Inhibitors of Trypanosoma brucei trypanothione reductase: comparative molecular field analysis modeling and structural basis for selective inhibition

Background: Sleeping sickness is a major cause of death in Africa. Since no secure treatment is available, the development of novel therapeutic agents is urgent. In this context, the enzyme trypanothione reductase (TR) is a prominent molecular target that has been investigated in drug design for sleeping sickness. Results: In this study, comparative molecular field analysis models were generated for a series of Trypanosoma brucei TR inhibitors. Statistically significant results were obtained and the models were applied to predict the activity of external test sets, with good correlation between predicted and experimental results. We have also investigated the structural requirements for the selective inhibition of the parasite's enzyme over the human glutathione reductase. Conclusion: The quantitative structure-activity relationship models provided valuable information regarding the essential molecular requirements for the inhibitory activity upon the target protein, providing important insights into the design of more potent and selective TR inhibitors.

Limiting theorems in statistical mechanics. The mean-field case.

The Curie-Weiss model is defined by ah Hamiltonian according to spins interact. For some particular values of the parameters, the sum of the spins normalized with square-root normalization converges or not toward Gaussian distribution. In the thesis we investigate some correlations between the behaviour of the sum and the central limit for interacting random variables.

Experimental validation of a mean field model of mineralized collagen fiber arrays at two levels of hierarchy

In the course of this study, stiffness of a fibril array of mineralized collagen fibrils modeled with a mean field method was validated experimentally at site-matched two levels of tissue hierarchy using mineralized turkey leg tendons (MTLT). The applied modeling approaches allowed to model the properties of this unidirectional tissue from nanoscale (mineralized collagen fibrils) to macroscale (mineralized tendon). At the microlevel, the indentation moduli obtained with a mean field homogenization scheme were compared to the experimental ones obtained with microindentation. At the macrolevel, the macroscopic stiffness predicted with micro finite element (μFE) models was compared to the experimental stiffness measured with uniaxial tensile tests. Elastic properties of the elements in μFE models were injected from the mean field model or two-directional microindentations. Quantitatively, the indentation moduli can be properly predicted with the mean-field models. Local stiffness trends within specific tissue morphologies are very weak, suggesting additional factors responsible for the stiffness variations. At macrolevel, the μFE models underestimate the macroscopic stiffness, as compared to tensile tests, but the correlations are strong.

Field analysis of solar PV-based collective systems for rural electrification.

This article analyses the long-term performance of collective off-grid photovoltaic (PV) systems in rural areas. The use of collective PV systems for the electrification of small medium-size villages in developing countries has increased in the recent years. They are basically set up as stand-alone installations (diesel hybrid or pure PV) with no connection with other electrical grids. Their particular conditions (isolated) and usual installation places (far from commercial/industrial centers) require an autonomous and reliable technology. Different but related factors affect their performance and the energy supply; some of them are strictly technical but others depend on external issues like the solar energy resource and users’ energy and power consumption. The work presented is based on field operation of twelve collective PV installations supplying the electricity to off-grid villages located in the province of Jujuy, Argentina. Five of them have PV generators as unique power source while other seven include the support of diesel groups. Load demand evolution, energy productivity and fuel consumption are analyzed. Besides, energy generation strategies (PV/diesel) are also discussed.

Development of a Uniform Theory of Diffraction for Scattered and Surface Electromagnetic Field Analysis on a Cylinder

Con esta tesis ”Desarrollo de una Teoría Uniforme de la Difracción para el Análisis de los Campos Electromagnéticos Dispersados y Superficiales sobre un Cilindro” hemos iniciado una nueva línea de investigación que trata de responder a la siguiente pregunta: ¿cuál es la impedancia de superficie que describe una estructura de conductor eléctrico perfecto (PEC) convexa recubierta por un material no conductor? Este tipo de estudios tienen interés hoy en día porque ayudan a predecir el campo electromagnético incidente, radiado o que se propaga sobre estructuras metálicas y localmente convexas que se encuentran recubiertas de algún material dieléctrico, o sobre estructuras metálicas con pérdidas, como por ejemplo se necesita en determinadas aplicaciones aeroespaciales, marítimas o automovilísticas. Además, desde un punto de vista teórico, la caracterización de la impedancia de superficie de una estructura PEC recubierta o no por un dieléctrico es una generalización de varias soluciones que tratan ambos tipos de problemas por separado. En esta tesis se desarrolla una teoría uniforme de la difracción (UTD) para analizar el problema canónico del campo electromagnético dispersado y superficial en un cilindro circular eléctricamente grande con una condición de contorno de impedancia (IBC) para frecuencias altas. Construir una solución basada en UTD para este problema canónico es crucial en el desarrollo de un método UTD para el caso más general de una superficie arbitrariamente convexa, mediante el uso del principio de localización de los campos electromagnéticos a altas frecuencias. Esta tesis doctoral se ha llevado a cabo a través de una serie de hitos que se enumeran a continuación, enfatizando las contribuciones a las que ha dado lugar. Inicialmente se realiza una revisión en profundidad del estado del arte de los métodos asintóticos con numerosas referencias. As í, cualquier lector novel puede llegar a conocer la historia de la óptica geométrica (GO) y la teoría geométrica de la difracción (GTD), que dieron lugar al desarrollo de la UTD. Después, se investiga ampliamente la UTD y los trabajos más importantes que pueden encontrarse en la literatura. As í, este capítulo, nos coloca en la posición de afirmar que, hasta donde nosotros conocemos, nadie ha intentado antes llevar a cabo una investigación rigurosa sobre la caracterización de la impedancia de superficie de una estructura PEC recubierta por un material dieléctrico, utilizando para ello la UTD. Primero, se desarrolla una UTD para el problema canónico de la dispersión electromagnética de un cilindro circular eléctricamente grande con una IBC uniforme, cuando es iluminado por una onda plana con incidencia oblicua a frecuencias altas. La solución a este problema canónico se construye a partir de una solución exacta mediante una expansión de autofunciones de propagación radial. Entonces, ésta se convierte en una nueva expansión de autofunciones de propagación circunferencial muy apropiada para cilindros grandes, a través de la transformación de Watson. De esta forma, la expresión del campo se reduce a una integral que se evalúa asintóticamente, para altas frecuencias, de manera uniforme. El resultado se expresa según el trazado de rayos descrito en la UTD. La solución es uniforme porque tiene la importante propiedad de mantenerse continua a lo largo de la región de transición, a ambos lados de la superficie del contorno de sombra. Fuera de la región de transición la solución se reduce al campo incidente y reflejado puramente ópticos en la región iluminada del cilindro, y al campo superficial difractado en la región de sombra. Debido a la IBC el campo dispersado contiene una componente contrapolar a causa de un acoplamiento entre las ondas TEz y TMz (donde z es el eje del cilindro). Esta componente contrapolar desaparece cuando la incidencia es normal al cilindro, y también en la región iluminada cuando la incidencia es oblicua donde el campo se reduce a la solución de GO. La solución UTD presenta una muy buena exactitud cuando se compara numéricamente con una solución de referencia exacta. A continuación, se desarrolla una IBC efectiva para el cálculo del campo electromagnético dispersado en un cilindro circular PEC recubierto por un dieléctrico e iluminado por una onda plana incidiendo oblicuamente. Para ello se derivan dos impedancias de superficie en relación directa con las ondas creeping y de superficie TM y TE que se excitan en un cilindro recubierto por un material no conductor. Las impedancias de superficie TM y TE están acopladas cuando la incidencia es oblicua, y dependen de la geometría del problema y de los números de onda. Además, se ha derivado una impedancia de superficie constante, aunque con diferente valor cuando el observador se encuentra en la zona iluminada o en la zona de sombra. Después, se presenta una solución UTD para el cálculo de la dispersión de una onda plana con incidencia oblicua sobre un cilindro eléctricamente grande y convexo, mediante la generalización del problema canónico correspondiente al cilindro circular. La solución asintótica es uniforme porque se mantiene continua a lo largo de la región de transición, en las inmediaciones del contorno de sombra, y se reduce a la solución de rayos ópticos en la zona iluminada y a la contribución de las ondas de superficie dentro de la zona de sombra, lejos de la región de transición. Cuando se usa cualquier material no conductor se excita una componente contrapolar que tiende a desaparecer cuando la incidencia es normal al cilindro y en la región iluminada. Se discuten ampliamente las limitaciones de las fórmulas para la impedancia de superficie efectiva, y se compara la solución UTD con otras soluciones de referencia, donde se observa una muy buena concordancia. Y en tercer lugar, se presenta una aproximación para una impedancia de superficie efectiva para el cálculo de los campos superficiales en un cilindro circular conductor recubierto por un dieléctrico. Se discuten las principales diferencias que existen entre un cilindro PEC recubierto por un dieléctrico desde un punto de vista riguroso y un cilindro con una IBC. Mientras para un cilindro de impedancia se considera una impedancia de superficie constante o uniforme, para un cilindro conductor recubierto por un dieléctrico se derivan dos impedancias de superficie. Estas impedancias de superficie están asociadas a los modos de ondas creeping TM y TE excitadas en un cilindro, y dependen de la posición y de la orientación del observador y de la fuente. Con esto en mente, se deriva una solución UTD con IBC para los campos superficiales teniendo en cuenta las dependencias de la impedancia de superficie. La expansión asintótica se realiza, mediante la transformación de Watson, sobre la representación en serie de las funciones de Green correspondientes, evitando as í calcular las derivadas de orden superior de las integrales de tipo Fock, y dando lugar a una solución rápida y precisa. En los ejemplos numéricos realizados se observa una muy buena precisión cuando el cilindro y la separación entre el observador y la fuente son grandes. Esta solución, junto con el método de los momentos (MoM), se puede aplicar para el cálculo eficiente del acoplamiento mutuo de grandes arrays conformados de antenas de parches. Los métodos propuestos basados en UTD para el cálculo del campo electromagnético dispersado y superficial sobre un cilindro PEC recubierto de dieléctrico con una IBC efectiva suponen un primer paso hacia la generalización de una solución UTD para superficies metálicas convexas arbitrarias cubiertas por un material no conductor e iluminadas por una fuente electromagnética arbitraria. ABSTRACT With this thesis ”Development of a Uniform Theory of Diffraction for Scattered and Surface Electromagnetic Field Analysis on a Cylinder” we have initiated a line of investigation whose goal is to answer the following question: what is the surface impedance which describes a perfect electric conductor (PEC) convex structure covered by a material coating? These studies are of current and future interest for predicting the electromagnetic (EM) fields incident, radiating or propagating on locally smooth convex parts of highly metallic structures with a material coating, or by a lossy metallic surfaces, as for example in aerospace, maritime and automotive applications. Moreover, from a theoretical point of view, the surface impedance characterization of PEC surfaces with or without a material coating represents a generalization of independent solutions for both type of problems. A uniform geometrical theory of diffraction (UTD) is developed in this thesis for analyzing the canonical problem of EM scattered and surface field by an electrically large circular cylinder with an impedance boundary condition (IBC) in the high frequency regime, by means of a surface impedance characterization. The construction of a UTD solution for this canonical problem is crucial for the development of the corresponding UTD solution for the more general case of an arbitrary smooth convex surface, via the principle of the localization of high frequency EM fields. The development of the present doctoral thesis has been carried out through a series of landmarks that are enumerated as follows, emphasizing the main contributions that this work has given rise to. Initially, a profound revision is made in the state of art of asymptotic methods where numerous references are given. Thus, any reader may know the history of geometrical optics (GO) and geometrical theory of diffraction (GTD), which led to the development of UTD. Then, the UTD is deeply investigated and the main studies which are found in the literature are shown. This chapter situates us in the position to state that, as far as we know, nobody has attempted before to perform a rigorous research about the surface impedance characterization for material-coated PEC convex structures via UTD. First, a UTD solution is developed for the canonical problem of the EM scattering by an electrically large circular cylinder with a uniform IBC, when it is illuminated by an obliquely incident high frequency plane wave. A solution to this canonical problem is first constructed in terms of an exact formulation involving a radially propagating eigenfunction expansion. The latter is converted into a circumferentially propagating eigenfunction expansion suited for large cylinders, via the Watson transformation, which is expressed as an integral that is subsequently evaluated asymptotically, for high frequencies, in a uniform manner. The resulting solution is then expressed in the desired UTD ray form. This solution is uniform in the sense that it has the important property that it remains continuous across the transition region on either side of the surface shadow boundary. Outside the shadow boundary transition region it recovers the purely ray optical incident and reflected ray fields on the deep lit side of the shadow boundary and to the modal surface diffracted ray fields on the deep shadow side. The scattered field is seen to have a cross-polarized component due to the coupling between the TEz and TMz waves (where z is the cylinder axis) resulting from the IBC. Such cross-polarization vanishes for normal incidence on the cylinder, and also in the deep lit region for oblique incidence where it properly reduces to the GO or ray optical solution. This UTD solution is shown to be very accurate by a numerical comparison with an exact reference solution. Then, an effective IBC is developed for the EM scattered field on a coated PEC circular cylinder illuminated by an obliquely incident plane wave. Two surface impedances are derived in a direct relation with the TM and TE surface and creeping wave modes excited on a coated cylinder. The TM and TE surface impedances are coupled at oblique incidence, and depend on the geometry of the problem and the wave numbers. Nevertheless, a constant surface impedance is found, although with a different value when the observation point lays in the lit or in the shadow region. Then, a UTD solution for the scattering of an obliquely incident plane wave on an electrically large smooth convex coated PEC cylinder is introduced, via a generalization of the canonical circular cylinder problem. The asymptotic solution is uniform because it remains continuous across the transition region, in the vicinity of the shadow boundary, and it recovers the ray optical solution in the deep lit region and the creeping wave formulation within the deep shadow region. When a coating is present a cross-polar field term is excited, which vanishes at normal incidence and in the deep lit region. The limitations of the effective surface impedance formulas are discussed, and the UTD solution is compared with some reference solutions where a very good agreement is met. And in third place, an effective surface impedance approach is introduced for determining surface fields on an electrically large coated metallic circular cylinder. Differences in analysis of rigorouslytreated coated metallic cylinders and cylinders with an IBC are discussed. While for the impedance cylinder case a single constant or uniform surface impedance is considered, for the coated metallic cylinder case two surface impedances are derived. These are associated with the TM and TE creeping wave modes excited on a cylinder and depend on observation and source positions and orientations. With this in mind, a UTD based method with IBC is derived for the surface fields by taking into account the surface impedance variation. The asymptotic expansion is performed, via the Watson transformation, over the appropriate series representation of the Green’s functions, thus avoiding higher-order derivatives of Fock-type integrals, and yielding a fast and an accurate solution. Numerical examples reveal a very good accuracy for large cylinders when the separation between the observation and the source point is large. Thus, this solution could be efficiently applied in mutual coupling analysis, along with the method of moments (MoM), of large conformal microstrip array antennas. The proposed UTD methods for scattered and surface EM field analysis on a coated PEC cylinder with an effective IBC are considered the first steps toward the generalization of a UTD solution for large arbitrarily convex smooth metallic surfaces covered by a material coating and illuminated by an arbitrary EM source.

Revival of oscillation from mean-field-induced death : Theory and experiment

Submitted ACKNOWLEDGMENTS T. B. acknowledges the financial support from SERB, Department of Science and Technology (DST), India [Project Grant No.: SB/FTP/PS-005/2013]. D. G. acknowledges DST, India, for providing support through the INSPIRE fellowship. J. K. acknowledges Government of the Russian Federation (Agreement No. 14.Z50.31.0033 with Institute of Applied Physics RAS).

Mean-field phase diagrams of imbalanced Fermi gases near a Feshbach resonance

We propose phase diagrams for an imbalanced (unequal number of atoms or Fermi surface in two pairing hyperfine states) gas of atomic fermions near a broad Feshbach resonance using mean-field theory. Particularly, in the plane of interaction and polarization we determine the region for a mixed phase composed of normal and superfluid components. We compare our prediction of phase boundaries with the recent measurement and find a good qualitative agreement.

Advanced mean field methods:theory and practice

A major problem in modern probabilistic modeling is the huge computational complexity involved in typical calculations with multivariate probability distributions when the number of random variables is large. Because exact computations are infeasible in such cases and Monte Carlo sampling techniques may reach their limits, there is a need for methods that allow for efficient approximate computations. One of the simplest approximations is based on the mean field method, which has a long history in statistical physics. The method is widely used, particularly in the growing field of graphical models. Researchers from disciplines such as statistical physics, computer science, and mathematical statistics are studying ways to improve this and related methods and are exploring novel application areas. Leading approaches include the variational approach, which goes beyond factorizable distributions to achieve systematic improvements; the TAP (Thouless-Anderson-Palmer) approach, which incorporates correlations by including effective reaction terms in the mean field theory; and the more general methods of graphical models. Bringing together ideas and techniques from these diverse disciplines, this book covers the theoretical foundations of advanced mean field methods, explores the relation between the different approaches, examines the quality of the approximation obtained, and demonstrates their application to various areas of probabilistic modeling.

Mean field methods for classification with Gaussian processes

We discuss the Application of TAP mean field methods known from Statistical Mechanics of disordered systems to Bayesian classification with Gaussian processes. In contrast to previous applications, no knowledge about the distribution of inputs is needed. Simulation results for the Sonar data set are given.

Gaussian processes for classification: mean field algorithms:mean-field algorithms

We derive a mean field algorithm for binary classification with Gaussian processes which is based on the TAP approach originally proposed in Statistical Physics of disordered systems. The theory also yields an approximate leave-one-out estimator for the generalization error which is computed with no extra computational cost. We show that from the TAP approach, it is possible to derive both a simpler 'naive' mean field theory and support vector machines (SVM) as limiting cases. For both mean field algorithms and support vectors machines, simulation results for three small benchmark data sets are presented. They show 1. that one may get state of the art performance by using the leave-one-out estimator for model selection and 2. the built-in leave-one-out estimators are extremely precise when compared to the exact leave-one-out estimate. The latter result is a taken as a strong support for the internal consistency of the mean field approach.

Gaussian processes and SVM: Mean field results and leave-one-out

In this chapter, we elaborate on the well-known relationship between Gaussian processes (GP) and Support Vector Machines (SVM). Secondly, we present approximate solutions for two computational problems arising in GP and SVM. The first one is the calculation of the posterior mean for GP classifiers using a `naive' mean field approach. The second one is a leave-one-out estimator for the generalization error of SVM based on a linear response method. Simulation results on a benchmark dataset show similar performances for the GP mean field algorithm and the SVM algorithm. The approximate leave-one-out estimator is found to be in very good agreement with the exact leave-one-out error.

A mean field theory of coded CDMA systems

We present a mean field theory of code-division multiple access (CDMA) systems with error-control coding. On the basis of the relation between the free energy and mutual information, we obtain an analytical expression of the maximum spectral efficiency of the coded CDMA system, from which a mean field description of the coded CDMA system is provided in terms of a bank of scalar Gaussian channels whose variances in general vary at different code symbol positions. Regular low-density parity-check (LDPC)-coded CDMA systems are also discussed as an example of the coded CDMA systems.

Flow field analysis of some mixing and conveying screw element regions, within a closely intermeshing, co-rotating twin-screw extruder.

Grafting of antioxidants and other modifiers onto polymers by reactive extrusion, has been performed successfully by the Polymer Processing and Performance Group at Aston University. Traditionally the optimum conditions for the grafting process have been established within a Brabender internal mixer. Transfer of this batch process to a continuous processor, such as an extruder, has, typically, been empirical. To have more confidence in the success of direct transfer of the process requires knowledge of, and comparison between, residence times, mixing intensities, shear rates and flow regimes in the internal mixer and in the continuous processor.The continuous processor chosen for the current work in the closely intermeshing, co-rotating twin-screw extruder (CICo-TSE). CICo-TSEs contain screw elements that convey material with a self-wiping action and are widely used for polymer compounding and blending. Of the different mixing modules contained within the CICo-TSE, the trilobal elements, which impose intensive mixing, and the mixing discs, which impose extensive mixing, are of importance when establishing the intensity of mixing. In this thesis, the flow patterns within the various regions of the single-flighted conveying screw elements and within both the trilobal element and mixing disc zones of a Betol BTS40 CICo-TSE, have been modelled using the computational fluid dynamics package Polyflow. A major obstacle encountered when solving the flow problem within all of these sets of elements, arises from both the complex geometry and the time-dependent flow boundaries as the elements rotate about their fixed axes. Simulation of the time dependent boundaries was overcome by selecting a number of sequential 2D and 3D geometries, used to represent partial mixing cycles. The flow fields were simulated using the ideal rheological properties of polypropylene and characterised in terms of velocity vectors, shear stresses generated and a parameter known as the mixing efficiency. The majority of the large 3D simulations were performed on the Cray J90 supercomputer situated at the Rutherford-Appleton laboratories, with pre- and postprocessing operations achieved via a Silicon Graphics Indy workstation. A mechanical model was constructed consisting of various CICo-TSE elements rotating within a transparent outer barrel. A technique has been developed using coloured viscous clays whereby the flow patterns and mixing characteristics within the CICo-TSE may be visualised. In order to test and verify the simulated predictions, the patterns observed within the mechanical model were compared with the flow patterns predicted by the computational model. The flow patterns within the single-flighted conveying screw elements in particular, showed good agreement between the experimental and simulated results.