755 research outputs found

    A general Markov chain approach for disease and rumour spreading in complex networks

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    Spreading processes are ubiquitous in natural and artificial systems. They can be studied via a plethora of models, depending on the specific details of the phenomena under study. Disease contagion and rumour spreading are among the most important of these processes due to their practical relevance. However, despite the similarities between them, current models address both spreading dynamics separately. In this article, we propose a general spreading model that is based on discrete time Markov chains. The model includes all the transitions that are plausible for both a disease contagion process and rumour propagation. We show that our model not only covers the traditional spreading schemes but that it also contains some features relevant in social dynamics, such as apathy, forgetting, and lost/recovering of interest. The model is evaluated analytically to obtain the spreading thresholds and the early time dynamical behaviour for the contact and reactive processes in several scenarios. Comparison with Monte Carlo simulations shows that the Markov chain formalism is highly accurate while it excels in computational efficiency. We round off our work by showing how the proposed framework can be applied to the study of spreading processes occurring on social networks

    Development of COVID-19 monoclonal antibodies and recombinant proteins as reagents for biomedical research and diagnostic test

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    Since SARS-COV-2 virus spread worldwide and COVID-19 turned rapidly into a pandemic illness, the necessity for vaccines and diagnostic tests became crucial. The viral surface is decorated with Spike, the major antigenic determinant and main target for vaccine development. Within Spike, the receptor binding domain (RBD), constitutes the main target of highly neutralizing antibodies found in COVID-19 convalescent plasma. Besides vaccination, another important aspect of Spike (and RBD) is their use as immunogen for the development of poli- and monoclonal antibodies (mAbs) for therapeutic and diagnostic purposes. Here we report the development and preliminary biochemical characterization of a set of monoclonal antibodies against the Spike RBD domain along with the recombinant expression of two mayor COVID-19 protein reagents: the viral Spike RBD domain and the extracellular domain of the human receptor ACE2. RBD and the extracellular domain of ACE2 (aa 1-740) were obtained through transient gene transfection (TGE) in two different mammalian cell culture systems: HEK293T adherent monolayers and Expi293 suspension cultures. Due to its low cost and ease scale-up, all transfections were carried with polyethyleneimine (PEI). Expressed proteins were purified from culture supernatants by immobilized metal affinity chromatography. Anti-RBD mAbs were developed from two different immunization schemes: one aimed to elicit antibodies with viral neutralizing potential, and the other with the ability to recognize denatured RBD for routinary lab immunoassays. To achieve this, the first group of mice was immunized with RBD in aluminium salts (RBD/Al) and the other with RBD emulsified in Freunds adyuvant (RBD/FA). Polyclonal and monoclonal antibody reactivities against native or denatured RBD forms were then assessed by ELISA. Complete RBD denaturation was followed by intrinsic fluorescence spectral changes upon different physicochemical stress treatments. As expected, RBD/Al immunized mice developed an antibody response shifted to native RBD while those immunized with RBD/FA showed a high response against both forms of the protein. In accordance with the observed polyclonal response, RBD/FA derived mAbs recognize both, native and denatured RBD. On the contrary, hybridomas generated from the RBD/Al protocol mostly recognize RBD in its native state. Further ELISA binding assays revealed that all RBD/FA derived mAbs can form a trimeric complex with ACE2 and RBD, denoting they would not have viral neutralizing activity. ELISA competition assays with the RBD/ACE2 complex aimed to determine the neutralization potential of the RBD/Al derived mAbs are under way. Overall, the anti-Spike RBD mAbs and the recombinant RBD and ACE2 proteins presented here constitute valuable tools for diverse COVID-19 academic research projects and local immunity surveillance testing.Fil: AcuĂąa Intrieri, M. E. Universidad Nacional de San Martin. Centro de RediseĂąo E Ingenieria de Proteinas.; ArgentinaFil: Deriane, M.A. Universidad Nacional de San Martin. Centro de RediseĂąo E Ingenieria de Proteinas.; ArgentinaFil: Miller, C.. Universidad Nacional de San Martin. Centro de RediseĂąo E Ingenieria de Proteinas.; ArgentinaFil: Czibener, Cecilia. Consejo Nacional de Investigaciones CientĂ­ficas y TĂŠcnicas. Centro CientĂ­fico TecnolĂłgico Conicet - La Plata. Instituto de Investigaciones BiotecnolĂłgicas. Universidad Nacional de San MartĂ­n. Instituto de Investigaciones BiotecnolĂłgicas; ArgentinaFil: Correa, E.. No especifĂ­ca;Fil: Cragnaz, L.. No especifĂ­ca;Fil: Guerra, L.. No especifĂ­ca;Fil: Rodriguez, S.. No especifĂ­ca;Fil: Goldbaum, F.A.. Universidad Nacional de San Martin. Centro de RediseĂąo E Ingenieria de Proteinas.; ArgentinaFil: Seigelchifer, M.. No especifĂ­ca;Fil: Comerci, Diego JosĂŠ. Consejo Nacional de Investigaciones CientĂ­ficas y TĂŠcnicas. Centro CientĂ­fico TecnolĂłgico Conicet - La Plata. Instituto de Investigaciones BiotecnolĂłgicas. Universidad Nacional de San MartĂ­n. Instituto de Investigaciones BiotecnolĂłgicas; ArgentinaFil: Montagna, Georgina Nuri. Consejo Nacional de Investigaciones CientĂ­ficas y TĂŠcnicas. Centro CientĂ­fico TecnolĂłgico Conicet - La Plata. Instituto de Investigaciones BiotecnolĂłgicas. Universidad Nacional de San MartĂ­n. Instituto de Investigaciones BiotecnolĂłgicas; ArgentinaFil: Cerutti, Maria Laura. Universidad Nacional de San Martin. Centro de RediseĂąo E Ingenieria de Proteinas.; Argentina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂŠcnicas; ArgentinaLVII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research y XVI Annual Meeting of the Argentinean Society for General MicrobiologyVirtualArgentinaSociedad Argentina de InvestigaciĂłn BioquĂ­mica y BiologĂ­a MolecularAsociaciĂłn Civil de MicrobiologĂ­a Genera

    Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate.

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    OBJECTIVES: Tenofovir disoproxil fumarate (TDF) is widely used in the treatment or prevention of HIV and hepatitis B infection. TDF may cause renal tubulopathy in a small proportion of recipients. We aimed to study the risk factors for developing severe renal tubulopathy. METHODS: We conducted an observational cohort study with retrospective identification of cases of treatment-limiting tubulopathy during TDF exposure. We used multivariate Poisson regression analysis to identify risk factors for tubulopathy, and mixed effects models to analyse adjusted estimated glomerular filtration rate (eGFR) slopes. RESULTS: Between October 2002 and June 2013, 60 (0.4%) of 15,983 patients who had received TDF developed tubulopathy after a median exposure of 44.1 (IQR 20.4, 64.4) months. Tubulopathy cases were predominantly male (92%), of white ethnicity (93%), and exposed to antiretroviral regimens that contained boosted protease inhibitors (PI, 90%). In multivariate analysis, age, ethnicity, CD4 cell count and use of didanosine or PI were significantly associated with tubulopathy. Tubulopathy cases experienced significantly greater eGFR decline while receiving TDF than the comparator group (-6.60 [-7.70, -5.50] vs. -0.34 [-0.43, -0.26] mL/min/1.73 m2/year, p < 0.0001). CONCLUSIONS: Older age, white ethnicity, immunodeficiency and co-administration of ddI and PI were risk factors for tubulopathy in patients who received TDF-containing antiretroviral therapy. The presence of rapid eGFR decline identified TDF recipients at increased risk of tubulopathy

    Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

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    A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

    Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

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    A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

    Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

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    Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

    Measurement of isolated photon production in pp and PbPb collisions at sqrt(sNN) = 2.76 TeV

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    Isolated photon production is measured in proton-proton and lead-lead collisions at nucleon-nucleon centre-of-mass energies of 2.76 TeV in the pseudorapidity range |eta|<1.44 and transverse energies ET between 20 and 80 GeV with the CMS detector at the LHC. The measured ET spectra are found to be in good agreement with next-to-leading-order perturbative QCD predictions. The ratio of PbPb to pp isolated photon ET-differential yields, scaled by the number of incoherent nucleon-nucleon collisions, is consistent with unity for all PbPb reaction centralities.Comment: Submitted to Physics Letters

    Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV

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    A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 inverse femtobarns. Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO
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