Generation of nanobodies by phage display for the detection of Chlamydia trachomatis

Las infecciones causadas por la bacteria de transmisión sexual Chlamydia trachomatis representan un problema importante en salud pública por su elevada incidencia y prevalencia. La falta de sintomatología dificulta el diagnóstico clínico y los métodos de laboratorio son complejos (PCR, cultivo celular) o poco sensibles (IF, ELISA). Existe además una gran proporción de infecciones persistentes que generan inflamación crónica, con secuelas irreversibles como cicatrización y obstrucción de las trompas de Falopio, embarazos ectópicos e infertilidad femenina. Proponemos introducir en nuestro medio la tecnología de producción de nanoanticuerpos por phage display. Estos pequeños anticuerpos recombinantes presentan la ventaja de ser producidos completamente in vitro, en bacterias, sin la necesidad de ratones o conejos, lo que abarata costos y reduce los tiempos de producción. En 2018, la generación de la tecnología de producción de nanoanticuerpos le valió el Premio Nobel de Química a Smith y Winter; y su aplicación en inmunoterapia, el Premio Nobel de Medicina a Honjo y Allison. La especificidad y resistencia a la degradación de los nanoanticuerpos propicia su utilización para el diagnóstico de algunas enfermedades y de la presencia de agentes infecciosos. Uno de los pilares para el tratamiento de las enfermedades de transmisión sexual es el diagnóstico precoz y certero, y para países con escasos recursos en salud, lo ideal es utilizar test rápidos que sean específicos y altamente sensibles como pruebas de tamizaje o screening. Frente a las deficiencias que presentan las pruebas inmunológicas actuales para el diagnóstico de infecciones clamidiales, se considera que la generación de nanoanticuerpos sería una herramienta útil para el desarrollo de pruebas de screening o tamizaje para el diagnóstico de la infección causada por C. trachomatis. Además sería una herramienta muy ventajosa para el laboratorio, ya que nos especializamos en el estudio de los mecanismos moleculares que determinan el establecimiento de las infecciones clamidiales, y cómo la bacteria se adapta y parasita a las células que infecta.Infections caused by the sexually-transmitted bacterium Chlamydia trachomatis are a major public health concern for its high incidence and prevalence among the population. The lack of symptoms makes clinical diagnosis difficult while the laboratory methods are complex (PCR, cell culture) or poorly sensitive (IF, ELISA). A large proportion of infections are persistent and generate chronic inflammation, with irreversible sequelae such as scarring and obstruction of the fallopian tubes, leading to ectopic pregnancies or female infertility. We propose to introduce here the technology of production of nanoantibodies by phage display. These small recombinant antibodies have the advantage of being produced completely in vitro, in bacteria, without the need for mice or rabbits, reducing costs and time of production. In 2018, Smith and Winter were awarded the Nobel Prize in Chemistry for the discovery of nanoantibody production technology, whereas Honjo and Allison earned the Nobel Prize in Medicine for its application in immunotherapy. The specificity and resistance to the degradation of the nanoantibodies favor its use for the diagnosis of some diseases and the presence of infectious agents. To use screening tests, highly sensitive and specific, easy to perform and cheap, is fundamental for succeeding in the detection of sexually-transmitted diseases. Therefore, we consider that the generation of nanoantibodies would be useful for the development of screening tests for the diagnosis of chlamydial infections. It would also be a very advantageous tool for the laboratory since we specialize in the study of the molecular mechanisms that determine the establishment of chlamydial infections, and how the bacteria adapt and parasitize the cells that they infect

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

Bose-Einstein correlations of charged hadrons in proton-proton collisions at s\sqrt s = 13 TeV

Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at $\sqrt{s}$ = 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at $\sqrt{s}$ = 7 TeV, as well as with theoretical predictions.[graphic not available: see fulltext]Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at $\sqrt{s} =$ 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at $\sqrt{s} =$ 7 TeV, as well as with theoretical predictions

Search for dark matter in events with a leptoquark and missing transverse momentum in proton-proton collisions at 13 TeV

A search is presented for dark matter in proton-proton collisions at a center-of-mass energy of root s= 13 TeV using events with at least one high transverse momentum (p(T)) muon, at least one high-p(T) jet, and large missing transverse momentum. The data were collected with the CMS detector at the CERN LHC in 2016 and 2017, and correspond to an integrated luminosity of 77.4 fb(-1). In the examined scenario, a pair of scalar leptoquarks is assumed to be produced. One leptoquark decays to a muon and a jet while the other decays to dark matter and low-p(T) standard model particles. The signature for signal events would be significant missing transverse momentum from the dark matter in conjunction with a peak at the leptoquark mass in the invariant mass distribution of the highest p(T) muon and jet. The data are observed to be consistent with the background predicted by the standard model. For the first benchmark scenario considered, dark matter masses up to 500 GeV are excluded for leptoquark masses m(LQ) approximate to 1400 GeV, and up to 300 GeV for m(LQ) approximate to 1500 GeV. For the second benchmark scenario, dark matter masses up to 600 GeV are excluded for m(LQ) approximate to 1400 GeV. (C) 2019 The Author(s). Published by Elsevier B.V.Peer reviewe

Search for an L-mu - L-tau gauge boson using Z -> 4 mu events in proton-proton collisions at root s=13 TeV

A search for a narrow Z' gauge boson with a mass between 5 and 70 GeV resulting from an L-mu - L-tau U (1) local gauge symmetry is reported. Theories that predict such a particle have been proposed as an explanation of various experimental discrepancies, including the lack of a dark matter signal in direct-detection experiments, tension in the measurement of the anomalous magnetic moment of the muon, and reports of possible lepton flavor universality violation in B meson decays. A data sample of proton-proton collisions at a center-of-mass energy of 13 TeV is used, corresponding to an integrated luminosity of 77.3 fb(-1) recorded in 2016 and 2017 by the CMS detector at the LHC. Events containing four muons with an invariant mass near the standard model Z boson mass are analyzed, and the selection is further optimized to be sensitive to the events that may contain Z -> Z'mu mu -> 4 mu decays. The event yields are consistent with the standard model predictions. Upper limits of 10(-8)-10(-7) at 95% confidence level are set on the product of branching fractions B(Z -> Z'mu mu)B(Z' -> mu mu), depending on the Z' mass, which excludes a Z' boson coupling strength to muons above 0.004-0.3. These are the first dedicated limits on L-mu - L-tau models at the LHC and result in a significant increase in the excluded model parameter space. The results of this search may also be used to constrain the coupling strength of any light Z' gauge boson to muons. (C) 2019 The Author(s). Published by Elsevier B.V.Peer reviewe

Measurement of electroweak WZ boson production and search for new physics in WZ + two jets events in pp collisions at √s=13TeV

A measurement of WZ electroweak (EW) vector boson scattering is presented. The measurement is performed in the leptonic decay modes WZ→ℓνℓ′ℓ′, where ℓ,ℓ′=e,μ. The analysis is based on a data sample of proton-proton collisions at √s=13 TeV at the LHC collected with the CMS detector and corresponding to an integrated luminosity of 35.9 fb−1. The WZ plus two jet production cross section is measured in fiducial regions with enhanced contributions from EW production and found to be consistent with standard model predictions. The EW WZ production in association with two jets is measured with an observed (expected) significance of 2.2 (2.5) standard deviations. Constraints on charged Higgs boson production and on anomalous quartic gauge couplings in terms of dimension-eight effective field theory operators are also presented

Azimuthal separation in nearly back-to-back jet topologies in inclusive 2-and 3-jet events in pp collisions at root s=13TeV

A measurement for inclusive 2- and 3-jet events of the azimuthal correlation between the two jets with the largest transverse momenta, Delta phi(12), is presented. The measurement considers events where the two leading jets are nearly collinear ("back-to-back") in the transverse plane and is performed for several ranges of the leading jet transverse momentum. Proton-proton collision data collected with the CMS experiment at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 35.9 fb(-1) are used. Predictions based on calculations using matrix elements at leading-order and next-to-leading-order accuracy in perturbative quantum chromodynamics supplemented with leading-log parton showers and hadronization are generally in agreement with themeasurements. Discrepancies between the measurement and theoretical predictions are as large as 15%, mainly in the region 177 degrees <Delta phi(12) <180 degrees. The 2- and 3-jet measurements are not simultaneously described by any of models.Peer reviewe

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| &lt; 0.03 at 95% confidence level. [Figure not available: see fulltext.

Measurement of the t(t)over-bar production cross section, the top quark mass, and the strong coupling constant using dilepton events in pp collisions at root s=13TeV

A measurement of the top quark-antiquark pair production cross section sigma(t (t) over bar) in proton-proton collisions at a centre-of-mass energy of 13 TeV is presented. The data correspond to an integrated luminosity of 35.9 fb(-1), recorded by the CMS experiment at the CERN LHC in 2016. Dilepton events (e(+/-) mu(-/+), mu(+) mu(-), e(+) e(-)) are selected and the cross section is measured from a likelihood fit. For a top quark mass parameter in the simulation of m(t)(MC) = 172.5 GeV the fit yields a measured cross section sigma(t (t) over bar) = 803 +/- 2 (stat) +/- 25 (syst) +/- 20 (lumi) pb, in agreement with the expectation from the standard model calculation at next-to-next-to-leading order. A simultaneous fit of the cross section and the top quark mass parameter in the POWHEG simulation is performed. The measured value of m(t)(MC) = 172.33 +/- 0.14 (stat)(-0.72)(+0.66) (syst) GeV is in good agreement with previous measurements. The resulting cross section is used, together with the theoretical prediction, to determine the top quark mass and to extract a value of the strong coupling constant with different sets of parton distribution functions.Peer reviewe