3,705 research outputs found
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 -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 to provide the most stringent constraint yet on
the left-right symmetric scale TeV.Comment: 20 pages and 8 figure
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