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

A ratio model of perceived speed in the human visual system

The perceived speed of moving images changes over time. Prolonged viewing of a pattern (adaptation) leads to an exponential decrease in its perceived speed. Similarly, responses of neurones tuned to motion reduce exponentially over time. It is tempting to link these phenomena. However, under certain conditions, perceived speed increases after adaptation and the time course of these perceptual effects varies widely. We propose a model that comprises two temporally tuned mechanisms whose sensitivities reduce exponentially over time. Perceived speed is taken as the ratio of these filters' outputs. The model captures increases and decreases in perceived speed following adaptation and describes our data well with just four free parameters. Whilst the model captures perceptual time courses that vary widely, parameter estimates for the time constants of the underlying filters are in good agreement with estimates of the time course of adaptation of direction selective neurones in the mammalian visual system

Comparison of physiological and perceptual responses to a maximal exhaustive test performed on the SRM and the Cyclus2 ergometer

Background: No cycle ergometer perfectly replicates the physiological demands and movement patterns associated with real world cycling (Abbiss et al., 2009: International Journal of Sports Medicine, 30(2), 107-112). The purpose of this research was to compare physiological and perceptual responses during a standardized exercise test using the classical SRM ergometer (Schoberer Rad Messtechnik, GmbH, Jülich, Germany) and the Cyclus2 ergometer (RBM elektronik-automation GmbH, Leipzig, Germany) which allows the use of personal bikes and allows lateral movement. Methods: 13 moderately trained cyclists (mean ± SD: age 35 ± 7 years, body mass 74.1 ± 9.6 kg) performed two graded cycling tests to volitional exhaustion in a randomized order on the SRM and the Cyclus2 ergometer. Maximal aerobic capacity (VO2max), maximal aerobic power (MAP), blood lactate concentrations and heart rate responses were compared using a paired t-test. Participants were also required to fill in the NASA Task Load Index (TLX) questionnaire (Hart, 2006: NASA-Task Load Index, 50th Human Factors and Ergonomics Society Meeting, Santa Monica, USA) after each test to assess the perceived workload in an effort to understand if one ergometer is perceived to be more or less of a workload than its counterpart. In order to analyse the workload from each participant, individual TXL factors were summed for each ergometer TLX administration creating an overall workload score per ergometer. After conclusion of the experiment participants were asked to state their preference in ergometers. Lastly, a correlation was performed on the level of performance within the ergometer testing and the perceived performance. Results: Compared physiological responses and MAP (321 ± 44 W; SRM and 326 ± 41 W; Cyclus2) did not find any significant differences. A constructed ANOVA model which examined the difference of the overall workload scores between the two ergometers did not show any significant difference (F(1,12) = .025, p = .876). In order to examine if there were individual factor differences between the six TLX factors of each ergometer, a constructed repeated measure MANOVA did not reveal any significant differences between ergometers and within individual TLX scores (F(5,8) = .995, p = .477). Interestingly, the absolute VO2max performance score was significantly correlated on the Cyclus2 ergometer with the self-reported performance TLX factor (r = .560, p = .047) while the same score was not significant for the SRM ergometer (r = .247, p = .415). However, participants were highly positively correlated between perceived performance on each ergometer (r = .736, p = .004). Participants were asked to name which ergometer they felt they performed better on. Eight participants named the SRM Ergometer, while 5 named the Cyclus2. When asked which ergometer they preferred to use, 4 named the SRM Ergometer, while 9 named the Cyclus2. When asked which ergometer the participant would prefer to use if the test were to be run again, 5 named the SRM Ergometer, while 8 named the Cyclus2. Participants were lastly asked to think of how comfortable they were for each of the ergometers. A paired t-test examined the differences between the comfort ratings of revealed a significant difference (t = -2.803, p = .016), with this being driven by the higher favourable ratings of the Cyclus2 compared to the SRM (Figure 1). These differences can be accounted for by 6 participants stating that they preferred the Cyclus2 and increased comfort owning to the usage of their own bike. Those that preferred the SRM stated it was more solid and stable (n = 4). Discussion: Biomechanical factors can influence physiological responses, perception of exercise and efficiency of an individual riding a bicycle or ergometer at a given power output (Patterson and Moreno, 1990: Medicine & Science in Sports & Exercise, 22(4), 512-516. Whilst not demonstrating any differences in physiological variables and MAP, participants generally felt more comfortable on the ergometer, which allows the use of personal bikes and which appears to replicate real world cycling more closel

Genetic Variability of Ruminal Starch Degradation of Corn Harvested at Two Silage Maturities

This trial was carried out to determine the influence of genotype and maturity stage on ruminal starch degradation of corn harvested at silage maturity. Two types of corn (Zea mays L.), differing in their endosperm texture, flint or dent, were harvested at 30 and 35 % whole plant DM. The degradation rate in the rumen of grains (oven dried at 40°C and ground through a 3-mm screen) was determined by the in situ technique. Mean ruminal starch degradability was 69 %. With maturity, the content of grain in the whole plant increased and ruminal starch degradability decreased (15 points). Starch of dent corn was always more degradable than starch of flint corn (22 points). Particulate starch losses through the bag pores were low and they varied little. Harvested at silage maturity, ruminal starch degradation of corn grain varied widely

Residential mobility in divided societies: How individual religion and geographical context influenced housing moves in Northern Ireland 2001–2011

Residential segregation is pervasive in many societies. People making residential moves in these divided contexts may increase or decrease segregation levels. In this paper, the divided society of Northern Ireland is used as an example to explore how residential mobility relates to residential segregation by religion. Survey evidence for this country consistently shows a preference for mixed neighbourhoods, yet actual patterns of geographical mobility suggest people move to same‐religion areas. The paper uses the Northern Ireland Longitudinal Study (NILS) to explore the individual and contextual factors that influence the destinations of internal migrants by religion between 2001 and 2011. How they move up or down the contextual ‘religion ladder’ of localities is modelled with reference to both their individual socio‐demographic and neighbourhood characteristics in 2001. It is found that there are still individual religious differentials in people's destinations. Catholics, for instance, are more likely than Protestants to move to more Catholic areas, suggesting that individual religion remains important despite the Peace Process. Some possible reasons for this are considered with a partial explanation being found in the geographical patterning of the population. Existing patterns of residential segregation constrain moves in religious space for the majority of people. It is concluded, nevertheless, that an individual's religion remains a considerable factor contrary to expectations

Can we see pulsars around Sgr A*? - The latest searches with the Effelsberg telescope

Radio pulsars in relativistic binary systems are unique tools to study the curved space-time around massive compact objects. The discovery of a pulsar closely orbiting the super-massive black hole at the centre of our Galaxy, Sgr A*, would provide a superb test-bed for gravitational physics. To date, the absence of any radio pulsar discoveries within a few arc minutes of Sgr A* has been explained by one principal factor: extreme scattering of radio waves caused by inhomogeneities in the ionized component of the interstellar medium in the central 100 pc around Sgr A*. Scattering, which causes temporal broadening of pulses, can only be mitigated by observing at higher frequencies. Here we describe recent searches of the Galactic centre region performed at a frequency of 18.95 GHz with the Effelsberg radio telescope.Comment: 3 pages, 2 figures, Proceedings of IAUS 291 "Neutron Stars and Pulsars: Challenges and Opportunities after 80 years", 201

The Cellular Metabolism and Effects of Gold Complexes

Leads to the cellular effects of the anti-arthritic gold complexes may come from the determination of their metabolism by target cells and, possibly, cells in the immediate environment of the target cells. Polymorphonuclear leukocytes (PMN) and mononuclear cells (monocytes and lymphocytes) are present in inflamed joints of patients with rheumatoid arthritis and these cells have been widely used in pharmacological studies on the gold complexes. It is suggested that the cellular effects of the gold complexes are mediated by the production of aurocyanide. According to this hypothesis, PMN metabolize small quantities of thiocyanate to cyanide which, in turn, converts gold complexes, such as aurothiomalate, to aurocyanide (dicyanogold(I)) which inhibits the functions of PMN and other cells. There is now considerable evidence for this hypothesis from in vitro studies but there is little in vivo work to back up the hypothesis. One of the few in vivo studies which tested the hypothesis involved the examination of the activity of aurothiomalate in the treatment of polyarthritis in Hooded Wistar rats. Activity of aurothiomalate is only shown in animals which received thiocyanate. Hydrogen cyanide is a constituent of cigarette smoke and the aurocyanide formed by the interaction with gold complexes and inhaled hydrogen cyanide rapidly diffuses into red blood cells. Because of the metabolism of hydrogen cyanide to thiocyanate in the liver, there are higher plasma levels of thiocyanate in smokers than in non-smokers. Smokers may have a greater incidence of side effects than non-smokers but there appears to be little difference in therapeutic response, possibly because there is sufficient thiocyanate in extracellular fluid, even in non-smokers, to support the conversion of gold complexes to aurocyanide. The relationship between the metabolism and effects of the orally active gold complex, auranofin are less clear. Auranofin itself is taken up by cells with the loss of the ligands bound to gold while its inhibitory activity against the oxidative burst of PMN decreases with increasing cell density. For example, the lucigenin-dependent chemiluminescence of 106 PMN/ml is 46 percent of control at 0.5 μM auranofin but only 2.2 percent in 2.105 PMN/ml in the presence of the same concentration of auranofin. A potentially active gold complex is a plasma component which is taken up by red blood cells

XY checkerboard antiferromagnet in external field

Ordering by thermal fluctuations is studied for the classical XY antiferromagnet on a checkerboard lattice in zero and finite magnetic fields by means of analytical and Monte Carlo methods. The model exhibits a variety of novel broken symmetries including states with nematic ordering in zero field and with triatic order parameter at high fields.Comment: 6 page

Sediment Sorting and Rounding in a Basaltic Glacio-Fluvio-Aeolian Environment: hrisjkull Glacier, Iceland

Sediments and sedimentary rocks preserve a rich history of environment and climate. Identifying these signals requires an understanding of the physical and chemical processes that have affected sedimentary deposits [1]. Such processes include sorting and rounding during transport and chemical alteration through weathering and diagenesis. Although these processes have long been studied in quartz-dominated sedimentary systems [2], a lack of studies of basaltic sedimentary systems limits our interpretations of the environment and climate where mafic source rocks dominate, such as on Mars [3,4]. As part of the SAND-E: Semi-Autonomous Navigation for Detrital Environments project [5], which uses robotic operations to examine physical and chemical changes to sediments in basaltic glacio-fluvialaeolian environments, this research studies changes in sorting and rounding of fluvial-aeolian sediments along a glacier-proximal-to-glacier-distal transect in the outwash-plain of the risjkull glacier in SW Iceland (Fig. 1