Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative Stress

Sildenafil citrate revolutionized the practice of sexual medicine upon its federal regulatory agency approval approximately 15 years ago as the prototypical phosphodiesterase type 5 inhibitor indicated for the treatment of male erectile dysfunction. We now provide scientific support for its alternative use in the management of priapism, a clinical disorder of prolonged and uncontrolled penile erection. Sildenafil administered continuously to sickle cell mice, which show a priapism phenotype, reverses oxidative/nitrosative stress effects in the penis, mainly via reversion of uncoupled endothelial nitric oxide synthase to the functional coupled state of the enzyme, which in turn corrects aberrant signaling and function of the nitric oxide/cyclic GMP/protein kinase G/phosphodiesterase type 5 cascade. Priapism tendencies in these mice are reverted partially toward normal neurostimulated erection frequencies and durations after sildenafil treatment in association with normalized cyclic GMP concentration, protein kinase G activity and phosphodiesterase type 5 activity in the penis. Thus, sildenafil exerts pleiotropic effects in the penis that extend to diverse erection disorders. © 2013 Bivalacqua et al

Application of semiconductor industry cleaning technologies for Genesis sample collectors

Genesis array collectors recovered after the sub-nominal landing have been exposed to particulate and molecular contamination. In this study, semiconductor industry based cleaning technologies are being evaluated for their efficacy in contaminant removal

Innovation Capacity: A Firm Level Response to Subsidy Activity in a National Setting

The purpose of this paper is to investigate the effect subsidies have on firm-level innovation across Eastern European and Central Asian countries and to assess if these effects move to increase firm-level capability. Specifically, we investigate the extent subsidy programs act to shape and guide firm-level innovative capabilities and how the presence of such capabilities affect operational performance. We employ a Probit model to investigate firm-level innovation and OLS regression to assess how subsidies, in association with the decision to adopt foreign technology and in-house research and development (R&D) affect firm productive capacity. Results suggest subsidies promote innovation and that when these subsidies are contemporaneously considered in the face of the decision to adopt foreign technologies and employ in-house R&D, firm-level capacity increases

Mott insulators in an optical lattice with high filling factors

We discuss the superfluid to Mott insulator transition of an atomic Bose gas in an optical lattice with high filling factors. We show that also in this multi-band situation, the long-wavelength physics is described by a single-band Bose-Hubbard model. We determine the many-body renormalization of the tunneling and interaction parameters in the effective Bose-Hubbard Hamiltonian, and consider the resulting model at nonzero temperatures. We show that in particular for a one or two-dimensional optical lattice, the Mott insulator phase is more difficult to realize than anticipated previously.Comment: 5 pages, 3 figures, title changed, major restructuring, resubmitted to PR

A low-voltage retarding-field Mott polarimeter for photocathode characterization

Nuclear physics experiments at Thomas Jefferson National Accelerator Facility's CEBAF rely on high polarization electron beams. We describe a recently commissioned system for prequalifying and studying photocathodes for CEBAF with a load-locked, low-voltage polarized electron source coupled to a compact retarding-field Mott polarimeter. The polarimeter uses simplified electrode structures and operates from 5 to 30 kV. The effective Sherman function for this device has been calibrated by comparison with the CEBAF 5 MeV Mott polarimeter. For elastic scattering from a thick gold target at 20 keV, the effective Sherman function is 0.201(5). Its maximum efficiency at 20 keV, defined as the detected count rate divided by the incident particle current, is 5.4(2) x 10-4, yielding a figure-of-merit, or analyzing power squared times efficiency, of 1.0(1) x 10-5. The operating parameters of this new polarimeter design are compared to previously published data for other compact Mott polarimeters of the retarding-field type.Comment: 9 figure

Alignment in Gamma-Hadron Families of Cosmic Rays

Alignment of main fluxes of energy in a target plane is found in families of cosmic ray particles detected in deep lead X-ray chambers. The fraction of events with alignment is unexpectedly large for families with high energy and large number of hadrons. This can be considered as evidence for the existence of coplanar scattering of secondary particles in interaction of particles with superhigh energy, $E_0 > 10^{16}$ eV. Data analysis suggests that production of most aligned groups occurs low above the chamber and is characterized by a coplanar scattering and quasiscaling spectrum of secondaries in the fragmentation region. The most elaborated hypothesis for explanation of alignment is related to the quark-gluon string rupture. However, the problem of theoretical interpretation of our results still remains open.Comment: 15 pages, 2 tables, 6 figures (not included), Stanford University preprint SU-ITP-94-2

Endogenous Urotensin II Selectively Modulates Erectile Function through eNOS

Urotensin II (U-II) is a cyclic peptide originally isolated from the neurosecretory system of the teleost fish and subsequently found in other species, including man. U-II was identified as the natural ligand of a G-protein coupled receptor, namely UT receptor. U-II and UT receptor are expressed in a variety of peripheral organs and especially in cardiovascular tissue. Recent evidence indicates the involvement of U-II/UT pathway in penile function in human, but the molecular mechanism is still unclear. On these bases the aim of this study is to investigate the mechanism(s) of U-II-induced relaxation in human corpus cavernosum and its relationship with L-arginine/Nitric oxide (NO) pathway.Human corpus cavernosum tissue was obtained following in male-to-female transsexuals undergoing surgical procedure for sex reassignment. Quantitative RT-PCR clearly demonstrated the U-II expression in human corpus cavernosum. U-II (0.1 nM-10 µM) challenge in human corpus cavernosum induced a significant increase in NO production as revealed by fluorometric analysis. NO generation was coupled to a marked increase in the ratio eNOS phosphorilated/eNOS as determined by western blot analysis. A functional study in human corpus cavernosum strips was performed to asses eNOS involvement in U-II-induced relaxation by using a pharmacological modulation. Pre-treatment with both wortmannin or geldanamycinin (inhibitors of eNOS phosphorylation and heath shock protein 90 recruitment, respectively) significantly reduced U-II-induced relaxation (0.1 nM-10 µM) in human corpus cavernosum strips. Finally, a co-immunoprecipitation study demonstrated that UT receptor and eNOS co-immunoprecipitate following U-II challenge of human corpus cavernosum tissue.U-II is endogenously synthesized and locally released in human corpus cavernosum. U-II elicited penile erection through eNOS activation. Thus, U-II/UT pathway may represent a novel therapeutical target in erectile dysfunction