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.

Carbon and nitrogen emissions from stored manure and cropped fields in irrigated mountain oases of Oman

Little is known about gaseous carbon (C) and nitrogen (N) emissions from traditional terrace agriculture in irrigated high mountain agroecosystems of the subtropics. In an effort towards filling this knowledge gap measurements of carbon dioxide (CO_2), methane (CH_4), ammonia (NH_3) and dinitrous oxide (N_2O) were taken with a mobile photoacoustic infrared multi-gas monitor on manure-filled PE-fibre storage bags and on flood-irrigated untilled and tilled fields in three mountain oases of the northen Omani Al Jabal al Akhdar mountains. During typical 9-11 day irrigation cycles of March, August and September 2006 soil volumetric moisture contents of fields dominated by fodder wheat, barley, oats and pomegranate ranged from 46-23%. While manure incorporation after application effectively reduced gaseous N losses, prolonged storage of manure in heaps or in PE-fibre bags caused large losses of C and N. Given the large irrigation-related turnover of organic C, sustainable agricultural productivity of oasis agriculture in Oman seems to require the integration of livestock which allows for several applications of manure per year at individual rates of 20 t dry matter ha^−1.

Factors influencing the use of selected inputs in yam production in Nigeria and Ghana

In West Africa, yam can be an important crop to reduce poverty and hunger if Research and Development measures identify and properly engage its key production factors for enhanced outputs and better income. Data from 1400 households in Ghana and Nigeria were collected in a multistage random sampling survey (and complementary data from 76 farm family fields) with a structured questionnaire and qualitative interview questions. The results showed that yam is produced mainly with crude inputs/technologies to reduce high dependence on labour, seed production and control of pests and diseases. Yam is produced widely with purchased inputs including seed yam and hired labour; chemical fertiliser, herbicide and pesticides are less often used. Analyses of determinants of use of purchased inputs reveal three serious impediments to expansion in yam production: the increasing scarcity and high cost of hired labour, shortage of suitable land and poor farm roads. As employment opportunities for unskilled labour in urban centres are presently expanding, increased yam production will be hard to achieve without labour-saving inputs for at least some of the production tasks, especially seedbed preparation and weeding, and without improvement in infrastructure.

Measure Fields for Function Approximation

The computation of a piecewise smooth function that approximates a finite set of data points may be decomposed into two decoupled tasks: first, the computation of the locally smooth models, and hence, the segmentation of the data into classes that consist on the sets of points best approximated by each model, and second, the computation of the normalized discriminant functions for each induced class. The approximating function may then be computed as the optimal estimator with respect to this measure field. We give an efficient procedure for effecting both computations, and for the determination of the optimal number of components.

Exploring Object Perception with Random Image Structure Evolution

We have developed a technique called RISE (Random Image Structure Evolution), by which one may systematically sample continuous paths in a high-dimensional image space. A basic RISE sequence depicts the evolution of an object's image from a random field, along with the reverse sequence which depicts the transformation of this image back into randomness. The processing steps are designed to ensure that important low-level image attributes such as the frequency spectrum and luminance are held constant throughout a RISE sequence. Experiments based on the RISE paradigm can be used to address some key open issues in object perception. These include determining the neural substrates underlying object perception, the role of prior knowledge and expectation in object perception, and the developmental changes in object perception skills from infancy to adulthood.

Evaluation of sets of oriented and non-oriented receptive fields as local descriptors

Local descriptors are increasingly used for the task of object recognition because of their perceived robustness with respect to occlusions and to global geometrical deformations. We propose a performance criterion for a local descriptor based on the tradeoff between selectivity and invariance. In this paper, we evaluate several local descriptors with respect to selectivity and invariance. The descriptors that we evaluated are Gaussian derivatives up to the third order, gray image patches, and Laplacian-based descriptors with either three scales or one scale filters. We compare selectivity and invariance to several affine changes such as rotation, scale, brightness, and viewpoint. Comparisons have been made keeping the dimensionality of the descriptors roughly constant. The overall results indicate a good performance by the descriptor based on a set of oriented Gaussian filters. It is interesting that oriented receptive fields similar to the Gaussian derivatives as well as receptive fields similar to the Laplacian are found in primate visual cortex.

Predicting random level and seasonality of hotel prices. A structural equation growth curve approach

This article examines the effect on price of different characteristics of holiday hotels in the sun-and-beach segment, under the hedonic function perspective. Monthly prices of the majority of hotels in the Spanish continental Mediterranean coast are gathered from May to October 1999 from the tour operator catalogues. Hedonic functions are specified as random-effect models and parametrized as structural equation models with two latent variables, a random peak season price and a random width of seasonal fluctuations. Characteristics of the hotel and the region where they are located are used as predictors of both latent variables. Besides hotel category, region, distance to the beach, availability of parking place and room equipment have an effect on peak price and also on seasonality. 3- star hotels have the highest seasonality and hotels located in the southern regions the lowest, which could be explained by a warmer climate in autumn

Coordinating Inventory Control and Pricing Strategies with Random Demand and Fixed Ordering Cost: The Finite Horizon Case

We analyze a finite horizon, single product, periodic review model in which pricing and production/inventory decisions are made simultaneously. Demands in different periods are random variables that are independent of each other and their distributions depend on the product price. Pricing and ordering decisions are made at the beginning of each period and all shortages are backlogged. Ordering cost includes both a fixed cost and a variable cost proportional to the amount ordered. The objective is to find an inventory policy and a pricing strategy maximizing expected profit over the finite horizon. We show that when the demand model is additive, the profit-to-go functions are k-concave and hence an (s,S,p) policy is optimal. In such a policy, the period inventory is managed based on the classical (s,S) policy and price is determined based on the inventory position at the beginning of each period. For more general demand functions, i.e., multiplicative plus additive functions, we demonstrate that the profit-to-go function is not necessarily k-concave and an (s,S,p) policy is not necessarily optimal. We introduce a new concept, the symmetric k-concave functions and apply it to provide a characterization of the optimal policy.

Coordinating Inventory Control and Pricing Strategies with Random Demand and Fixed Ordering Cost: the Infinite Horizon Case

We analyze an infinite horizon, single product, periodic review model in which pricing and production/inventory decisions are made simultaneously. Demands in different periods are identically distributed random variables that are independent of each other and their distributions depend on the product price. Pricing and ordering decisions are made at the beginning of each period and all shortages are backlogged. Ordering cost includes both a fixed cost and a variable cost proportional to the amount ordered. The objective is to maximize expected discounted, or expected average profit over the infinite planning horizon. We show that a stationary (s,S,p) policy is optimal for both the discounted and average profit models with general demand functions. In such a policy, the period inventory is managed based on the classical (s,S) policy and price is determined based on the inventory position at the beginning of each period.

Time-delayed fronts from biased random walks

We generalize a previous model of time-delayed reaction–diffusion fronts (Fort and Méndez 1999 Phys. Rev. Lett. 82 867) to allow for a bias in the microscopic random walk of particles or individuals. We also present a second model which takes the time order of events (diffusion and reproduction) into account. As an example, we apply them to the human invasion front across the USA in the 19th century. The corrections relative to the previous model are substantial. Our results are relevant to physical and biological systems with anisotropic fronts, including particle diffusion in disordered lattices, population invasions, the spread of epidemics, etc

Effect of arousal increase in predictable and random task switching : Evidence for the involvement of the anterior attentional network in random but not in predictable task switching

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Vector Fields

Exercises and solutions about vector fields. Diagrams for the questions are all together in the support.zip file, as .eps files

Estudio preliminar del retardo mental en la población de Rovira (Tolima, Colombia)

El retardo mental se caracteriza por limitaciones en el desempeño como resultado de significativas deficiencias de la inteligencia y la conducta adaptativa. En Colombia, la mayor parte de los pacientes con esta alteración no reciben evaluación genética. El objetivo de este trabajo es evaluar y caracterizar el retardo mental en un grupo de personas con esta condición en la población de Rovira (Tolima, Colombia) e identificar los posibles factores asociados. La metodología consistió en realizar un diagnóstico clínico preliminar de 25 pacientes con retardo mental y realizar la correspondiente toma de muestras de sangre y orina para efectuar los exámenes correspondientes. Se realizaron estudios bioquímicos (cloruro férrico, nitrosonaftol, nitroprusiato de sodio, Benedict, cromatografía para la detección de aminoácidos y carbohidratos) y citogenéticos (bandeo G). Para la detección de plaguicidas, se realizó un muestreo aleatorio en diferentes puntos de todo el recorrido del sistema de distribución de agua y ciertos lugares del centro del municipio de Rovira. Con este fin, se recolectaron 20 muestras de agua y 20 muestras de tomate, elegidas al azar, de los diferentes sitios de distribución y cultivos de la hortaliza. Se identificó una familia de tres hijos afectados (dos mujeres y un hombre) con retardo mental, lo cual sugiere un componente genético en este caso. Las pruebas metabólicas fueron negativas y los cariotipos normales. Se plantea la necesidad de realizar pruebas moleculares que incluyan el síndrome de X-frágil para complementar el estudio y realizar consejería genética. En cuanto a los resultados y el análisis pertinente de las muestras para organofosforados, el 100% de éstas resultaron positivas. Se reportó un 60% de positividad en las muestras de agua y del 100% en las muestras de tomate, para el caso de los carbamatos; sin embargo, para el caso de los organoclorados, el 100% de las muestras estudiadas resultaron negativas.

Option pricing in market models driven by telegraph processes with jumps

Esta tesis está dividida en dos partes: en la primera parte se presentan y estudian los procesos telegráficos, los procesos de Poisson con compensador telegráfico y los procesos telegráficos con saltos. El estudio presentado en esta primera parte incluye el cálculo de las distribuciones de cada proceso, las medias y varianzas, así como las funciones generadoras de momentos entre otras propiedades. Utilizando estas propiedades en la segunda parte se estudian los modelos de valoración de opciones basados en procesos telegráficos con saltos. En esta parte se da una descripción de cómo calcular las medidas neutrales al riesgo, se encuentra la condición de no arbitraje en este tipo de modelos y por último se calcula el precio de las opciones Europeas de compra y venta.

Guanxi y el estilo de negociación chino: desde la relación hacia la transacción

La problemática parte de que las interacciones entre China y América Latina han sido pocas. En particular, las negociaciones con China han probado ser difíciles y en algunos casos han fracasado. Motivo parece ser que la negociación china difiere