Protein Folding Simulations: Confinement, External Fields and Sequence Design

The present Thesis looks at the problem of protein folding using Monte Carlo and Langevin simulations, three topics in protein folding have been studied: 1) the effect of confining potential barriers, 2) the effect of a static external field and 3) the design of amino acid sequences which fold in a short time and which have a stable native state (global minimum). Regarding the first topic, we studied the confinement of a small protein of 16 amino acids known as 1NJ0 (PDB code) which has a beta-sheet structure as a native state. The confinement of proteins occurs frequently in the cell environment. Some molecules called Chaperones, present in the cytoplasm, capture the unfolded proteins in their interior and avoid the formation of aggregates and misfolded proteins. This mechanism of confinement mediated by Chaperones is not yet well understood. In the present work we considered two kinds of potential barriers which try to mimic the confinement induced by a Chaperon molecule. The first kind of potential was a purely repulsive barrier whose only effect is to create a cavity where the protein folds up correctly. The second kind of potential was a barrier which includes both attractive and repulsive effects. We performed Wang-Landau simulations to calculate the thermodynamical properties of 1NJ0. From the free energy landscape plot we found that 1NJ0 has two intermediate states in the bulk (without confinement) which are clearly separated from the native and the unfolded states. For the case of the purely repulsive barrier we found that the intermediate states get closer to each other in the free energy landscape plot and eventually they collapse into a single intermediate state. The unfolded state is more compact, compared to that in the bulk, as the size of the barrier decreases. For an attractive barrier modifications of the states (native, unfolded and intermediates) are observed depending on the degree of attraction between the protein and the walls of the barrier. The strength of the attraction is measured by the parameter $\epsilon$. A purely repulsive barrier is obtained for $\epsilon=0$ and a purely attractive barrier for $\epsilon=1$. The states are changed slightly for magnitudes of the attraction up to $\epsilon=0.4$. The disappearance of the intermediate states of 1NJ0 is already observed for $\epsilon =0.6$. A very high attractive barrier ($\epsilon \sim 1.0$) produces a completely denatured state. In the second topic of this Thesis we dealt with the interaction of a protein with an external electric field. We demonstrated by means of computer simulations, specifically by using the Wang-Landau algorithm, that the folded, unfolded, and intermediate states can be modified by means of a field. We have found that an external field can induce several modifications in the thermodynamics of these states: for relatively low magnitudes of the field ($<2.06 \times 10^8$ V/m) no major changes in the states are observed. However, for higher magnitudes than ($6.19 \times 10^8$ V/m) one observes the appearance of a new native state which exhibits a helix-like structure. In contrast, the original native state is a $\beta$-sheet structure. In the new native state all the dipoles in the backbone structure are aligned parallel to the field. The design of amino acid sequences constitutes the third topic of the present work. We have tested the Rate of Convergence criterion proposed by D. Gridnev and M. Garcia ({\it work unpublished}). We applied it to the study of off-lattice models. The Rate of Convergence criterion is used to decide if a certain sequence will fold up correctly within a relatively short time. Before the present work, the common way to decide if a certain sequence was a good/bad folder was by performing the whole dynamics until the sequence got its native state (if it existed), or by studying the curvature of the potential energy surface. There are some difficulties in the last two approaches. In the first approach, performing the complete dynamics for hundreds of sequences is a rather challenging task because of the CPU time needed. In the second approach, calculating the curvature of the potential energy surface is possible only for very smooth surfaces. The Rate of Convergence criterion seems to avoid the previous difficulties. With this criterion one does not need to perform the complete dynamics to find the good and bad sequences. Also, the criterion does not depend on the kind of force field used and therefore it can be used even for very rugged energy surfaces.

Alignment by Maximization of Mutual Information

A new information-theoretic approach is presented for finding the pose of an object in an image. The technique does not require information about the surface properties of the object, besides its shape, and is robust with respect to variations of illumination. In our derivation, few assumptions are made about the nature of the imaging process. As a result the algorithms are quite general and can foreseeably be used in a wide variety of imaging situations. Experiments are presented that demonstrate the approach registering magnetic resonance (MR) images with computed tomography (CT) images, aligning a complex 3D object model to real scenes including clutter and occlusion, tracking a human head in a video sequence and aligning a view-based 2D object model to real images. The method is based on a formulation of the mutual information between the model and the image called EMMA. As applied here the technique is intensity-based, rather than feature-based. It works well in domains where edge or gradient-magnitude based methods have difficulty, yet it is more robust than traditional correlation. Additionally, it has an efficient implementation that is based on stochastic approximation. Finally, we will describe a number of additional real-world applications that can be solved efficiently and reliably using EMMA. EMMA can be used in machine learning to find maximally informative projections of high-dimensional data. EMMA can also be used to detect and correct corruption in magnetic resonance images (MRI).

Alternative ways to estimate change points in multinomial sequences. An application to an authorship attribution problem

The statistical analysis of literary style is the part of stylometry that compares measurable characteristics in a text that are rarely controlled by the author, with those in other texts. When the goal is to settle authorship questions, these characteristics should relate to the author’s style and not to the genre, epoch or editor, and they should be such that their variation between authors is larger than the variation within comparable texts from the same author. For an overview of the literature on stylometry and some of the techniques involved, see for example Mosteller and Wallace (1964, 82), Herdan (1964), Morton (1978), Holmes (1985), Oakes (1998) or Lebart, Salem and Berry (1998). Tirant lo Blanc, a chivalry book, is the main work in catalan literature and it was hailed to be “the best book of its kind in the world” by Cervantes in Don Quixote. Considered by writters like Vargas Llosa or Damaso Alonso to be the first modern novel in Europe, it has been translated several times into Spanish, Italian and French, with modern English translations by Rosenthal (1996) and La Fontaine (1993). The main body of this book was written between 1460 and 1465, but it was not printed until 1490. There is an intense and long lasting debate around its authorship sprouting from its first edition, where its introduction states that the whole book is the work of Martorell (1413?-1468), while at the end it is stated that the last one fourth of the book is by Galba (?-1490), after the death of Martorell. Some of the authors that support the theory of single authorship are Riquer (1990), Chiner (1993) and Badia (1993), while some of those supporting the double authorship are Riquer (1947), Coromines (1956) and Ferrando (1995). For an overview of this debate, see Riquer (1990). Neither of the two candidate authors left any text comparable to the one under study, and therefore discriminant analysis can not be used to help classify chapters by author. By using sample texts encompassing about ten percent of the book, and looking at word length and at the use of 44 conjunctions, prepositions and articles, Ginebra and Cabos (1998) detect heterogeneities that might indicate the existence of two authors. By analyzing the diversity of the vocabulary, Riba and Ginebra (2000) estimates that stylistic boundary to be near chapter 383. Following the lead of the extensive literature, this paper looks into word length, the use of the most frequent words and into the use of vowels in each chapter of the book. Given that the features selected are categorical, that leads to three contingency tables of ordered rows and therefore to three sequences of multinomial observations. Section 2 explores these sequences graphically, observing a clear shift in their distribution. Section 3 describes the problem of the estimation of a suden change-point in those sequences, in the following sections we propose various ways to estimate change-points in multinomial sequences; the method in section 4 involves fitting models for polytomous data, the one in Section 5 fits gamma models onto the sequence of Chi-square distances between each row profiles and the average profile, the one in Section 6 fits models onto the sequence of values taken by the first component of the correspondence analysis as well as onto sequences of other summary measures like the average word length. In Section 7 we fit models onto the marginal binomial sequences to identify the features that distinguish the chapters before and after that boundary. Most methods rely heavily on the use of generalized linear models

Estimating the motion of an underwater robot from a monocular image sequence

When underwater vehicles perform navigation close to the ocean floor, computer vision techniques can be applied to obtain quite accurate motion estimates. The most crucial step in the vision-based estimation of the vehicle motion consists on detecting matchings between image pairs. Here we propose the extensive use of texture analysis as a tool to ameliorate the correspondence problem in underwater images. Once a robust set of correspondences has been found, the three-dimensional motion of the vehicle can be computed with respect to the bed of the sea. Finally, motion estimates allow the construction of a map that could aid to the navigation of the robot

Visual SLAM for underwater vehicles using video velocity log and natural landmarks

A visual SLAM system has been implemented and optimised for real-time deployment on an AUV equipped with calibrated stereo cameras. The system incorporates a novel approach to landmark description in which landmarks are local sub maps that consist of a cloud of 3D points and their associated SIFT/SURF descriptors. Landmarks are also sparsely distributed which simplifies and accelerates data association and map updates. In addition to landmark-based localisation the system utilises visual odometry to estimate the pose of the vehicle in 6 degrees of freedom by identifying temporal matches between consecutive local sub maps and computing the motion. Both the extended Kalman filter and unscented Kalman filter have been considered for filtering the observations. The output of the filter is also smoothed using the Rauch-Tung-Striebel (RTS) method to obtain a better alignment of the sequence of local sub maps and to deliver a large-scale 3D acquisition of the surveyed area. Synthetic experiments have been performed using a simulation environment in which ray tracing is used to generate synthetic images for the stereo system

Estimation of zero-sequence impedance of undergrounds cables for single-phase fault location in distribution systems with electric arc

This paper focus on the problem of locating single-phase faults in mixed distribution electric systems, with overhead lines and underground cables, using voltage and current measurements at the sending-end and sequence model of the network. Since calculating series impedance for underground cables is not as simple as in the case of overhead lines, the paper proposes a methodology to obtain an estimation of zero-sequence impedance of underground cables starting from previous single-faults occurred in the system, in which an electric arc occurred at the fault location. For this reason, the signal is previously pretreated to eliminate its peaks voltage and the analysis can be done working with a signal as close as a sinus wave as possible

Municipio saludable como polo de desarrollo local "diagnóstico situación láctea Macheta"

Este proyecto hace parte de un convenio entre la Gobernación de Cundinamarca y la Universidad del Rosario para desarrollar el proyecto Municipio Saludable como Polo de Desarrollo Local en tres municipios de Cundinamarca: Machetá, Sesquilé y Mesitas de El Colegio. Dicho programa tiene cuatro ejes, de los cuales la Facultad de Administración desarrolla el primer eje que se relaciona con la Generación de empleo e Ingresos. La investigación, objeto de estudio se llevó a cabo en el municipio de Machetá, donde se trabajó el tema lácteo con pequeños productores y se desarrolló el módulo de marco lógico, en el que se llevaron a cabo las siguientes actividades: a) Contacto con la comunidad, visitas periódicas al Municipio. b) Elaboración y aplicación de encuestas a funcionarios de la Alcaldía, vendedores de plaza y productores. c) Procesamiento y análisis de resultados. d) Construcción de árbol de problemas con la comunidad, e) Construcción de árbol de objetivos. f) Socialización con la comunidad. g) Elaboración de estrategias. h) Conclusiones y recomendaciones. Para mejorar las condiciones de vida de los pequeños productores de leche se recomienda la organización de una cooperativa u otro tipo de asociación que les permita ofertar un producto con cantidades, con la calidad que requieren las empresas procesadoras o entrar en un proceso mas elaborado que implica el montaje de un tanque de enfriamiento con capacidad mínima de 3.000 litros/diarios y /o procesar la leche para producir quesos y otros productos derivados de leche. Obtener esto, estabilizaría precios, ingresos y les daría poder de negociación que es algo con lo que no cuentan actualmente los pequeños productores.

Using Problem Steps Recorder on Windows 7

Problem Steps Recorder is a standard piece of software on Windows 7 computers, which allows you to record a sequence of actions on your computer, along with screenshots. It can help ServiceLine diagnose any problems that you might be experiencing.

Valores del capital humano y las competencias del líder que facilitan la implantación de la estrategia organizacional

La obtención de una ventaja competitiva, el desarrollo, el crecimiento, la perdurabilidad, entre otros, son los aspectos que buscan las organizaciones a través de las estrategias que se definen. Sin embargo, no es suficiente con diseñar las metas y los objetivos que se quieren alcanzar, es necesario aterrizar estos propósitos en planes de acción e involucrar a todos los miembros de la organización, lo cual se consigue a través de la implantación de la estrategia. En este sentido, la etapa de implantación de la estrategia en una organización, da curso al camino establecido en la etapa de formulación de la estrategia, por lo tanto, se relaciona directamente con su éxito o su fracaso. No obstante, este proceso no depende de algunos pocos miembros de la organización, de directivos o de funcionarios, sino que depende de la buena sincronización y armonía de todos aquellos que hacen parte de ella. La presente investigación a través de la revisión teórica y de evidencias empíricas, busca poner de manifiesto la incidencia de dos aspectos clave en la organización sobre la implantación de la estrategia, por un lado, los líderes, a partir de sus competencias interpersonales y por otro el capital humano, a partir de sus valores. Los resultados obtenidos muestran que tanto las competencias del líder como los valores del capital humano son determinantes para la adecuada implantación de la estrategia organizacional.

Aproximaci?? a la problem??tica de l'atur juvenir a Ciutadella. 'Aproximaci??n a la problem??tica del paro juvenil en Ciutadella'

Este trabajo gan?? el primer premio Joan Mercadal sobre la juventud en Menorca

Territorialización de la inseguridad ciudadana en Bogotá: La Calle del Bronx

La tesis devela la connotación sistemática y multicausal de lo que a través de la investigación se denomina como "Procesos de Territorialización de la Inseguridad Ciudadana". Mediante un estudio de caso, se pone en evidencia la apropiación y captura sostenida en el tiempo de fenómenos como la inseguridad y la criminalidad, sobre determinadas zonas o barrios urbanos que por sus características socioeconómicas, políticas, geográficas, culturales, laborales y de mercado de quienes los habitan o frecuentan, se consideran como sectores "críticos y/o vulnerables".

Rol y habilidades del CIO. Tres casos de estudio en Colombia: Alpina, Banco de Bogotá, Grupo Aval

Con base en la revisión de la literatura realizada acerca de los roles directivos y del rol de uno en particular que es el CIO, y tomando como referencia la información suministrada por los directivos de tecnologías de Información de las organizaciones Alpina, Banco de Bogotá y Grupo AVAL, el trabajo de investigación hace una descripción del contenido del rol de CIO e identifica las habilidades requeridas para el ejercicio de este rol en dichas organizaciones. Se espera que los resultados del presente estudio generen un valioso aporte como retroalimentación para la academia y las empresas acerca de la formación de los futuros CIO.

Un modelo para el an??lisis de objetos matem??ticos en libros de texto chilenos : situaciones problem??ticas, lenguaje y conceptos sobre probabilidad

Resumen basado en el de la publicaci??n

Making 'dirty' nations look clean? The nation state and the problem of selecting and weighting indices as tools for measuring progress towards sustainability

Pressing global environmental problems highlight the need to develop tools to measure progress towards "sustainability." However, some argue that any such attempt inevitably reflects the views of those creating such tools and only produce highly contested notions of "reality." To explore this tension, we critically assesses the Environmental Sustainability Index (ESI), a well-publicized product of the World Economic Forum that is designed to measure 'sustainability' by ranking nations on league tables based on extensive databases of environmental indicators. By recreating this index, and then using statistical tools (principal components analysis) to test relations between various components of the index, we challenge ways in which countries are ranked in the ESI. Based on this analysis, we suggest (1) that the approach taken to aggregate, interpret and present the ESI creates a misleading impression that Western countries are more sustainable than the developing world; (2) that unaccounted methodological biases allowed the authors of the ESI to over-generalize the relative 'sustainability' of different countries; and, (3) that this has resulted in simplistic conclusions on the relation between economic growth and environmental sustainability. This criticism should not be interpreted as a call for the abandonment of efforts to create standardized comparable data. Instead, this paper proposes that indicator selection and data collection should draw on a range of voices, including local stakeholders as well as international experts. We also propose that aggregating data into final league ranking tables is too prone to error and creates the illusion of absolute and categorical interpretations. (c) 2004 Elsevier Ltd. All rights reserved.

A phylogenetic mixture model for detecting pattern-heterogeneity in gene sequence or character-state data

We describe a general likelihood-based 'mixture model' for inferring phylogenetic trees from gene-sequence or other character-state data. The model accommodates cases in which different sites in the alignment evolve in qualitatively distinct ways, but does not require prior knowledge of these patterns or partitioning of the data. We call this qualitative variability in the pattern of evolution across sites "pattern-heterogeneity" to distinguish it from both a homogenous process of evolution and from one characterized principally by differences in rates of evolution. We present studies to show that the model correctly retrieves the signals of pattern-heterogeneity from simulated gene-sequence data, and we apply the method to protein-coding genes and to a ribosomal 12S data set. The mixture model outperforms conventional partitioning in both these data sets. We implement the mixture model such that it can simultaneously detect rate- and pattern-heterogeneity. The model simplifies to a homogeneous model or a rate- variability model as special cases, and therefore always performs at least as well as these two approaches, and often considerably improves upon them. We make the model available within a Bayesian Markov-chain Monte Carlo framework for phylogenetic inference, as an easy-to-use computer program.