Thymidylate synthase gene variants as predictors of clinical response and toxicity to fluoropyrimidine-based chemotherapy for colorectal cancer

Abstract Background: Fluoropyrimidines form the chemotherapy backbone of advanced and metastatic colorectal cancer (CRC). These drugs are frequently associated with toxicity events that result in dose adjustments and even suspension of the treatment. The thymidylate synthase (TYMS) gene is a potential marker of response and toxicity to fluoropyirimidines as this enzyme is the molecular target of these drugs. Our aim was to assess the association between variants of TYMS with response and toxicity to fluoropyrimidines in patients with CRC in independent retrospective and prospective studies. Methods: Variants namely rs45445694, rs183205964, rs2853542 and rs151264360 of TYMS were genotyped in 105 CRC patients and were evaluated to define their association with clinical response and toxicity to fluoropyrimidines. Additionally, the relationship between genotypes and tumor gene expression was analyzed by quantitative polymerase chain reaction. Results: The 2R/2R (rs45445694) was associated with clinical response (p = 0.05, odds ratio (OR) = 3.45) and severe toxicity (p = 0.0014, OR = 5.21, from pooled data). Expression analysis in tumor tissues suggested a correlation between the 2R/2R genotype and low TYMS expression. Conclusions: The allele 2R (rs45445694) predicts severe toxicity and objective response in advanced CRC patients. In addition, the alleles G(rs2853542) and 6bp-(rs151264360) are independent predictors of response failure to chemotherapy. This is the first study made on a Latin American population that points out TYMS gene variants have predictive values for response and toxicity in patients with CRC treated with fluoropyrimidine-based chemotherapy

Observation of long-range, near-side angular correlations in proton-proton collisions at the LHC

Results on two-particle angular correlations for charged particles emitted in proton-proton collisions at center-of-mass energies of 0.9, 2.36, and 7 TeV are presented, using data collected with the CMS detector over a broad range of pseudorapidity (?) and azimuthal angle (?). Short-range correlations in ??, which are studied in minimum bias events, are characterized using a simple ?independent cluster? parametrization in order to quantify their strength (cluster size) and their extent in ? (cluster decay width). Long-range azimuthal correlations are studied differentially as a function of charged particle multiplicity and particle transverse momentum using a 980 nb?1 data set at 7 TeV. In high multiplicity events, a pronounced structure emerges in the two-dimensional correlation function for particle pairs with intermediate p T of 1?3 GeV/c, 2.0 < |??| < 4.8 and ?? ? 0. This is the first observation of such a long-range, near-side feature in two-particle correlation functions in pp or pp¯¯¯ collisions.We thank the technical and administrative staff at CERN and other CMS institutes. This work was supported by the Austrian Federal Ministry of Science and Research; the Belgium Fonds de la Recherche Scientifique, and Fonds voor Wetenschappelijk Onderzoek; the Brazilian Funding Agencies (CNPq, CAPES, FAPERJ, and FAPESP); the Bulgarian Ministry of Education and Science; CERN; the Chinese Academy of Sciences, Ministry of Science and Technology, and National Natural Science Foundation of China; the Colombian Funding Agency (COLCIENCIAS); the Croatian Ministry of Science, Education and Sport; the Research Promotion Foundation, Cyprus; the Estonian Academy of Sciences and NICPB; the Academy of Finland, Finnish Ministry of Education, and Helsinki Institute of Physics; the Institut National de Physique Nucléaire et de Physique des Particules / CNRS, and Commissariat à l’Energie Atomique, France; the Bundesministerium für Bildung und Forschung, Deutsche Forschungsgemeinschaft, and Helmholtz-Gemeinschaft Deutscher Forschungszentren, Germany; the General Secretariat for Research and Technology, Greece; the National Scientific Research Foundation, and National Office for Research and Technology, Hungary; the Department of Atomic Energy, and Department of Science and Technology, India; the Institute for Studies in Theoretical Physics and Mathematics, Iran; the Science Foundation, Ireland; the Istituto Nazionale di Fisica Nucleare, Italy; the Korean Ministry of Education, Science and Technology and the World Class University program of NRF, Korea; the Lithuanian Academy of Sciences; the Mexican Funding Agencies (CINVESTAV, CONACYT, SEP, and UASLP-FAI); the Pakistan Atomic Energy Commission; the State Commission for Scientific Research, Poland; the Fundaçao para a Cîencia e a Tecnologia, Portugal; JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); the Ministry of Science and Technologies of the Russian Federation, and Russian Ministry of Atomic Energy; the Ministry of Science and Technological Development of Serbia; the Ministerio de Ciencia e Innovación, and Programa Consolider-Ingenio 2010, Spain; the Swiss Funding Agencies (ETH Board, ETH Zurich, PSI, SNF, UniZH, Canton Zurich, and SER); the National Science Council, Taipei; the Scientific and Technical Research Council of Turkey, and Turkish Atomic Energy Authority; the Science and Technology Facilities Council, UK; the US Department of Energy, and the US National Science Foundation. Individuals have received support from the Marie-Curie IEF program (European Union); the Leventis Foundation; the A. P. Sloan Foundation; the Alexander von Humboldt Foundation; and the Associazione per lo Sviluppo Scientifico e Tecnologico del Piemonte (Italy)

