Modeling repeated ordinal responses using a family of power transformations: application to neonatal hypothermia data

BACKGROUND: For analyzing a repeated ordinal response, it is common to use a multivariate cumulative logit model. This model may fit poorly, especially when a nonsymmetric response is available. In these cases, alternative strategies should be utilized. METHODS: In this paper, we present a family of power transformations for the cumulative probabilities to model asymmetric departures from the random-intercept cumulative logit model. To illustrate this method, we analyze the data from an epidemiologic study to identify risk factors of hypothermia among newly born infants in some referral university hospitals in Tehran, Iran. RESULTS: For hypothermia data, using this family of transformations and comparing the goodness-of-fit statistics showed that a model with the cumulative complementary log-log link gives us a better fit compared to a model with the cumulative logit link. CONCLUSION: In some areas, using the ordinary cumulative logit link function does not lead to the best fit. So, other link functions should be evaluated to discover the best transformation for the cumulative probabilities

Protección de la Heparina a las células B- pancreáticas frente a radicales libres de Oxígeno.

La diabetes autoinmune tipo 1 se caracteriza por la invasión de células mononucleares en los islotes pancreáticos, destruyendo así las células beta productoras de insulina. Se ha visto que in vivo la destrucción autoinmune de los islotes se asocia con la producción de heparanasa, la cual degrada heparán sulfato (molécula imprescindible para la supervivencia de los islotes) y se permite la entrada de las células inmunitarias que atacarán los islotes beta pancreáticos. Se han obtenido resultados mediante la adición de concentraciones conocidas de heparina, la cual confiere una protección extra frente a radicales libres de oxígeno y como consecuencia hay una disminución de la mortalidad celular.A través de tres líneas celulares distintas se ha llevado a cabo el experimento. Primeramente con Rinm5F productora de insulina y somatostatina, con células Ins capaces de responder al estímulo de glucosa produciendo y secretando insulina y finalmente con fibroblastos. El experimento se basa en dejar crecer las cepas celulares en un número determinado de flacs según el tratamiento. Se añade heparina a una concentración conocida y establecida anteriormente y al día siguiente con una concentración exacta de agua oxigenada (aporta los radicales libres de oxígeno) se la añadimos al cultivo. Recogemos las células y gracias al ioduro de propidio con concentración 1 mg/ml marcamos las células muertas para así poder comprobar el porcentaje de supervivencia celular que le ha conferido la heparina a cada línea celular. Procedemos a realizar el contaje con el citómetro que indica el % de muerte celular, ya que el ioduro de propidio es un agente intercalante que se une a los ácidos nucleicos. Esta molécula fluorescente se utiliza para evaluar la viabilidad celular o el contenido de ADN en las células. Se puede utilizar para diferenciar células necróticas, apoptóticas o vivas.Los resultados obtenidos con las líneas celulares Rinm5F y las Ins nos muestran que a bajas concentraciones de agua oxigenada y con heparina, efectivamente hay protección ya que la muerte celular se reduce de un 10 a un 15%. En cambio con los fibroblastos no vemos protección a ninguna de las concentraciones establecidas, resultado que ya esperábamos en nuestra hipótesis inicial. Estos resultados sólo son el inicio de un largo estudio, ya que  primero se ajustan las concentraciones a trabajar con radicales libres de oxígeno, pero en un  futuro el estudio se realizará también con radicales de nitrógeno

Relación entre muerte celular y mantenimiento de la pluripotencialidad de células mES en protocolos de diferenciación con óxido nítrico

En este proyecto se pretende estudiar la relación entre la muerte celular y la diferenciación durante el desarrollo usando como modelo experimental células madre embrionarias de ratón (mESC). Se ha descrito que las altas concentraciones de DETA-NO (500uM) provocan la diferenciación de estas mESC hacia endodermo (Mora-Castilla et al., 2010), pero en estos protocolos no todas consiguen sobrevivir y un alto porcentaje de células muere. Es por ello que se quiere analizar la relación entre ambos eventos. Se estudiará, por un lado, si el bloqueo de la apoptosis con inhibidores de caspasas tiene efectos sobre la diferenciación; y por otro lado si es probable que exista una liberación de moléculas al medio por parte de las células apoptóticas que contribuya a la pérdida de la pluripotencialidad de sus vecinas. Para ello se ha analizado el mantenimiento del estado pluripotente en dos tipos de ensayos. Por un lado se ha estudiado el efecto de inhibidores de caspasas en tratamientos con DETA-NO en dos líneas de mESC (D3 y R1/E), y por otro lado se ha evaluado el efecto del reciclaje de medios de cultivo en la línea celular D3. Para medir el mantenimiento de la pluripotencialidad se han empleado distintas técnicas de biología molecular (extracción de RNA, PCR, qPCR, Western Blotting…) y técnicas de microscopía. Con ello se han buscado diferencias de expresión de los marcadores de pluripotencia (Nanog y Oct4) y marcadores de endodermo (Pdx1, Cxcr4), mesodermo (Brachyury) y ectodermo (Zic1). Se ha demostrado que el uso de inhibidores de caspasas en tratamientos con DETA-NO bloquea la regulación a la baja de Nanog, tanto en niveles de RNAm como de proteína, y disminuye la expresión de los marcadores de diferenciación. Por otro lado, el uso de medios de cultivo reciclados procedentes de tratamientos anteriores con y sin DETA-NO, suplementados y con el factor inhibidor de la diferenciación LIF (Leukemia Inhibitory Factor) estimula la diferenciación de las células. Los resultados obtenidos apuntan a que podría existir una relación entre la muerte celular y la diferenciación, ya que al inhibir la muerte por apoptosis se favorece el mantenimiento del estado pluripotente . Además, el uso de medios reciclados ayuda a la diferenciación de las células incluso en presencia de LIF. Por ello se cree que células apoptóticas podrían estar secretando sustancias al medio que las células vecinas estarían utilizando como señales para diferenciarse

Expression of Glucose Transporters in the Prelaminar Region of the Optic-Nerve Head of the Pig as Determined by Immunolabeling and Tissue Culture

Background: To develop the use of cultured tissue of the prelaminar optic nerve of the pig to explore possible alterations of the astrocyte-axon metabolic pathways in glaucoma, we map the distribution of the glucose transporters GLUT1 and GLUT3 in fresh and cultured tissue.Methods: We monitor cell survival in cultures of the prelaminar optic-nerve tissue, measuring necrosis and apoptosis markers biochemically as well as morphologically, and establish the presence of the glucose transporters GLUT1 and GLUT3. We map the distribution of these transporters with immunolabeling in histological sections of the optic nerve using confocal and electronic transmission microscopy.Results: We find that the main death type in prelaminar culture is apoptosis. Caspase 7 staining reveals an increment in apoptosis from day 1 to day 4 and a reduction from day 4 to day 8. Western blotting for GLUT1 shows stability with increased culture time. CLSM micrographs locate GLUT1 in the columnar astrocytes and in the area of axonal bundles. Anti-GLUT3 predominantly labels axonal bundles. TEM immunolabeling with colloidal gold displays a very specific distribution of GLUT-1 in the membranes of vascular endothelial cells and in periaxonal astrocyte expansions. The GLUT-3 isoform is observed with TEM only in axons in the axonal bundles.Conclusions: Tissue culture is suitable for apoptosis-induction experiments. The results suggest that glucose is transported to the axonal cleft intracytoplasmically and delivered to the cleft by GLUT1 transporters. As monocarboxylate transporters have been reported in the prelaminar region of the optic-nerve head, this area is likely to use both lactate and glucose as energy sources.This work was supported by a grant from the Consejería de Salud, Junta de Andalucia, Spain, Project PI-0655-2013

Intraspecific Variation in Pinus Pinaster PSII Photochemical Efficiency in Response to Winter Stress and Freezing Temperatures

As part of a program to select maritime pine (Pinus pinaster Ait.) genotypes for resistance to low winter temperatures, we examined variation in photosystem II activity by chlorophyll fluorescence. Populations and families within populations from contrasting climates were tested during two consecutive winters through two progeny trials, one located at a continental and xeric site and one at a mesic site with Atlantic influence. We also obtained the LT50, or the temperature that causes 50% damage, by controlled freezing and the subsequent analysis of chlorophyll fluorescence in needles and stems that were collected from populations at the continental trial site

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques