SwissParam: a fast force field generation tool for small organic molecules.

The drug discovery process has been deeply transformed recently by the use of computational ligand-based or structure-based methods, helping the lead compounds identification and optimization, and finally the delivery of new drug candidates more quickly and at lower cost. Structure-based computational methods for drug discovery mainly involve ligand-protein docking and rapid binding free energy estimation, both of which require force field parameterization for many drug candidates. Here, we present a fast force field generation tool, called SwissParam, able to generate, for arbitrary small organic molecule, topologies, and parameters based on the Merck molecular force field, but in a functional form that is compatible with the CHARMM force field. Output files can be used with CHARMM or GROMACS. The topologies and parameters generated by SwissParam are used by the docking software EADock2 and EADock DSS to describe the small molecules to be docked, whereas the protein is described by the CHARMM force field, and allow them to reach success rates ranging from 56 to 78%. We have also developed a rapid binding free energy estimation approach, using SwissParam for ligands and CHARMM22/27 for proteins, which requires only a short minimization to reproduce the experimental binding free energy of 214 ligand-protein complexes involving 62 different proteins, with a standard error of 2.0 kcal mol(-1), and a correlation coefficient of 0.74. Together, these results demonstrate the relevance of using SwissParam topologies and parameters to describe small organic molecules in computer-aided drug design applications, together with a CHARMM22/27 description of the target protein. SwissParam is available free of charge for academic users at www.swissparam.ch.

Magnetic field generation during intense laser channelling in underdense plasma

Channel formation during the propagation of a high-energy (120 J) and long duration (30 ps) laser pulse through an underdense deuterium plasma has been spatially and temporally resolved via means of a proton imaging technique, with intrinsic resolutions of a few micron and a few ps, respectively. Conclusive proof is provided that strong azimuthally symmetric magnetic fields with a strength of around 0.5 MG are created inside the channel, consistent with the generation of a collimated beam of
relativistic electrons. The inferred electron beam characteristics may have implications for the cone-free fast-ignition scheme of inertial confinement fusion

Quantum-state protection in cavities

We show how an initially prepared quantum state of a radiation mode in a cavity can be preserved for a long time using a feedback scheme based on the injection of appropriately prepared atoms. We present a feedback scheme both for optical cavities, which can be continuously monitored by a photodetector, and for microwave cavities, which can be monitored only indirectly via the detection of atoms that have interacted with the cavity field. We also discuss the possibility of applying these methods for decoherence control in quantum information processing.

Infrared seeded parametric four-wave mixing for sensitive detection of molecules

We have developed a sensitive resonant four-wave mixing technique based on two-photon parametric four-wave mixing with the addition of a phase matched ''seeder'' field. Generation of the seeder field via the same four-wave mixing process in a high pressure cell enables automatic phase matching to be achieved in a low pressure sample cell. This arrangement facilitates sensitive detection of complex molecular spectra by simply tuning the pump laser. We demonstrate the technique with the detection of nitric oxide down to concentrations more than 4 orders of magnitude below the capability of parametric four-wave mixing alone, with an estimated detection threshold of 10(12) molecules/cm(3).

Técnicas de avaliação da confiabilidade em estruturas de concreto armado

Neste trabalho é dado ênfase à inclusão das incertezas na avaliação do comportamento estrutural, objetivando uma melhor representação das características do sistema e uma quantificação do significado destas incertezas no projeto. São feitas comparações entre as técnicas clássicas existentes de análise de confiabilidade, tais como FORM, Simulação Direta Monte Carlo (MC) e Simulação Monte Carlo com Amostragem por Importância Adaptativa (MCIS), e os métodos aproximados da Superfície de Resposta( RS) e de Redes Neurais Artificiais(ANN). Quando possível, as comparações são feitas salientando- se as vantagens e inconvenientes do uso de uma ou de outra técnica em problemas com complexidades crescentes. São analisadas desde formulações com funções de estado limite explícitas até formulações implícitas com variabilidade espacial de carregamento e propriedades dos materiais, incluindo campos estocásticos. É tratado, em especial, o problema da análise da confiabilidade de estruturas de concreto armado incluindo o efeito da variabilidade espacial de suas propriedades. Para tanto é proposto um modelo de elementos finitos para a representação do concreto armado que incorpora as principais características observadas neste material. Também foi desenvolvido um modelo para a geração de campos estocásticos multidimensionais não Gaussianos para as propriedades do material e que é independente da malha de elementos finitos, assim como implementadas técnicas para aceleração das avaliações estruturais presentes em qualquer das técnicas empregadas. Para o tratamento da confiabilidade através da técnica da Superfície de Resposta, o algoritmo desenvolvido por Rajashekhar et al(1993) foi implementado. Já para o tratamento através de Redes Neurais Artificias, foram desenvolvidos alguns códigos para a simulação de redes percéptron multicamada e redes com função de base radial e então implementados no algoritmo de avaliação de confiabilidade desenvolvido por Shao et al(1997). Em geral, observou-se que as técnicas de simulação tem desempenho bastante baixo em problemas mais complexos, sobressaindo-se a técnica de primeira ordem FORM e as técnicas aproximadas da Superfície de Resposta e de Redes Neurais Artificiais, embora com precisão prejudicada devido às aproximações presentes.

Coronal fluid-dynamics in laser fusion

The fluid-dynamics of the corona ejected by laser-fusion targets in the direct-drive approach (thermal radiation and atomic physics unimportant) is discussed. A two-fluid model involves inverse bremsstrahlung absorption, refraction, different ion and electron temperatures with energy exchange, different ion and electron velocities and magnetic field generation, and their effect on ion-electron friction and heat flux. Four dimensionless parameters determine coronal regimes for one-dimensional flows under uniform irradiation. One additional parameter is involved in two-dimensional problems,including the stability of one-dimensional flows, and the smoothing of nonuniform driving.

Edén: relato, imagen y proyecto. El concepto de paraíso terrenal como generador de arquitecturas

Esta tesis, Edén: relato, imagen y proyecto. El concepto de Paraíso terrenal como generador de arquitecturas se realiza con el objetivo de estudiar los vínculos entre la idea de Edén, o Paraíso y la arquitectura. Siempre trabajando desde los tres niveles de representación, relato, imagen y proyecto. En la aproximación al objeto de estudio, se procede a estudiar el relato en sí, y se hallan, en la forma misma del relato, unas implicaciones relacionadas con el mundo mitológico y arquetípico. Estos resultados iniciales son la detección de que cada una de las partes que forman el conjunto edénico, han sido previamente objetos de culto en religiones corte pagano o chamánico, desde la prehistoria. El agua, los árboles, los animales, la tierra y los surcos del huerto, todos ellos han sido objetos de veneración desde tiempos inmemoriales. Trazando la genealogía de estos objetos de culto se acude al análisis arquetípico, que relaciona estos objetos venerados con el inconsciente y con la manifestación espontanea de los mismos en la realidad. Estos estudios arrojan resultados con implicaciones espaciales, arquitectónicas y se concluye que más que un ideal o un lugar en concreto, en el mito o en la realidad, lo que definitivamente parece (y demuestra) ser, es una tipología arquitectónica relacionada en su estructura formal y teórica con la del jardín cerrado. La manifestación en imagen de estos resultados y la investigación misma, llevan a acudir a unas de las imágenes más primitivas del Jardín del Edén, y que de hecho son previas a la “invención” del Hortus Conclusus como tal. Estas son las representaciones mozárabes del Paraíso Terrenal como lugar cierto en la tierra, que aparecen en los mappaemundi incluidos en los Códices de los Beatos. En el estudio de los mismos se comprende la estructura formal y teórica de lo que son las arquitecturas paradisíacas. Su calado en la cultura occidental hace que estos documentos sirvan como exoesqueletos del proyecto paradisíaco. Además, por su variedad arrojan gran número de resultados de índole espacial. Los resultados arrojados por el estudio de las representaciones edénicas de los Beatos llevan la investigación a otro momento e imágenes de la historia de la arquitectura donde, por su radicalidad de planteamientos y tabula rasa con las arquitecturas previas son necesarios nuevos lenguajes de aproximación al tema proyectual por el deseo globalizador que implican estas arquitecturas, esto es en el periodo de la arquitectura moderna. Se utiliza como elemento calibrador El poema del ángulo recto de Le Corbusier. Este documento gráfico no sólo nos da la clave que bullía en este periodo con respecto a una nueva aproximación a la superficie terrestre y al medio. Este instrumento también sirve de catalizador entre lo real y lo ideal y es una síntesis de operaciones arquitectónicas, que mediante la comparación y/o oposición con los resultados previos del estudio arquetípico y de los Beatos, genera grandes grupos de características que se hallan entrelazadas en los proyectos paradisíacos. Gracias a estos documentos se puede concluir con una síntesis de características que comparten los proyectos paradisiacos, que en todo caso son esto, proyectos en plural. No existe la unicidad, ya que se infiere de este estudio que son, en conjunto, una forma de hacer ciertas arquitecturas. Tienen características medibles y reproducibles y unas condiciones tipológicas y de generación de campos que permiten producir muchos tipos de proyectos, todos ellos de tipología paradisíaca. ABSTRACT This thesis, Eden: Tale, Image and Project. The Concept of Terrestrial Paradise as a Generator of Architectures, is carried out with the objective of studying the relations between the idea of Eden or Paradise and architecture. In every case working from the three levels of representation, tale, image and project. On the approximation to the object of study, the investigation is centered on the tale itself, and in the same core of it, are found some implications that relate it with the world of mythology and archetype. These initial results consist of detecting that each one of the parts that form the edenic set; have previously been objects of cult in religions of a pagan or shamanic nature, since pre-historic times. Water, animals, earth and the grooves of the orchard, have all been objects of reverence since the dawn of time. Tracing the genealogy of these objects an archetypal type of analysis is taken on, which relates the revered objects with the subconscious and with the spontaneous manifestation of these in reality. These studies also provide results with spatial and architectonic implications, and it is concluded that more than an ideal or a concrete place, in myth or reality, what it definitely seems (and shows to be) is an architectonic typology, related in its formal and theoretical structure with that of the enclosed garden. The manifestation in image of these results, and the investigation itself, lead to reach for one of the most primitive set of images of the Garden of Eden, and that are in fact previous to the “invention” of the Hortus Conclusus as such. A collection of mozárabe representations of the Terrestrial Paradise as a concrete place on Earth. These are the mappaemundi included in the Codexes of the Beatos. By their study, the formal and theoretical structure of paradisal architectures is understood. Their importance in occidental culture makes these documents bring out their side as exoskeletons of the paradisal Project. Also, for their variety, they cast a great number of results of a spatial nature. The results released by the study of the edenic representations of the Beatos take the investigation to another moment and set of images within the history of architecture, where the radicality of the approaches to architecture, and the tabula rasa in relation to previous architectures make it necessary to invent new languages of approximation to the subject of project. This happens because of the globalizing tones that imply these architectures. The lapse of time referred to would be during the general practice of modern architecture. The object of calibration would be The Poem of the Right Angle, by Le Corbusier. The graphic document not only gives us the key of what flowed during that time when a new approximation to the surface of earth and to the environment was retrieved. This instrument also serves as a catalyst between real and ideal, and it is a synthesis of architectural operations that by comparison and/or opposition with the previous results of the archetypal study, and of the Beatos, generates large groups of characteristics that are intertwined in the paradisal project. Due to these documents we can conclude the investigation with a series of characteristics that share the paradisal projects, which in any case are this, projects, in plural. There is no uniqueness. From these findings, it can be inferred that a Paradisal Project is a way to undertake a project, and certain kinds of architecture. They are measurable and are underlaid by a consistent pattern, they also have typological conditions and of field generation, that make it possible to produce many kinds of projects, all of a paradisal typology.

Methane generation in tropical landfills: Simplified methods and field results

This paper deals with the use of simplified methods to predict methane generation in tropical landfills. Methane recovery data obtained on site as part of a research program being carried Out at the Metropolitan Landfill, Salvador, Brazil, is analyzed and used to obtain field methane generation over time. Laboratory data from MSW samples of different ages are presented and discussed: and simplified procedures to estimate the methane generation potential, L(o), and the constant related to the biodegradation rate, k are applied. The first order decay method is used to fit field and laboratory results. It is demonstrated that despite the assumptions and the simplicity of the adopted laboratory procedures, the values L(o) and k obtained are very close to those measured in the field, thus making this kind of analysis very attractive for first approach purposes. (C) 2008 Elsevier Ltd. All rights reserved.

Catalytic enantioselective arylations: boron to zinc exchange as a powerful tool for the generation of transferable aryl groups

The transmetalation between boron and zinc is of great importance for application in organic synthesis, since it allows the formation of new carbon-carbon bonds between organometallic units and electrophiles. The direct arylation of aldehydes or more scarcely ketones, in a catalytic, enantioselective manner using chiral catalysts has been described recently. The enantiomerically enriched diarylmethanols obtained in these reactions are valuable precursors for important bioactive molecules. This review provides a synopsis of this ever-growing field and highlights some of the challenges that still remain.

Optical second harmonic generation in the centrosymmetric magnetic semiconductors EuTe and EuSe

The magnetic europium chalcogenide semiconductors EuTe and EuSe are investigated by the spectroscopy of second harmonic generation (SHG) in the vicinity of the optical band gap formed by transitions involving the 4f and 5d electronic orbitals of the magnetic Eu(2+) ions. In these materials with centrosymmetric crystal lattice the electric-dipole SHG process is symmetry forbidden so that no signal is observed in zero magnetic field. Signal appears, however, in applied magnetic field with the SHG intensity being proportional to the square of magnetization. The magnetic field and temperature dependencies of the induced SHG allow us to introduce a type of nonlinear optical susceptibility determined by the magnetic-dipole contribution in combination with a spontaneous or induced magnetization. The experimental results can be described qualitatively by a phenomenological model based on a symmetry analysis and are in good quantitative agreement with microscopic model calculations accounting for details of the electronic energy and spin structure.

Theory of near-gap second harmonic generation in centrosymmetric magnetic semiconductors: Europium chalcogenides

Second harmonic generation is strictly forbidden in centrosymmetric materials, within the electric dipole approximation. Recently, it was found that the centrosymmetric magnetic semiconductors EuTe and EuSe can generate near-gap second harmonics, if the system is submitted to an external magnetic field. Here, a theoretical model is presented, which well describes the observed phenomena. The model shows that second harmonic generation becomes efficient when the magnetic dipole oscillations between the band-edge excited states of the system, induced by the excitation light, enter the in-phase regime, which can be achieved by applying a magnetic field to the material.

Spin-Induced Optical Second Harmonic Generation in the Centrosymmetric Magnetic Semiconductors EuTe and EuSe

Spectroscopy of the centrosymmetric magnetic semiconductors EuTe and EuSe reveals spin-induced optical second harmonic generation (SHG) in the band gap vicinity at 2.1-2.4 eV. The magnetic field and temperature dependence demonstrates that the SHG arises from the bulk of the materials due to a novel type of nonlinear optical susceptibility caused by the magnetic dipole contribution combined with spontaneous or induced magnetization. This spin-induced susceptibility opens access to a wide class of centrosymmetric systems by harmonics generation spectroscopy.