Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer

Although systemic androgen deprivation prolongs life in advanced prostate cancer, remissions are temporary because patients almost uniformly progress to a state of a castration-resistant prostate cancer (CRPC) as indicated by recurring PSA. This complex process of progression does not seem to be stochastic as the timing and phenotype are highly predictable, including the observation that most androgen-regulated genes are reactivated despite castrate levels of serum androgens. Recent evidence indicates that intraprostatic levels of androgens remain moderately high following systemic androgen deprivation therapy, whereas the androgen receptor (AR) remains functional, and silencing the AR expression following castration suppresses tumor growth and blocks the expression of genes known to be regulated by androgens. From these observations, we hypothesized that CRPC progression is not independent of androgen-driven activity and that androgens may be synthesized de novo in CRPC tumors leading to AR activation. Using the LNCaP xenograft model, we showed that tumor androgens increase during CRPC progression in correlation to PSA up-regulation. We show here that all enzymes necessary for androgen synthesis are expressed in prostate cancer tumors and some seem to be up-regulated during CRPC progression. Using an ex vivo radiotracing assays coupled to high-performance liquid chromatography-radiometric/mass spectrometry detection, we show that tumor explants isolated from CRPC progression are capable of de novo conversion of [(14)C]acetic acid to dihydrotestosterone and uptake of [(3)H]progesterone allows detection of the production of six other steroids upstream of dihydrotestosterone. This evidence suggests that de novo androgen synthesis may be a driving mechanism leading to CRPC progression following castration.

The first x-ray diffraction peak of water as a function of temperature in the range 4 – 63 °C

X-ray diffraction structure functions for water flowing in a 1.5 mm diameter siphon in the temperature range 4 – 63 °C were obtained using a 20 keV beam at the Australian Synchrotron. These functions were compared with structure functions obtained at the Advanced Light Source for a 0.5 mm thick sample of water in the temperature range 1 – 77 °C irradiated with an 11 keV beam. The two sets of structure functions are similar, but there are subtle differences in the shape and relative position of the two functions suggesting a possible differences between the structure of bulk and siphon water. In addition, the first structural peak (Q0) for water in a siphon, showed evidence of a step-wise increase in Q0 with increasing temperature rather than a smoothly varying increase. More experiments are required to investigate this apparent difference.

Tectonometamorphic evolution of the Åreskutan Nappe-Caledonian history revealed by SIMS U–Pb zircon geochronology

Secondary ionization mass spectrometry (SIMS) U–Pb dating of zircons from the Åreskutan Nappe in the central part of the Seve Nappe Complex of western central Jämtland provides new constraints on the timing of granulite–amphibolite-facies metamorphism and tectonic stacking of the nappe during the Caledonian orogeny. Peak-temperature metamorphism in garnet migmatites is constrained to c. 442 ± 4 Ma, very similar to the ages of leucogranites at 442 ± 3 and 441 ± 4 Ma. Within a migmatitic amphibolite, felsic segregations crystallized at 436 ± 2 Ma. Pegmatites, cross-cutting the dominant Caledonian foliation in the Nappe, yield 428 ± 4 and 430 ± 3 Ma ages. The detrital zircon cores in the migmatites and leucogranites provide evidence of Late Palaeoproterozoic, Mesoproterozoic to Early Neoproterozoic source terranes for the metasedimentary rocks. The formation of the ductile and hot Seve migmatites, with their inverted metamorphism and thinning towards the hinterland, can be explained by an extrusion model in which the allochthon stayed ductile for a period of at least 10 million years during cooling from peak-temperature metamorphism early in the Silurian. In our model, Baltica–Laurentia collision occurred in the Late Ordovician–earliest Silurian, with emplacement of the nappes far on to the Baltoscandian platform during the Silurian and early Devonian, Scandian Orogeny lasting until c. 390 Ma.

Comparison between ACI 440 and FIB 14 design guidelines in using CFRP for strengthening of a concrete bridge headstock

This paper compares and reviews the recommendations and contents of the guide for the design and construction of externally bonded FRP systems for strengthening concrete structures reported by ACI committee 440 and technical report of Externally bonded FRP reinforcement for RC structures (FIB 14) in application of carbon fiber reinforced polymer (CFRP) composites in strengthening of an aging reinforced concrete headstock. The paper also discusses the background, limitations, strengthening for flexure and shear, and other related issues in use of FRP for strengthening of a typical reinforced concrete headstock structure such as durability, de-bonding, strengthening limits, fire and environmental conditions. A case study of strengthening of a bridge headstock using FRP composites is presented as a worked example in order to illustrate and compare the differences between these two design guidelines when used in conjunction with the philosophy of the Austroads (1992) bridge design code.

Dating and intimacy in the 21st century : the use of online dating sites in Australia

This article examines the growing phenomenon of online dating and intimacy in the 21st century. The exponential rise of communications technologies, which is both reflective and constitutive of an increasingly networked and globalized society, has the potential to significantly influence the nature of intimacy in everyday life. Yet, to date, there has been a minimal response by sociologists to seek, describe and understand this influence. In this article, we present some of the key findings of our research on online dating in Australia, in order to foster a debate about the sociological impacts on intimacy in the postmodern world. Based on a web audit of more than 60 online dating sites and in-depth interviews with 23 users of online dating services, we argue that recent global trends are influencing the uptake of online technologies for the purposes of forming intimate relations. Further, some of the mediating effects of these technologies – in particular, the hypercommunication – may have specific implications for the nature of intimacy in the global era.

Social network analysis of an online dating network

Online social networks can be found everywhere from chatting websites like MSN, blogs such as MySpace to social media such as YouTube and second life. Among them, there is one interesting type of online social networks, online dating network that is growing fast. This paper analyzes an online dating network from social network analysis point of view. Observations are made and results are obtained in order to suggest a better recommendation system for people-to-people networks.

Effects of whole-body cryotherapy (-110 degrees C) on proprioception and indices of muscle damage

The purpose of this study was to investigate the effects of whole-body cryotherapy (WBC) on proprioceptive function, muscle force recovery following eccentric muscle contractions and tympanic temperature (TTY). Thirty-six subjects were randomly assigned to a group receiving two 3-min treatments of −110 ± 3 °C or 15 ± 3 °C. Knee joint position sense (JPS), maximal voluntary isometric contraction (MVIC) of the knee extensors, force proprioception and TTY were recorded before, immediately after the exposure and again 15 min later. A convenience sample of 18 subjects also underwent an eccentric exercise protocol on their contralateral left leg 24 h before exposure. MVIC (left knee), peak power output (PPO) during a repeated sprint on a cycle ergometer and muscles soreness were measured pre-, 24, 48 and 72 h post-treatment. WBC reduced TTY, by 0.3 °C, when compared with the control group (P<0.001). However, JPS, MVIC or force proprioception was not affected. Similarly, WBC did not effect MVIC, PPO or muscle soreness following eccentric exercise. WBC, administered 24 h after eccentric exercise, is ineffective in alleviating muscle soreness or enhancing muscle force recovery. The results of this study also indicate no increased risk of proprioceptive-related injury following WBC.

Synthesizing and databasing fossil calibrations: divergence dating and beyond

Divergence dating studies, which combine temporal data from the fossil record with branch length data from molecular phylogenetic trees, represent a rapidly expanding approach to understanding the history of life. National Evolutionary Synthesis Center hosted the first Fossil Calibrations Working Group (3–6 March, 2011, Durham, NC, USA), bringing together palaeontologists, molecular evolutionists and bioinformatics experts to present perspectives from disciplines that generate, model and use fossil calibration data. Presentations and discussions focused on channels for interdisciplinary collaboration, best practices for justifying, reporting and using fossil calibrations and roadblocks to synthesis of palaeontological and molecular data. Bioinformatics solutions were proposed, with the primary objective being a new database for vetted fossil calibrations with linkages to existing resources, targeted for a 2012 launch.

