575 research outputs found
The role of microRNA-binding site polymorphisms in DNA repair genes as risk factors for bladder cancer and breast cancer and their impact on radiotherapy outcomes
MicroRNAs (miRNAs) are involved in post-transcriptional regulation of gene expression through binding to messenger RNAs (mRNA) thereby promoting mRNA degradation or altered translation. A single-nucleotide polymorphism (SNP) located within a miRNA-binding site could thus alter mRNA translation and influence cancer risk and treatment response. The common SNPs located within the 3âČ-untranslated regions of 20 DNA repair genes were analysed for putative miRNA-binding sites using bioinformatics algorithms, calculating the difference in Gibbs free binding energy (ÎÎG) for each wild-type versus variant allele. Seven SNPs were selected to be genotyped in germ line DNAs both from a bladder cancer caseâcontrol series (752 cases and 704 controls) and 202 muscle-invasive bladder cancer radiotherapy cases. The PARP-1 SNP rs8679 was also genotyped in a breast cancer caseâcontrol series (257 cases and 512 controls). Without adjustment for multiple testing, multivariate analysis demonstrated an association with increased bladder cancer risk with PARP1 rs8679 (Ptrend = 0.05) while variant homozygotes of PARP1 rs8679 were also noted to have an increased breast cancer risk (P = 0.03). In the radiotherapy cases, carriers of the RAD51 rs7180135 minor allele had improved cancer-specific survival (hazard ratio 0.52, 95% confidence interval 0.31â0.87, P = 0.01). This is the first report of associations between DNA repair gene miRNA-binding site SNPs with bladder and breast cancer risk and radiotherapy outcomes. If validated, these findings may give further insight into the biology of bladder carcinogenesis, allow testing of the RAD51 SNP as a potential predictive biomarker and also reveal potential targets for new cancer treatments
Remodeling the B-model
We propose a complete, new formalism to compute unambiguously B-model open
and closed amplitudes in local Calabi-Yau geometries, including the mirrors of
toric manifolds. The formalism is based on the recursive solution of matrix
models recently proposed by Eynard and Orantin. The resulting amplitudes are
non-perturbative in both the closed and the open moduli. The formalism can then
be used to study stringy phase transitions in the open/closed moduli space. At
large radius, this formalism may be seen as a mirror formalism to the
topological vertex, but it is also valid in other phases in the moduli space.
We develop the formalism in general and provide an extensive number of checks,
including a test at the orbifold point of A_p fibrations, where the amplitudes
compute the 't Hooft expansion of Wilson loops in lens spaces. We also use our
formalism to predict the disk amplitude for the orbifold C^3/Z_3.Comment: 83 pages, 9 figure
Thermoelectric effects of an Aharonov-Bohm interferometer with an embedded quantum dot in the Kondo regime
Thermoelectric effects are studied in an Aharonov-Bohm (AB) interferometer
with an embedded quantum dot in the Kondo regime. The AB flux-dependent
transmission probability has an asymmetrical shape arising from the Fano
interference between the direct tunneling path and the Kondo-resonant tunneling
path through a quantum dot. The sign and magnitude of thermopower can be
modulated by the AB flux and the direct tunneling amplitude. In addition, the
thermopower is anomalously enhanced by the Kondo correlation in the quantum dot
near the Kondo temperature (). The Kondo correlation in the quantum dot
also leads to crossover behavior in diagonal transport coefficients as a
function of temperature. The amplitude of an AB oscillation in electric and
thermal conductances is small at temperatures far above , but becomes
enhanced as the system is cooled below . The AB oscillation is strong in
the thermopower and Lorenz number within the crossover region near the Kondo
temperature.Comment: 16 pages, 10 figure
Questions of fairness and anti-doping in US cycling: The contrasting experiences of professionals and amateurs
The focus of researchers, media and policy on doping in cycling is often limited to the professional level of the sport. However, anti-doping test results since 2001 demonstrate that banned substances are also used by US cyclists at lower levels of the sport, necessitating a broader view of the patterns and motivations of substance use within the sport. In this article, we describe and explain the doping culture that has emerged in domestic US cycling among amateur and semi-professionals. Through analysis of records from sports governing bodies and journalistic reports, we assess the range of violation types and discuss the detection and punishing of riders who were not proven to have intended to cheat but became "collateral damage" in the war on doping. We argue that the phenomenon of doping is more complex than what has been shown to occur in elite sport, as it includes a wider variety of behaviours, situations and motivations. We develop fresh insights by examining cases where doping has been accidental, intrinsically motivated, non-performance enhancing or the result of prescribed medical treatments banned by anti-doping authorities. Such trends call into question the fairness of anti-doping measures, and we discuss the possibility of developing localised solutions to testing and sanctioning amateur athletes
A role for XRCC2 gene polymorphisms in breast cancer risk and survival
Background
The XRCC2 gene is a key mediator in the homologous recombination repair of DNA double strand breaks. It is hypothesised that inherited variants in the XRCC2 gene might also affect susceptibility to, and survival from, breast cancer.
Methods
The study genotyped 12 XRCC2 tagging single nucleotide polymorphisms (SNPs) in 1131 breast cancer cases and 1148 controls from the Sheffield Breast Cancer Study (SBCS), and examined their associations with breast cancer risk and survival by estimating ORs and HRs, and their corresponding 95% CIs. Positive findings were further investigated in 860 cases and 869 controls from the Utah Breast Cancer Study (UBCS) and jointly analysed together with available published data for breast cancer risk. The survival findings were further confirmed in studies (8074 cases) from the Breast Cancer Association Consortium (BCAC).
Results
The most significant association with breast cancer risk in the SBCS dataset was the XRCC2 rs3218408 SNP (recessive model p=2.3Ă10â4, minor allele frequency (MAF)=0.23). This SNP yielded an ORrec of 1.64 (95% CI 1.25 to 2.16) in a two-site analysis of SBCS and UBCS, and a meta-ORrec of 1.33 (95% CI 1.12 to 1.57) when all published data were included. This SNP may mark a rare risk haplotype carried by two in 1000 of the control population. Furthermore, the XRCC2 coding R188H SNP (rs3218536, MAF=0.08) was significantly associated with poor survival, with an increased per-allele HR of 1.58 (95% CI 1.01 to 2.49) in a multivariate analysis. This effect was still evident in a pooled meta-analysis of 8781 breast cancer patients from the BCAC (HR 1.19, 95% CI 1.05 to 1.36; p=0.01).
Conclusions
These findings suggest that XRCC2 SNPs may influence breast cancer risk and survival
Origin of the Local Bubble
We present a new unbiased search for OB associations in the Solar neighbourhood
which have hosted the progenitor stars of the core collapse supernovae responsible for the
Local Bubble in the interstellar gas. For this purpose we have analyzed a volume complete
set (with a diameter of 400 pc) of B stars drawn from the Hipparcos catalogue and the Arivel
data base, from which candidate members were selected by a kinematical criterion. After
careful dereddening the star colours we have constructed a colour-magnitude diagram and
confirmed that the Upper Scorpius, Upper Centaurus Lupus, and Lower Centaurus Crux
subgroups of the Sco OB2 association are the youngest nearby OB associations. We dated
their ages with theoretical isochrones in the range of 20â30 Myr, in agreement with previous
work. We have traced backwards in time the paths of the stars and found that they entered
the volume of the present bubble at 10 to 15 Myr ago. We argue that the Local Bubble began
to form then and estimate that 14 to 20 supernovae have exploded since. The implied energy
input into the ambient medium can be shown to be sufficient to excavate a bubble of the
presently observed size
Heavy quarkonium: progress, puzzles, and opportunities
A golden age for heavy quarkonium physics dawned a decade ago, initiated by
the confluence of exciting advances in quantum chromodynamics (QCD) and an
explosion of related experimental activity. The early years of this period were
chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in
2004, which presented a comprehensive review of the status of the field at that
time and provided specific recommendations for further progress. However, the
broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles
could only be partially anticipated. Since the release of the YR, the BESII
program concluded only to give birth to BESIII; the -factories and CLEO-c
flourished; quarkonium production and polarization measurements at HERA and the
Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the
deconfinement regime. All these experiments leave legacies of quality,
precision, and unsolved mysteries for quarkonium physics, and therefore beg for
continuing investigations. The plethora of newly-found quarkonium-like states
unleashed a flood of theoretical investigations into new forms of matter such
as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the
spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b},
and b\bar{c} bound states have been shown to validate some theoretical
approaches to QCD and highlight lack of quantitative success for others. The
intriguing details of quarkonium suppression in heavy-ion collisions that have
emerged from RHIC have elevated the importance of separating hot- and
cold-nuclear-matter effects in quark-gluon plasma studies. This review
systematically addresses all these matters and concludes by prioritizing
directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K.
Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D.
Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A.
Petrov, P. Robbe, A. Vair
Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS
We present the results of a search for new, heavy particles that decay at a
significant distance from their production point into a final state containing
charged hadrons in association with a high-momentum muon. The search is
conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV
and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS
detector operating at the Large Hadron Collider. Production of such particles
is expected in various scenarios of physics beyond the standard model. We
observe no signal and place limits on the production cross-section of
supersymmetric particles in an R-parity-violating scenario as a function of the
neutralino lifetime. Limits are presented for different squark and neutralino
masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final
version to appear in Physics Letters
Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment
This paper describes an analysis of the angular distribution of W->enu and
W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with
the ATLAS detector at the LHC in 2010, corresponding to an integrated
luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and
the missing transverse energy, the W decay angular distribution projected onto
the transverse plane is obtained and analysed in terms of helicity fractions
f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV
and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw
> 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour,
are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017
+/- 0.030, where the first uncertainties are statistical, and the second
include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables,
revised author list, matches European Journal of Physics C versio
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