1,121 research outputs found
DNA damage induced via independent generation of the radical resulting from formal hydrogen atom abstraction from the C1′-position of a nucleotide
AbstractBackground: Deoxyribonucleotide radicals resulting from formal C1′-hydrogen atom abstraction are important reactive intermediates in a variety of DNA-damage processes. The reactivity of these radicals can be affected by the agents that generate them and the environment in which they are produced. As an initial step in determining the factors that control the reactivity of these important radical species, we developed a mild method for their generation at a defined site within a biopolymer.Results: Irradiation of oligonucleotides containing a photolabile nucleotide produced C1'-DNA radicals. In the absence of potential reactants other than O2, approximately 90% of the damage events involve formation of alkaline-labile lesions, with the remainder resulting in direct strand breaks. The ratio of alkaline-labile lesions to direct strand breaks (∼ 9:1) is independent of whether the radical is generated in single-stranded DNA or double-stranded DNA. Strand damage is almost completely quenched under anaerobic conditions in the presence of low thiol concentrations. Competition studies with 02 indicate that the trapping rate of C1′-DNA radicals by β-mercaptoethanol is ∼ 1.1 x 107 M−1s−1Conclusions: The mild generation of the C1'-DNA radical in the absence of exogenous oxidants makes it possible to examine their intrinsic reactivity. In the absence of other reactants, the formation of direct strand breaks from C1′-radicals is, at most, a minor pathway. Competition studies between β-mercaptoethanol and 02 indicate that significantly higher thiol concentrations than those in vivo or some means of increasing the effective thiol concentration near DNA are needed for these reagents to prevent the formation of DNA lesions arising from the C1'-radical under aerobic conditions
The association of statin use after cancer diagnosis with survival in pancreatic cancer patients: a SEER-medicare analysis.
BackgroundPancreatic cancer has poor prognosis and existing interventions provide a modest benefit. Statin has anti-cancer properties that might enhance survival in pancreatic cancer patients. We sought to determine whether statin treatment after cancer diagnosis is associated with longer survival in those with pancreatic ductal adenocarcinoma (PDAC).MethodsWe analyzed data on 7813 elderly patients with PDAC using the linked Surveillance, Epidemiology, and End Results (SEER) - Medicare claims files. Information on the type, intensity and duration of statin use after cancer diagnosis was extracted from Medicare Part D. We treated statin as a time-dependent variable in a Cox regression model to determine the association with overall survival adjusting for follow-up, age, sex, race, neighborhood income, stage, grade, tumor size, pancreatectomy, chemotherapy, radiation, obesity, dyslipidemia, diabetes, chronic pancreatitis and chronic obstructive pulmonary disease (COPD).ResultsOverall, statin use after cancer diagnosis was not significantly associated with survival when all PDAC patients were considered (HR = 0.94, 95%CI 0.89, 1.01). However, statin use after cancer diagnosis was associated with a 21% reduced hazard of death (Hazard ratio = 0.79, 95% confidence interval (CI) 0.67, 0.93) in those with grade I or II PDAC and to a similar extent in those who had undergone a pancreatectomy, in those with chronic pancreatitis and in those who had not been treated with statin prior to cancer diagnosis.ConclusionsWe found that statin treatment after cancer diagnosis is associated with enhanced survival in patients with low-grade, resectable PDAC
Semi-classical buckling of stiff polymers
A quantitative theory of the buckling of a worm like chain based on a
semi-classical approximation of the partition function is presented. The
contribution of thermal fluctuations to the force-extension relation that
allows to go beyond the classical Euler buckling is derived in the linear and
non-linear regime as well. It is shown that the thermal fluctuations in the
nonlinear buckling regime increase the end-to-end distance of the semiflexible
rod if it is confined to 2 dimensions as opposed to the 3 dimensional case. Our
approach allows a complete physical understanding of buckling in D=2 and in D=3
below and above the Euler transition.Comment: Revtex, 17 pages, 4 figure
What Can the Accretion Induced Collapse of White Dwarfs Really Explain?
The accretion induced collapse (AIC) of a white dwarf into a neutron star has
been invoked to explain gamma-ray bursts, Type Ia supernovae, and a number of
problematic neutron star populations and specific binary systems. The ejecta
from this collapse has also been claimed as a source of r-process
nucleosynthesis. So far, most AIC studies have focussed on determining the
event rates from binary evolution models and less attention has been directed
toward understanding the collapse itself. However, the collapse of a white
dwarf into a neutron star is followed by the ejection of rare neutron-rich
isotopes. The observed abundance of these chemical elements may set a more
reliable limit on the rate at which AICs have taken place over the history of
the galaxy.
In this paper, we present a thorough study of the collapse of a massive white
dwarf in 1- and 2-dimensions and determine the amount and composition of the
ejected material. We discuss the importance of the input physics (equation of
state, neutrino transport, rotation) in determining these quantities. These
simulations affirm that AICs are too baryon rich to produce gamm-ray bursts and
do not eject enough nickel to explain Type Ia supernovae (with the possible
exception of a small subclass of extremely low-luminosity Type Ias). Although
nucleosynthesis constraints limit the number of neutron stars formed via AICs
to <0.1% of the total galactic neutron star population, AICs remain a viable
scenario for forming systems of neutron stars which are difficult to explain
with Type II core-collapse supernovae.Comment: Latex File, aaspp4 style, 18 pages total (5 figures), accepted by Ap
End of an Era? The Decline of Student Press Rights in the Wake of Hazelwood School District v. Kuhlmeier
Henipavirus and Tioman Virus Antibodies in Pteropodid Bats, Madagascar
Specimens were obtained from the 3 Malagasy fruit bats, Pteropus rufus, Eidolon dupreanum, and Rousettus madagascariensis. Antibodies against Nipah, Hendra, and Tioman viruses were detected by immunoassay in 23 and by serum neutralization tests in 3 of 427 serum samples, which suggests that related viruses have circulated in Madagascar
High and Persistent HIV Seroincidence in Men Who Have Sex with Men across 47 U.S. Cities
OBJECTIVE: To provide HIV seroincidence data among men who have sex with men (MSM) in the United States and to identify predictive factors for seroconversion. METHODS: From 1998-2002, 4684 high-risk MSM, age 18-60 years, participated in a randomized, placebo-controlled HIV vaccine efficacy trial at 56 U.S. clinical trial sites. Demographics, behavioral data, and HIV status were assessed at baseline and 6 month intervals. Since no overall vaccine efficacy was detected, data were combined from both trial arms to calculate HIV incidence based on person-years (py) of follow-up. Predictors of seroconversion, adjusted hazards ratio (aHR), were evaluated using a Cox proportional hazard model with time-varying covariates. RESULTS: Overall, HIV incidence was 2.7/100 py and was relatively uniform across study sites and study years. HIV incidence was highest among young men and men reporting unprotected sex, recreational drug use, and a history of a sexually transmitted infection. Independent predictors of HIV seroconversion included: age 18-30 years (aHR = 2.4; 95% CI 1.4,4.0), having >10 partners (aHR = 2.4; 95% CI 1.7,3.3), having a known HIV-positive male sex partner (aHR = 1.6; 95% CI 1.2, 2.0), unprotected anal intercourse with HIV positive/unknown male partners (aHR = 1.7; 95% CI 1.3, 2.3), and amphetamine (aHR = 1.6; 95% CI 1.1, 2.1) and popper (aHR = 1.7; 95% CI 1.3, 2.2) use. CONCLUSIONS: HIV seroincidence was high among MSM despite repeated HIV counseling and reported declines in sexual risk behaviors. Continuing development of new HIV prevention strategies and intensification of existing efforts will be necessary to reduce the rate of new HIV infections, especially among young men
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