QUANTIFYING UNCERTAINTY IN GENOTYPE CALLS

Genome-wide association studies (GWAS) are used to discover genes underlying complex, heritable disorders for which less powerful study designs have failed in the past. The number of GWAS has skyrocketed recently with findings reported in top journals and the mainstream media. Mircorarrays are the genotype calling technology of choice in GWAS as they permit exploration of more than a million single nucleotide polymorphisms (SNPs)simultaneously. The starting point for the statistical analyses used by GWAS, to determine association between loci and disease, are genotype calls (AA, AB, or BB). However, the raw data, microarray probe intensities, are heavily processed before arriving at these calls. Various sophisticated statistical procedures have been proposed for transforming raw data into genotype calls. We find that variability in microarray output quality across different SNPs, different arrays, and different sample batches has substantial inuence on the accuracy of genotype calls made by existing algorithms. Failure to account for these sources of variability, GWAS run the risk of adversely affecting the quality of reported findings. In this paper we present solutions based on a multi-level mixed model. Software implementation of the method described in this paper is available as free and open source code in the crlmm R/BioConductor.

Corporate social responsibility in portfolio selection: A "goal games" against nature approach

Nowadays, there is an uprising social pressure on big companies to incorporate into their decision-making process elements of the so-called social responsibility. Among the many implications of this fact, one relevant one is the need to include this new element in classic portfolio selection models. This paper meets this challenge by formulating a model that combines goal programming with "goal games" against nature in a scenario where the social responsibility is defined through the introduction of a battery of sustainability indicators amalgamated into a synthetic index. In this way, we have obtained an efficient model that only implies solving a small number of linear programming problems. The proposed approach has been tested and illustrated by using a case study related to the selection of securities in international markets.

Optimización de operaciones unitarias utilizando líquidos iónicos como agentes materiales de separación

En este trabajo se estudia la modelización y optimización de procesos industriales de separación mediante el empleo de mezclas de líquidos iónicos como disolventes. Los disolventes habitualmente empleados en procesos de absorción o extracción suelen ser componentes orgánicos muy volátiles y dañinos para la salud humana. Las innovadoras propiedades que presentan los líquidos iónicos, los convierten en alternativas adecuadas para solucionar estos problemas. La presión de vapor de estos compuestos es muy baja y apenas varía con la temperatura. Por tanto, estos compuestos apenas se evaporan incluso a temperaturas altas. Esto supone una gran ventaja en cuanto al empleo de estos compuestos como disolventes industriales ya que permite el reciclaje continuo del disolvente al final del proceso sin necesidad de introducir disolvente fresco debido a la evaporación del mismo. Además, al no evaporarse, estos compuestos no suponen un peligro para la salud humana por inhalación; al contrario que otros disolventes como el benceno. El único peligro para la salud que tienen estos compuestos es por tanto el de contacto directo o ingesta, aunque de hecho muchos Líquidos Iónicos son inocuos con lo cual no existe peligro para la salud ni siquiera a través de estas vías. Los procesos de separación estudiados en este trabajo, se rigen por la termodinámica de fases, concretamente el equilibrio líquido-vapor. Para la predicción de los equilibrios se ha optado por el empleo de modelos COSMO (COnductor-like Screening MOdel). Estos modelos tienen su origen en el empleo de la termodinámica de solvatación y en la mecánica cuántica. En el desarrollo de procesos y productos, químicos e ingenieros frecuentemente precisan de la realización de cálculos de predicción de equilibrios de fase. Previamente al desarrollo de los modelos COSMO, se usaban métodos de contribución de grupos como UNIFAC o modelos de coeficientes de actividad como NRTL.La desventaja de estos métodos, es que requieren parámetros de interacción binaria que únicamente pueden obtenerse mediante ajustes por regresión a partir de resultados experimentales. Debido a esto, estos métodos apenas tienen aplicabilidad para compuestos con grupos funcionales novedosos debido a que no se dispone de datos experimentales para llevar a cabo los ajustes por regresión correspondientes. Una alternativa a estos métodos, es el empleo de modelos de solvatación basados en la química cuántica para caracterizar las interacciones moleculares y tener en cuenta la no idealidad de la fase líquida. Los modelos COSMO, permiten la predicción de equilibrios sin la necesidad de ajustes por regresión a partir de resultados experimentales. Debido a la falta de resultados experimentales de equilibrios líquido-vapor de mezclas en las que se ven involucrados los líquidos iónicos, el empleo de modelos COSMO es una buena alternativa para la predicción de equilibrios de mezclas con este tipo de materiales. Los modelos COSMO emplean las distribuciones superficiales de carga polarizada (sigma profiles) de los compuestos involucrados en la mezcla estudiada para la predicción de los coeficientes de actividad de la misma, definiéndose el sigma profile de una molécula como la distribución de probabilidad de densidad de carga superficial de dicha molécula. Dos de estos modelos son COSMO-RS (Realistic Solvation) y COSMO-SAC (Segment Activity Coefficient). El modelo COSMO-RS fue la primera extensión de los modelos de solvatación basados en continuos dieléctricos a la termodinámica de fases líquidas mientras que el modelo COSMO-SAC es una variación de este modelo, tal y como se explicará posteriormente. Concretamente en este trabajo se ha empleado el modelo COSMO-SAC para el cálculo de los coeficientes de actividad de las mezclas estudiadas. Los sigma profiles de los líquidos iónicos se han obtenido mediante el empleo del software de química computacional Turbomole y el paquete químico-cuántico COSMOtherm. El software Turbomole permite optimizar la geometría de la molécula para hallar la configuración más estable mientras que el paquete COSMOtherm permite la obtención del perfil sigma del compuesto mediante el empleo de los datos proporcionados por Turbomole. Por otra parte, los sigma profiles del resto de componentes se han obtenido de la base de datos Virginia Tech-2005 Sigma Profile Database. Para la predicción del equilibrio a partir de los coeficientes de actividad se ha empleado la Ley de Raoult modificada. Se ha supuesto por tanto que la fracción de cada componente en el vapor es proporcional a la fracción del mismo componente en el líquido, dónde la constante de proporcionalidad es el coeficiente de actividad del componente en la mezcla multiplicado por la presión de vapor del componente y dividido por la presión del sistema. Las presiones de vapor de los componentes se han obtenido aplicando la Ley de Antoine. Esta ecuación describe la relación entre la temperatura y la presión de vapor y se deduce a partir de la ecuación de Clausius-Clapeyron. Todos estos datos se han empleado para la modelización de una separación flash usando el algoritmo de Rachford-Rice. El valor de este modelo reside en la deducción de una función que relaciona las constantes de equilibrio, composición total y fracción de vapor. Para llevar a cabo la implementación del modelado matemático descrito, se ha programado un código empleando el software MATLAB de análisis numérico. Para comprobar la fiabilidad del código programado, se compararon los resultados obtenidos en la predicción de equilibrios de mezclas mediante el código con los resultados obtenidos mediante el simulador ASPEN PLUS de procesos químicos. Debido a la falta de datos relativos a líquidos iónicos en la base de datos de ASPEN PLUS, se han introducido estos componentes como pseudocomponentes, de manera que se han introducido únicamente los datos necesarios de estos componentes para realizar las simulaciones. El modelo COSMO-SAC se encuentra implementado en ASPEN PLUS, de manera que introduciendo los sigma profiles, los volúmenes de la cavidad y las presiones de vapor de los líquidos iónicos, es posible predecir equilibrios líquido-vapor en los que se ven implicados este tipo de materiales. De esta manera pueden compararse los resultados obtenidos con ASPEN PLUS y como el código programado en MATLAB y comprobar la fiabilidad del mismo. El objetivo principal del presente Trabajo Fin de Máster es la optimización de mezclas multicomponente de líquidos iónicos para maximizar la eficiencia de procesos de separación y minimizar los costes de los mismos. La estructura de este problema es la de un problema de optimización no lineal con variables discretas y continuas, es decir, un problema de optimización MINLP (Mixed Integer Non-Linear Programming). Tal y como se verá posteriormente, el modelo matemático de este problema es no lineal. Por otra parte, las variables del mismo son tanto continuas como binarias. Las variables continuas se corresponden con las fracciones molares de los líquidos iónicos presentes en las mezclas y con el caudal de la mezcla de líquidos iónicos. Por otra parte, también se ha introducido un número de variables binarias igual al número de líquidos iónicos presentes en la mezcla. Cada una de estas variables multiplican a las fracciones molares de sus correspondientes líquidos iónicos, de manera que cuando dicha variable es igual a 1, el líquido se encuentra en la mezcla mientras que cuando dicha variable es igual a 0, el líquido iónico no se encuentra presente en dicha mezcla. El empleo de este tipo de variables obliga por tanto a emplear algoritmos para la resolución de problemas de optimización MINLP ya que si todas las variables fueran continuas, bastaría con el empleo de algoritmos para la resolución de problemas de optimización NLP (Non-Linear Programming). Se han probado por tanto diversos algoritmos presentes en el paquete OPTI Toolbox de MATLAB para comprobar cuál es el más adecuado para abordar este problema. Finalmente, una vez validado el código programado, se han optimizado diversas mezclas de líquidos iónicos para lograr la máxima recuperación de compuestos aromáticos en un proceso de absorción de mezclas orgánicas. También se ha usado este código para la minimización del coste correspondiente a la compra de los líquidos iónicos de la mezcla de disolventes empleada en la operación de absorción. En este caso ha sido necesaria la introducción de restricciones relativas a la recuperación de aromáticos en la fase líquida o a la pureza de la mezcla obtenida una vez separada la mezcla de líquidos iónicos. Se han modelizado los dos problemas descritos previamente (maximización de la recuperación de Benceno y minimización del coste de operación) empleando tanto únicamente variables continuas (correspondientes a las fracciones o cantidades molares de los líquidos iónicos) como variables continuas y binarias (correspondientes a cada uno de los líquidos iónicos implicados en las mezclas).

Isobutane Alkylation Process Synthesis by means of Hybrid Simulation-Multiobjective Optimization

Multiobjective Generalized Disjunctive Programming (MO-GDP) optimization has been used for the synthesis of an important industrial process, isobutane alkylation. The two objective functions to be simultaneously optimized are the environmental impact, determined by means of LCA (Life Cycle Assessment), and the economic potential of the process. The main reason for including the minimization of the environmental impact in the optimization process is the widespread environmental concern by the general public. For the resolution of the problem we employed a hybrid simulation- optimization methodology, i.e., the superstructure of the process was developed directly in a chemical process simulator connected to a state of the art optimizer. The model was formulated as a GDP and solved using a logic algorithm that avoids the reformulation as MINLP -Mixed Integer Non Linear Programming-. Our research gave us Pareto curves compounded by three different configurations where the LCA has been assessed by two different parameters: global warming potential and ecoindicator-99.

Optimization of physical distribution problem in logistics management

Physical distribution plays an imporant role in contemporary logistics management. Both satisfaction level of of customer and competitiveness of company can be enhanced if the distribution problem is solved optimally. The multi-depot vehicle routing problem (MDVRP) belongs to a practical logistics distribution problem, which consists of three critical issues: customer assignment, customer routing, and vehicle sequencing. According to the literatures, the solution approaches for the MDVRP are not satisfactory because some unrealistic assumptions were made on the first sub-problem of the MDVRP, ot the customer assignment problem. To refine the approaches, the focus of this paper is confined to this problem only. This paper formulates the customer assignment problem as a minimax-type integer linear programming model with the objective of minimizing the cycle time of the depots where setup times are explicitly considered. Since the model is proven to be MP-complete, a genetic algorithm is developed for solving the problem. The efficiency and effectiveness of the genetic algorithm are illustrated by a numerical example.

An integrated multiple criteria decision making approach for resource allocation in higher education

Resource allocation is one of the major decision problems arising in higher education. Resources must be allocated optimally in such a way that the performance of universities can be improved. This paper applies an integrated multiple criteria decision making approach to the resource allocation problem. In the approach, the Analytic Hierarchy Process (AHP) is first used to determine the priority or relative importance of proposed projects with respect to the goals of the universities. Then, the Goal Programming (GP) model incorporating the constraints of AHP priority, system, and resource is formulated for selecting the best set of projects without exceeding the limited available resources. The projects include 'hardware' (tangible university's infrastructures), and 'software' (intangible effects that can be beneficial to the university, its members, and its students). In this paper, two commercial packages are used: Expert Choice for determining the AHP priority ranking of the projects, and LINDO for solving the GP model. Copyright © 2007 Inderscience Enterprises Ltd.

