St. George's Respiratory Questionnaire (SGRQ) scores, COPD exacerbation frequency and rescue medication use. Relationships between changes in trough forced expiratory volume in one second (ΔFEV1) and outcomes following treatment were assessed using correlations of data summaries and model-based analysis: generalized linear mixed-effect regression modeling to determine if ΔFEV1 could predict patient outcomes with different treatments. RESULTS: Mean age was 64 years, 73% were male, and most had moderate (45%) or severe (52%) disease. Statistically significant correlations were observed between ΔFEV1 and each outcome measure (exacerbations Rs = 0.05; rescue medication, SGRQ, TDI, r = 0.11-0.16; all p < .001). Patients with greater improvements in trough FEV1 had on average better SGRQ and TDI scores, fewer exacerbations, and used less rescue medication. For SGRQ and TDI scores, minimal clinically important differences were observed over the range of pooled ΔFEV1 values. Model-based predictions confirmed the treatment effect was partly explained by changes in FEV1 from baseline with improvements in PROs observed across all treatments when trough FEV1 improved. Across all endpoints active treatments were better than placebo (p < .0001), and LABA/LAMA treatment resulted in numerically better treatment outcomes than either monocomponent. CONCLUSIONS: These data suggest that FEV1 improvements post-bronchodilation correlate with PRO improvements. Further improvements in patient outcomes may be expected by maximizing lung function improvements. TRIAL REGISTRATION: Registration details for the 23 randomised controlled studies used in this pooled analysis are supplied in Additional File 4
Local Optical Spectroscopy in Quantum Confined Systems: A Theoretical Description
A theoretical description of local absorption is proposed in order to
investigate spectral variations on a length scale comparable with the extension
of the relevant quantum states. A general formulation is derived within the
density-matrix formalism including Coulomb correlation, and applied to the
prototypical case of coupled quantum wires. The results show that excitonic
effects may have a crucial impact on the local absorption with implications for
the spatial resolution and the interpretation of near-field optical spectra.Comment: To appear in Phys. Rev. Lett. - 11 pages, 3 PostScript figures (1
figure in colors) embedded. Uses RevTex, and psfig style
Supernova Simulations and Strategies For the Dark Energy Survey
We present an analysis of supernova light curves simulated for the upcoming
Dark Energy Survey (DES) supernova search. The simulations employ a code suite
that generates and fits realistic light curves in order to obtain distance
modulus/redshift pairs that are passed to a cosmology fitter. We investigated
several different survey strategies including field selection, supernova
selection biases, and photometric redshift measurements. Using the results of
this study, we chose a 30 square degree search area in the griz filter set. We
forecast 1) that this survey will provide a homogeneous sample of up to 4000
Type Ia supernovae in the redshift range 0.05<z<1.2, and 2) that the increased
red efficiency of the DES camera will significantly improve high-redshift color
measurements. The redshift of each supernova with an identified host galaxy
will be obtained from spectroscopic observations of the host. A supernova
spectrum will be obtained for a subset of the sample, which will be utilized
for control studies. In addition, we have investigated the use of combined
photometric redshifts taking into account data from both the host and
supernova. We have investigated and estimated the likely contamination from
core-collapse supernovae based on photometric identification, and have found
that a Type Ia supernova sample purity of up to 98% is obtainable given
specific assumptions. Furthermore, we present systematic uncertainties due to
sample purity, photometric calibration, dust extinction priors, filter-centroid
shifts, and inter-calibration. We conclude by estimating the uncertainty on the
cosmological parameters that will be measured from the DES supernova data.Comment: 46 pages, 30 figures, resubmitted to ApJ as Revision 2 (final author
revision), which has subtle editorial differences compared to the published
paper (ApJ, 753, 152). Note that this posting includes PDF only due to a bug
in either the latex macros or the arXiv submission system. The source files
are available in the DES document database:
http://des-docdb.fnal.gov/cgi-bin/ShowDocument?docid=624
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