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.

Conceptual knowledge processing with formal concept analysis and ontologies

Among many other knowledge representations formalisms, Ontologies and Formal Concept Analysis (FCA) aim at modeling ‘concepts’. We discuss how these two formalisms may complement another from an application point of view. In particular, we will see how FCA can be used to support Ontology Engineering, and how ontologies can be exploited in FCA applications. The interplay of FCA and ontologies is studied along the life cycle of an ontology: (i) FCA can support the building of the ontology as a learning technique. (ii) The established ontology can be analyzed and navigated by using techniques of FCA. (iii) Last but not least, the ontology may be used to improve an FCA application.

Attitudes and behaviour towards food attributes and organic food – a triangular methodological investigation of occasional organic consumers

Organic food is increasingly available in the conventional food retail, where organic products are offered alongside with various other types of products and compete mainly with conventional and the so-called conventional-plus products. The latter are conventional products displaying particular quality attributes on the product packaging, such as ‘no artificial additives’, or ‘from animal welfare husbandry’. Often, these quality attributes also apply to organic products. Occasional organic consumers might prefer such conventional-plus alternatives that are perceived to be ‘between’ organic and conventional products. The overall objective of this PhD thesis was to provide information about the segment of occasional organic consumers. In particular, the thesis focussed on consumer perceptions and attitudes towards the quality of, and preferences for, organic, conventional and conventional-plus products in two countries: Germany and Switzerland. To achieve these objectives, qualitative and quantitative consumer research was combined in order to explore occasional organic consumers’ perceptions and attitudes as well as to observe their preferences and buying behaviour regarding different types of food products: organic, conventional and conventional-plus products. The qualitative research showed that, depending on single criteria, organic production was both positively as well as negatively assessed by consumers. Consumer perception of organic food was found to be highly selective and primarily focussed on the final stage of the particular production process. A major problem is that consumers are still mostly unfamiliar with factors associated with organic production, have a lack of confidence, and often confuse organic with conventional products. Besides this, consumer expectations of organic products are different from the expectations of conventional products. The quantitative research revealed that attitudes strongly determine consumers’ preferences for organic, conventional and conventional-plus products. Consumer attitudes tended to differ more between organic and conventional choices rather than conventional-plus and conventional choices. Furthermore, occasional organic consumers are heterogeneous in their preferences. They can be grouped into two segments: the consumers in one segment were less price sensitive and preferred organic products. The consumers in the other segment were more price sensitive and rather preferred conventional-plus or conventional products. To conclude, given the selective and subjective nature of consumer perception and the strong focus of consumer perception on the final stage of the food production process, specific additional values of organic farming should be communicated in clear and catchy messages. At the same time, these messages should be particularly focussed on the final stage of organic food production. The communication of specific added values in relation with organic products to improve the perceived price-performance-ratio is important since conventional-plus products represent an interesting alternative particularly for price sensitive occasional organic consumers. Besides this, it is important to strengthen affirmative consumer attitudes towards organic production. Therefore, policy support should emphasise on long-term communication campaigns and education programmes to increase the consumer awareness and knowledge of organic food and farming. Since consumers expect that organic food is regionally or at least domestically produced while they less accept organic imports, policy support of domestic and regional producers is a crucial measure to fill the current gap between the increasing consumer demand of organic food and the stagnation of the domestic and regional organic food supply.

Finding Spaces for Urban Food Production – Matching Spatial and Stakeholder Analysis with Urban Agriculture Approaches in the Urban Renewal Area of Dortmund-Hörde, Germany

Using the case of an economically declined neighbourhood in the post-industrial German Ruhr Area (sometimes characterized as Germany’s “Rust Belt”), we analyse, describe and conclude how urban agriculture can be used as a catalyst to stimulate and support urban renewal and regeneration, especially from a socio-cultural perspective. Using the methodological framework of participatory action research, and linking bottom-up and top-down planning approaches, a project path was developed to include the population affected and foster individual responsibility for their district, as well as to strengthen inhabitants and stakeholder groups in a permanent collective stewardship for the individual forms of urban agriculture developed and implemented. On a more abstract level, the research carried out can be characterized as a form of action research with an intended transgression of the boundaries between research, planning, design, and implementation. We conclude that by synchronously combining those four domains with intense feedback loops, synergies for the academic knowledge on the potential performance of urban agriculture in terms of sustainable development, as well as the benefits for the case-study area and the interests of individual urban gardeners can be achieved.