Zero weights and non-zero slacks:different solution to the same problem

This paper re-assesses three independently developed approaches that are aimed at solving the problem of zero-weights or non-zero slacks in Data Envelopment Analysis (DEA). The methods are weights restricted, non-radial and extended facet DEA models. Weights restricted DEA models are dual to envelopment DEA models with restrictions on the dual variables (DEA weights) aimed at avoiding zero values for those weights; non-radial DEA models are envelopment models which avoid non-zero slacks in the input-output constraints. Finally, extended facet DEA models recognize that only projections on facets of full dimension correspond to well defined rates of substitution/transformation between all inputs/outputs which in turn correspond to non-zero weights in the multiplier version of the DEA model. We demonstrate how these methods are equivalent, not only in their aim but also in the solutions they yield. In addition, we show that the aforementioned methods modify the production frontier by extending existing facets or creating unobserved facets. Further we propose a new approach that uses weight restrictions to extend existing facets. This approach has some advantages in computational terms, because extended facet models normally make use of mixed integer programming models, which are computationally demanding.

Applied operational research with SAS

Using a wide range of operational research (OR) optimization examples, Applied Operational Research with SAS demonstrates how the OR procedures in SAS work. The book is one of the first to extensively cover the application of SAS procedures to OR problems, such as single criterion optimization, project management decisions, printed circuit board assembly, and multiple criteria decision making. The text begins with the algorithms and methods for linear programming, integer linear programming, and goal programming models. It then describes the principles of several OR procedures in SAS. Subsequent chapters explain how to use these procedures to solve various types of OR problems. Each of these chapters describes the concept of an OR problem, presents an example of the problem, and discusses the specific procedure and its macros for the optimal solution of the problem. The macros include data handling, model building, and report writing. While primarily designed for SAS users in OR and marketing analytics, the book can also be used by readers interested in mathematical modeling techniques. By formulating the OR problems as mathematical models, the authors show how SAS can solve a variety of optimization problems.

A bi-objective weighted model for improving the discrimination power in MCDEA

Lack of discrimination power and poor weight dispersion remain major issues in Data Envelopment Analysis (DEA). Since the initial multiple criteria DEA (MCDEA) model developed in the late 1990s, only goal programming approaches; that is, the GPDEA-CCR and GPDEA-BCC were introduced for solving the said problems in a multi-objective framework. We found GPDEA models to be invalid and demonstrate that our proposed bi-objective multiple criteria DEA (BiO-MCDEA) outperforms the GPDEA models in the aspects of discrimination power and weight dispersion, as well as requiring less computational codes. An application of energy dependency among 25 European Union member countries is further used to describe the efficacy of our approach. © 2013 Elsevier B.V. All rights reserved.

Multiple criteria optimization of contemporary logistics distribution network problems

In the contemporary customer-driven supply chain, maximization of customer service plays an equally important role as minimization of costs for a company to retain and increase its competitiveness. This article develops a multiple-criteria optimization approach, combining the analytic hierarchy process (AHP) and an integer linear programming (ILP) model, to aid the design of an optimal logistics distribution network. The proposed approach outperforms traditional cost-based optimization techniques because it considers both quantitative and qualitative factors and also aims at maximizing the benefits of deliverer and customers. In the approach, the AHP is used to determine the relative importance weightings or priorities of alternative warehouses with respect to some critical customer-oriented criteria. The results of AHP prioritization are utilized as the input of the ILP model, the objective of which is to select the best warehouses at the lowest possible cost. In this article, two commercial packages are used: including Expert Choice and LINDO.

Method of Linear Programming as an Idea for High School Curriculum

2010 Mathematics Subject Classification: 97D40, 97M10, 97M40, 97N60, 97N80, 97R80

Branch and price solution approach for order acceptance and capacity planning in make -to -order operations

The increasing emphasis on mass customization, shortened product lifecycles, synchronized supply chains, when coupled with advances in information system, is driving most firms towards make-to-order (MTO) operations. Increasing global competition, lower profit margins, and higher customer expectations force the MTO firms to plan its capacity by managing the effective demand. The goal of this research was to maximize the operational profits of a make-to-order operation by selectively accepting incoming customer orders and simultaneously allocating capacity for them at the sales stage. ^ For integrating the two decisions, a Mixed-Integer Linear Program (MILP) was formulated which can aid an operations manager in an MTO environment to select a set of potential customer orders such that all the selected orders are fulfilled by their deadline. The proposed model combines order acceptance/rejection decision with detailed scheduling. Experiments with the formulation indicate that for larger problem sizes, the computational time required to determine an optimal solution is prohibitive. This formulation inherits a block diagonal structure, and can be decomposed into one or more sub-problems (i.e. one sub-problem for each customer order) and a master problem by applying Dantzig-Wolfe’s decomposition principles. To efficiently solve the original MILP, an exact Branch-and-Price algorithm was successfully developed. Various approximation algorithms were developed to further improve the runtime. Experiments conducted unequivocally show the efficiency of these algorithms compared to a commercial optimization solver.^ The existing literature addresses the static order acceptance problem for a single machine environment having regular capacity with an objective to maximize profits and a penalty for tardiness. This dissertation has solved the order acceptance and capacity planning problem for a job shop environment with multiple resources. Both regular and overtime resources is considered. ^ The Branch-and-Price algorithms developed in this dissertation are faster and can be incorporated in a decision support system which can be used on a daily basis to help make intelligent decisions in a MTO operation.^

