Androgen receptor phosphorylation status at serine 578 predicts poor outcome in prostate cancer patients

Purpose: Prostate cancer growth is dependent upon androgen receptor (AR) activation, regulated via phosphorylation. Protein kinase C (PKC) is one kinase that can mediate AR phosphorylation. This study aimed to establish if AR phosphorylation by PKC is of prognostic significance. Methods: Immunohistochemistry for AR, AR phosphorylated at Ser-81 (pARS81), AR phosphorylated at Ser-578 (pARS578), PKC and phosphorylated PKC (pPKC) was performed on 90 hormone-naïve prostate cancer specimens. Protein expression was quantified using the weighted histoscore method and examined with regard to clinico-pathological factors and outcome measures; time to biochemical relapse, survival from biochemical relapse and disease-specific survival. Results: Nuclear PKC expression strongly correlated with nuclear pARS578 (c.c. 0.469, p=0.001) and cytoplasmic pARS578 (c.c. 0.426 p=0.002). High cytoplasmic and nuclear pARS578 were associated with disease-specific survival (p<0.001 and p=0.036 respectively). High nuclear PKC was associated with lower disease-specific survival when combined with high pARS578 in the cytoplasm (p=0.001) and nucleus (p=0.038). Combined high total pARS81 and total pARS578 was associated with decreased disease-specific survival (p=0.005) Conclusions: pARS578 expression is associated with poor outcome and is a potential independent prognostic marker in hormone-naïve prostate cancer. Furthermore, PKC driven AR phosphorylation may promote prostate cancer progression and provide a novel therapeutic target

An idealized numerical study of tropical cyclogenesis and evolution at the Equator

Tropical cyclone formation and evolution at, or near, the Equator is explored using idealized three‐dimensional model simulations, starting from a prescribed, initial, weak counterclockwise rotating vortex in an otherwise quiescent, nonrotating environment. Three simulations are carried out in which the maximum tangential wind speed (5 m surn:x-wiley:qj:media:qj3701:qj3701-math-0001) is specified at an initial radius of 50, 100, or 150 km. After a period of gestation lasting between 30 and 60 hr, the vortices intensify rapidly, the evolution being similar to that for vortices away from the Equator. In particular, the larger the initial vortex size, the longer the gestation period, the larger the maximum intensity attained, and the longer the vortex lifetime. Beyond a few days, the vortices decay as the cyclonic vorticity source provided by the initial vortex is depleted and negative vorticity surrounding the vortex core is drawn inwards by the convectively driven overturning circulation. In these negative vorticity regions, the flow is inertially/centrifugally unstable. The vortex evolution during the mature and decay phases differs from that in simulations away from the Equator, where inertially unstable regions are much more limited in area. Vortex decay in the simulations appears to be related intimately to the development of inertial instability, which is accompanied by an outward‐propagating band of deep convection. The degree to which this band of deep convection is realistic is unknown

Testing and Acceptance of Fuel Plates for RERTR Fuel Development Experiments

This paper discusses how candidate fuel plates for RERTR Fuel Development experiments are examined and tested for acceptance prior to reactor insertion. These tests include destructive and nondestructive examinations (DE and NDE). The DE includes blister annealing for dispersion fuel plates, bend testing of adjacent cladding, and microscopic examination of archive fuel plates. The NDE includes Ultrasonic (UT) scanning and radiography. UT tests include an ultrasonic scan for areas of “debonds” and a high frequency ultrasonic scan to determine the "minimum cladding" over the fuel. Radiography inspections include identifying fuel outside of the maximum fuel zone and measurements and calculations for fuel density. Details of each test are provided and acceptance criteria are defined. These tests help to provide a high level of confidence the fuel plate will perform in the reactor without a breach in the cladding

On the harmonic measure of stable processes

Using three hypergeometric identities, we evaluate the harmonic measure of a finite interval and of its complementary for a strictly stable real L{\'e}vy process. This gives a simple and unified proof of several results in the literature, old and recent. We also provide a full description of the corresponding Green functions. As a by-product, we compute the hitting probabilities of points and describe the non-negative harmonic functions for the stable process killed outside a finite interval

Treatment of transient phenomena in analysis of slag-metal-gas reaction kinetics

Equations commonly used in describing reaction kinetics are examined and the problem of applying such equations to transient processes is discussed. Three examples of transient phenomena are examined in detail. It is shown that for carbon injection into slag, the reaction can be described by employing data for carbon oxidation in CO/CO2 by assuming reaction conditions approximately halfway between those in equilibrium with the slag and those in equilibrium with carbon. It is demonstrated that, when the time averaged interfacial area is employed, the rate of reaction between slag and iron-aluminum alloys can be described by a single first order rate equation, accommodating a 300% change in interfacial area. Creation of surface area in oxygen steelmaking is discussed and a method to determine the size distribution of droplets that are generated is proposed. It is concluded that changes in conditions during reaction complicate the analysis of kinetics. However, it should be possible to develop quantitative kinetic models to describe real processes

