Cardiac and arterial interactions in end-stage renal disease

Cardiac and arterial interactions in end-stage renal disease. Although cardiac hypertrophy is a frequent complication of end-stage renal disease (ESRD), relatively little is known about large arterial geometry and function in vivo in these patients, and the relationship between arterial changes and cardiac hypertrophy is unknown. Common carotid artery (CCA) intima-media thickness and internal diameter and left ventricular geometry and function were determined by ultrasound imaging in 70 uncomplicated ESRD patients and in 50 age-, sex-, and blood pressure-matched controls. Arterial distensibility and compliance were determined from simultaneously recorded CCA diameter and stroke changes in diameter and CCA pressure waveforms, obtained by applanation tonometry, and also by the measurement of carotid-femoral pulse wave velocity. Compared with control subjects, ESRD patients had greater left ventricular diameter (P < 0.01), wall thicknesses and mass (P < 0.001), increased CCA diameter (6.25 ± 0.87 vs. 5.55 ± 0.65 mm; P < 0.001), larger CCA intima-media thickness (777 ± 115 vs. 678 ± 105 µ m; P < 0.001) and intima-media cross-sectional area (17.5 ± 4.5 vs. 13.4 ± 3.3mm2; P < 0.001). In uremic patients, arterial hypertrophy was associated with decreased CCA distensibility (17.8 ± 8.8 vs. 24.0 ± 12.7kPa−1 · 10−3; P < 0.001) and compliance (5.15 ± 2 vs. 6.0 ± 2.5m2 · kPa−1 · 10−7; P < 0.05), accelerated carotid-femoral pulse wave velocity (1055 ± 290 vs. 957 ± 180 cm/seconds; P < 0.001), early return and increased effect of arterial wave reflections (20.5 ± 15.4 vs. 9.2 ± 18.4%; P < 0.001). The latter phenomenons were responsible for increased pulsatile pressure load in CCA (58.3 ± 21 vs. 48 ± 17mm Hg; P < 0.01) and were associated with a decreased subendocardial viability index (157 ± 31 vs. 173 ± 30%; P < 0.001). The CCA diameter was correlated with the left ventricular diameter (P < 0.01), and a significant correlations existed between CCA wall thickness or CCA intima-media cross-sectional area and left ventricular wall thicknesses and/or left ventricular mass (P < 0.01). In multivariate analysis, these relationships were independent regarding age, sex, blood pressure and body surface area. The present study documents parallel cardiac and vascular adaptation in ESRD, and demonstrates the potential contribution of structural and functional large artery alterations to the pathogenesis of left ventricular hypertrophy and functional alterations

Multiscale Theory of Finite Size Bose Systems: Implications for Collective and Single-Particle Excitations

Boson droplets (i.e., dense assemblies of bosons at low temperature) are shown to mask a significant amount of single-particle behavior and to manifest collective, droplet-wide excitations. To investigate the balance between single-particle and collective behavior, solutions to the wave equation for a finite size Bose system are constructed in the limit where the ratio \varepsilon of the average nearest-neighbor boson distance to the size of the droplet or the wavelength of density disturbances is small. In this limit, the lowest order wave function varies smoothly across the system, i.e., is devoid of structure on the scale of the average nearest-neighbor distance. The amplitude of short range structure in the wave function is shown to vanish as a power of \varepsilon when the interatomic forces are relatively weak. However, there is residual short range structure that increases with the strength of interatomic forces. While the multiscale approach is applied to boson droplets, the methodology is applicable to any finite size bose system and is shown to be more direct than field theoretic methods. Conclusions for Helium-4 nanodroplets are drawn.Comment: 28 pages, 5 figure

Diverse roles of androgen receptor (AR) domains in AR-mediated signaling

Androgens control male sexual development and maintenance of the adult male phenotype. They have very divergent effects on their target organs like the reproductive organs, muscle, bone, brain and skin. This is explained in part by the fact that different cell types respond differently to androgen stimulus, even when all these responses are mediated by the same intracellular androgen receptor. To understand these tissue- and cell-specific readouts of androgens, we have to learn the many different steps in the transcription activation mechanisms of the androgen receptor (NR3C4). Like all nuclear receptors, the steroid receptors have a central DNA-binding domain connected to a ligand-binding domain by a hinge region. In addition, all steroid receptors have a relatively large amino-terminal domain. Despite the overall structural homology with other nuclear receptors, the androgen receptor has several specific characteristics which will be discussed here. This receptor can bind two types of androgen response elements (AREs): one type being similar to the classical GRE/PRE-type elements, the other type being the more divergent and more selective AREs. The hormone-binding domain has low intrinsic transactivation properties, a feature that correlates with the low affinity of this domain for the canonical LxxLL-bearing coactivators. For the androgen receptor, transcriptional activation involves the alternative recruitment of coactivators to different regions in the amino-terminal domain, as well as the hinge region. Finally, a very strong ligand-induced interaction between the amino-terminal domain and the ligand-binding domain of the androgen receptor seems to be involved in many aspects of its function as a transcription factor. This review describes the current knowledge on the structure-function relationships within the domains of the androgen receptor and tries to integrate the involvement of different domains, subdomains and motifs in the functioning of this receptor as a transcription factor with tissue- and cell-specific readouts

Multifragment production in Au+Au at 35 MeV/u

Multifragment disintegration has been measured with a high efficiency detection system for the reaction $Au + Au$ at $E/A = 35\ MeV$. From the event shape analysis and the comparison with the predictions of a many-body trajectories calculation the data, for central collisions, are compatible with a fast emission from a unique fragment source.Comment: 9 pages, LaTex file, 4 postscript figures available upon request from [email protected]. - to appear in Phys. Lett.