Branch and Price Solution Approach for Order Acceptance and Capacity Planning in Make-to-Order Operations

The increasing emphasis on mass customization, shortened product lifecycles, synchronized supply chains, when coupled with advances in information system, is driving most firms towards make-to-order (MTO) operations. Increasing global competition, lower profit margins, and higher customer expectations force the MTO firms to plan its capacity by managing the effective demand. The goal of this research was to maximize the operational profits of a make-to-order operation by selectively accepting incoming customer orders and simultaneously allocating capacity for them at the sales stage. For integrating the two decisions, a Mixed-Integer Linear Program (MILP) was formulated which can aid an operations manager in an MTO environment to select a set of potential customer orders such that all the selected orders are fulfilled by their deadline. The proposed model combines order acceptance/rejection decision with detailed scheduling. Experiments with the formulation indicate that for larger problem sizes, the computational time required to determine an optimal solution is prohibitive. This formulation inherits a block diagonal structure, and can be decomposed into one or more sub-problems (i.e. one sub-problem for each customer order) and a master problem by applying Dantzig-Wolfe’s decomposition principles. To efficiently solve the original MILP, an exact Branch-and-Price algorithm was successfully developed. Various approximation algorithms were developed to further improve the runtime. Experiments conducted unequivocally show the efficiency of these algorithms compared to a commercial optimization solver. The existing literature addresses the static order acceptance problem for a single machine environment having regular capacity with an objective to maximize profits and a penalty for tardiness. This dissertation has solved the order acceptance and capacity planning problem for a job shop environment with multiple resources. Both regular and overtime resources is considered. The Branch-and-Price algorithms developed in this dissertation are faster and can be incorporated in a decision support system which can be used on a daily basis to help make intelligent decisions in a MTO operation.

Cooperative routing for collision minimization in wireless sensor networks

Cooperative communication has gained much interest due to its ability to exploit the broadcasting nature of the wireless medium to mitigate multipath fading. There has been considerable amount of research on how cooperative transmission can improve the performance of the network by focusing on the physical layer issues. During the past few years, the researchers have started to take into consideration cooperative transmission in routing and there has been a growing interest in designing and evaluating cooperative routing protocols. Most of the existing cooperative routing algorithms are designed to reduce the energy consumption; however, packet collision minimization using cooperative routing has not been addressed yet. This dissertation presents an optimization framework to minimize collision probability using cooperative routing in wireless sensor networks. More specifically, we develop a mathematical model and formulate the problem as a large-scale Mixed Integer Non-Linear Programming problem. We also propose a solution based on the branch and bound algorithm augmented with reducing the search space (branch and bound space reduction). The proposed strategy builds up the optimal routes from each source to the sink node by providing the best set of hops in each route, the best set of relays, and the optimal power allocation for the cooperative transmission links. To reduce the computational complexity, we propose two near optimal cooperative routing algorithms. In the first near optimal algorithm, we solve the problem by decoupling the optimal power allocation scheme from optimal route selection. Therefore, the problem is formulated by an Integer Non-Linear Programming, which is solved using a branch and bound space reduced method. In the second near optimal algorithm, the cooperative routing problem is solved by decoupling the transmission power and the relay node se- lection from the route selection. After solving the routing problems, the power allocation is applied in the selected route. Simulation results show the algorithms can significantly reduce the collision probability compared with existing cooperative routing schemes.

How effective are heuristic solutions for electricity planning in developing countries

Acknowledgement The first author would like to acknowledge the University of Aberdeen and the Henderson Economics Research Fund for funding his PhD studies in the period 2011-2014 which formed the basis for the research presented in this paper. The first author would also like to acknowledge the Macaulay Development Trust which funds his postdoctoral fellowship with The James Hutton Institute, Aberdeen, Scotland. The authors thank two anonymous referees for valuable comments and suggestions on earlier versions of this paper. All usual caveats apply