The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 2: androgen-receptor cofactors and bypass pathways

Prostate cancer is the second leading cause of cancer related deaths in men from the western world. Treatment of prostate cancer has relied on androgen deprivation therapy for the past 50 years. Response rates are initially high (70-80%), however almost all patients develop androgen escape and subsequently die within 1-2 years. Unlike breast cancer, alternative approaches (chemotherapy and radiotherapy) do not increase survival time. The high rate of prostate cancer mortality is therefore strongly linked to both development of androgen escape and the lack of alternate therapies. AR mutations and amplifications can not explain all cases of androgen escape and post-translational modification of the AR has become an alternative theory. However recently it has been suggested that AR co-activators e.g. SRC-1 or pathways the bypass the AR (Ras/MAP kinase or PI3K/Akt) may stimulated prostate cancer progression independent of the AR. This review will focus on how AR coactivators may act to increase AR transactivation during sub-optimal DHT concentrations and also how signal transduction pathways may promote androgen escape via activation of transcription factors, e.g. AP-1, c-Myc and Myb, that induce cell proliferation or inhibit apoptosis

Super-lattice, rhombus, square, and hexagonal standing waves in magnetically driven ferrofluid surface

Standing wave patterns that arise on the surface of ferrofluids by (single frequency) parametric forcing with an ac magnetic field are investigated experimentally. Depending on the frequency and amplitude of the forcing, the system exhibits various patterns including a superlattice and subharmonic rhombuses as well as conventional harmonic hexagons and subharmonic squares. The superlattice arises in a bicritical situation where harmonic and subharmonic modes collide. The rhombic pattern arises due to the non-monotonic dispersion relation of a ferrofluid

Examining the Acute Effects of Virtual Reality on the Star Excursion Balance Test in Chronic Ankle Instability

Chronic ankle instability (CAI) patients display mechanical and functional restrictions, along with neurocognitive dysfunction after lateral ankle sprains. Athletes need to divide their attention to effectively multitask during sports activities. Recent studies have utilized virtual reality (VR) to simulate dynamic sporting environments, aiming to enhance cognitive and postural control. However, little is known about the acute effects of VR on dynamic postural control in CAI patients. PURPOSE: To identify the acute effects of VR gear on dynamic postural control in CAI patients. METHODS: This study was a cross-over study. Twenty CAI patients (11males, 9females; age=21±3year; height=1.63±0.28m; mass=74±13.1kg). We used the Foot and Ankle Ability Measures and Ankle Instability Instrument questionnaires for CAI. VR training included 3 trials of single-leg stance; double and single-leg drop landings; and 5 trials of jump landing/cutting. Before and after VR training, participants performed 3 trials each in 3 directions: anterior (ANT), posteromedial (PM), and posterolateral (PL). The average reach distance was normalized by an individual’s leg length from the anterior superior iliac spine to the distal end of the medial malleolus. Matched paired t-tests were used to evaluate the acute effect (posttest-pretest difference) of VR training. The significance level for all analyses was set at a priori of p≤0.05. RESULTS: Acute effects were not observed in both ANT and PM directions (60.2±7.2 vs. 60.9±6.9, p=0.15 and 103.3±10.4 vs. 104.6±11.2, p=0.31). CAI patients showed an acute effect, improving PL reach distance (98.3±11.2 vs. 102.1±13.3, p=0.006) during the star excursion balance test after VR training. CONCLUSION: VR resulted in no difference in ANT direction, which is related to the dorsiflexion range of motion, suggesting that VR training had no improvement in mechanical restriction. After VR training, PL reach distance was increased, suggesting improvement in functional restriction in CAI patients. Therefore, VR training may affect functional restriction, by potentially increasing eversion strength and improving mediolateral static postural control. More data are needed to determine if VR may reduce the risk of recurrent ankle sprains in CAI patients

Excited states of a dilute Bose-Einstein condensate in a harmonic trap

The low-lying hydrodynamic normal modes of a dilute Bose-Einstein gas in an isotropic harmonic trap determine the corresponding Bogoliubov amplitudes. In the Thomas-Fermi limit, these modes have large low-temperature occupation numbers, and they permit an explicit construction of the dynamic structure function $S(q,\omega)$. The total noncondensate number $N'(0)$ at zero temperature increases like $R^6$, where $R$ is the condensate radius measured in units of the oscillator length. The lowest dipole modes are constructed explicitly in the Bogoliubov approximation.Comment: 15 pages, REVTE

A quantum mechanical NMR simulation algorithm for protein-scale spin systems

Nuclear magnetic resonance spectroscopy is one of the few remaining areas of physical chemistry for which polynomially scaling simulation methods have not so far been available. Here, we report such a method and illustrate its performance by simulating common 2D and 3D liquid state NMR experiments (including accurate description of spin relaxation processes) on isotopically enriched human ubiquitin - a protein containing over a thousand nuclear spins forming an irregular polycyclic three-dimensional coupling lattice. The algorithm uses careful tailoring of the density operator space to only include nuclear spin states that are populated to a significant extent. The reduced state space is generated by analyzing spin connectivity and decoherence properties: rapidly relaxing states as well as correlations between topologically remote spins are dropped from the basis set. In the examples provided, the resulting reduction in the quantum mechanical simulation time is by many orders of magnitude.Comment: Submitted for publicatio

Roper Resonance and S_{11}(1535) from Lattice QCD

Using the constrained curve fitting method and overlap fermions with the lowest pion mass at $180 {\rm MeV}$, we observe that the masses of the first positive and negative parity excited states of the nucleon tend to cross over as the quark masses are taken to the chiral limit. Both results at the physical pion mass agree with the experimental values of the Roper resonance ($N^{1/2+}(1440)$) and $S_{11}$ ($N^{1/2-}(1535)$). This is seen for the first time in a lattice QCD calculation. These results are obtained on a quenched Iwasaki $16^3 \times 28$ lattice with $a = 0.2 {\rm fm}$. We also extract the ghost $\eta' N$ states (a quenched artifact) which are shown to decouple from the nucleon interpolation field above $m_{\pi} \sim 300 {\rm MeV}$. From the quark mass dependence of these states in the chiral region, we conclude that spontaneously broken chiral symmetry dictates the dynamics of light quarks in the nucleon.Comment: 10 pages, 5 figures, revised version to appear in PL

A pragmatic randomised controlled trial of healing therapy in a gastroenterology outpatient setting

Introduction: To determine the benefits of healing therapy (spiritual healing) as an adjunct to conventional management in irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Methods: 200 outpatients with IBS or IBD were randomised to either conventional treatment (control) or conventional plus five sessions of healing therapy (intervention). After 12 weeks controls also had healing therapy. Outcomes used were, the Measure Yourself Medical Outcomes Profile (MYMOP). IBS-QOL, IBDQ, and symptom measures. Results: There was a significant improvement in the MYMOP score at week 6 (p < 0.001) which was maintained to week 12 (p < 0.001) and 24 (p < 0.001). Improvements in MYMOP were significantly greater in the intervention group at both 6 (p < 0.001) and 12 weeks (p < 0.001) with effect sizes of 0.7 (95% CI: 0.4–1.1) and 0.8 (95% CI: 0.4–1.2). Condition-specific data for IBS showed that most QoL dimensions had a significant minimum 10-point score improvement at 6 and 12 weeks. The overall score improvement was 12.9 units at week 6 (p < 0.001), 12.4 units at week 12 (p < 0.001) and 13.8 units at week 24 (p < 0.001). In IBD there was also similar score improvement, but only up to week 12 were there associations of improved social and bowel functions (p < 0.001, respectively). Between group differences were identified for QoL scores in IBS at both week 6 (p < 0.001) and 12 (p < 0.001) but only for week 12 (p < 0.001) in the IBD group. Conclusions: The addition of healing therapy to conventional treatment was associated with improvement in symptoms and QoL in IBS, and to a lesser extent in IBD

Path Integrals in Polar Field Variables in QFT

We show how to transform a $d$-dimensional Euclidean path integral in terms of two (Cartesian) fields to a path integral in terms of polar field variables. First we present a conjecture that states how this transformation should be done. Then we show that this conjecture is correct in the case of two toy models. Finally the conjecture will be proven for a general QFT model with two fields