Future prospects of Higgs Physics at CMS

The Higgs boson physics reach of the CMS detector with 300(0) fb-1 of proton-proton collisions at sqrt{s} = 14 TeV is presented. Precision measurements of the Higgs boson properties, Higgs boson pair production and self-coupling, rare Higgs boson decays, and the potential for additional Higgs bosons are discussed

Averaged Singular Integral Estimation as a Bias Reduction Technique

This paper proposes an averaged version of singular integral estimators, whose bias achieves higher rates of convergence under smoothing assumptions. We derive exact bias bounds, without imposing smoothing assumptions, which are a basis for deriving the rates of convergence under differentiability assumptions.Publicad

Explicit tensor network representation for the ground states of string-net models

The structure of string-net lattice models, relevant as examples of topological phases, leads to a remarkably simple way of expressing their ground states as a tensor network constructed from the basic data of the underlying tensor categories. The construction highlights the importance of the fat lattice to understand these models.Comment: 5 pages, pdf figure

Chemical modulation of the nociceptive receptor TRPV1: Synthetic, biological and computational studies

El canal iònic Receptor Vanil·loide Tipus 1 (sigles en anglès TRPV1) es considera un important integrador de diverses senyals de dolor. D'entre tots els productes que interaccionen amb TRPV1, aquells que bloquegen el senyal doloros de forma no competitiva han atret l'interès dels investigadors que treballen en el camp. A partir de resultats prèviament obtinguts per a diversos peptoides que van mostrar activitat com antagonistes no competitius de TRPV1 i que van permetre proposar una senzilla hipòtesi farmacoforica que incloïa un grup catiònic i dos aromàtics idèntics, la present tesi es va centrar en el disseny i preparació de productes amb estructures més rígides, no peptoides, capaços d'interaccionar amb TRPV1 com bloquejadors no competitius. L'avaluació biològica d'una col·lecció de nous antagonistes i un estudi en profunditat in vitro i in vivo del compost més actiu van proporcionar informació sobre el mode d'acció d'aquests compostos. Entre diferents alternatives considerades, l'esquelet d'1,3,5-triazina va ser seleccionat com el més adequat per albergar els requisits estructurals del farmacòfor proposat. Es van sintetitzar un total de 38 1,3,5-triazines-2,4,6-trisubstituidas amb estructures químicament diverses utilitzant un procediment prèviament optimitzat. Un estudi per RMN combinat amb càlculs teòrics va permetre determinar que moltes d'aquestes triazines presenten diferents confórmers en equilibri en solució, derivats de la rotació dels enllaços que uneixen les tres cadenes laterals a l'anell de triazina. Deu d'aquestes van resultar especialment actives, bloquejant el canal TRPV1 amb valors de IC50 en el rang submicromolar. D'entre les triazines sintetitzades destaca el compost 46 per la seva elevada potència (IC50 = 50 nM), trobant-se entre els bloquejadors de TRPV1 més potents descrits fins al moment. La triazina 46 presenta una activitat polimodal capaç d'inhibir l'activació de TRPV1 per capsaïcina i pH, una toxicitat reduïda tant en assajos in vitro com in vivo i actua de forma selectiva sobre TRPV1. Quant a la seva manera d'acció, 46 actua com un bloquejador de canal obert que s'uneix en una posició relativament profunda dins del porus aquós del canal. S'han construït models 3D-QSAR emprant la tècnica CoMSIA, que correlacionen les propietats estructurals de la col·lecció de compostos sintetitzats amb la seva activitat. Aquests models donen suport a la hipòtesi inicial sobre els determinants estructurals de l'activitat antagonista TRPV1, i constitueixen una eina per a la predicció de l'activitat de nous compostos. Emprant aquests models es va predir una activitat en el rang baix micromolar per membres d'una família de analegs basats en un esquelet central de pirrolidina. La síntesi i avaluació de l'activitat antagonista de TRPV1 d'alguns d'aquests anàlegs va confirmar les prediccions, validant els models 3D-QSAR i establint aquests compostos com un interessant punt de partida per al desenvolupament d'una nova família d'antagonistes.El canal iónico Receptor Vanilloide Tipo 1 (siglas en ingles TRPV1) se considera un importante integrador de diversas señales de dolor. De entre todos los productos que interaccionan con TRPV1, aquellos que bloquean la señal dolorosa de forma no competitiva han atraído el interés de los investigadores que trabajan en el campo. A partir de resultados previamente obtenidos para varios peptoides que mostraron actividad como antagonistas no competitivos de TRPV1 y que permitieron proponer una sencilla hipótesis farmacoforica que incluía un grupo catiónico y dos aromáticos idénticos, la presente tesis se centró en el diseño y preparación de productos con estructuras más rígidas, no peptoides, capaces de interaccionar con TRPV1 como bloqueadores no competitivos. La evaluación biológica de una colección de nuevos antagonistas y un estudio en profundidad in vitro e in vivo del compuesto más activo proporcionaron información sobre el modo de acción de estos compuestos. Entre diferentes alternativas consideradas, el esqueleto de 1,3,5-triazina fue seleccionado como el más adecuado para albergar los requisitos estructurales del farmacóforo propuesto. Se sintetizaron un total de 38 1,3,5-triazinas-2,4,6-trisubstituidas con estructuras químicamente diversas utilizando un procedimiento previamente optimizado. Un estudio por RMN combinado con cálculos teóricos permitió determinar que muchas de estas triazinas presentan diferentes conformeros en equilibrio en solución, derivados de la rotación de los enlaces que unen las tres cadenas laterales al anillo de triazina. Diez de de ellas resultaron especialmente activas, bloqueando el canal TRPV1 con valores de IC50 en el rango submicromolar. De entre las triazinas sintetizadas destaca el compuesto 46 por su elevada potencia (IC50 = 50 nM), encontrandose entre los bloqueadores de TRPV1 más potentes descritos hasta el momento. La triazina 46 presenta una actividad polimodal capaz de inhibir la activacion de TRPV1 por capsaicina y pH, una toxicidad reducida tanto en ensayos in vitro como in vivo y actúa de forma selectiva sobre TRPV1. En cuanto a su modo de acción, 46 actúa como un bloqueador de canal abierto que se une en una posición relativamente profunda dentro del poro acuoso del canal. Se han construido modelos 3D-QSAR empleando la técnica CoMSIA, que correlacionan las propiedades estructurales de la colección de compuestos sintetizados con su actividad. Estos modelos dan soporte a la hipótesis inicial sobre los determinantes estructurales de la actividad antagonista de TRPV1, y constituyen una herramienta para la predicción de la actividad de nuevos compuestos. Usando dichos modelos se predijo una actividad en el rango bajo micromolar para miembros de una familia de analogos basados en un esqueleto central de pirrolidina. La síntesis y evaluación de la actividad antagonista de TRPV1 de alguno de estos análogos confirmó las predicciones, validando dichos modelos 3D-QSAR y estableciendo dichos compuestos como un interesante punto de partida para el desarrollo de una nueva familia de antagonistas.The ion channel Vanilloid receptor type 1 (TRPV1) is considered an important integrator of various pain stimuli. Among the products that interact with TRPV1, the ones blocking the “pain signal” in an uncompetitive manner have attracted the attention of researchers working in the field. Based on previously obtained results for several peptoid hits that showed activity as uncompetitive TRPV1 antagonists, and that allowed to propose a basic pharmacophoric hypothesis consisting on one cationic and two identical aromatic moieties, this thesis focused on the design and synthesis of new antagonists with a more rigid non-peptoid structure. Biological evaluation of a collection of new blockers and an in depth in vitro and in vivo study of the most active one provided knowledge about their mode of action. In addition, a 3D-quantitative structure-activity relationship study (3D-QSAR) allowed to generate models that explain the observed biological activity and can help to predict the activities of new compounds. The 1,3,5-triazine skeleton was selected as rigid non-peptoid scaffold that can hold the three required pharmacophoric features. A total of 38 2,4,6-trisubstituted-1,3,5-triazines were synthesized using an optimized procedure. An in depth NMR study combined with theoretical calculations allowed to determine that most of these triazines present different conformers in equilibrium in solution, derived from the rotation of the bonds that joint the three side chains to the triazine ring. Ten of those triazines were particularly active blocking TRPV1 with submicromolar IC50 values. Triazine 46 exhibited a remarkably high activity (IC50 = 50 nM) being one of the most potent TRPV1 blockers described. It behaves as a polymodal antagonist against capsaicin and pH activation signals, exhibiting a low toxicity profile both in vitro and in vivo. Concerning its mechanism of action, 46 acts as an open channel blocker that locates relatively deep within the aqueous channel pore. Statistically significant 3D-QSAR models were generated, using the CoMSIA methodology, for the anti-TRPV1 activity of the newly synthesized compounds. Those models reinforced the initial hypothesis on the structural requirements for uncompetitive TRPV1 antagonists and provided a quantitative tool that could help to predict the activity of new compounds. Using these models, an activity in the low micromolar range was estimated for a few members of a new family of pyrrolidine based TRPV1 antagonists. The synthesis and biological evaluation of some of them confirmed the activity prediction, further validating the 3D-QSAR models and establishing these pyrrolidine analogues as an interesting starting point for further development of new anti-TRPV1 compounds.

