237 research outputs found
The Origin of Black Hole Entropy in String Theory
I review some recent work in which the quantum states of string theory which
are associated with certain black holes have been identified and counted. For
large black holes, the number of states turns out to be precisely the
exponential of the Bekenstein-Hawking entropy. This provides a statistical
origin for black hole thermodynamics in the context of a potential quantum
theory of gravity.Comment: 18 pages (To appear in the proceedings of the Pacific Conference on
Gravitation and Cosmology, Seoul, Korea, February 1-6, 1996.
"It's making contacts" : notions of social capital and implications for widening access to medical education
Acknowledgements Our thanks to the Medical Schools Council (MSC) of the UK for funding Study A; REACH Scotland for funding Study B; and Queen Mary University of London, and to the medical school applicants and students who gave their time to be interviewed. Our thanks also to Dr Sean Zhou and Dr Sally Curtis, and Manjul Medhi, for their help with data collection for studies A and B respectively. Our thanks also to Dr Lara Varpio, Uniformed Services University of the USA, for her advice and guidance on collating data sets and her comments on the draft manuscript.Peer reviewedPublisher PD
High energy emission from microquasars
The microquasar phenomenon is associated with the production of jets by X-ray
binaries and, as such, may be associated with the majority of such systems. In
this chapter we briefly outline the associations, definite, probable, possible,
and speculative, between such jets and X-ray, gamma-ray and particle emission.Comment: Contributing chapter to the book Cosmic Gamma-Ray Sources, K.S. Cheng
and G.E. Romero (eds.), to be published by Kluwer Academic Publishers,
Dordrecht, 2004. (19 pages
Intact interferon signaling in peripheral blood leukocytes of high-grade osteosarcoma patients
High-grade osteosarcoma has a poor prognosis with an overall survival rate of about 60 percent. The recently closed European and American Osteosarcoma Study Group (EURAMOS)-1 trial investigates the efficacy of adjuvant chemotherapy with or without interferon-α. It is however unknown whether the interferon-signaling pathways in immune cells of osteosarcoma patients are functional. We studied the molecular and functional effects of interferon treatment on peripheral blood lymphocytes and monocytes of osteosarcoma patients, both in vivo and ex vivo. In contrast to other tumor types, in osteosarcoma, interferon signaling as determined by the phosphorylation of signal transducer and activator of transcription (STAT)1 at residue 701 was intact in immune cell subsets of 33 osteosarcoma patients as compared to 19 healthy controls. Also, cytolytic activity of interferon-α stimulated natural killer cells against allogeneic (n = 7 patients) and autologous target cells (n = 3 patients) was not impaired. Longitudinal monitoring of three osteosarcoma patients on interferon-α monotherapy revealed a relative increase in the CD16-positive subpopulation of monocytes during treatment. Since interferon signaling is intact in immune cells of osteosarcoma patients, there is a potential for indirect immunological effects of interferon-α treatment in osteosarcoma
Enhancement of Vaccinia Virus Based Oncolysis with Histone Deacetylase Inhibitors
Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells
Quantum Measurement Theory in Gravitational-Wave Detectors
The fast progress in improving the sensitivity of the gravitational-wave (GW)
detectors, we all have witnessed in the recent years, has propelled the
scientific community to the point, when quantum behaviour of such immense
measurement devices as kilometer-long interferometers starts to matter. The
time, when their sensitivity will be mainly limited by the quantum noise of
light is round the corner, and finding the ways to reduce it will become a
necessity. Therefore, the primary goal we pursued in this review was to
familiarize a broad spectrum of readers with the theory of quantum measurements
in the very form it finds application in the area of gravitational-wave
detection. We focus on how quantum noise arises in gravitational-wave
interferometers and what limitations it imposes on the achievable sensitivity.
We start from the very basic concepts and gradually advance to the general
linear quantum measurement theory and its application to the calculation of
quantum noise in the contemporary and planned interferometric detectors of
gravitational radiation of the first and second generation. Special attention
is paid to the concept of Standard Quantum Limit and the methods of its
surmounting.Comment: 147 pages, 46 figures, 1 table. Published in Living Reviews in
Relativit
How reliably can we predict the reliability of protein structure predictions?
Background:
Comparative methods have been the standard techniques for in silico protein structure prediction. The prediction is based on a multiple alignment that contains both reference sequences with known structures and the sequence whose unknown structure is predicted. Intensive research has been made to improve the quality of multiple alignments, since misaligned parts of the multiple alignment yield misleading predictions. However, sometimes all methods fail to predict the correct alignment, because the evolutionary signal is too weak to find the homologous parts due to the large number of mutations that separate the sequences.
Results:
Stochastic sequence alignment methods define a posterior distribution of possible multiple alignments. They can highlight the most likely alignment, and above that, they can give posterior probabilities for each alignment column. We made a comprehensive study on the HOMSTRAD database of structural alignments, predicting secondary structures in four different ways. We showed that alignment posterior probabilities correlate with the reliability of secondary structure predictions, though the strength of the correlation is different for different protocols. The correspondence between the reliability of secondary structure predictions and alignment posterior probabilities is the closest to the identity function when the secondary structure posterior probabilities are calculated from the posterior distribution of multiple alignments. The largest deviation from the identity function has been obtained in the case of predicting secondary structures from a single optimal pairwise alignment. We also showed that alignment posterior probabilities correlate with the 3D distances between C α amino acids in superimposed tertiary structures.
Conclusion:
Alignment posterior probabilities can be used to a priori detect errors in comparative models on the sequence alignment level. </p
Physics, Astrophysics and Cosmology with Gravitational Waves
Gravitational wave detectors are already operating at interesting sensitivity
levels, and they have an upgrade path that should result in secure detections
by 2014. We review the physics of gravitational waves, how they interact with
detectors (bars and interferometers), and how these detectors operate. We study
the most likely sources of gravitational waves and review the data analysis
methods that are used to extract their signals from detector noise. Then we
consider the consequences of gravitational wave detections and observations for
physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version
<http://www.livingreviews.org/lrr-2009-2
Dynamical Boson Stars
The idea of stable, localized bundles of energy has strong appeal as a model
for particles. In the 1950s John Wheeler envisioned such bundles as smooth
configurations of electromagnetic energy that he called {\em geons}, but none
were found. Instead, particle-like solutions were found in the late 1960s with
the addition of a scalar field, and these were given the name {\em boson
stars}. Since then, boson stars find use in a wide variety of models as sources
of dark matter, as black hole mimickers, in simple models of binary systems,
and as a tool in finding black holes in higher dimensions with only a single
killing vector. We discuss important varieties of boson stars, their dynamic
properties, and some of their uses, concentrating on recent efforts.Comment: 79 pages, 25 figures, invited review for Living Reviews in
Relativity; major revision in 201
Probabilistic Phylogenetic Inference with Insertions and Deletions
A fundamental task in sequence analysis is to calculate the probability of a multiple alignment given a phylogenetic tree relating the sequences and an evolutionary model describing how sequences change over time. However, the most widely used phylogenetic models only account for residue substitution events. We describe a probabilistic model of a multiple sequence alignment that accounts for insertion and deletion events in addition to substitutions, given a phylogenetic tree, using a rate matrix augmented by the gap character. Starting from a continuous Markov process, we construct a non-reversible generative (birth–death) evolutionary model for insertions and deletions. The model assumes that insertion and deletion events occur one residue at a time. We apply this model to phylogenetic tree inference by extending the program dnaml in phylip. Using standard benchmarking methods on simulated data and a new “concordance test” benchmark on real ribosomal RNA alignments, we show that the extended program dnamlε improves accuracy relative to the usual approach of ignoring gaps, while retaining the computational efficiency of the Felsenstein peeling algorithm
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