Evidence for carbonate platform failure during rapid sea-level rise; ca 14 000 year old bioclastic flow deposits in the Lesser Antilles

Bioclastic flow deposits offshore from the Soufrie`re Hills volcano on Montserrat in the Lesser Antilles were deposited by the largest volume sediment flows near this active volcano in the last 26 kyr. The volume of these deposits exceeds that of the largest historic volcanic dome collapse in the world, which occurred on Montserrat in 2003. These flows were most probably generated by a large submarine slope failure of the carbonate shelf comprising the south west flank of Antigua or the east flank of Redonda; adjacent islands that are not volcanically active. The bioclastic flow deposits are relatively coarse-grained and either ungraded or poorly graded, and were deposited by non cohesive debris flow and high density turbidity currents. The bioclastic deposit often comprises multiple sub-units that cannot be correlated between core sites; some located just 2 km apart. Multiple sub-units in the bioclastic deposit result from either flow reflection, stacking of multiple debris flow lobes, and/or multi-stage collapse of the initial landslide. This study provides unusually precise constraints on the age of this mass flow event that occurred at ca 14 ka. Few large submarine landslides have been well dated, but the slope failures that have been dated are commonly associated with periods of rapid sea-level change.

A practical signal processing approach for condition monitoring of low speed machinery using Peak-Hold-Down-Sample algorithm

A simple and effective down-sample algorithm, Peak-Hold-Down-Sample (PHDS) algorithm is developed in this paper to enable a rapid and efficient data transfer in remote condition monitoring applications. The algorithm is particularly useful for high frequency Condition Monitoring (CM) techniques, and for low speed machine applications since the combination of the high sampling frequency and low rotating speed will generally lead to large unwieldy data size. The effectiveness of the algorithm was evaluated and tested on four sets of data in the study. One set of the data was extracted from the condition monitoring signal of a practical industry application. Another set of data was acquired from a low speed machine test rig in the laboratory. The other two sets of data were computer simulated bearing defect signals having either a single or multiple bearing defects. The results disclose that the PHDS algorithm can substantially reduce the size of data while preserving the critical bearing defect information for all the data sets used in this work even when a large down-sample ratio was used (i.e., 500 times down-sampled). In contrast, the down-sample process using existing normal down-sample technique in signal processing eliminates the useful and critical information such as bearing defect frequencies in a signal when the same down-sample ratio was employed. Noise and artificial frequency components were also induced by the normal down-sample technique, thus limits its usefulness for machine condition monitoring applications.

The effect of post-match alcohol ingestion on recovery from competitive Rugby League matches

This study investigated the effects of alcohol ingestion on lower body strength and power, and physiological and cognitive recovery following competitive Rugby League matches. Nine male Rugby players participated in two matches, followed by one of two randomized interventions; a control or alcohol ingestion session. Four hours post-match, participants consumed either beverages containing a total of 1g of ethanol per kg bodyweight (vodka and orange juice; ALC) or a caloric and taste matched non-alcoholic beverage (orange juice; CONT). Pre, post, 2 h post and 16 h post match measures of countermovement jump (CMJ), maximal voluntary contraction(MVC), voluntary activation (VA), damage and stress markers of creatine kinase (CK), C-reactive protein (CRP), cortisol, and testosterone analysed from venous blood collection, and cognitive function (modified Stroop test) were determined. Alcohol resulted in large effects for decreased CMJ height(-2.35 ± 8.14 and -10.53 ± 8.36 % decrement for CONT and ALC respectively; P=0.15, d=1.40), without changes in MVC (P=0.52, d=0.70) or VA (P=0.15, d=0.69). Furthermore, alcohol resulted in a significant slowing of total time in a cognitive test (P=0.04, d=1.59), whilst exhibiting large effects for detriments in congruent reaction time (P=0.19, d=1.73). Despite large effects for increased cortisol following alcohol ingestion during recovery (P=0.28, d=1.44), post-match alcohol consumption did not unduly affect testosterone (P-0.96, d=0.10), CK (P=0.66, d=0.70) or CRP(P=0.75, d=0.60). It appears alcohol consumption during the evening following competitive rugby matches may have some detrimental effects on peak power and cognitive recovery the morning following a Rugby League match. Accordingly, practitioners should be aware of the potential associated detrimental effects of alcohol consumption on recovery and provide alcohol awareness to athletes at post-match functions.

