Papers by Karol Contreras
Toxicological Sciences, 2003
Short-term assays for carcinogenicity testing of chemicals that use transgenic mice designed to h... more Short-term assays for carcinogenicity testing of chemicals that use transgenic mice designed to have altered expression of genes mechanistically relevant to carcinogenesis are attractive alternatives to two-year dosing studies in rodents. The models that have been the received the greatest level of performance evaluation include p53(؉/-), rasH2, Xpa/p53(؉/-), and Tg.AC mice. For use of these models in a regulatory setting to evaluate the carcinogenic potential of pharmaceuticals, it is important to establish an assurance of assay specificity and positive predictivity based on studies using drugs with a wide spectrum of pharmacologic activity. For this purpose, 99 noncarcinogenic drugs were prioritized based on their activity in an in vitro induction assay correlative with a positive response in the Tg.AC assay (induction of the gadd153 promoter in HepG2 cells). Activities in two assays less predictive of Tg.AC activity (induction of c-fos and -globin gene promoters) were also measured. Nine percent of the screened drugs induced the gadd153 promoter by at least fourfold. Several criteria were used to select candidates for subsequent in vivo testing in the Tg.AC assay: (1) sufficient drug solubility in appropriate skin paint vehicles to elicit systemic toxicity, (2) the level of induction of the gadd153 promoter by the drug, (3) the in vitro potency of the drug, and (4) the cost of the drug required for a 6-month study. Based on these criteria, amiloride, dipyridamole, and pyrimethamine were selected from 99 rodent noncarcinogens in a drug database for testing the specificity of the Tg.AC assay. Downloaded from FIG. 3. Dose response of induction of -globin gene promoter-driven GFP expression (closed squares) and of cellular toxicity (open squares) by amiloride, dipyridamole, and pyrimethamine. Stably transfected clonal lines of K562 cells were treated with drug 24 h after plating, and intracellular GFP levels were quantitated 48 h later using a fluorescence plate reader. Cell number was calculated using a Coulter counter. Dipyridamole autofluorescence was corrected for by subtracting the values obtained from parental K562 cells dosed with drug.
Journal of High Energy Physics, 2011
A measurement is presented of the charged hadron multiplicity in hadronic PbPb collisions, as a f... more A measurement is presented of the charged hadron multiplicity in hadronic PbPb collisions, as a function of pseudorapidity and centrality, at a collision energy of 2.76 TeV per nucleon pair. The data sample is collected using the CMS detector and a minimum-bias trigger, with the CMS solenoid off. The number of charged hadrons is measured both by counting the number of reconstructed particle hits and by forming hit doublets of pairs of layers in the pixel detector. The two methods give consistent results. The charged hadron multiplicity density, dN ch /dη| η=0 , for head-on collisions is found to be 1612 ± 55, where the uncertainty is dominated by systematic effects. Comparisons of these results to previous measurements and to various models are also presented.
Search for the standard model Higgs boson decaying to W + W − in the fully leptonic final state i... more Search for the standard model Higgs boson decaying to W + W − in the fully leptonic final state in pp collisions at √ s = 7 TeV
Toxicological Sciences, 2000
Under ICH guidelines, short-term carcinogenicity assays such as the Tg.AC assay are allowed alter... more Under ICH guidelines, short-term carcinogenicity assays such as the Tg.AC assay are allowed alternatives for one species in the 2-year rodent bioassay. The Tg.AC transgenic mouse, which carries the v-Ha-ras oncogene under control of the -globin promoter, develops skin papillomas in response to dermal application of carcinogens and tumor promoters. The appropriate specificity of the Tg.AC model for testing pharmaceuticals has not been systematically evaluated. The selection of candidate test compounds among noncarcinogenic pharmaceuticals would be aided by a high-throughput in vitro prescreen correlative of activity in the in vivo Tg.AC assay. Here we describe the development of a prescreen based on correct response to 24 compounds tested previously in Tg.AC mice. The in vitro prescreens, chosen to reflect molecular pathways possibly involved in Tg.AC papilloma formation, consisted of a -globin promoter-luciferase construct stably expressed in K562 cells (Zeta-Luc) and three of the stress-response element-chloramphenicol acetyltransferase (CAT) fusion constructs stably expressed in HepG2 cells that are part of the CAT-Tox (L)iver assay. The stress response elements chosen were the c-fos promoter, the gadd153 promoter, and p53 response element repeats. Of the four assays, the gadd153-CAT assay showed the strongest concordance with activity in the Tg.AC assay, correctly classifying 78% of Tg.AC positive and 83% of Tg.AC negative compounds. The correlation was further improved by adding the Zeta-Luc assay as a second-stage screen. These cell-based assays will be used in a novel approach to selecting candidate compounds that challenge the specificity of the Tg.AC assay toward pharmaceuticals.
