Targeting the vasopressin type-2 receptor for renal cell carcinoma therapy.

Arginine vasopressin (AVP) and its type-2 receptor (V2R) play an essential role in the regulation of salt and water homeostasis by the kidneys. V2R activation also stimulates proliferation of renal cell carcinoma (RCC) cell lines in vitro. The current studies investigated V2R expression and activity in human RCC tumors, and its role in RCC tumor growth. Examination of the cancer genome atlas (TCGA) database, and analysis of human RCC tumor tissue microarrays, cDNA arrays and tumor biopsy samples demonstrated V2R expression and activity in clear cell RCC (ccRCC). In vitro, V2R antagonists OPC31260 and Tolvaptan, or V2R gene silencing reduced wound closure and cell viability of 786-O and Caki-1 human ccRCC cell lines. Similarly in mouse xenograft models, Tolvaptan and OPC31260 decreased RCC tumor growth by reducing cell proliferation and angiogenesis, while increasing apoptosis. In contrast, the V2R agonist dDAVP significantly increased tumor growth. High intracellular cAMP levels and ERK1/2 activation were observed in human ccRCC tumors. In mouse tumors and Caki-1 cells, V2R agonists reduced cAMP and ERK1/2 activation, while dDAVP treatment had the reverse effect. V2R gene silencing in Caki-1 cells also reduced cAMP and ERK1/2 activation. These results provide novel evidence for a pathogenic role of V2R signaling in ccRCC, and suggest that inhibitors of the AVP-V2R pathway, including the FDA-approved drug Tolvaptan, could be utilized as novel ccRCC therapeutics

Negative time delay for wave reflection from a one-dimensional semi-harmonic well

It is reported that the phase time of particles which are reflected by a one-dimensional semi-harmonic well includes a time delay term which is negative for definite intervals of the incoming energy. In this interval, the absolute value of the negative time delay becomes larger as the incident energy becomes smaller. The model is a rectangular well with zero potential energy at its right and a harmonic-like interaction at its left.Comment: 6 pages, 5 eps figures. Talk presented at the XXX Workshop on Geometric Methods in Physics, Bialowieza, Poland, 201

Managing BRCA Mutation Carriers in China: Reply

published_or_final_versionSpringer Open Choice, 31 May 201

Two-phonon 1- state in 112Sn observed in resonant photon scattering

Results of a photon scattering experiment on 112Sn using bremsstrahlung with an endpoint energy of E_0 = 3.8 MeV are reported. A J = 1 state at E_x = 3434(1) keV has been excited. Its decay width into the ground state amounts to Gamma_0 = 151(17) meV, making it a candidate for a [2+ x 3-]1- two-phonon state. The results for 112Sn are compared with quasiparticle-phonon model calculations as well as the systematics of the lowest-lying 1- states established in other even-mass tin isotopes. Contrary to findings in the heavier stable even-mass Sn isotopes, no 2+ states between 2 and 3.5 MeV excitation energy have been detected in the present experiment.Comment: 10 pages, including 2 figures, Phys. Rev. C, in pres

Effect of non-abrupt doping and interfacial profiles on the carrier sheet density in one-side modulation-doped GaN/AlGaN quantum wells

The results of an accurate theoretical study on the effects of non-abrupt doping and interfacial profiles on the electron sheet density in one-side modulation-doped wurtzite GaN/AlGaN single quantum wells at low temperatures are presented. We solve coupled Schr¨odinger and Poisson equations self-consistently via the finite difference method. By employing a proper discretization on a nonuniform grid and taking into account the strong piezoelectric and spontaneous polarization fields exhibited by the wurtzite III-nitride heterostructures, a substantial increase in the 2DEG density is predicted with the increase of the donor diffusion length and the reduction of the spacer thickness

Quantitative prediction of stone fragility from routine single and dual energy CT: proof of feasibility

Rationale and Objectives Previous studies have demonstrated a qualitative relationship between stone fragility and internal stone morphology. The goal of this study was to quantify morphological features from dual-energy CT images and assess their relationship to stone fragility. Materials and Methods Thirty-three calcified urinary stones were scanned with micro CT. Next, they were placed within torso-shaped water phantoms and scanned with the dual-energy CT stone composition protocol in routine use at our institution. Mixed low-and high-energy images were used to measure volume, surface roughness, and 12 metrics describing internal morphology for each stone. The ratios of low- to high-energy CT numbers were also measured. Subsequent to imaging, stone fragility was measured by disintegrating each stone in a controlled ex vivo experiment using an ultrasonic lithotripter and recording the time to comminution. A multivariable linear regression model was developed to predict time to comminution. Results The average stone volume was 300 mm3 (range 134–674 mm3). The average comminution time measured ex vivo was 32 s (range 7–115 s). Stone volume, dual-energy CT number ratio and surface roughness were found to have the best combined predictive ability to estimate comminution time (adjusted R2= 0.58). The predictive ability of mixed dual-energy CT images, without use of the dual-energy CT number ratio, to estimate comminution time was slightly inferior, with an adjusted R2 of 0.54. Conclusion Dual-energy CT number ratios, volume, and morphological metrics may provide a method for predicting stone fragility, as measured by time to comminution from ultrasonic lithotripsy