Deformation of the Planetary Orbits Caused by the Time Dependent Gravitational Potential in the Universe

In the paper are studied the deformations of the planetary orbits caused by the time dependent gravitational potential in the universe. It is shown that the orbits are not axially symmetric and the time dependent potential does not cause perihelion precession. It is found a simple formula for the change of the orbit period caused by the time dependent gravitational potential and it is tested for two binary pulsars.Comment: 7 page

Measurement of the 6s - 7p transition probabilities in atomic cesium and a revised value for the weak charge Q_W

We have measured the 6s - 7p_{1/2,3/2} transition probabilities in atomic cesium using a direct absorption technique. We use our result plus other previously measured transition rates to derive an accurate value of the vector transition polarizability \beta and, consequently, re-evaluate the weak charge Q_W. Our derived value Q_W=-72.65(49) agrees with the prediction of the standard model to within one standard deviation.Comment: 4 pages, 2 figure

NONDESTRUCTIVE EXAMINATION OF FUEL PLATES FOR THE RERTR FUEL DEVELOPMENT EXPERIMENTS

Nuclear fuel is the core component of reactors that is used to produce the neutron flux required for irradiation research purposes as well as commercial power generation. The development of nuclear fuels with low enrichments of uranium is a major endeavor of the RERTR program. In the development of these fuels, the RERTR program uses nondestructive examination (NDE) techniques for the purpose of determining the properties of nuclear fuel plate experiments without imparting damage or altering the fuel specimens before they are irradiated in a reactor. The vast range of properties and information about the fuel plates that can be characterized using NDE makes them highly useful for quality assurance and for analyses used in modeling the behavior of the fuel while undergoing irradiation. NDE is also particularly useful for creating a control group for post-irradiation examination comparison. The two major categories of NDE discussed in this paper are X-ray radiography and ultrasonic testing (UT) inspection/evaluation. The radiographic scans are used for the characterization of fuel meat density and homogeneity as well as the determination of fuel location within the cladding. The UT scans are able to characterize indications such as voids, delaminations, inclusions, and other abnormalities in the fuel plates which are generally referred to as debonds as well as to determine the thickness of the cladding using ultrasonic acoustic microscopy methods. Additionally, the UT techniques are now also being applied to in-canal interim examination of fuel experiments undergoing irradiation and the mapping of the fuel plate surface profile to determine fuel swelling. The methods used to carry out these NDE techniques, as well as how they operate and function, are described along with a description of which properties are characterized

The effect of stopping before turning on the direct observational measure of whole body turning bias

Turning bias, the preferential tendency to turn toward a given direction has been reported in both rodents and human participants. The observational gait method of determining turning bias in humans requires a stop prior to turning. This study removed the stop and hypothesised that turning bias would remain the same between stop and non-stop conditions if bias was solely under the control of neurochemical asymmetries. The results showed that statistically turning bias remained the same (to the left) regardless of method used but there was no agreement between the methods thus rejecting the hypothesis. It is likely that when not stopping biomechanical factors related to gait when turning influence the direction of turn rather than solely neurochemical asymmetries

Stimulation of inositol 1,4,5-trisphosphate (IP₃) receptor subtypes by Adenophostin A and its analogues

Inositol 1,4,5-trisphosphate receptors (IP3R) are intracellular Ca(2+) channels. Most animal cells express mixtures of the three IP3R subtypes encoded by vertebrate genomes. Adenophostin A (AdA) is the most potent naturally occurring agonist of IP3R and it shares with IP3 the essential features of all IP3R agonists, namely structures equivalent to the 4,5-bisphosphate and 6-hydroxyl of IP3. The two essential phosphate groups contribute to closure of the clam-like IP3-binding core (IBC), and thereby IP3R activation, by binding to each of its sides (the α- and β-domains). Regulation of the three subtypes of IP3R by AdA and its analogues has not been examined in cells expressing defined homogenous populations of IP3R. We measured Ca(2+) release evoked by synthetic adenophostin A (AdA) and its analogues in permeabilized DT40 cells devoid of native IP3R and stably expressing single subtypes of mammalian IP3R. The determinants of high-affinity binding of AdA and its analogues were indistinguishable for each IP3R subtype. The results are consistent with a cation-π interaction between the adenine of AdA and a conserved arginine within the IBC α-domain contributing to closure of the IBC. The two complementary contacts between AdA and the α-domain (cation-π interaction and 3″-phosphate) allow activation of IP3R by an analogue of AdA (3″-dephospho-AdA) that lacks a phosphate group equivalent to the essential 5-phosphate of IP3. These data provide the first structure-activity analyses of key AdA analogues using homogenous populations of all mammalian IP3R subtypes. They demonstrate that differences in the Ca(2+) signals evoked by AdA analogues are unlikely to be due to selective regulation of IP3R subtypes