Mechanism of dehydroxylation temperature decrease and high temperature phase transition of coal-bearing strata kaolinite intercalated by potassium acetate

The thermal decomposition and dehydroxylation process of coal-bearing strata kaolinite–potassium acetate intercalation complex (CSKK) has been studied using X-ray diffraction (XRD), infrared spectroscopy (IR), thermal analysis, mass spectrometric analysis and infrared emission spectroscopy. The XRD results showed that the potassium acetate (KAc) have been successfully intercalated into coal-bearing strata kaolinite with an obvious basal distance increase of the first basal peak, and the positive correlation was found between the concentration of intercalation regent KAc and the degree of intercalation. As the temperature of the system is raised, the formation of KHCO3, KCO3 and KAlSiO4, which is derived from the thermal decomposition or phase transition of CSKK, is observed in sequence. The IR results showed that new bands appeared, the position and intensities shift can also be found when the concentration of intercalation agent is raised. The thermal analysis and mass spectrometric analysis results revealed that CSKK is stable below 300 °C, and the thermal decomposition products (H2O and CO2) were further proved by the mass spectrometric analysis. A comparison of thermal analysis results of original coal-bearing strata kaolinite and its intercalation complex gives new discovery that not only a new mass loss peak is observed at 285 °C, but also the temperature of dehydroxylation and dehydration of coal bearing strata kaolinite is decreased about 100 °C. This is explained on the basis of the interlayer space of the kaolinite increased obviously after being intercalated by KAc, which led to the interlayer hydrogen bonds weakened, enables the dehydroxylation from kaolinite surface more easily. Furthermore, the possible structural model for CSKK has been proposed, with further analysis required in order to prove the most possible structures.

Evaluating the role of deep granitic rocks in generating anomalous temperatures in SW-Queensland

Across central Australia and south-west Queensland, a large (~800,000km2) subsurface temperature anomaly occurs (Figure 1). Temperatures are interpreted to be greater than 235°C at 5km depth, ca. 85°C higher than the average geothermal gradient for the upper continental crust (Chopra & Holgate, 2005; Holgate & Gerner, 2011). This anomaly has driven the development of Engineered Geothermal Systems (EGS) at Innamincka, where high temperatures have been related to the radiogenic heat production of High Heat Producing Granites (HHPG) at depth, below thermally insulative sedimentary cover (Chopra & Holgate, 2005; Draper & D’Arcy, 2006; Meixner & Holgate, 2009). To evaluate the role of granitic rocks at depth in generating the broader temperature anomaly in SW-Queensland, we sampled 25 granitic rocks from basement intervals of petroleum drill cores below thermal insulative cover along two transects (WNW–ESE and NNE–SSW — Figure 1) and performed a multidisciplinary study involving petrography, whole-rock chemistry, zircon dating and thermal conductivity measurements.

Sensitivity of peak positions to flight-path parameters in a deep-inelastic scattering neutron TOF spectrometer

The effects of small changes in flight-path parameters (primary and secondary flight paths, detector angles), and of displacement of the sample along the beam axis away from its ideal position, are examined for an inelastic time-of-flight (TOF) neutron spectrometer, emphasising the deep-inelastic regime. The aim was to develop a rational basis for deciding what measured shifts in the positions of spectral peaks could be regarded as reliable in the light of the uncertainties in the calibrated flight-path parameters. Uncertainty in the length of the primary or secondary flight path has the least effect on the positions of the peaks of H, D and He, which are dominated by the accuracy of the calibration of the detector angles. This aspect of the calibration of a TOF spectrometer therefore demands close attention to achieve reliable outcomes where the position of the peaks is of significant scientific interest and is discussed in detail. The corresponding sensitivities of the position of peak of the Compton profile, J(y), to flight-path parameters and sample position are also examined, focusing on the comparability across experiments of results for H, D and He. We show that positioning the sample to within a few mm of the ideal position is required to ensure good comparability between experiments if data from detectors at high forward angles are to be reliably interpreted.

An Introduction to Dating Techniques : A Guide for Geomorphologists

This chapter provides researchers with a guide to some of the types of dating techniques that can be used in geomorpological investigations and issues that need to be addressed when using gechronological data, specifically issues relating to accuracy and precision. This chapter also introduces the 'types' of dating methods that are commonly used in geomorphological studies. This includes sidereal, isotopic, radiogenic, and chemical dating methods.