Hypertension and albuminuria in chronic kidney disease mapped to a mouse chromosome 11 locus

Chronic kidney disease (CKD) is a key cause of hypertension and a potent independent risk for cardiovascular disease. Epidemiological studies suggest a strong genetic component determining susceptibility for renal disease and, by inference, the associated cardiovascular risk. With a subtotal nephrectomy model of kidney disease, we found the 129S6 mouse strain to be very susceptible to the development of hypertension, albuminuria, and kidney injury, whereas the C57BL/6 strain is relatively resistant. Accordingly, we set out to map quantitative trait loci conferring susceptibility to hypertension and albuminuria using this model with F2 mice. We found significant linkage of the blood pressure trait to two loci. At D11Mit143, mice homozygous for the 129S6 allele had significantly higher systolic blood pressure than mice heterozygous or homozygous for the C57BL/6 allele. Similarly, at D1Mit308, there was an excellent correlation between genotype and the blood pressure phenotype. The effect of the chromosome 11 locus was verified with a separate cohort of F2 mice. For the albuminuria trait, a significant locus was found at D11Mit143, which overlaps the blood pressure trait locus. Our studies have identified a region spanning ∼8 cM on mouse chromosome 11 that is associated with susceptibility to hypertension and albuminuria in CKD

Bethe-Salpeter Approach for the P33P_{33} Elastic Pion-Nucleon Scattering in Heavy Baryon Chiral Perturbation Theory

Heavy Baryon Chiral Perturbation Theory (HBChPT) to leading order provides a kernel to solve the Bethe-Salpeter equation for the $P_{33}$ ($\Delta(1232)$-channel) $\pi-N$ system, in the infinite nucleon mass limit. Crossed Born terms include, when iterated within the Bethe-Salpeter equation, both {\it all} one- and {\it some} two-pion intermediate states, hence preserving elastic unitarity below the two-pion production threshold. This suggests searching for a solution with the help of dispersion relations and suitable subtraction constants, when all in-elasticities are explicitly neglected. The solution allows for a successful description of the experimental phase shift from threshold up to $\sqrt{s}=1500$ MeV in terms of four subtraction constants. Next-to-leading order HBChPT calculations are also used to estimate the unknown subtraction constants which appear in the solution. Large discrepancies are encountered which can be traced to the slow convergence rate of HBChPT.Comment: 11 pages, 3 figure

Influence of Growth Method on K3Sb Photocathode Structure and Performance

Future high brightness photoelectron sources delivering gt;100 mA average current call for a new generation of photocathodes. Materials which qualify for this purpose should exhibit low intrinsic emittance, long lifetime and high quantum efficiency at photon energies in the visible range of the spectrum to relax drive laser requirements. A combination of material science techniques are used to determine the influence of the growth parameters on structure and performance of photocathode materials . In situ XRR, XRD and GiSAXS measurements were performed at the synchrotron radiation sources, NSLS and CHESS. The growth of K3Sb, a precursor material of one of the prime candidates CsK2Sb, was studied intensively to optimize this intermediate growth step in terms of quantum efficiency and roughness. Three methods, a layer by layer type and a super lattice type were examined. K3Sb exists in two crystallographic phases, namely cubic and hexagonal. The cubic phase exhibits a higher quantum efficiency at 532 nm than the hexagonal phase and transforms more easily into CsK2Sb, tuning this phase is believed to be one of the key parameters in the CsK2Sb growt

T-Wave Morphology Changes as Surrogate for Blood Potassium Concentration in Hemodialysis Patients

