358 research outputs found
Fragile histidine triad gene inactivation in lung cancer: the European Early Lung Cancer project.
Rationale: Fragile histidine triad (FHIT) is a tumor suppressor gene
involved in the pathogenesis of lung cancer.
Objectives: The purpose of this study was to investigate the different
molecular alterations leading to the inactivation of FHIT gene
function and to validate their use as biomarkers of risk for progression
of the disease in patients belonging to the multicentric
European study for the Early detection of Lung Cancer (EUELC) who
were resected for early-stage lung tumors.
Methods: FHIT immunostaining was performed on 305 tumor samples.
Themethylation status of FHIT promoterwas assessed by nested
methylation-specific polymerase chain reaction (MSP-PCR) in 232
tumor and 225 normal lung samples ofwhich a subset of 187 patients
had available normal/tumorDNA pairs. Loss of heterozygosity (LOH)
at the FHIT locus was analyzed in 202 informative cases by D3S1300
and D3S1234 microsatellite markers.
Measurements and Main Results: Lost or reduced FHIT expression was
found in 36.7 and 75.7% of the tumor samples, respectively. Methylation
of the FHIT promoter was found in 36.7%of tumor and 32.7%
of normal lung samples, whereas LOH was detected in 61.9% of the
tumors. A strong association with complete loss of FHIT expression
was presentwhenmethylation and LOHwere analyzed together (P5
0.0064). Loss of FHIT protein expression was significantly more
frequent in squamous cell carcinoma histotype (P , 0.0001) and in
smokers (P5 0.008). FHIT methylation in normal lung was associated
with an increased risk of progressive disease (OR, 2.27; P 5 0.0415).
Conclusions:Our results indicate thatdifferentmolecularmechanisms
interplay to inactivate FHIT expression and support the proposition
that FHIT methylation in normal lung tissue could represent a prognostic
marker for progressive disease
Grain Surface Models and Data for Astrochemistry
AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions
Neutral-Current Four-Fermion Production in e+e- Interactions at LEP
Neutral-current four-fermion production, e+e- -> ffff is studied in 0.7/fb of
data collected with the L3 detector at LEP at centre-of-mass energies
root(s)=183-209GeV. Four final states are considered: qqvv, qqll, llll and
llvv, where l denotes either an electron or a muon. Their cross sections are
measured and found to agree with the Standard Model predictions. In addition,
the e+e- -> Zgamma* -> ffff process is studied and its total cross section at
the average centre-of-mass energy 196.6GeV is found to be 0.29 +/- 0.05 +/-
0.03 pb, where the first uncertainty is statistical and the second systematic,
in agreement with the Standard Model prediction of 0.22 pb. Finally, the mass
spectra of the qqll final states are analysed to search for the possible
production of a new neutral heavy particle, for which no evidence is found
Genome‐wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk
Genome‐wide association studies (GWAS) have identified 45 susceptibility loci associated with lung cancer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant genetic polymorphisms in the human genome. INDELs are highly associated with multiple human diseases, including lung cancer. However, limited studies with large‐scale samples have been available to systematically evaluate the effects of INDELs on lung cancer risk. Here, we performed a large‐scale meta‐analysis to evaluate INDELs and their risk for lung cancer in 23,202 cases and 19,048 controls. Functional annotations were performed to further explore the potential function of lung cancer risk INDELs. Conditional analysis was used to clarify the relationship between INDELs and SNPs. Four new risk loci were identified in genome‐wide INDEL analysis (1p13.2: rs5777156, Insertion, OR = 0.92, P = 9.10 × 10−8; 4q28.2: rs58404727, Deletion, OR = 1.19, P = 5.25 × 10−7; 12p13.31: rs71450133, Deletion, OR = 1.09, P = 8.83 × 10−7; and 14q22.3: rs34057993, Deletion, OR = 0.90, P = 7.64 × 10−8). The eQTL analysis and functional annotation suggested that INDELs might affect lung cancer susceptibility by regulating the expression of target genes. After conducting conditional analysis on potential causal SNPs, the INDELs in the new loci were still nominally significant. Our findings indicate that INDELs could be potentially functional genetic variants for lung cancer risk. Further functional experiments are needed to better understand INDEL mechanisms in carcinogenesis
Measurement of the Cross Section of W-boson pair production at LEP
The cross section of W-boson pair-production is measured with the L3 detector
at LEP. In a data sample corresponding to a total luminosity of 629.4/pb,
collected at centre-of-mass energies ranging from 189 to 209 GeV, 9834
four-fermion events with W bosons decaying into hadrons or leptons are
selected. The total cross section is measured with a precision of 1.4 % and
agrees with the Standard Model expectation. Assuming charged-lepton
universality, the branching fraction for hadronic W-boson decays is measured to
be: Br(W-->hadrons) = 67.50 +- 0.42 (stat.) +- 0.30(syst.) %, in agreement with
the Standard Model. Differential cross sections as a function of the W-
production angle are also measured for the semi-leptonic channels qqev and
qqmv
Determination of alphaS from Hadronic Event Shapes in e+e- Annihilation at 192 < sqrt(s) < 208 GeV
Results are presented from a study of the structure of high energy hadronic
events recorded by the L3 detector at sqrt(s)>192 GeV. The distributions of
several event shape variables are compared to resummed O(alphaS^2) QCD
calculations. We determine the strong coupling constant at three average
centre-of-mass energies: 194.4, 200.2 and 206.2 GeV. These measurements,
combined with previous L3 measurements at lower energies, demonstrate the
running of alphaS as expected in QCD and yield alphaS(mZ) = 0.1227 +- 0.0012 +-
0.0058, where the first uncertainty is experimental and the second is
theoretical
Measurement of the Topological Branching Fractions of the tau lepton at LEP
Using data collected with the L3 detector at LEP from 1992 to 1995 on the Z
peak, we determine the branching fractions of the tau lepton into one, three
and five charged particles to be:
B(tau->(1-prong)) = 85.274 +- 0.105 +- 0.073 %,
B(tau->(3-prong)) = 14.556 +- 0.105 +- 0.076 %,
B(tau->(5-prong)) = 0.170 +- 0.022 +- 0.026 %.
The first uncertainties are statistical and the second systematic. The
accuracy of these measurements alone is similar to that of the current world
average
Measurement of W Polarisation at LEP
The three different helicity states of W bosons produced in the reaction e+
e- -> W+ W- -> l nu q q~ at LEP are studied using leptonic and hadronic W
decays. Data at centre-of-mass energies \sqrt s = 183-209 GeV are used to
measure the polarisation of W bosons, and its dependence on the W boson
production angle. The fraction of longitudinally polarised W bosons is measured
to be 0.218 \pm 0.027 \pm 0.016 where the first uncertainty is statistical and
the second systematic, in agreement with the Standard Model expectation
Measurement of the Tau Branching Fractions into Leptons
Using data collected with the L3 detector near the Z resonance, corresponding
to an integrated luminosity of 150pb-1, the branching fractions of the tau
lepton into electron and muon are measured to be
B(tau->e nu nu) = (17.806 +- 0.104 (stat.) +- 0.076 (syst.)) %,
B(tau->mu nu nu) = (17.342 +- 0.110 (stat.) +- 0.067 (syst.)) %.
From these results the ratio of the charged current coupling constants of the
muon and the electron is determined to be g_mu/g_e = 1.0007 +- 0.0051. Assuming
electron-muon universality, the Fermi constant is measured in tau lepton decays
as G_F = (1.1616 +- 0.0058) 10^{-5} GeV^{-2}. Furthermore, the coupling
constant of the strong interaction at the tau mass scale is obtained as
alpha_s(m_tau^2) = 0.322 +- 0.009 (exp.) +- 0.015 (theory)
Search for Anomalous Couplings in the Higgs Sector at LEP
Anomalous couplings of the Higgs boson are searched for through the processes
e^+ e^- -> H gamma, e^+ e^- -> e^+ e^- H and e^+ e^- -> HZ. The mass range 70
GeV < m_H < 190 GeV is explored using 602 pb^-1 of integrated luminosity
collected with the L3 detector at LEP at centre-of-mass energies
sqrt(s)=189-209 GeV. The Higgs decay channels H -> ffbar, H -> gamma gamma, H
-> Z\gamma and H -> WW^(*) are considered and no evidence is found for
anomalous Higgs production or decay. Limits on the anomalous couplings d, db,
Delta(g1z), Delta(kappa_gamma) and xi^2 are derived as well as limits on the H
-> gamma gamma and H -> Z gamma decay rates
- …