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

Other race effect on amygdala response during affective facial processing in major depression

Objective The other race effect, also known as own race bias, refers to the enhanced ability to recognize faces belonging to one's own race relative to faces from another race. The other race effect is associated with increased amygdala response in healthy individuals. The amygdala is a key node in emotion processing which shows impaired functioning in depression and has been proposed to be a marker of depressive state. We investigated the impact of the other race effect on amygdala responses in depression. Methods Participants were 30 individuals with major depression (mean age 39.4 years) and 23 healthy individuals (mean age: 38.8 years) recruited from the community. Participants were Asian, Black/African American and Caucasian. During a functional MRI scan, participants viewed Caucasian faces which displayed a range of sad expressions. A region of interest analysis of left and right amygdala responses was performed. Results Increased bilateral amygdala responses were observed in response to the Caucasian face stimuli in participants who were Asian or Black/African American as compared to Caucasian participants in both healthy individuals and individuals with major depression. There was no significant group by race interaction effect. Conclusions Increased amygdala responses associated with the other race effect were evident in both individuals with major depression and in healthy participants. Increased amygdala responses with the other race effect is a potential confound of the neural correlates of facial processing in healthy participants and in mental health disorders. The implications of the other race effect on impairments in interpersonal functioning in depression require further investigation

Mott physics and band topology in materials with strong spin-orbit interaction

Recent theory and experiment have revealed that strong spin-orbit coupling can have dramatic qualitative effects on the band structure of weakly interacting solids. Indeed, it leads to a distinct phase of matter, the topological band insulator. In this paper, we consider the combined effects of spin-orbit coupling and strong electron correlation, and show that the former has both quantitative and qualitative effects upon the correlation-driven Mott transition. As a specific example we take Ir-based pyrochlores, where the subsystem of Ir 5d electrons is known to undergo a Mott transition. At weak electron-electron interaction, we predict that Ir electrons are in a metallic phase at weak spin-orbit interaction, and in a topological band insulator phase at strong spin-orbit interaction. Very generally, we show that with increasing strength of the electron-electron interaction, the effective spin-orbit coupling is enhanced, increasing the domain of the topological band insulator. Furthermore, in our model, we argue that with increasing interactions, the topological band insulator is transformed into a "topological Mott insulator" phase, which is characterized by gapless surface spin-only excitations. The full phase diagram also includes a narrow region of gapless Mott insulator with a spinon Fermi surface, and a magnetically ordered state at still larger electron-electron interaction.Comment: 10+ pages including 3+ pages of Supplementary Informatio

Observation of symmetrical reflection sidebands in a silica suspended-core fiber Bragg grating

Author name used in this publication: K. C. D. ChengAuthor name used in this publication: C. LuAuthor name used in this publication: H. Y. Tam2010-2011 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Spin-related tunneling through a nanostructured electric-magnetic barrier on the surface of a topological insulator

We investigate quantum tunneling through a single electric and/or magnetic barrier on the surface of a three-dimensional topological insulator. We found that (1) the propagating behavior of electrons in such system exhibits a strong dependence on the direction of the incident electron wavevector and incident energy, giving the possibility to construct a wave vector and/or energy filter; (2) the spin orientation can be tuned by changing the magnetic barrier structure as well as the incident angles and energies

Computing the Spectrum of a Heterotic Flux Vacuum

We compute the massless spectra of a set of flux vacua of the heterotic string. The vacua we study include well-known non-Kahler T^2-fibrations over K3 with SU(3) structure and intrinsic torsion. Following gauged linear sigma models of these vacua into phases governed by asymmetric Landau-Ginzburg orbifolds allows us to compute the spectrum using generalizations of familiar LG-orbifold techniques. We study several four- and six-dimensional examples with N=2 spacetime supersymmetry in detail.Comment: 1+49 pages, updated to JHEP version (added appendix and minor revisions

A fresh look at the evolution and diversification of photochemical reaction centers

In this review, I reexamine the origin and diversification of photochemical reaction centers based on the known phylogenetic relations of the core subunits, and with the aid of sequence and structural alignments. I show, for example, that the protein folds at the C-terminus of the D1 and D2 subunits of Photosystem II, which are essential for the coordination of the water-oxidizing complex, were already in place in the most ancestral Type II reaction center subunit. I then evaluate the evolution of reaction centers in the context of the rise and expansion of the different groups of bacteria based on recent large-scale phylogenetic analyses. I find that the Heliobacteriaceae family of Firmicutes appears to be the earliest branching of the known groups of phototrophic bacteria; however, the origin of photochemical reaction centers and chlorophyll synthesis cannot be placed in this group. Moreover, it becomes evident that the Acidobacteria and the Proteobacteria shared a more recent common phototrophic ancestor, and this is also likely for the Chloroflexi and the Cyanobacteria. Finally, I argue that the discrepancies among the phylogenies of the reaction center proteins, chlorophyll synthesis enzymes, and the species tree of bacteria are best explained if both types of photochemical reaction centers evolved before the diversification of the known phyla of phototrophic bacteria. The primordial phototrophic ancestor must have had both Type I and Type II reaction centers

LIGHT Induces Distinct Signals to Clear an AAV-Expressed Persistent Antigen in the Mouse Liver and to Induce Liver Inflammation

Background: Infection with adeno-associated virus (AAV) vector with liver tropism leads to persistent expression of foreign antigens in the mouse liver, with no significant liver inflammation or pathology. This provides a model to investigate antigen persistence in the liver and strategies to modulate host immunity to reduce or clear the foreign antigen expressed from AAV vector in the liver. Methods/Principal Findings: We showed that expressing LIGHT with an adenovirus vector (Ad) in mice with established AAV in the liver led to clearance of the AAV. Ad-LIGHT enhanced CD8 effector T cells in the liver, correlated with liver inflammation. LTbR-Ig proteins blocked Ad-LIGHT in clearing AAV. Interestingly, in LTbR-null mice, Ad-LIGHT still cleared AAV but caused no significant liver inflammation. Conclusions/Significance: Our data suggest that LIGHT interaction with the LTbR plays a critical role in liver inflammation but is not required for LIGHT-mediated AAV clearance. These findings will shed light on developing novel immunotherapeutic

Health status, use of healthcare, and socio-economic implications of cancer survivorship in Portugal : results from the fourth national health survey

Health status, use of healthcare, and socio-economic implications of cancer survivorship in Portugal: results from the Fourth National Health SurveyUnderstanding the morbidity and socio-economic implications of cancer survivorship is essential for a comprehensive management of oncological diseases. We compared cancer survivors (CS) with the general population regarding health status, use of healthcare resources and socio-economic condition. We analyzed data from a representative sample of the Portuguese population aged a parts per thousand yen15 years (n = 35,229). We defined three groups of CS, according to the time since diagnosis and the latest cancer treatment: CS 1 diagnosis within 12 months of interview; CS 2 diagnosis more than 12 months before and treatment in the previous 12 months; CS 3 diagnosis and treatment more than 12 months before. These were compared with the general population, adjusting for differences in sex, age, and place of residence. The prevalence of CS was 2.2 % (CS 1: 0.2 %; CS 2: 0.9 %, CS 3: 1.1 %). Self-perceived health status was worse among CS and short-time incapacity more frequent among CS 1 and CS 2. Health expenses were higher in the early stages of survivorship. Lower household income and financial difficulties were more frequent in CS 1 and CS 3 men, respectively. This study confirmed the higher consumption of healthcare resources and worse financial situation among CS. Our study provides valuable information for understanding the global impact of cancer survivorship.The authors thank the National Health Systems Observatory (Observatorio Nacional de Saude), National Institute of Health Dr. Ricardo Jorge (INSA), Ministry of Health and the National Institute of Statistics (INE) for providing the data (Ministerio da Saude, Instituto Nacional de Saude Dr. Ricardo Jorge; IP, Departamento de Epidemiologia/Instituto Nacional de Estatistica: Inquerito Nacional de Saude 2005/2006). Luis Pacheco-Figueiredo received a grant from the Fundacao para a Ciencia e a Tecnologia (SFRH/SINTD/60124/2009)

Potential application of mesh-free SPH method in turbulent river flows

A comprehensive review has been completed on the simulation of turbulent flow over rough beds using mesh-free particle models. Based on the outcomes of this review, an improved Smoothed Particle Hydrodynamics (SPH) method has been developed for open channel flows over a rough bed, in which a mixing length model is used for modeling the 2D turbulence and a drag force equation is proposed for treating the boundary shear. The proposed model was applied to simulate a depth-limited open channel flow over a rough bed surface. The results of the velocity profile and shear stress distribution show a good agreement with the experimental data and existing analytical solutions. This work reveals that in order to correctly model turbulent open channel flow over a rough bed, the treatment of both flow turbulence and bed roughness effect is equally important