246 research outputs found
Histone H2AX Is Phosphorylated at Sites of Retroviral DNA Integration but Is Dispensable for Postintegration Repair
The histone variant H2AX is rapidly phosphorylated (denoted {gamma}H2AX) in large chromatin domains (foci) flanking double strand DNA (dsDNA) breaks that are produced by ionizing radiation or genotoxic agents and during V(D)J recombination. H2AX-deficient cells and mice demonstrate increased sensitivity to dsDNA break damage, indicating an active role for {gamma}H2AX in DNA repair; however, {gamma}H2AX formation is not required for V(D)J recombination. The latter finding has suggested a greater dependence on {gamma}H2AX for anchoring free broken ends versus ends that are held together during programmed breakage-joining reactions. Retroviral DNA integration produces a unique intermediate in which a dsDNA break in host DNA is held together by the intervening viral DNA, and such a reaction provides a useful model to distinguish {gamma}H2AX functions. We found that integration promotes transient formation of {gamma}H2AX at retroviral integration sites as detected by both immunocytological and chromatin immunoprecipitation methods. These results provide the first direct evidence for the association of newly integrated viral DNA with a protein species that is an established marker for the onset of a DNA damage response. We also show that H2AX is not required for repair of the retroviral integration intermediate as determined by stable transduction. These observations provide independent support for an anchoring model for the function of {gamma}H2AX in chromatin repair
Nonsteroidal Anti-Inflammatory Drugs and Risk of Melanoma
Because nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit tumor growth in vitro, we investigated the association between NSAIDs and melanoma to determine if there was epidemiologic evidence of a chemopreventive effect from these medications. Three hundred twenty-seven subjects with incident melanoma and 119 melanoma-free controls completed a structured interview assessing melanoma risk factors. The unadjusted odds ratio (OR) for use of nonaspirin NSAIDs was 0.58 (95% CI 0.31–1.11), in a comparison of subjects with melanoma to controls. After adjustment for melanoma risk factors, the OR was 0.71 (95% CI 0.23–2.02). Aspirin users had an unadjusted OR of 0.85 (95% CI 0.45–1.69) and an adjusted OR of 1.45 (95% CI 0.44–4.74). In this pilot study, we found no evidence of a significant association between analgesic use and melanoma risk when potential confounders are assessed. Based on conflicting reports in the literature, meta-analysis may be appropriate
Pretreatment minimal staging for non-small cell lung cancer: an updated consensus report
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31247/1/0000153.pd
Colorectal Polyps in Carriers of the APC I1307K Polymorphism
The probability of colorectal cancer is moderately increased among carriers of the APC I1307K polymorphism. However, it is not known if endoscopic surveillance of this high-risk group is warranted. The prevalence of polyps and adenomas in specimens of colorectal cancer who are carriers and noncarriers of the APC I1307K polymorphism is compared.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41394/1/10350_2005_Article_167.pd
Observation of charge-dependent azimuthal correlations and possible local strong parity violation in heavy ion collisions
Parity-odd domains, corresponding to non-trivial topological solutions of the
QCD vacuum, might be created during relativistic heavy-ion collisions. These
domains are predicted to lead to charge separation of quarks along the orbital
momentum of the system created in non-central collisions. To study this effect,
we investigate a three particle mixed harmonics azimuthal correlator which is a
\P-even observable, but directly sensitive to the charge separation effect. We
report measurements of this observable using the STAR detector in Au+Au and
Cu+Cu collisions at =200 and 62~GeV. The results are presented
as a function of collision centrality, particle separation in rapidity, and
particle transverse momentum. A signal consistent with several of the
theoretical expectations is detected in all four data sets. We compare our
results to the predictions of existing event generators, and discuss in detail
possible contributions from other effects that are not related to parity
violation.Comment: 17 pages, 14 figures, as accepted for publication in Physical Review
C
Longitudinal Spin Transfer to and Hyperons in Polarized Proton-Proton Collisions at = 200 GeV
The longitudinal spin transfer, , from high energy polarized protons
to and hyperons has been measured for the first time
in proton-proton collisions at with the STAR
detector at RHIC. The measurements cover pseudorapidity, , in the range
and transverse momenta, , up to . The longitudinal spin transfer is found to be for inclusive
and for
inclusive hyperons with and . The dependence on and is presented.Comment: 5 pages, 4 figure
Cost-Effectiveness of Adding Cetuximab to Platinum-Based Chemotherapy for First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer
To assess the cost effectiveness of adding cetuximab to platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) from the perspective of the Canadian public healthcare system.We developed a Markov state transition model to project the lifetime clinical and economic consequences of recurrent or metastatic HNSCC. Transition probabilities were derived from a phase III trial of cetuximab in patients with recurrent or metastatic HNSCC. Cost estimates were obtained from London Health Sciences Centre and the Ontario Case Costing Initiative, and expressed in 2011 CAD. A three year time horizon was used. Future costs and health benefits were discounted at 5%.In the base case, cetuximab plus platinum-based chemotherapy compared to platinum-based chemotherapy alone led to an increase of 0.093 QALY and an increase in cost of 386,000 per QALY gained. The cost effectiveness ratio was most sensitive to the cost per mg of cetuximab and the absolute risk of progression among patients receiving cetuximab.The addition of cetuximab to standard platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic HNSCC has an ICER that exceeds $100,000 per QALY gained. Cetuximab can only be economically attractive in this patient population if the cost of cetuximab is substantially reduced or if future research can identify predictive markers to select patients most likely to benefit from the addition of cetuximab to chemotherapy
Charged and strange hadron elliptic flow in Cu+Cu collisions at = 62.4 and 200 GeV
We present the results of an elliptic flow analysis of Cu+Cu collisions
recorded with the STAR detector at 62.4 and 200GeV. Elliptic flow as a function
of transverse momentum is reported for different collision centralities for
charged hadrons and strangeness containing hadrons , ,
, in the midrapidity region . Significant reduction in
systematic uncertainty of the measurement due to non-flow effects has been
achieved by correlating particles at midrapidity, , with those at
forward rapidity, . We also present azimuthal correlations in
p+p collisions at 200 GeV to help estimating non-flow effects. To study the
system-size dependence of elliptic flow, we present a detailed comparison with
previously published results from Au+Au collisions at 200 GeV. We observe that
() of strange hadrons has similar scaling properties as were
first observed in Au+Au collisions, i.e.: (i) at low transverse momenta,
, scales with transverse kinetic energy, , and
(ii) at intermediate , , it scales with the number of
constituent quarks, . We have found that ideal hydrodynamic calculations
fail to reproduce the centrality dependence of () for
and . Eccentricity scaled values, , are larger
in more central collisions, suggesting stronger collective flow develops in
more central collisions. The comparison with Au+Au collisions which go further
in density shows depend on the system size, number of
participants . This indicates that the ideal hydrodynamic limit is
not reached in Cu+Cu collisions, presumably because the assumption of
thermalization is not attained.Comment: 18 pages, 14 figure
- …