A search for the standard model Higgs boson decaying into two Z bosons with subsequent decay into... more A search for the standard model Higgs boson decaying into two Z bosons with subsequent decay into a final state containing two quark jets and two leptons, H → ZZ ( * ) → qq − + is presented. Results are based on data corresponding to an integrated luminosity of 4.6 fb −1 of proton-proton collisions at √ s = 7 TeV, collected with the CMS detector at the LHC. In order to discriminate between signal and background events, kinematic and topological quantities, including the angular spin correlations of the decay products, are employed. Events are further classified according to the probability of the jets to originate from quarks of light or heavy flavor or from gluons. No evidence for the Higgs boson is found, and upper limits on its production cross section are determined for a Higgs boson of mass between 130 and 600 GeV.
Neuroscience Letters, 2011
Procedural learning refers to the acquisition of motor skills and the practice that refines their... more Procedural learning refers to the acquisition of motor skills and the practice that refines their performance. The striatum participates in this learning through a function regulated by endocannabinoid signaling and other systems. This study relates the efficiency in learning a procedural task with the AATn polymorphism of the CNR1 gene, which encodes for the CB1 receptor. The mirror-drawing star task was solved by 99 healthy young subjects in three trials. The sample was divided into high- and low-performance groups based on performance efficiency. AAT12/14 carriers were more frequent in the former group, while there were more AAT12/13 carriers in the latter, which also made more errors/min. Therefore, we characterized two efficiency phenotypes: high- vs. low-performers associated with the two AATn genotypes, AAT12/14 vs. AAT12/13. The findings suggest that AATn polymorphism modifies CNR1 translation, indicating a different modulation of CB1.
Results are presented from a search for a W boson using a dataset corresponding to 5.0 fb −1 of i... more Results are presented from a search for a W boson using a dataset corresponding to 5.0 fb −1 of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at √ s = 7 TeV. The W boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both lefthanded and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W → tb, leading to a final state signature with a single electron or muon, missing transverse energy, and jets, at least one of which is identified as a b-jet. A W boson that couples to the right-handed (left-handed) chiral projections of the fermions with the same coupling constants as the W is excluded for masses below 1.85 (1.51) TeV at the 95% confidence level. For the first time using LHC data, constraints on the W gauge couplings for a set of left-and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.
Yields of prompt and non-prompt J/ψ, as well as Υ(1S) mesons, are measured by the CMS experiment ... more Yields of prompt and non-prompt J/ψ, as well as Υ(1S) mesons, are measured by the CMS experiment via their µ + µ − decays in PbPb and pp collisions at √ s NN = 2.76 TeV for quarkonium rapidity |y| < 2.4. Differential cross sections and nuclear modification factors are reported as functions of y and transverse momentum p T , as well as collision centrality. For prompt J/ψ with relatively high p T (6.5 < p T < 30 GeV/c), a strong, centrality-dependent suppression is observed in PbPb collisions, compared to the yield in pp collisions scaled by the number of inelastic nucleon-nucleon collisions.
Search for the standard model Higgs boson in the H → ZZ → 2 2ν channel in pp collisions at √ s = ... more Search for the standard model Higgs boson in the H → ZZ → 2 2ν channel in pp collisions at √ s = 7 TeV
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Papers by Karol Contreras