TGF-β-Mediated Sustained ERK1/2 Activity Promotes the Inhibition of Intracellular Growth of Mycobacterium avium in Epithelioid Cells Surrogates

Transforming growth factor beta (TGF-β) has been implicated in the pathogenesis of several diseases including infection with intracellular pathogens such as the Mycobacterium avium complex. Infection of macrophages with M. avium induces TGF-β production and neutralization of this cytokine has been associated with decreased intracellular bacterial growth. We have previously demonstrated that epithelioid cell surrogates (ECs) derived from primary murine peritoneal macrophages through a process of differentiation induced by IL-4 overlap several features of epithelioid cells found in granulomas. In contrast to undifferentiated macrophages, ECs produce larger amounts of TGF-β and inhibit the intracellular growth of M. avium. Here we asked whether the levels of TGF-β produced by ECs are sufficient to induce a self-sustaining autocrine TGF-β signaling controlling mycobacterial replication in infected-cells. We showed that while exogenous addition of increased concentration of TGF-β to infected-macrophages counteracted M. avium replication, pharmacological blockage of TGF-β receptor kinase activity with SB-431542 augmented bacterial load in infected-ECs. Moreover, the levels of TGF-β produced by ECs correlated with high and sustained levels of ERK1/2 activity. Inhibition of ERK1/2 activity with U0126 increased M. avium replication in infected-cells, suggesting that modulation of intracellular bacterial growth is dependent on the activation of ERK1/2. Interestingly, blockage of TGF-β receptor kinase activity with SB-431542 in infected-ECs inhibited ERK1/2 activity, enhanced intracellular M. avium burden and these effects were followed by a severe decrease in TGF-β production. In summary, our findings indicate that the amplitude of TGF-β signaling coordinates the strength and duration of ERK1/2 activity that is determinant for the control of intracellular mycobacterial growth

Evaluación de la seguridad de productos cosméticos

ilustracionesLa Organización de las Naciones Unidas para el Desarrollo Industrial (onudi), a través del programa Safe+, coordinó varias estrategias de cooperación internacional para apoyar el crecimiento de la industria cosmética colombiana, entre ellas la capacitación en evaluación de la seguridad de productos cosméticos. En este contexto, en 2018, una de las acciones que emprendió la Universidad Nacional de Colombia, fue ofertar el Curso de Formación de Consultores en Evaluación de Seguridad de Productos Cosméticos, a través del Departamento de Farmacia de la Facultad de Ciencias, con la asesoría y el diseño del consultor internacional Dr. Philippe Masson. En 2022, esta capacitación fue ampliada en número de horas impartidas, lo que permitió realizar el Diplomado en Evaluación de la Seguridad de Productos Cosméticos (Safety Assessor Training), en la modalidad telepresencial, el cual contó con la participación de más de 30 expertos. Este documento presenta los resúmenes de 53 conferencias, que hicieron parte de seis módulos: 1) contexto regulatorio de las materias primas y cosméticos; 2) aspectos de seguridad relacionados con ingredientes y productos cosméticos; 3) fundamentos de fisiología, inmunología y toxicología; 4) herramientas de evaluación toxicológica; 5) gestión del riesgo y gestión documental en la evaluación de seguridad de cosméticos; y 6) asuntos de interés en la actualidad. Esperamos con este diplomado contribuir con los fines misionales de la Universidad Nacional de Colombia, a través de la educación continua y permanente con carácter científico y tecnológico dirigida a profesionales de la industria cosmética. (Texto tomado de la fuente)Introducción -- Importancia de la formación en evaluación de seguridad para el sector cosmético -- Evaluación de calidad de productos cosméticos: introducción -- Bibliografía recomendadaMódulo 1. Contexto regulatorio de las materias primas y cosméticos -- Situación normativa en Latinoamérica con relación a la seguridad de cosméticos -- Legislación de cosméticos en la Comunidad Andina de Naciones (can) y su influencia en Colombia -- Referencias regulatorias con relación a la seguridad de cosméticos: Unión Europea y Estados Unidos -- Referencias regulatorias con relación a la seguridad de cosméticos: Asia -- Normas técnicas internacionales en seguridad de productos cosméticos -- Bibliografía recomendadaMódulo 2: aspectos de seguridad relacionados con ingredientes y productos cosméticos -- Seguridad de productos cosméticos – Quality by Design -- Origen de los ingredientes cosméticos -- Ingredientes cosméticos obtenidos por síntesis química -- Ingredientes cosméticos de origen natural -- Ingredientes cosméticos de origen biológico y biotecnológico -- Disposiciones particulares relativas a las fragancias -- Clasificación de ingredientes cosméticos y restricciones -- Estabilidad a lo largo del ciclo de vida del producto -- Estabilidad fisicoquímica -- Estabilidad microbiológica -- Envase seguro: ingeniería de envases -- Envase seguro: extractables y lixiviados de envases -- Bibliografía recomendadaMódulo 3. Fundamentos de fisiología, inmunología y toxicología -- Fundamentos: sistema inmune y piel -- Fundamentos: piel y mucosas, organización y funciones -- Evolución de la piel con la edad -- Irritación cutánea, ocular y mucosas -- Alergenicidad y sensibilización cutánea -- Fotosensibilidad cutánea y fotoirritación -- Conceptos generales en toxicología: evaluación del riesgo toxicológico -- Penetración y absorción percutánea -- Toxicidad general por vía oral y tópica -- Toxicidad de la reproducción -- Genotoxicidad, mutagenicidad y cáncer -- Bibliografía recomendadaMódulo 4. Herramientas de evaluación toxicológica -- Métodos experimentales in vivo y sus límites -- Metodologías in vitro para la evaluación de seguridad de ingredientes cosméticos -- Métodos in vitro. Experiencias en el laboratorio -- Evaluación de la penetración cutánea -- Métodos in silico como fuentes adicionales de información -- Estudios clínicos para la evaluación de cosméticos -- Cálculo del margen de seguridad -- Umbral de preocupación toxicológica (ttc) -- Bibliografía recomendadaMódulo 5. Gestión del riesgo y gestión documental en la evaluación de la seguridad de cosméticos -- Buenas prácticas de laboratorio -- Calidad de los datos experimentales -- Dossier, pif o expediente de información de producto -- Gestión del riesgo -- Caracterización y gestión del riesgo -- Acceso a los datos de ingredientes cosméticos a través de los comités científicos sccs, cir -- Claims / proclamas -- Claims vs. Soportes -- Bibliografía recomendadaMódulo 6. Asuntos de interés en la actualidad -- Uso de nanomateriales en productos cosméticos: ¿es un riesgo? -- Disrupción endocrina -- Impacto de los cosméticos en el ambiente – Cosmetovigilancia -- Pieles sensibles: consideraciones generales y aspectos reglamentarios -- Ética y estudios de seguridad -- Nuevas aproximaciones metodológicas (nam) -- Bibliografía recomendad

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

Measurement of b jet shapes in proton-proton collisions at root s=5.02 TeV

We present the first study of charged-hadron production associated with jets originating from b quarks in proton-proton collisions at a center-of-mass energy of 5.02 TeV. The data sample used in this study was collected with the CMS detector at the CERN LHC and corresponds to an integrated luminosity of 27.4 pb(-1). To characterize the jet substructure, the differential jet shapes, defined as the normalized transverse momentum distribution of charged hadrons as a function of angular distance from the jet axis, are measured for b jets. In addition to the jet shapes, the per-jet yields of charged particles associated with b jets are also quantified, again as a function of the angular distance with respect to the jet axis. Extracted jet shape and particle yield distributions for b jets are compared with results for inclusive jets, as well as with the predictions from the pythia and herwig++ event generators.Peer reviewe

Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at root s(NN)=5.02 TeV

The second-order Fourier coefficients (v(2)) characterizing the azimuthal distributions of Y(1S) and Y(2S) mesons produced in PbPb collisions at root s(NN) = 5.02 TeV are studied. The Y mesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb(-1). The scalar product method is used to extract the v2 coefficients of the azimuthal distributions. Results are reported for the rapidity range vertical bar y vertical bar < 2.4, in the transverse momentum interval 0 < pT < 50 GeV/c, and in three centrality ranges of 10-30%, 30-50% and 50-90%. In contrast to the J/psi mesons, the measured v(2) values for the Y mesons are found to be consistent with zero. (C) 2021 The Author(s). Published by Elsevier B.V.Peer reviewe

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

Search for Physics beyond the Standard Model in Events with Overlapping Photons and Jets

Results are reported from a search for new particles that decay into a photon and two gluons, in events with jets. Novel jet substructure techniques are developed that allow photons to be identified in an environment densely populated with hadrons. The analyzed proton-proton collision data were collected by the CMS experiment at the LHC, in 2016 at root s = 13 TeV, and correspond to an integrated luminosity of 35.9 fb(-1). The spectra of total transverse hadronic energy of candidate events are examined for deviations from the standard model predictions. No statistically significant excess is observed over the expected background. The first cross section limits on new physics processes resulting in such events are set. The results are interpreted as upper limits on the rate of gluino pair production, utilizing a simplified stealth supersymmetry model. The excluded gluino masses extend up to 1.7 TeV, for a neutralino mass of 200 GeV and exceed previous mass constraints set by analyses targeting events with isolated photons.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV