111 research outputs found

    A CMV connection between orthogonal polynomials on the unit circle and the real line

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    M. Derevyagin, L. Vinet and A. Zhedanov introduced in Derevyagin et al. (2012) a new connection between orthogonal polynomials on the unit circle and the real line. It maps any real CMV matrix into a Jacobi one depending on a real parameter λ. In Derevyagin et al. (2012) the authors prove that this map yields a natural link between the Jacobi polynomials on the unit circle and the little and big −1 Jacobi polynomials on the real line. They also provide explicit expressions for the measure and orthogonal polynomials associated with the Jacobi matrix in terms of those related to the CMV matrix, but only for the value λ = 1 which simplifies the connection –basic DVZ connection–. However, similar explicit expressions for an arbitrary value of λ –(general) DVZ connection– are missing in Derevyagin et al. (2012). This is the main problem overcome in this paper. This work introduces a new approach to the DVZ connection which formulates it as a two-dimensional eigenproblem by using known properties of CMV matrices. This allows us to go further than Derevyagin et al. (2012), providing explicit relations between the measures and orthogonal polynomials for the general DVZ connection. It turns out that this connection maps a measure on the unit circle into a rational perturbation of an even measure supported on two symmetric intervals of the real line, which reduce to a single interval for the basic DVZ connection, while the perturbation becomes a degree one polynomial. Some instances of the DVZ connection are shown to give new one-parameter families of orthogonal polynomials on the real line.The work of the first, third and fourth authors has been supported in part by the research project MTM2017-89941-P from Ministerio de Economía, Industria y Competitividad of Spain and the European Regional Development Fund (ERDF), by project UAL18-FQM-B025-A (UAL/CECEU/FEDER) and by projects E26 17R and E48 20R of Diputación General de Aragón (Spain) and the ERDF 2014–2020 “Construyendo Europa desde Aragón”. The work of the second author has been partially supported by the research project PGC2018–096504-B-C33 supported by Agencia Estatal de Investigación of Spain

    Adherencia al tratamiento con fármacos moduladores de la enfermedad sintéticos en la artritis reumatoide. Resultados del estudio OBSERVAR

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    [Abstract] Background: Treatment compliance with disease-modifying antirheumatic drugs (DMARD) is essential to achieve the therapeutic goals in rheumatoid arthritis (RA). However, despite the need for good compliance, there is evidence that patients with RA frequently fail to use DMARD for the control of RA. Thus, the main objective of the OBSERVAR study is to evaluate the reasons for the lack of therapeutic adherence to synthetic DMARD in these patients. Patients and methods: A Delphi process involving 18 randomly selected Spanish rheumatologists determined the level of agreement with 66 causes of noncompliance selected from the literature in relation to synthetic DMARD in RA. Results: The reasons for noncompliance were consistent in 75.7%, although 3 reasons (4.5%) were highly consistent: 1) not knowing what to do in the case of an adverse event with DMARD; 2) not having undergone adherence screening by health personnel for early detection of "noncompliant patients"; and 3) not having undergone interventions or strategies that improve adherence. Conclusion: In order to improve adherence to RA treatment with synthetic DMARD, the patient should be adequately informed of each new treatment introduced, the patient's compliance profile should be incorporated into the clinical routine and the patient's motivation for therapeutic compliance be reinforced through the methods available to us.[Resumen] Introducción. La cumplimentación del tratamiento modificador de la enfermedad es esencial para alcanzar los objetivos terapéuticos en la artritis reumatoide (AR). Sin embargo, y a pesar de la necesidad de una buena adherencia, existe evidencia de que muchos pacientes con AR no cumplen adecuadamente con la prescripción del tratamiento indicado con fármacos moduladores de la enfermedad de acción lenta (FAME) sintéticos o convencionales. Conscientes de la importancia de este hecho, el estudio sobre observancia terapéutica en AR (estudio OBSERVAR) tiene como objetivo principal valorar los motivos de la falta de adherencia terapéutica a los FAME sintéticos en estos pacientes. Pacientes y métodos. Mediante un proceso Delphi entre 18 reumatólogos españoles seleccionados aleatoriamente se determinó el grado de acuerdo con 66 causas de incumplimiento seleccionadas de la bibliografía, en relación con los FAME sintéticos en la AR. Resultados. Los motivos de incumplimiento fueron consistentes en el 75,7%, si bien 3 razones (4,5%) destacaron como muy consistentes: 1) desconocer qué hacer cuando se sufre un acontecimiento adverso con el FAME; 2) no llevar a cabo métodos de cribado de la adherencia por el personal sanitario para detectar a los «pacientes incumplidores» de forma temprana y 3) no aplicar intervenciones o estrategias que mejoren la adherencia terapéutica. Conclusión. Para mejorar la adherencia al tratamiento de la AR con FAME sintéticos se debe informar al paciente de cada tratamiento nuevo introducido, incorporar el perfil de cumplimiento del paciente en la rutina clínica, y reforzar la motivación del paciente al cumplimiento terapéutico mediante los métodos a nuestro alcance

    Functional expression of a penicillin acylase from the extreme thermophile Thermus thermophilus HB27 in Escherichia coli

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    Background: Penicillin acylases (PACs) are enzymes of industrial relevance in the manufacture of beta-lactam antibiotics. Development of a PAC with a longer half-life under the reaction conditions used is essential for the improvement of the operational stability of the process. A gene encoding a homologue to Escherichia coli PAC was found in the genome of the thermophilic bacterium Thermus thermophilus (Tth) HB27. Because of the nature of this PAC and its complex maturation that is crucial to reach its functional heterodimeric final conformation, the overexpression of this enzyme in a heterologous mesophilic host was a challenge. Here we describe the purification and characterization of the PAC protein from Tth HB27 overexpressed in Escherichia coli. Results: Fusions to a superfolder green fluorescent protein and differential membrane solubilization assays indicated that the enzyme remains attached through its amino-terminal end to the outer side of the cytoplasmic membrane of Tth cells. In order to overexpress this PAC in E. coli cells, a variant of the protein devoid of its membrane anchoring segment was constructed. The effect of the co-expression of chaperones and calcium supplementation of the culture medium was investigated. The total production of PAC was enhanced by the presence of DnaK/J and GrpE and even more by trigger factor and GroEL/ES. In addition, 10 mM calcium markedly improved both PAC specific and volumetric activities. Recombinant PAC was affinity-purified and proper maturation of the protein was confirmed by SDS-PAGE and MALDI-TOF analysis of the subunits. The recombinant protein was tested for activity towards several penicillins, cephalosporins and homoserine lactones. Hydrophobic acyl-chain penicillins were preferred over the rest of the substrates. Penicillin K (octanoyl penicillin) was the best substrate, with the highest specificity constant value (16.12 mM-1.seg-1). The optimum pH was aprox. 4 and the optimum temperature was 75 [DEGREE SIGN]C. The half-life of the enzyme at this temperature was 9.2 h. Conclusions: This is the first report concerning the heterologous expression of a pac gene from a thermophilic microorganism in the mesophilic host E. coli. The recombinant protein was identified as a penicillin K-deacylating thermozymeL.T., A.H. and J.B. acknowledge funding from the Spanish Ministry of Science (grants CIT 010000-2009-29, RyC2006-02441) and an institutional grant from Fundación Ramón Areces to CBMS

    Engineering the substrate specificity of a thermophilic penicillin acylase from thermus thermophilus

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    A homologue of the Escherichia coli penicillin acylase is encoded in the genomes of several thermophiles, including in different Thermus thermophilus strains. Although the natural substrate of this enzyme is not known, this acylase shows a marked preference for penicillin K over penicillin G. Three-dimensional models were created in which the catalytic residues and the substrate binding pocket were identified. Through rational redesign, residues were replaced to mimic the aromatic binding site of the E. coli penicillin G acylase. A set of enzyme variants containing between one and four amino acid replacements was generated, with altered catalytic properties in the hydrolyses of penicillins K and G. The introduction of a single phenylalanine residue in position α188, α189, or β24 improved the Km for penicillin G between 9- and 12-fold, and the catalytic efficiency of these variants for penicillin G was improved up to 6.6-fold. Structural models, as well as docking analyses, can predict the positioning of penicillins G and K for catalysis and can demonstrate how binding in a productive pose is compromised when more than one bulky phenylalanine residue is introduced into the active site. © 2013, American Society for Microbiology.Spanish Ministry of Science (CIT no. 010000-2009-29, RyC2006-02441, and BIO2010-18875); Fundación Ramón ArecesPeer Reviewe

    Zero-lag long-range synchronization via hippocampal dynamical relaying

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    2 páginas, 1 figura.-- Póster presentado al Nineteenth Annual Computational Neuroscience Meeting: CNS*2010 San Antonio, TX, USA; 24-30 July 2010.Peer reviewe

    Cerebral changes and disrupted gray-matter cortical networks in asymptomatic older adults at risk for Alzheimer's disease

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    The diagnostic value of cerebrospinal fluid (CSF) biomarkers is well established in Alzheimer's disease, but our current knowledge about how abnormal CSF levels affect cerebral integrity, at local and network levels, is incomplete in asymptomatic older adults. Here, we have collected CSF samples and performed structural magnetic resonance imaging scans in cognitively normal elderly as part of a cross-sectional multicenter study (SIGNAL project). To identify group differences in cortical thickness, white matter volume, and properties of structural networks, participants were split into controls (N = 20), positive amyloid-? (A?1?42 +) (N = 19), and positive phosphorylated tau (N = 18). The A?1?42 + group exhibited thickening of middle temporal regions, while positive phosphorylated tau individuals showed thinning in the superior parietal and orbitofrontal cortices. Subjects with abnormal CSF biomarkers further showed regional white matter atrophy and more segregated cortical networks, the A?1?42 + group showing heightened isolation of cingulate and temporal cortices. Collectively, these findings highlight the relevance of combining structural brain imaging and connectomics for in vivo tracking of Alzheimer's disease lesions in asymptomatic stages.This work was supported by research grants from the Spanish Ministry of Economy and Competitiveness (SAF2011-25463 to J.L.C., PSI2014-55747-R to M.A.), the Carlos III Institute of Health, Spain (PI11/02425 and PI14/01126 to J.F.; PI11/3035 and PI14/1561 to A.L.; PI08/0139, PI12/02288 and PI16/01652 to P.S.J.), jointly funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, “Una manera de hacer Europa”, the Joint Programming in Neurodegenerative Disease Research (DEMTEST to P.S.J.), “Marató TV3” (project 20141210 to J.F. and 20142610 to A.L.), the Regional Ministry of Innovation, Science and Enterprise, Junta de Andalucia (P12- CTS-2327 to J.C.L.), and the CIBERNED program (Signal project)

    Search for a light charged Higgs boson in t -> H±b decays, with H± -> cb, in the lepton plus jets final state in proton-proton collisions at root s=13 TeV with the ATLAS detector

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    A search for a charged Higgs boson, H-+/-, produced in top-quark decays, t -> H(+/-)b, is presented. The search targets H-+/- decays into a bottom and a charm quark, H-+/- -> cb. The analysis focuses on a selection enriched in top-quark pair production, where one top quark decays into a leptonically decaying W boson and a bottom quark, and the other top quark decays into a charged Higgs boson and a bottom quark. This topology leads to a lepton-plus-jets final state, characterised by an isolated electron or muon and at least four jets. The search exploits the high multiplicity of jets containing b-hadrons, and deploys a neural network classifier that uses the kinematic differences between the signal and the background. The search uses a dataset of proton-proton collisions collected at a centre-of-mass energy root s = 13TeV between 2015 and 2018 with the ATLAS detector at CERN's Large Hadron Collider, amounting to an integrated luminosity of 139 fb(-1). Observed (expected) 95% confidence-level upper limits between 0.15% (0.09%) and 0.42% (0.25%) are derived for the product of branching fractions B( t -> H-+/- b) x B( H +/- -> cb) for charged Higgs boson masses between 60 and 160 GeV, assuming the SM production of the top-quark pairs

    Test of CP Invariance in Higgs Boson Vector-Boson-Fusion Production Using the H→γγ Channel with the ATLAS Detector

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    A test of CP invariance in Higgs boson production via vector-boson fusion has been performed in the H→γγ channel using 139  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV collected by the ATLAS detector at the LHC. The optimal observable method is used to probe the CP structure of interactions between the Higgs boson and electroweak gauge bosons, as described by an effective field theory. No sign of CP violation is observed in the data. Constraints are set on the parameters describing the strength of the CP-odd component in the coupling between the Higgs boson and the electroweak gauge bosons in two effective field theory bases: d[over ˜] in the HISZ basis and c_{HW[over ˜]} in the Warsaw basis. The results presented are the most stringent constraints on CP violation in the coupling between Higgs and weak bosons. The 95% C.L. constraint on d[over ˜] is derived for the first time and the 95% C.L. constraint on c_{HW[over ˜]} has been improved by a factor of 5 compared to the previous measurement

    Observation of the γγ→ττ Process in Pb+Pb Collisions and Constraints on the τ-Lepton Anomalous Magnetic Moment with the ATLAS Detector

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    This Letter reports the observation of τ-lepton-pair production in ultraperipheral lead-lead collisions Pb+Pb→Pb(γγ→ττ)Pb and constraints on the τ-lepton anomalous magnetic moment a_{τ}. The dataset corresponds to an integrated luminosity of 1.44  nb^{-1} of LHC Pb+Pb collisions at sqrt[s_{NN}]=5.02  TeV recorded by the ATLAS experiment in 2018. Selected events contain one muon from a τ-lepton decay, an electron or charged-particle track(s) from the other τ-lepton decay, little additional central-detector activity, and no forward neutrons. The γγ→ττ process is observed in Pb+Pb collisions with a significance exceeding 5 standard deviations and a signal strength of μ_{ττ}=1.03_{-0.05}^{+0.06} assuming the standard model value for a_{τ}. To measure a_{τ}, a template fit to the muon transverse-momentum distribution from τ-lepton candidates is performed, using a dimuon (γγ→μμ) control sample to constrain systematic uncertainties. The observed 95% confidence-level interval for a_{τ} is -0.057<a_{τ}<0.024

    Observation of Single-Top-Quark Production in Association with a Photon Using the ATLAS Detector

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    This Letter reports the observation of single top quarks produced together with a photon, which directly probes the electroweak coupling of the top quark. The analysis uses 139  fb^{-1} of 13 TeV proton-proton collision data collected with the ATLAS detector at the Large Hadron Collider. Requiring a photon with transverse momentum larger than 20 GeV and within the detector acceptance, the fiducial cross section is measured to be 688±23(stat) _{-71}^{+75}(syst)  fb, to be compared with the standard model prediction of 515_{-42}^{+36}  fb at next-to-leading order in QCD
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