Soft Computing Approach for Optimization of siRNA Efficiency Prediction for Post-transcriptional Gene Silencing

Post-transcriptional gene silencing by RNA interference is mediated by small interfering RNA called siRNA. This gene silencing mechanism can be exploited therapeutically to a wide variety of disease-associated targets, especially in AIDS, neurodegenerative diseases, cholesterol and cancer on mice with the hope of extending these approaches to treat humans. Over the recent past, a significant amount of work has been undertaken to understand the gene silencing mediated by exogenous siRNA. The design of efficient exogenous siRNA sequences is challenging because of many issues related to siRNA. While designing efficient siRNA, target mRNAs must be selected such that their corresponding siRNAs are likely to be efficient against that target and unlikely to accidentally silence other transcripts due to sequence similarity. So before doing gene silencing by siRNAs, it is essential to analyze their off-target effects in addition to their inhibition efficiency against a particular target. Hence designing exogenous siRNA with good knock-down efficiency and target specificity is an area of concern to be addressed. Some methods have been developed already by considering both inhibition efficiency and off-target possibility of siRNA against agene. Out of these methods, only a few have achieved good inhibition efficiency, specificity and sensitivity. The main focus of this thesis is to develop computational methods to optimize the efficiency of siRNA in terms of “inhibition capacity and off-target possibility” against target mRNAs with improved efficacy, which may be useful in the area of gene silencing and drug design for tumor development. This study aims to investigate the currently available siRNA prediction approaches and to devise a better computational approach to tackle the problem of siRNA efficacy by inhibition capacity and off-target possibility. The strength and limitations of the available approaches are investigated and taken into consideration for making improved solution. Thus the approaches proposed in this study extend some of the good scoring previous state of the art techniques by incorporating machine learning and statistical approaches and thermodynamic features like whole stacking energy to improve the prediction accuracy, inhibition efficiency, sensitivity and specificity. Here, we propose one Support Vector Machine (SVM) model, and two Artificial Neural Network (ANN) models for siRNA efficiency prediction. In SVM model, the classification property is used to classify whether the siRNA is efficient or inefficient in silencing a target gene. The first ANNmodel, named siRNA Designer, is used for optimizing the inhibition efficiency of siRNA against target genes. The second ANN model, named Optimized siRNA Designer, OpsiD, produces efficient siRNAs with high inhibition efficiency to degrade target genes with improved sensitivity-specificity, and identifies the off-target knockdown possibility of siRNA against non-target genes. The models are trained and tested against a large data set of siRNA sequences. The validations are conducted using Pearson Correlation Coefficient, Mathews Correlation Coefficient, Receiver Operating Characteristic analysis, Accuracy of prediction, Sensitivity and Specificity. It is found that the approach, OpsiD, is capable of predicting the inhibition capacity of siRNA against a target mRNA with improved results over the state of the art techniques. Also we are able to understand the influence of whole stacking energy on efficiency of siRNA. The model is further improved by including the ability to identify the “off-target possibility” of predicted siRNA on non-target genes. Thus the proposed model, OpsiD, can predict optimized siRNA by considering both “inhibition efficiency on target genes and off-target possibility on non-target genes”, with improved inhibition efficiency, specificity and sensitivity. Since we have taken efforts to optimize the siRNA efficacy in terms of “inhibition efficiency and offtarget possibility”, we hope that the risk of “off-target effect” while doing gene silencing in various bioinformatics fields can be overcome to a great extent. These findings may provide new insights into cancer diagnosis, prognosis and therapy by gene silencing. The approach may be found useful for designing exogenous siRNA for therapeutic applications and gene silencing techniques in different areas of bioinformatics.

Swamp buffalo keeping – an out-dated farming activity? A case study in smallholder farming systems in Xishuangbanna, Yunnan Province, PR China

Expansion of rubber tree plantations and agricultural mechanization caused a decline of swamp buffalo numbers in the Naban River National Nature Reserve (NRNNR), Yunnan Province, China. We analysed current use of buffaloes for field work and the recent development of the regional buffalo population, based on interviews with 184 farmers in 2007/2008 and discussions with 62 buffalo keepers in 2009. Three types of NRNNR farms were distinguished, differing mainly in altitude, area under rubber, and involvement in livestock husbandry. While pig based farms (PB; n=37) have abandoned buffalo keeping, 11% of the rubber based farms (RB; n=71) and 100% of the livestock-corn based farms (LB; n=76) kept buffaloes in 2008. Herd size was 2.5 +/-1.80 (n=84) buffaloes in early 2008 and 2.2 +/-1.69 (n=62) in 2009. Field work on own land was the main reason for keeping buffaloes (87.3 %), but lending work buffaloes to neighbours (79.0%) was also important. Other purposes were transport of goods (16.1%), buffalo trade (11.3%) and meat consumption (6.4%). Buffalo care required 6.2 +/-3.00 working hours daily, while annual working time of a buffalo was 294 +/-216.6 hours. The area ploughed with buffaloes remained constant during the past 10 years despite an expansion of land cropped per farm. Although further replacement of buffaloes by tractors occurs rapidly, buffaloes still provide cheap work force and buffer risks on poor NRNNR farms. Appropriate advice is needed for improved breeding management to increase the efficiency of buffalo husbandry and provide better opportunities for buffalo meat sale in the region.

Contradictions within the Modern Food System: Nutritional Disbalance across the Globe, Its Main Drivers and Possible Ways Out

Contemporary food production, given the degree of technology being applied in it and the present state of scientific knowledge, should be able to feed the world. Corresponding statistics show that in fact the volumes of modern food production confirm this statement. Yet, the present nutritional situation across the globe leaves much to be desired: on the one hand the numbers of undernourished and malnourished people are still high and even growing in some regions, and on the other hand there is an increasing number of overweight and obese people who are experiencing (or are at risk of) adverse health impacts as consequences. The question arises how this situation is possible given the present state of food production and knowledge, and also in terms of nutrition basics when talking about the latter. When arguing about the main causes of the present situation with nutrition across the globe, it is the modern food system with its distortions that is often criticised with emphasis placed on inappropriate food distribution as one of the key problems. However it is not only food distribution that shapes inequalities in terms of food availability and accessibility – there is a number of other factors contributing to this situation including political influences. Each of the drivers of the present situation might affect more than one part and have outcomes in different dimensions. Therefore it makes sense to apply a holistic approach when viewing the modern food system, embracing all the elements and existing relationships between them for this will facilitate taking appropriate actions in order to target the desired outcome in the best possible way. Applying a systematic approach and linking various elements with corresponding interactions among them allows for picturing all the possible outcomes and hence finding the way for a better solution on global level – a solution to the present problem with nutritional disbalance across the globe.

Find out in English. 'Descubre en inglés'.

Materiales didácticos (guías didácticas y manuales para profesores) del proyecto titulado 'Find out in English' que aúna varios objetivos a través de la utilización de diferentes disciplinas que convergen para lograr un mejor conocimiento del patrimonio histórico-artístico regional, mediante la utilización, como vehículo, de una lengua extranjera. La explotación didáctica de los materiales se realiza en tres fases. La primera que se basa en el tratamiento en el aula de los contenidos y procedimientos, la segunda, que consiste en la visita a diversos museos de la región en los que se asiste a una dramatización en lengua inglesa que supone un acercamiento histórico a los fondos de los museos visitados y la tercera que pretende consolidar los conocimientos adquiridos en las dos anteriores mediante actividades y juegos diversos. Los museos son el Medina Siyasa (Cieza - Murcia) y el Salzillo (Murcia).

Lecture 1 - Starting out

What is Programming? A useful definition Object Orientation (and it’s counterparts) Thinking OO Programming Blocks Variables Logic Data Structures Methods

Plan de negocios construcción de edificio para uso habitacional en la ciudad de Bogotá

Con este trabajo, se pretende elaborar una evaluación a nivel de prefactibilidad administrativa, técnica y financiera de la construcción de un edificio, partiendo del modelo de compra de vivienda existente, su posterior demolición y construcción del proyecto. Para llevar a cabo la evaluación a nivel de prefactibilidad, se tienen en cuenta los objetivos: •Estructurar y evaluar la propuesta técnica, financiera y administrativa a nivel de prefactibilidad. •Determinar el tamaño adecuado del proyecto de acuerdo a los planes zonales y de ordenamiento territorial de la ciudad. •Identificación de las posibles formas de financiación del proyecto. •Identificación de los futuros compradores del producto final, diagnostico y perspectivas del sector. •Evaluar la mejor estrategia de mercadeo y venta del producto final, ya sea de forma directa o con un intermediario especializado.

Out there

Slides on how to utilize the web to create an online portfolio using social network and tumblr. Also introduction to basic CMS's including indexhibit, for setting up a simple portfolio website.

Programming Principles: Starting Out

In this lecture we describe the structure of the Programming Principles course at Southampton, look at the definitions and paradigms of programming, and take a look ahead to the key things that we will be covering in the weeks ahead.

"Tell me who you hang out with": Classroom peer effects on psychoactive substances consumption

I look for classroom peer effects for psychoactive substance consumption among Colombian high school students and attempt to identify channels that rationalize for these effects. To do so, I use data for Colombian schools from 2011. I identify peer effects using household consumption behavior to instrument average classroom consumption. I find that an increase of 10% in the proportion of classroom users of alcohol, cannabis, and cocaine increases the probability of students to use alcohol, cannabis, and cocaine in 3.14%, 4.29%, and 2.38% respectively. I find no significant effect on cigarette smoking for the full sample but after exploring heterogeneous effects I find suggestive evidence that the effect is positive in some grades. I find some evidence that indicate that peer effects on alcohol, cannabis, and cocaine consumption operate through risk perception and easiness of access to psychoactive substances, meaning that the increase of likelihood of consumption could be explained because it is easier to access to drugs for students that interact with consumers or because a decrease in the risk students perceive of consuming these substances. Finally, through the use of a SUR and a 3SLS estimator I find strong correlations between smoking cigarettes and consuming cannabis (55 %), and cocaine (60 %).

All Lights y Light Out : una investigación entre luces y sombras.

Estudio del juego electrónico Lights Out y de la forma de resolverlo. Para ello se aplica la aritmética modular, que pretende localizar la solución sin ensayos ni errores. Se explica paso a paso el proceso hasta alcanzar esta solución.

Energy saving innovations, non-exhaustible sources of energy and long-run: what would happen if we run out of oil?

We formulate and solve a model of factor saving technological improvement considering three factors of production: labor, capital and energy. The productive activities have three main characteristics: first, in order to use capital goods firms need energy; second, there are two sources of energy: non-exhaustible and exhaustible; third, capital goods can be of different qualities and the quality of these goods can be changed along two dimensions -reducing the need of energy or changing the source of energy used in the production process. The economy goes through three stages of development after industrialization. In the first, firms make use of exhaustible energy and the e¢ ciency in the use of energy is constant. In the second stage, as the price of energy grows the e¢ ciency in its use is increased. In the third stage, the price of exhaustible sources is so high that firms have incentives to use non-exhaustible sources of energy. During this stage the price of energy is constant. In this set up, the end of the oil age has level effects on consumption and output but it does not cause the collapse of the economic system.

Energy Saving Innovations, Non-Exhaustible Sources of Energy and Long-Run: What Would Happen if we Run Out of Oil?

Se formula y resuelve un modelo de cambio tecnológico ahorrador de factores de producción que considera tres factores: capital, trabajo y energía. El modelo cuenta con características específicas con respecto a la interacción n entre la energía (la cual, de acuerdo a su fuente puede ser renovable y no renovable) y el capital. Una vez esta economía se ha definido, se supone que evoluciona en tres etapas luego de su industrialización, durante las cuales el carácter renovable o no renovable de la energía influye su precio relativo, eficiencia y afecta también el nivel agregado de consumo y producción de la economía, sin que esta evolución lleve al colapso del sistema económico.

A family in the First World War : Katy finds out about her great grandmother.

Primer volumen de una serie de seis libros que narra la historia de la familia de Katy desde 1910 a 1960. Éste se centra en la Primera Guerra Mundial y narra la vida cotidiana de sus bisabuelos hasta el estallido de la Gran Guerra. El texto se acompaña de una pequeña tabla con el precio de algunos alimentos y productos y el sueldo en algunos oficios.