Investment in telecommunications infrastructure, growth, and employment - recent research

Telecommunications investment has been identified as one with a strong potential to spur economic growth and create employment. Investments in telecommunications infrastructure could not only provide a short-term boost to the economy, but also lay the groundwork for long-term improved growth and employment perspectives. Many fiscal stimulus programs adopted by national governments to lessen the impact of the recession and boost economic recovery include substantial stimulus investments related to digital infrastructure. Indeed research findings indicate that telecom investment has an impact far beyond the scope of the industry itself, promoting growth in adjacent industries and creating new industries. Telecommuni-cations investment explains up to one third of economic growth. With regard to employment, telecommunications investments have contrary effects: On the one hand, it is widely acknowledged telecom investments lead to significant productivity improvements. Increased efficiency is certainly beneficial for the economy; however, process optimization may lead to job losses. On the other hand, various direct and indirect employment effects can be identified that contribute to create new jobs. Therefore, the question arises whether negative or positive effects prevail. Our article gives an overview of the most important studies and their key findings, addressing methodology and assessing total contributions of telecom infrastructure investment to GDP growth and employment in important economies in Europe, North America and other parts of the world. We review ICT productivity studies, econometric studies analyzing the relationship between broadband infrastructure and economic development, and "forward looking" studies estimating the multiplier effects of telecom investments. Most evidence indicates a strong and robust positive relationship between telecom investment and both economic growth and employment. These results confirm that investments in digital infrastructure may significantly contribute to overcome the adverse effects of the economic crisis and improve long-term growth prospects

Gestión conjunta de la calidad en grupos empresariales de la economía social

Due to the growth in markets, social economy enterprises are seeking a competitive advantage through economies of scale. In this regard, these enterprises should pursue the coordinated implementation of shared quality management strategies within groups. Accordingly, quality benchmarking through self-evaluation models is a key instrument in providing a balanced quality standard within the group and also in helping create synergies in the group. Likewise, coordinated managed of the quality records should be sought by the companies with a view to introducing a joint Quality Information System. Finally, joint quality circles should also be involved in shared quality management within social economy groups.Groups, quality management, benchmarking, quality information system, quality circles.

Diversity mdir receiver for space-time dispersive channels

A particular property of the cellebrated MDIR receiver is introduced in this communication, namely, the fact that full exploitation of the diversity is obtained with multiple beamformers when the channel is spatially and timely dispersive. Therefore a new structure is developped which provides better performance. The hardware need for this new receiver may be obtained through reconfigurability of the RAKE architectures available at the base station. It will be tested in the FDD mode of UTRA.Peer ReviewedPostprint (published version