The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 1: modifications to the androgen receptor

Prostate cancer is the second most common male malignancy in the western world an increasing incidence in an ageing population. Treatment of advanced prostate cancer relies on androgen deprivation. Although the majority of patients initially respond favourably to androgen deprivation therapy, the mean time to relapse is 12-18 months. Currently there are few treatments available for men who have developed resistance to hormone therapy, due to the lack of understanding of the molecular mechanisms underlying development of this disease. Recently, however, major advances have been made in understanding both androgen receptor (AR) dependent and independent pathways which promote development of hormone resistant prostate cancer. This review will focus on modifications to the AR and associated pathways. Molecular modifications to the androgen receptor itself, e.g. mutations and/or amplification, although involved in the development of hormone resistance cannot explain all cases. Phosphorylation of AR, via either Ras/MAP kinase or PI3K/Akt signal transduction pathways, have been shown to activate AR in both a ligand (androgen) dependent and independent fashion. During this review we will discuss the clinical evidence to support AR dependent pathways as mediators of hormone resistance

The Weighted Independent Domination Problem: ILP Model and Algorithmic Approaches

This work deals with the so-called weighted independent domination problem, which is an $NP$-hard combinatorial optimization problem in graphs. In contrast to previous work, this paper considers the problem from a non-theoretical perspective. The first contribution consists in the development of three integer linear programming models. Second, two greedy heuristics are proposed. Finally, the last contribution is a population-based iterated greedy metaheuristic which is applied in two different ways: (1) the metaheuristic is applied directly to each problem instance, and (2) the metaheuristic is applied at each iteration of a higher-level framework---known as construct, merge, solve \& adapt---to sub-instances of the tackled problem instances. The results of the considered algorithmic approaches show that integer linear programming approaches can only compete with the developed metaheuristics in the context of graphs with up to 100 nodes. When larger graphs are concerned, the application of the populated-based iterated greedy algorithm within the higher-level framework works generally best. The experimental evaluation considers graphs of different types, sizes, densities, and ways of generating the node and edge weights

The weighted independent domination problem: ILP model and algorithmic approaches

This work deals with the so-called weighted independent domination problem, which is an N P -hard combinatorial optimization problem in graphs. In contrast to previous theoretical work from the liter- ature, this paper considers the problem from an algorithmic perspective. The first contribution consists in the development of an integer linear programming model and a heuristic that makes use of this model. Sec- ond, two greedy heuristics are proposed. Finally, the last contribution is a population-based iterated greedy algorithm that takes profit from the better one of the two developed greedy heuristics. The results of the compared algorithmic approaches show that small problem instances based on random graphs are best solved by an efficient integer linear programming solver such as CPLEX. Larger problem instances are best tackled by the population-based iterated greedy algorithm. The experimental evaluation considers random graphs of different sizes, densities, and ways of generating the node and edge weights

Inactivation of myosin binding protein C homolog in zebrafish as a model for human cardiac hypertrophy and diastolic dysfunction

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Fast Purcell-enhanced single photon source in 1,550-nm telecom band from a resonant quantum dot-cavity coupling

High-bit-rate nanocavity-based single photon sources in the 1,550-nm telecom band are challenges facing the development of fibre-based long-haul quantum communication networks. Here we report a very fast single photon source in the 1,550-nm telecom band, which is achieved by a large Purcell enhancement that results from the coupling of a single InAs quantum dot and an InP photonic crystal nanocavity. At a resonance, the spontaneous emission rate was enhanced by a factor of 5 resulting a record fast emission lifetime of 0.2 ns at 1,550 nm. We also demonstrate that this emission exhibits an enhanced anti-bunching dip. This is the first realization of nanocavity-enhanced single photon emitters in the 1,550-nm telecom band. This coupled quantum dot cavity system in the telecom band thus provides a bright high-bit-rate non-classical single photon source that offers appealing novel opportunities for the development of a long-haul quantum telecommunication system via optical fibres.Comment: 16 pages, 4 figure

Tutte polynomial of pseudofractal scale-free web

The Tutte polynomial of a graph is a 2-variable polynomial which is quite important in both combinatorics and statistical physics. It contains various numerical invariants and polynomial invariants, such as the number of spanning trees, the number of spanning forests, the number of acyclic orientations, the reliability polynomial, chromatic polynomial and flow polynomial. In this paper, we study and gain recursive formulas for the Tutte polynomial of pseudofractal scale-free web (PSW) which implies logarithmic complexity algorithm is obtained to calculate the Tutte polynomial of PSW although it is NP-hard for general graph. We also obtain the rigorous solution for the the number of spanning trees of PSW by solving the recurrence relations derived from Tutte polynomial, which give an alternative approach for explicitly determining the number of spanning trees of PSW. Further more, we analysis the all-terminal reliability of PSW and compare the results with that of Sierpinski gasket which has the same number of nodes and edges with PSW. In contrast with the well-known conclusion that scale-free networks are more robust against removal of nodes than homogeneous networks (e.g., exponential networks and regular networks). Our results show that Sierpinski gasket (which is a regular network) are more robust against random edge failures than PSW (which is a scale-free network). Whether it is true for any regular networks and scale-free networks, is still a unresolved problem.Comment: 19pages,7figures. arXiv admin note: text overlap with arXiv:1006.533

The Swiss cheese model of safety incidents: are there holes in the metaphor?

BACKGROUND: Reason's Swiss cheese model has become the dominant paradigm for analysing medical errors and patient safety incidents. The aim of this study was to determine if the components of the model are understood in the same way by quality and safety professionals. METHODS: Survey of a volunteer sample of persons who claimed familiarity with the model, recruited at a conference on quality in health care, and on the internet through quality-related websites. The questionnaire proposed several interpretations of components of the Swiss cheese model: a) slice of cheese, b) hole, c) arrow, d) active error, e) how to make the system safer. Eleven interpretations were compatible with this author's interpretation of the model, 12 were not. RESULTS: Eighty five respondents stated that they were very or quite familiar with the model. They gave on average 15.3 (SD 2.3, range 10 to 21) "correct" answers out of 23 (66.5%) – significantly more than 11.5 "correct" answers that would expected by chance (p < 0.001). Respondents gave on average 2.4 "correct" answers regarding the slice of cheese (out of 4), 2.7 "correct" answers about holes (out of 5), 2.8 "correct" answers about the arrow (out of 4), 3.3 "correct" answers about the active error (out of 5), and 4.1 "correct" answers about improving safety (out of 5). CONCLUSION: The interpretations of specific features of the Swiss cheese model varied considerably among quality and safety professionals. Reaching consensus about concepts of patient safety requires further work

Lactate Regulates Metabolic and Proinflammatory Circuits in Control of T Cell Migration and Effector Functions

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Neutron Electric Dipole Moment Constraint on Scale of Minimal Left-Right Symmetric Model

Using an effective theory approach, we calculate the neutron electric dipole moment (nEDM) in the minimal left-right symmetric model with both explicit and spontaneous CP violations. We integrate out heavy particles to obtain flavor-neutral CP-violating effective Lagrangian. We run the Wilson coefficients from the electroweak scale to the hadronic scale using one-loop renormalization group equations. Using the state-of-the-art hadronic matrix elements, we obtain the nEDM as a function of right-handed W-boson mass and CP-violating parameters. We use the current limit on nEDM combined with the kaon-decay parameter $\epsilon$ to provide the most stringent constraint yet on the left-right symmetric scale $M_{W_R} > (10 \pm 3)$ TeV.Comment: 20 pages and 8 figure