CMS tracking performance results from early LHC operation

The first LHC pp collisions at centre-of-mass energies of 0.9 and 2.36 TeV were recorded by the CMS detector in December 2009. The trajectories of charged particles produced in the collisions were reconstructed using the all-silicon Tracker and their momenta were measured in the 3.8 T axial magnetic field. Results from the Tracker commissioning are presented including studies of timing, efficiency, signal-to-noise, resolution, and ionization energy. Reconstructed tracks are used to benchmark the performance in terms of track and vertex resolutions, reconstruction of decays, estimation of ionization energy loss, as well as identification of photon conversions, nuclear interactions, and heavy-flavour decays

First measurement of the underlying event activity at the LHC with √ = 0.9 TeV

A measurement of the underlying activity in scattering processes with p T scale in the GeV region is performed in proton?proton collisions at s?=0.9?=0.9 TeV, using data collected by the CMS experiment at the LHC. Charged particle production is studied with reference to the direction of a leading object, either a charged particle or a set of charged particles forming a jet. Predictions of several QCD-inspired models as implemented in PYTHIA are compared, after full detector simulation, to the data. The models generally predict too little production of charged particles with pseudorapidity |?|0.5 GeV/c, and azimuthal direction transverse to that of the leading object

Measurement of the charge ratio of atmospheric muons with the CMS detector

We present a measurement of the ratio of positive to negative muon fluxes from cosmic ray interactions in the atmosphere, using data collected by the CMS detector both at ground level and in the underground experimental cavern at the CERN LHC. Muons were detected in the momentum range from 5 GeV/c to 1 TeV/c. The surface flux ratio is measured to be 1.2766 ± 0.0032 (stat.) ± 0.0032 (syst.), independent of the muon momentum, below 100 GeV/c. This is the most precise measurement to date. At higher momenta the data are consistent with an increase of the charge ratio, in agreement with cosmic ray shower models and compatible with previous measurements by deep-underground experimentsWe thank the technical and administrative staff at CERN and other CMS institutes. This work was supported by the Austrian Federal Ministry of Science and Research; the Belgium Fonds de la Recherche Scientifique, and Fonds voor Wetenschappelijk Onderzoek; the Brazilian Funding Agencies (CNPq, CAPES, FAPERJ, and FAPESP); the Bulgarian Ministry of Education and Science; CERN; the Chinese Academy of Sciences, Ministry of Science and Technology, and National Natural Science Foundation of China; the Colombian Funding Agency (COLCIENCIAS); the Croatian Ministry of Science, Education and Sport; the Research Promotion Foundation, Cyprus; the Estonian Academy of Sciences and NICPB; the Academy of Finland, Finnish Ministry of Education, and Helsinki Institute of Physics; the Institut National de Physique Nucléaire et de Physique des Particules/CNRS, and Commissariat à l'Énergie Atomique, France; the Bundesministerium für Bildung und Forschung, Deutsche Forschungsgemeinschaft, and Helmholtz–Gemeinschaft Deutscher Forschungszentren, Germany; the General Secretariat for Research and Technology, Greece; the National Scientific Research Foundation, and National Office for Research and Technology, Hungary; the Department of Atomic Energy, and Department of Science and Technology, India; the Institute for Studies in Theoretical Physics and Mathematics, Iran; the Science Foundation, Ireland; the Istituto Nazionale di Fisica Nucleare, Italy; the Korean Ministry of Education, Science and Technology and the World Class University program of NRF, Korea; the Lithuanian Academy of Sciences; the Mexican Funding Agencies (CINVESTAV, CONACYT, SEP, and UASLP-FAI); the Pakistan Atomic Energy Commission; the State Commission for Scientific Research, Poland; the Fundação para a Ciência e a Tecnologia, Portugal; JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); the Ministry of Science and Technologies of the Russian Federation, and Russian Ministry of Atomic Energy; the Ministry of Science and Technological Development of Serbia; the Ministerio de Ciencia e Innovación, and Programa Consolider-Ingenio 2010, Spain; the Swiss Funding Agencies (ETH Board, ETH Zurich, PSI, SNF, UniZH, Canton Zurich, and SER); the National Science Council, Taipei; the Scientific and Technical Research Council of Turkey, and Turkish Atomic Energy Authority; the Science and Technology Facilities Council, UK; the US Department of Energy, and the US National Science Foundation. Individuals have received support from the Marie-Curie IEF program (European Union); the Leventis Foundation; the A.P. Sloan Foundation; the Alexander von Humboldt Foundation; and the Associazione per lo Sviluppo Scientifico e Tecnologico del Piemonte (Italy)

Transverse-momentum and pseudorapidity distributions of charged hadrons in pp collisions at √s = 0.9 and 2.36TeV

Measurements of inclusive charged-hadron transverse-momentum and pseudorapidity distributions are presented for proton-proton collisions at s?=0.9?=0.9 and 2.36 TeV. The data were collected with the CMS detector during the LHC commissioning in December 2009. For non-single-diffractive interactions, the average charged-hadron transverse momentum is measured to be 0.46 ± 0.01 (stat.) ± 0.01 (syst.) GeV/c at 0.9 TeV and 0.50 ± 0.01 (stat.) ± 0.01 (syst.) GeV/c at 2.36 TeV, for pseudorapidities between --2.4 and +2.4. At these energies, the measured pseudorapidity densities in the central region, dN ch/d?||?|<0.5, are 3:48 ± 0:02 (stat.) ± 0.13 (syst.) and 4:47 ± 0:04 (stat.) ± 0.16 (syst.), respectively. The results at 0.9 TeV are in agreement with previous measurements and confirm the expectation of near equal hadron production in p¯¯¯p?¯? and pp collisions. The results at 2.36 TeV represent the highest-energy measurements at a particle collider to date

4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil. El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país. La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica. Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas