Desarrollo de una plataforma computacional para el modelado metabólico de microorganismos

La Biología Sintética (BS) se centra en el diseño y la construcción de sistemas genéticos artificiales, capaces de desarrollar una función específica después de haber sido introducidos en un sistema vivo. Con el desarrollo de la BS, se observa una nueva generación de bioingenieros que desarrollan complejos circuitos biológicos genéticos con un alto nivel de integración. La mejora de esta disciplina científica tiene por objeto establecer un marco computacional y conceptual que dé asistencia al desarrollo de sistemas biológicos artificiales modulares basándose en una metodología ingenieril y sistemática, para lo que se necesita proveer a la próxima generación de diseñadores en Biología Sintética y a los futuros biotecnólogos e ingenieros biológicos de nuevas herramientas computacionales integradas en un entorno común para el análisis de fenotipos metabólicos, el diseño de nuevos circuitos genéticos complejos y la visualización de mapas metabólicos. Como resultado de esta investigación se obtiene la plataforma Hydra (Hybrid Draw and Routes Analysis), que integra diversas herramientas para el diseño, análisis y visualización de las redes metabólicas.Synthetic biology focuses on the design and construction of artificial genetic systems that are capable of carrying out a specific function after being inserted into a living system. With the development of synthetic biology a new generation of bioengineers has appeared who develop complex, highly integrated genetic biological pathways. The improvement of this scientific discipline aims to establish a computational and conceptual framework that will support the development of modular artificial biological systems based on an engineering and systematic methodology. To achieve this, it will be necessary to provide new integrated computational tools in a common environment for the analysis of metabolic phenotypes, the design of new complex genetic pathways and the visualisation of metabolic maps to the next generation of designers in synthetic biology and future biotechnologists and biological engineers. A result of this research is the Hydra platform (Hybrid Draw and Routes Analysis) that integrates various tools for the design, analysis, and visualisation of metabolic networks.Ciencias Experimentale

First broadband characterization and redshift determination of the VHE blazar MAGIC J2001+439

We aim to characterize the broadband emission from 2FGL J2001.1+4352, which has been associated with the unknown-redshift blazar MG4 J200112+4352. Based on its gamma-ray spectral properties, it was identified as a potential very high energy (VHE; E > 100 GeV) gamma-ray emitter. The source was observed with MAGIC first in 2009 and later in 2010 within a multi-instrument observation campaign. The MAGIC observations yielded 14.8 hours of good quality stereoscopic data. The object was monitored at radio, optical and gamma-ray energies during the years 2010 and 2011. The source, named MAGIC J2001+439, is detected for the first time at VHE with MAGIC at a statistical significance of 6.3 {\sigma} (E > 70 GeV) during a 1.3-hour long observation on 2010 July 16. The multi-instrument observations show variability in all energy bands with the highest amplitude of variability in the X-ray and VHE bands. We also organized deep imaging optical observations with the Nordic Optical Telescope in 2013 to determine the source redshift. We determine for the first time the redshift of this BL Lac object through the measurement of its host galaxy during low blazar activity. Using the observational evidence that the luminosities of BL Lac host galaxies are confined to a relatively narrow range, we obtain z = 0.18 +/- 0.04. Additionally, we use the Fermi-LAT and MAGIC gamma-ray spectra to provide an independent redshift estimation, z = 0.17 +/- 0.10. Using the former (more accurate) redshift value, we adequately describe the broadband emission with a one-zone SSC model for different activity states and interpret the few-day timescale variability as produced by changes in the high-energy component of the electron energy distribution.Comment: 17 pages, 15 figures, Accepted for publication in A&

Desarrollo de una plataforma computacional para el modelado metabólico de microorganismos

[EN] Synthetic biology focuses on the design and construction of artificial genetic systems that are capable of carrying out a specific function after being inserted into a living system. With the development of synthetic biology a new generation of bioengineers has appeared who develop complex, highly integrated genetic biological pathways. Te improvement of this scientific discipline aims to establish a computational and conceptual framework that will support the development of modular artificial biological systems based on an engineering and systematic methodology. To achieve this, it will be necessary to provide new integrated computational tools in a common environment for the analysis of metabolic phenotypes, the design of new complex genetic pathways and the visualisation of metabolic maps to the next generation of designers in synthetic biology and future biotechnologists and biological engineers. A result of this research is the Hydra platform (Hybrid Draw and Routes Analysis) that integrates various tools for the design, analysis, and visualisation of metabolic networks.[ES] La Biología Sintética (BS) se centra en el diseño y la construcción de sistemas genéticos artificiales, capaces de desarrollar una función específica después de haber sido introducidos en un sistema vivo. Con el desarrollo de la BS, se observa una nueva generación de bioingenieros que desarrollan complejos circuitos biológicos genéticos con un alto nivel de integración. La mejora de esta disciplina científica tiene por objeto establecer un marco computacional y conceptual que dé asistencia al desarrollo de sistemas biológicos artificiales modulares basándose en una metodología ingenieril y sistemática, para lo que se necesita proveer a la próxima generación de diseñadores en Biología Sintética y a los futuros biotecnólogos e ingenieros biológicos de nuevas herramientas computacionales integradas en un entorno común para el análisis de fenotipos metabólicos, el diseño de nuevos circuitos genéticos complejos y la visualización de mapas metabólicos. Como resultado de esta investigación se obtiene la plataforma Hydra (Hybrid Draw and Routes Analysis), que integra diversas herramientas para el diseño, análisis y visualización de las redes metabólicas.Los autores desean agradecer el soporte financiero recibido por el Ministerio de Ciencia e Innovación a través de la concesión TIN2009- 12359; la Conselleria de Inmigración y Ciudadanía de la Generalitat Valenciana (concesión 3012/2009) y la Comisión Europea (Proyecto TARPOL FP7 EU KBBE 212894).Reyes, R.; Garrido, J.; Jaime, RA.; Córdova, V.; Triana, J.; Villar, L.; Castro, JC.... (2011). Desarrollo de una plataforma computacional para el modelado metabólico de microorganismos. Nereis. Revista Iberoamericana Interdisciplinar de Métodos, Modelización y Simulación. (3):25-31. http://hdl.handle.net/10251/91952S2531

Novel CTCF binding at a site in exon1A of BCL6 is associated with active histone marks and a transcriptionally active locus

BCL6 is a zinc-finger transcriptional repressor, which is highly expressed in germinal centre B-cells and is essential for germinal centre formation and T-dependent antibody responses. Constitutive BCL6 expression is sufficient to produce lymphomas in mice. Deregulated expression of BCL6 due to chromosomal rearrangements, mutations of a negative autoregulatory site in the BCL6 promoter region and aberrant post-translational modifications have been detected in a number of human lymphomas. Tight lineage and temporal regulation of BCL6 is, therefore, required for normal immunity, and abnormal regulation occurs in lymphomas. CCCTC-binding factor (CTCF) is a multi-functional chromatin regulator, which has recently been shown to bind in a methylation-sensitive manner to sites within the BCL6 first intron. We demonstrate a novel CTCF-binding site in BCL6 exon1A within a potential CpG island, which is unmethylated both in cell lines and in primary lymphoma samples. CTCF binding, which was found in BCL6-expressing cell lines, correlated with the presence of histone variant H2A.Z and active histone marks, suggesting that CTCF induces chromatin modification at a transcriptionally active BCL6 locus. CTCF binding to exon1A was required to maintain BCL6 expression in germinal centre cells by avoiding BCL6-negative autoregulation. Silencing of CTCF in BCL6-expressing cells reduced BCL6 mRNA and protein expression, which is sufficient to induce B-cell terminal differentiation toward plasma cells. Moreover, lack of CTCF binding to exon1A shifts the BCL6 local chromatin from an active to a repressive state. This work demonstrates that, in contexts in which BCL6 is expressed, CTCF binding to BCL6 exon1A associates with epigenetic modifications indicative of transcriptionally open chromatin

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu