302 research outputs found
Nucleolytic Cleavage of the Mixed Lineage Leukemia Breakpoint Cluster Region during Apoptosis
Site-Specific Topoisomerase I-Mediated DNA Cleavage Induced by Nogalamycin: A Potential Role of Ligand-Induced DNA Bending at a Distal Site
Sai Peng Sim, Daniel S. Pilch and LEroy F. Li
QRS duration and cardiovascular mortality in Asian patients with heart failure and preserved and reduced ejection fraction
Substituted benzo[i]phenanthridines as mammalian topoisomerase-Targeting agents
Several benzo[c]phenanthridine and protoberberine alkaloids, such as nitidine and berberrubine, are known to induce DNA cleavage in the presence of either topoisomerase I or II. Structure–activity studies performed on various analogues related to benzo[c]phenanthridine and protoberberine alkaloids have provided insights into structural features that influence this topoisomerase-targeting activity. Modifications within the A-ring of benzo[c]phenanthridine and protoberberine alkaloids can significantly alter their ability to enhance the cleavable complex formation that occurs between DNA and topoisomerases. Select benzo[i]phenanthridines were synthesized as potential bioisosteres of nitidine and its analogues. In the present study, 2,3-methylenedioxy-8,9-dimethoxybenzo[i]phenanthridine, 2,3-methylenedioxy-8,9-dimethoxy-5-methylbenzo[i]phenanthridine, 2,3,8,9-tetramethoxybenzo[i]phenanthridine and 5-methyl-2,3,8,9-tetramethoxybenzo[i]phenanthridine were synthesized. These benzo[i]phenanthridine derivatives were evaluated for their ability to enhance cleavable complex formation in the presence of topoisomerases and DNA as well as for their cytotoxicity against the human lymphoblastoma cell line, RPMI8402. 2,3-Methylenedioxy-8,9-dimethoxybenzo[i]phenanthridine (4a) and its 5-methyl derivative (4b) are active as topoisomerase I-targeting agents. In contrast to nitidine, the presence of the 5-methyl substituent in the case of 4b is not associated with enhanced activity. Consistent with previous structure–activity studies on nitidine and protoberberine alkaloids, 2,3,8,9-teramethoxybenzo[i]phenanthridine, 5a, and its 5-methyl derivative,5b, are inactive as topoisomerase I-targeting agents. These studies were extended to an evaluation of the relative pharmacological activities of 2,8,9-trimethoxybenzo[i]phenanthridine, 3,8,9-trimethoxybenzo[i]phenanthridine, and 2,3-methylenedioxy-8,9-methylenedioxybenzo[i]phenanthridine
Diagnostic Accuracy of the Electrocardiogram for Heart Failure With Reduced or Preserved Ejection Fraction
Current heart failure (HF) guidelines recommend electrocardiography (ECG) as an essential initial investigation in a patient's workup. 1 However, these recommendations were based on studies primarily including patients with HF with reduced ejection fraction (HFrEF). 1 , 2 , 3 Guidelines do not distinguish HFrEF from HF with preserved and mid-range ejection fraction (HFpEF and HFmrEF) in their ECG recommendations. We hypothesized that a normal ECG does not exclude HFpEF and has a considerably lower sensitivity for diagnosing HFpEF than HFrEF
Heavy Quarks and Heavy Quarkonia as Tests of Thermalization
We present here a brief summary of new results on heavy quarks and heavy
quarkonia from the PHENIX experiment as presented at the "Quark Gluon Plasma
Thermalization" Workshop in Vienna, Austria in August 2005, directly following
the International Quark Matter Conference in Hungary.Comment: 8 pages, 5 figures, Quark Gluon Plasma Thermalization Workshop
(Vienna August 2005) Proceeding
Single Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s) = 200 GeV
The invariant differential cross section for inclusive electron production in
p+p collisions at sqrt(s) = 200 GeV has been measured by the PHENIX experiment
at the Relativistic Heavy Ion Collider over the transverse momentum range $0.4
<= p_T <= 5.0 GeV/c at midrapidity (eta <= 0.35). The contribution to the
inclusive electron spectrum from semileptonic decays of hadrons carrying heavy
flavor, i.e. charm quarks or, at high p_T, bottom quarks, is determined via
three independent methods. The resulting electron spectrum from heavy flavor
decays is compared to recent leading and next-to-leading order perturbative QCD
calculations. The total cross section of charm quark-antiquark pair production
is determined as sigma_(c c^bar) = 0.92 +/- 0.15 (stat.) +- 0.54 (sys.) mb.Comment: 329 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett.
Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Nuclear Modification of Electron Spectra and Implications for Heavy Quark Energy Loss in Au+Au Collisions at sqrt(s_NN)=200 GeV
The PHENIX experiment has measured mid-rapidity transverse momentum spectra
(0.4 < p_T < 5.0 GeV/c) of electrons as a function of centrality in Au+Au
collisions at sqrt(s_NN)=200 GeV. Contributions from photon conversions and
from light hadron decays, mainly Dalitz decays of pi^0 and eta mesons, were
removed. The resulting non-photonic electron spectra are primarily due to the
semi-leptonic decays of hadrons carrying heavy quarks. Nuclear modification
factors were determined by comparison to non-photonic electrons in p+p
collisions. A significant suppression of electrons at high p_T is observed in
central Au+Au collisions, indicating substantial energy loss of heavy quarks.Comment: 330 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett.
Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
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