A Hierarchical Cache Coherent Protocol

As the number of processors in distributed-memory multiprocessors grows, efficiently supporting a shared-memory programming model becomes difficult. We have designed the Protocol for Hierarchical Directories (PHD) to allow shared-memory support for systems containing massive numbers of processors. PHD eliminates bandwidth problems by using a scalable network, decreases hot-spots by not relying on a single point to distribute blocks, and uses a scalable amount of space for its directories. PHD provides a shared-memory model by synthesizing a global shared memory from the local memories of processors. PHD supports sequentially consistent read, write, and test- and-set operations. This thesis also introduces a method of describing locality for hierarchical protocols and employs this method in the derivation of an abstract model of the protocol behavior. An embedded model, based on the work of Johnson[ISCA19], describes the protocol behavior when mapped to a k-ary n-cube. The thesis uses these two models to study the average height in the hierarchy that operations reach, the longest path messages travel, the number of messages that operations generate, the inter-transaction issue time, and the protocol overhead for different locality parameters, degrees of multithreading, and machine sizes. We determine that multithreading is only useful for approximately two to four threads; any additional interleaving does not decrease the overall latency. For small machines and high locality applications, this limitation is due mainly to the length of the running threads. For large machines with medium to low locality, this limitation is due mainly to the protocol overhead being too large. Our study using the embedded model shows that in situations where the run length between references to shared memory is at least an order of magnitude longer than the time to process a single state transition in the protocol, applications exhibit good performance. If separate controllers for processing protocol requests are included, the protocol scales to 32k processor machines as long as the application exhibits hierarchical locality: at least 22% of the global references must be able to be satisfied locally; at most 35% of the global references are allowed to reach the top level of the hierarchy.

A Note on the Generalization Performance of Kernel Classifiers with Margin

We present distribution independent bounds on the generalization misclassification performance of a family of kernel classifiers with margin. Support Vector Machine classifiers (SVM) stem out of this class of machines. The bounds are derived through computations of the $V_gamma$ dimension of a family of loss functions where the SVM one belongs to. Bounds that use functions of margin distributions (i.e. functions of the slack variables of SVM) are derived.

People Recognition in Image Sequences by Supervised Learning

We describe a system that learns from examples to recognize people in images taken indoors. Images of people are represented by color-based and shape-based features. Recognition is carried out through combinations of Support Vector Machine classifiers (SVMs). Different types of multiclass strategies based on SVMs are explored and compared to k-Nearest Neighbors classifiers (kNNs). The system works in real time and shows high performance rates for people recognition throughout one day.

Multivariate Density Estimation: An SVM Approach

We formulate density estimation as an inverse operator problem. We then use convergence results of empirical distribution functions to true distribution functions to develop an algorithm for multivariate density estimation. The algorithm is based upon a Support Vector Machine (SVM) approach to solving inverse operator problems. The algorithm is implemented and tested on simulated data from different distributions and different dimensionalities, gaussians and laplacians in $R^2$ and $R^{12}$. A comparison in performance is made with Gaussian Mixture Models (GMMs). Our algorithm does as well or better than the GMMs for the simulations tested and has the added advantage of being automated with respect to parameters.

Object Detection in Images by Components

In this paper we present a component based person detection system that is capable of detecting frontal, rear and near side views of people, and partially occluded persons in cluttered scenes. The framework that is described here for people is easily applied to other objects as well. The motivation for developing a component based approach is two fold: first, to enhance the performance of person detection systems on frontal and rear views of people and second, to develop a framework that directly addresses the problem of detecting people who are partially occluded or whose body parts blend in with the background. The data classification is handled by several support vector machine classifiers arranged in two layers. This architecture is known as Adaptive Combination of Classifiers (ACC). The system performs very well and is capable of detecting people even when all components of a person are not found. The performance of the system is significantly better than a full body person detector designed along similar lines. This suggests that the improved performance is due to the components based approach and the ACC data classification structure.

Modeling and Analysis of Two-Part Type Manufacturing Systems

This paper presents a model and analysis of a synchronous tandem flow line that produces different part types on unreliable machines. The machines operate according to a static priority rule, operating on the highest priority part whenever possible, and operating on lower priority parts only when unable to produce those with higher priorities. We develop a new decomposition method to analyze the behavior of the manufacturing system by decomposing the long production line into small analytically tractable components. As a first step in modeling a production line with more than one part type, we restrict ourselves to the case where there are two part types. Detailed modeling and derivations are presented with a small two-part-type production line that consists of two processing machines and two demand machines. Then, a generalized longer flow line is analyzed. Furthermore, estimates for performance measures, such as average buffer levels and production rates, are presented and compared to extensive discrete event simulation. The quantitative behavior of the two-part type processing line under different demand scenarios is also provided.

Scene Classification Using a Hybrid Generative/Discriminative Approach

We investigate whether dimensionality reduction using a latent generative model is beneficial for the task of weakly supervised scene classification. In detail, we are given a set of labeled images of scenes (for example, coast, forest, city, river, etc.), and our objective is to classify a new image into one of these categories. Our approach consists of first discovering latent ";topics"; using probabilistic Latent Semantic Analysis (pLSA), a generative model from the statistical text literature here applied to a bag of visual words representation for each image, and subsequently, training a multiway classifier on the topic distribution vector for each image. We compare this approach to that of representing each image by a bag of visual words vector directly and training a multiway classifier on these vectors. To this end, we introduce a novel vocabulary using dense color SIFT descriptors and then investigate the classification performance under changes in the size of the visual vocabulary, the number of latent topics learned, and the type of discriminative classifier used (k-nearest neighbor or SVM). We achieve superior classification performance to recent publications that have used a bag of visual word representation, in all cases, using the authors' own data sets and testing protocols. We also investigate the gain in adding spatial information. We show applications to image retrieval with relevance feedback and to scene classification in videos

The value of using short-format podcasts to enhance learning and teaching

This paper presents the findings of a podcasting trial held in 2007-2008 within the Faculty of Economics and Business at the University of Sydney, Australia. The trial investigates the value of using short-format podcasts to support assessment for postgraduate and undergraduate students. A multi-method approach is taken in investigating perceptions of the benefits of podcasting, incorporating surveys, focus groups and interviews. The results show that a majority of students believe they gained learning benefits from the podcasts and appreciated the flexibility of the medium to support their learning, and the lecturers felt the innovation helped diversify their pedagogical approach and support a diverse student population. Three primary conclusions are presented: (1) most students reject the mobile potential of podcasting in favour of their traditional study space at home; (2) what students and lecturers value about this podcasting design overlap; (3) the assessment-focussed, short-format podcast design may be considered a successful podcasting model. The paper finishes by identifying areas for future research on the effective use of podcasting in learning and teaching.

Scalable real-time crisis mapping and analytics of social media streams for disaster management and breaking news

Real-time geoparsing of social media streams (e.g. Twitter, YouTube, Instagram, Flickr, FourSquare) is providing a new 'virtual sensor' capability to end users such as emergency response agencies (e.g. Tsunami early warning centres, Civil protection authorities) and news agencies (e.g. Deutsche Welle, BBC News). Challenges in this area include scaling up natural language processing (NLP) and information retrieval (IR) approaches to handle real-time traffic volumes, reducing false positives, creating real-time infographic displays useful for effective decision support and providing support for trust and credibility analysis using geosemantics. I will present in this seminar on-going work by the IT Innovation Centre over the last 4 years (TRIDEC and REVEAL FP7 projects) in building such systems, and highlights our research towards improving trustworthy and credible of crisis map displays and real-time analytics for trending topics and influential social networks during major news worthy events.

salud financiera y riesgo en los estados financieros de la empresa avianca del sector aeronautico

La globalización y la competitividad como realidad de las empresas, implica que los gerentes preparen a sus empresas de la mejor manera para sobrevivir en este mundo tan inestable y cambiante. El primer paso consta de investigar y medir como se encuentra la empresa en cada uno de sus componentes, tales como recurso humano, mercadeo, logística, operación y por último y más importante las finanzas. El conocimiento de salud financiera y de los riesgos asociados a la actividad de las empresas, les permitirá a los gerentes tomar las decisiones correctas para ser rentables y perdurables en el mundo de los negocios inmerso en la globalización y competitividad. Esta apreciación es pertinente en Avianca S.A. esto teniendo en cuenta su progreso y evolución desde su primer vuelo el 5 de diciembre de 1919 comercial, hasta hoy cuando cotiza en la bolsa de Nueva York. Se realizó un análisis de tipo descriptivo, acompañado de la aplicación de ratios y nomenclaturas, dando lugar a establecer la salud financiera y los riesgos, no solo de Avianca sino también del sector aeronáutico. Como resultado se obtuvo que el sector aeronáutico sea financieramente saludable en el corto plazo, pero en el largo plazo su salud financiera se ve comprometida por los riegos asociados al sector y a la actividad desarrollada.

Labor's shares - aggregate and industry: accounting for both in a model of unbalanced growth with induced innovation

The relative stability of aggregate labor's share constitutes one of the great macroeconomic ratios. However, relative stability at the aggregate level masks the unbalanced nature of industry labor's shares – the Kuznets stylized facts underlie those of Kaldor. We present a two-sector – one labor-only and the other using both capital and labor – model of unbalanced economic development with induced innovation that can rationalize these phenomena as well as several other empirical regularities of actual economies. Specifically, the model features (i) one sector ("goods" production) becoming increasingly capital-intensive over time; (ii) an increasing relative price and share in total output of the labor-only sector ("services"); and (iii) diverging sectoral labor's shares despite (iii) an aggregate labor's share that converges from above to a value between 0 and unity. Furthermore, the model (iv) supports either a neoclassical steadystate or long-run endogenous growth, giving it the potential to account for a wide range of real world development experiences.