Stochastic Reaction-diffusion Equations Driven by Jump Processes

We establish the existence of weak martingale solutions to a class of second order parabolic stochastic partial differential equations. The equations are driven by multiplicative jump type noise, with a non-Lipschitz multiplicative functional. The drift in the equations contains a dissipative nonlinearity of polynomial growth.Comment: See journal reference for teh final published versio

Hydrological Behaviour of Tritium on the Former Semipalatinsk Nuclear Test Site (Kazakhstan) Determined using Stable Isotope Measurements

Tritium and stable isotope (deuterium 2H and 18O) concentrations have been determined in natural waters collected from shallow lakes, wells, streams and rivers inside and in the vicinity of the former Semipalatinsk Nuclear Test Site (NE Kazakhstan). The Semipalatinsk Test Site (STS) was one of the main proving grounds for the testing of nuclear weapons by the former Soviet Union. Tritium activity concentrations have been determined by liquid scintillation counting, while hydrogen isotopic composition have been determined using a GV-Isoprime mass spectrometer coupled to an elemental analyzer. Tritium activity concentrations recorded in lake waters (in most cases >10 Bq L-1) were significantly higher than those in well, stream and the Irtysh River waters. In lake waters, enrichments in deuterium and 18O (δD and δ18O varying between –5 and –64 ‰ V-SMOW and –8.4 and +5.5 ‰ V-SMOW, respectively), and high salt concentrations, strongly suggest that significant evaporation has occurred. In contrast, deuterium and tritium signatures of ‘common’ surface and underground waters at the STS were mostly typical of present-day isotope backgrounds of natural waters in NE Kazakhstan. In STS, come salt lakes like Bajansor and Tumatsor with elevated tritium activity from 12 to 15 Bq L-1 lie close to the Global Meteoric Water Line. The potential tritium source for these lakes is residual concentration of tritium after former nuclear test in STS. The study provides evidence to show that export of tritium from underground nuclear test areas and tritium enrichment produced by evaporation are both important determinants of tritium concentrations in standing waters on the Semipalatinsk test site

Dynamics of nuclear receptor target gene regulation

Ligand-regulated nuclear receptors, such as estrogen receptors, glucocorticoid receptor, vitamin D receptor, and peroxisome proliferator-activated receptors, belong to the most widely studied and best understood transcription factors. Therefore, the dynamic nature of transcriptional regulation was observed first with different members of the nuclear receptor superfamily, but is now also extended to other transcription factors, such as nuclear factor κB. Dynamic and in part cyclical processes were observed on the level of translocation into the nucleus, association with genomic binding sites, exchange of co-regulators and chromatin modifiers, occurrence of chromatin marks, and activities of RNA polymerase II resulting in mRNA synthesis. In this review, we summarize recent findings on the dynamic regulation of nuclear receptor target genes in the chromatin context

Retinoic Acid Mediates Long-Paced Oscillations in Retinoid Receptor Activity: Evidence for a Potential Role for RIP140

Mechanisms that underlie oscillatory transcriptional activity of nuclear receptors (NRs) are incompletely understood. Evidence exists for rapid, cyclic recruitment of coregulatory complexes upon activation of nuclear receptors. RIP140 is a NR coregulator that represses the transactivation of agonist-bound nuclear receptors. Previously, we showed that RIP140 is inducible by all-trans retinoic acid (RA) and mediates limiting, negative-feedback regulation of retinoid signaling.Here we report that in the continued presence of RA, long-paced oscillations of retinoic acid receptor (RAR) activity occur with a period ranging from 24 to 35 hours. Endogenous expression of RIP140 and other RA-target genes also oscillate in the presence of RA. Cyclic retinoid receptor transactivation is ablated by constitutive overexpression of RIP140. Further, depletion of RIP140 disrupts cyclic expression of the RA target gene HOXA5. Evidence is provided that RIP140 may limit RAR signaling in a selective, non-redundant manner in contrast to the classic NR coregulators NCoR1 and SRC1 that are not RA-inducible, do not cycle, and may be partially redundant in limiting RAR activity. Finally, evidence is provided that RIP140 can repress and be induced by other nuclear receptors in a manner that suggests potential participation in other NR oscillations.We provide evidence for novel, long-paced oscillatory retinoid receptor activity and hypothesize that this may be paced in part, by RIP140. Oscillatory NR activity may be involved in mediating hormone actions of physiological and pathological importance

Large Deviations for the Stochastic Shell Model of Turbulence

In this work we first prove the existence and uniqueness of a strong solution to stochastic GOY model of turbulence with a small multiplicative noise. Then using the weak convergence approach, Laplace principle for so- lutions of the stochastic GOY model is established in certain Polish space. Thus a Wentzell-Freidlin type large deviation principle is established utilizing certain results by Varadhan and Bryc.Comment: 21 pages, submitted for publicatio