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.

Nutrient cycling and nutrient use efficiency in urban and peri-urban agriculture of Kabul, Afghanistan

Like elsewhere also in Kabul, Afghanistan urban and peri-urban agriculture (UPA) has often been accused of being resource inefficient and unsustainable causing negatives externalities to community health and to the surroundings. These arise from the inappropriate management and use of agricultural inputs, including often pesticides and inter-city wastes containing heavy metal residues and pathogens. To address these concerns, parallel studies with the aims of quantification of carbon (C), nitrogen (N), phosphorus (P) and potassium (K) horizontal and vertical fluxes; the assessment of heavy metal and pathogen contaminations of UPA produce, and an economic analysis of cereal, vegetable and grape production systems conducted for two years in UPA of Kabul from April 2008 to October 2009. The results of the studies from these three UPA diverse production systems can be abridged as follows: Biennial net balances in vegetable production systems were positive for N (80 kg ha-1 ), P (75 kg ha-1) and C (3,927 kg ha-1), negative for K (-205 kg ha-1), whereas in cereal production systems biennial horizontal balances were positive for P (20 kg ha-1 ) and C (4,900 kg ha-1) negative for N (-155 kg ha-1) and K (-355 kg ha-1) and in vineyards corresponding values were highly positive for N (295 kg ha-1), P (235 kg ha-1), C (3,362 kg ha-1) and slightly positive for K (5 kg ha-1). Regardless of N and C gaseous emissions, yearly leaching losses of N and P in selected vegetable gardens varied from 70 - 205 kg N ha-1 and 5 - 10 kg P ha-1. Manure and irrigation water contributed on average 12 - 79% to total Inputs of N, P, K and C, 10 - 53% to total inputs of C in the gardens and fields. The elevated levels of heavy metal and pathogen loads on fresh UPA vegetables reflected contamination from increasing traffic in the city, deposits of the past decades of war, lacking collection and treatment of raw inter-city wastes which call for solutions to protect consumer and producer health and increase reliability of UPA productions. A cost-revenue analysis of all inputs and outputs of cereal, vegetable and grapes production systems over two years showed substantial differences in net UPA household income. To confirm these results, more detailed studies are needed, but tailoring and managing the optimal application of inputs to crop needs will significantly enhance farmer’s better revenues as will as environmental and produce quality.

Reciprocal and wage labour in rural Ecuador. A quantitative analysis

This paper analyses the determinants for rural Ecuadorian households to participate in community works, to exchange labour, and to use paid labour. The results show that participation in community work is more common among indigenous peoples who are more committed with community and live in areas with relatively high population densities. Exchange labour agreements are more common among indigenous households settled in areas where industrial agriculture has not penetrated yet. Instead, paid labour is used by small and educated households which have access to credit.

Technical and scale efficiency of cassava production system in Delta State, Nigeria: an application of Two-Stage DEA approach

The present study examines the level of pure technical and scale efficiencies of cassava production system including its sub-processes (that is production and processing stages) of 278 cassava farmers/processors from three regions of Delta State, Nigeria by applying Two-Stage Data Envelopment Analysis (DEA) approach. Results reveal that pure technical efficiency (PTE) is significantly lower at the production stage 0.41 vs 0.55 for the processing stage, but scale efficiency (SE) is high at both stages (0.84 and 0.87), implying that productivity can be improved substantially by reallocation of resources and adjusting operation size. The socio-economic determinants exert differential impacts on PTE and SE at each stage. Overall, education, experience and main occupation as farmer significantly improve SE while subsistence pressure reduces it. Extension contact significantly improves SE at the processing stage but reduces PTE and SE overall. Inverse size-PTE and size-SE relationships exist in cassava production system. In other words, large/medium farms are technically and scale inefficient. Gender gap exists in performance. Male farmers are technically efficient at processing stage but scale inefficient overall. Farmers in northern region are technically efficient. Investments in education, extension services and infrastructure are suggested as policy options to improve the cassava sector in Nigeria.

Determinants of technical efficiency of freshwater prawn farming in southwestern Bangladesh

This paper estimates a translog stochastic production function to examine the determinants of technical efficiency of freshwater prawn farming in Bangladesh. Primary data has been collected using random sampling from 90 farmers of three villages in southwestern Bangladesh. Prawn farming displayed much variability in technical efficiency ranging from 9.50 to 99.94% with mean technical efficiency of 65%, which suggested a substantial 35% of potential output can be recovered by removing inefficiency. For a land scarce country like Bangladesh this gain could help increase income and ensure better livelihood for the farmers. Based on the translog production function specification, farmers could be made scale efficient by providing more input to produce more output. The results suggest that farmers’ education and non-farm income significantly improve efficiency whilst farmers’ training, farm distance from the water canal and involvement in fish farm associations reduces efficiency. Hence, the study proposes strategies such as less involvement in farming-related associations and raising the effective training facilities of the farmers as beneficial adjustments for reducing inefficiency. Moreover, the key policy implication of the analysis is that investment in primary education would greatly improve technical efficiency.

The efficiency of direct payments versus tax reductions under uncertainty

This paper analyzes the optimal behavior of farmers in the presence of direct payments and uncertainty. In an empirical analysis for Switzerland, it confirms previously obtained theoretical results and determines the magnitude of the theoretical predicted effects. The results show that direct payments increase agricultural production between 3.7% to 4.8%. Alternatively to direct payments, the production effect of tax reductions is evaluated in order to determine its magnitude. The empirical analysis corroborates the theoretical results of the literature and demonstrates that tax reductions are also distorting, but to a substantially lesser degree if losses are not offset. However, tax reductions, independently whether losses are offset or not, lead to higher government spending than pure direct payments

An approximation to the informal-formal wage gap in Colombia 2008-2012

This document provides recent evidence about the persistency of wage gaps between formal and informal workers in Colombia by using a non-parametric method proposed by Ñopo (2008a). Over a rich dataset at a household level during 2008-2012, it is found that formal workers earn between 30 to 60 percent more, on average, than informal workers. Despite of the formality definition - structuralist or institucionalist- adopted, it is clear that formal workers have more economic advantages than informal ones, but after controlling by demographic and labor variables an important fraction of the gap still remains unexplained.

Teorías y algunas experiencias internacionales en el financiamiento de la educación superior: lecciones para Colombia

Se analizan diferentes alternativas para la financiación de la educación superior, teniendo en cuenta que la presencia de fallas de mercado -tanto por el lado de la demanda como por el de la oferta- hace de éste un sector muy particular. Las primeras se relacionan con las decisiones privadas en términos de educación de la población estudiantil, y las segundas con las asimetrías de información que caracterizan el lado de la oferta en el financiamiento de la educación. El documento hace una revisión de literatura académica y de algunas experiencias internacionales sobre las diferentes fuentes de financiación en este sector, así como sus potenciales efectos sobre ciertas variables. Así, esta revisión arroja luces sobre las alternativas para el caso Colombiano.

Tratado de libre comercio entre Colombia y Estados Unidos: ¿qué impacto puede tener en Colombia?

Para evaluar el impacto de un Tratado de libre comercio (TLC) entre Colombia y Estados Unidos, describimos las características de la economía colombiana, enfatizando en sus patrones y perspectivas de comercio, e identificando los sectores y regiones más sensibles a la firma de un TLC. Afirmamos que los efectos de un acuerdo bilateral entre Colombia y Estados Unidos, serán similares a los que han tenido anteriores reformas de liberalización comercial. Sin embargo, mientras Colombia espera la firma del TLC con Estados Unidos, ese país está cerca de firmar tratados bilaterales con algunos países de Latinoamérica. Por lo tanto, también puede haber efectos sobre la economía colombiana producto del cambio en las reglas comerciales entre sus socios. Primero analizamos el efecto de anteriores reformas comerciales en Colombia, México y Chile. Luego, a través de un modelo de equilibrio general multiregional aplicado, simulamos los efectos sobre la economía colombiana de un acuerdo bilateral con Estados Unidos. Concluimos que, aunque moderados, habrá aumentos en el bienestar y en la producción de los consumidores y firmas colombianos.

Conflict, wages, and multiple equilibria

Firms’ compensation practices affect the protection of investors’ interests and the degree of economic inequality by changing the stakes of engaging in appropriation activities versus respecting the status quo. We use a general equilibrium model where workers can either work peacefully or join a guerrilla movement that expropriates entrepreneurs. If workers are peaceful, they receive a competitive wage. If they join a guerrilla movement, they receive a share of the appropriated wealth, which depends positively on the number of guerrilla members. In this framework, we find one low-income, low-wage equilibrium with guerrilla activity and one peaceful, high-income, high-wage equilibrium. The peaceful equilibrium can be reached through redistribution policies, which can be implemented at the firm level. In essence, through their compensation policies entrepreneurs, not the state might be able to protect their assets against expropriation and simultaneously control the internal principal-agent problem.

Is there a motherhood penalty? decomposing the family wage gap in Colombia

The aim of this paper is to provide an estimation and decomposition of the motherhood wage penalty in Colombia. Our empirical strategy was based on the matching procedure designed by Ñopo (The Review of Economics and Statistics, 90(2), 290–299, 2008a ) for the case of gender wage gaps. This is an alternative procedure to the well-known Blinder–Oaxaca decomposition method. Using the cross-sectional data of the Colombian Living Standard Survey, the wage gap was decomposed into four components, according to the characteristics of mothers and non-mothers. Three of the components are explained by differences in observable characteristics of women, while the other is the unexplained part of the gap. We found that mothers earn, on average, 1.73 % less than their counterparts without children and that this gap slightly decreased when the group included older women. It is observed from the results that, once schooling was included as a matching variable, the unexplained part of the gap considerably decreased and became non-significant. Thus, we did not find evidence of wage discrimination against mothers in the Colombian labor market. Copyright Springer Science+Business Media New York 2013

Performance and efficiency in Colombia's power utilities: an assessment of the 1994 reform

El artículo describe las características centrales de la reforma regulatoria al sector eléctrico en 1994 y evalúa el desempeño y la eficiencia de las empresas públicas antes y después de la reforma. El análisis de desempeño evalúa los cambios en medias y medianas en ganancias, eficiencia, inversión y ventas de las empresas privatizadas en el sector. La eficiencia técnica es estimada mediante la técnica DEA en una muestra de 33 plantas térmicas de energía, que representan el 85% del parque térmico; y 12 empresas distribuidoras de energía. La muestra de plantas generadoras está compuesta por plantas que estaban activas antes de la reforma y plantas nuevas que entraron en operación después de la reforma. Los principales resultados muestran que la eficiencia mejoro después de la reforma y que la política regulatoria ha tenido un efecto positivo en la eficiencia de la generación térmica de energía. Por el contrario, las distribuidoras de energía menos eficientes empeoraron después de la reforma y no llevaron a cabo una reestructuración para alcanzar la eficiencia productiva respecto a las empresas que conforman la frontera de eficiencia en distribución de energía.