End-stage renal disease (ESRD) patients undergoing hemodialysis (HD) are at high risk of arrhythmias and sudden cardiac death as a result of blood potassium concentration ([K+ ]) changes. The aim of this study is to investigate if dw, a time-warping-based electrocardiogram (ECG) biomarker of T-wave morphology changes, reflects [K+] evolution in HD patients, facilitating noninvasive [K+] monitoring and avoiding in-hospital blood tests analysis. 48-hour ECGs and a set of hourly-collected blood samples from 12 ESRD patients were acquired and analyzed. dw was calculated between a reference T-wave, measured at the end of the HD session, and the T-waves corresponding to each hour along the whole HD session, when [K+] was measured from blood samples. The values of dw correlated with the relative variations in [K+] with respect to the reference value (end of HD, ¿[K+ ]), with a median (interquartile) correlation coefficient of 0.90 (0.30), evidencing a strong relation between them. Our findings support the use of dw as a surrogate of ¿[K+], suggesting a potential use of dw for non-invasive hyperkalemia monitoring both in hospital and ambulatory settings

Configuration Complexities of Hydrogenic Atoms

The Fisher-Shannon and Cramer-Rao information measures, and the LMC-like or shape complexity (i.e., the disequilibrium times the Shannon entropic power) of hydrogenic stationary states are investigated in both position and momentum spaces. First, it is shown that not only the Fisher information and the variance (then, the Cramer-Rao measure) but also the disequilibrium associated to the quantum-mechanical probability density can be explicitly expressed in terms of the three quantum numbers (n, l, m) of the corresponding state. Second, the three composite measures mentioned above are analytically, numerically and physically discussed for both ground and excited states. It is observed, in particular, that these configuration complexities do not depend on the nuclear charge Z. Moreover, the Fisher-Shannon measure is shown to quadratically depend on the principal quantum number n. Finally, sharp upper bounds to the Fisher-Shannon measure and the shape complexity of a general hydrogenic orbital are given in terms of the quantum numbers.Comment: 22 pages, 7 figures, accepted i

Films of Mn12-acetate deposited by low-energy laser ablation

Thin films of the molecular magnet Mn12-acetate, [Mn12 O12(CH3COO)16 (H2O)4] 2CH3COOH 4H2O, have been prepared using a laser ablation technique with a nitrogen laser at low laser energies of 0.8 and 2 mJ. Chemical and magnetic characterizations show that the Mn12-acetate cores remain intact and the films show similar magnetic properties to those of the parent molecular starting material. In addition, the magnetic data exhibit a peak in the magnetization at 27 K indicating the creation of an additional magnetic phase not noted in previous studies of crystalline phases.Comment: 8 pages, 5 figures, In Press - J. Mag. Mag. Ma

General structure of the photon self-energy in non-commutative QED

We study the behavior of the photon two point function, in non-commutative QED, in a general covariant gauge and in arbitrary space-time dimensions. We show, to all orders, that the photon self-energy is transverse. Using an appropriate extension of the dimensional regularization method, we evaluate the one-loop corrections, which show that the theory is renormalizable. We also prove, to all orders, that the poles of the photon propagator are gauge independent and briefly discuss some other related aspects.Comment: 16 pages, revtex4. This is the final version to be published in Phys. Rev.

The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation

VCP/p97 regulates numerous cellular functions by mediating protein degradation through its segregase activity. Its key role in governing protein homoeostasis has made VCP/p97 an appealing anticancer drug target. Here, we provide evidence that VCP/p97 acts as a regulator of cellular metabolism. We found that VCP/p97 was tied to multiple metabolic processes on the gene expression level in a diverse range of cancer cell lines and in patient-derived multiple myeloma cells. Cellular VCP/p97 dependency to maintain proteostasis was increased under conditions of glucose and glutamine limitation in a range of cancer cell lines from different tissues. Moreover, glutamine depletion led to increased VCP/p97 expression, whereas VCP/p97 inhibition perturbed metabolic processes and intracellular amino acid turnover. GCN2, an amino acid-sensing kinase, attenuated stress signalling and cell death triggered by VCP/p97 inhibition and nutrient shortages and modulated ERK activation, autophagy, and glycolytic metabolite turnover. Together, our data point to an interconnected role of VCP/p97 and GCN2 in maintaining cancer cell metabolic and protein homoeostasis

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe