Genetic variations of EBV-LMP1 from nasopharyngeal carcinoma biopsies: potential loss of T cell epitopes

To find Epstein-Barr virus (EBV) strains with genetic variations of EBV latent membrane protein 1 (EBV-LMP1) from nasopharyngeal carcinoma (NPC), the full-length DNA of LMP1 genes from 21 NPC biopsies obtained in Hunan province in southern China was amplified and sequenced. Our sequences were compared to those previously reported by the Clustal V method. Results showed that all 21 sequences displayed two amino acid changes most frequently in LMP1 of CD4+ T cell epitopes at codons 144 (F®I, 21/21) and 212 (G®S, 19/21) or (G®N, 2/21). We also show that type A EBV strain is prevalent in the cases of NPC from Hunan province with a 30-bp 18/21 deletion, and we highlight that this deletion resulted in loss of one of the CD4+ T cell-restricted epitopes. The other 3 sequences without this deletion all had a change at codon 344 (G®D). Furthermore, in the major epitope sequence of CD8+ T cells restricted by HLA-A2, all 21 sequences showed changes at codons 126 (L®F) and 129 (M®I). Our study discovered that one of the 21 sequence variations harbored a new change at codon 131 (W®C), and 5/21 specimens showed another novel change at codon 115 (G®A) in the major epitope sequence of CD8+ T cells restricted by HLA-A2. Our study suggests that these sequence variations of NPC-derived LMP1 may lead to a potential escape from host cell immune recognition, protecting latent EBV infection and causing an increase in tumorigenicity.

Using genetic algorithms for the single allocation hub location problem

Hub location problem is an NP-hard problem that frequently arises in the design of transportation and distribution systems, postal delivery networks, and airline passenger flow. This work focuses on the Single Allocation Hub Location Problem (SAHLP). Genetic Algorithms (GAs) for the capacitated and uncapacitated variants of the SAHLP based on new chromosome representations and crossover operators are explored. The GAs is tested on two well-known sets of real-world problems with up to 200 nodes. The obtained results are very promising. For most of the test problems the GA obtains improved or best-known solutions and the computational time remains low. The proposed GAs can easily be extended to other variants of location problems arising in network design planning in transportation systems.

Genetic programming for the RoboCup Rescue Simulation System

The Robocup Rescue Simulation System (RCRSS) is a dynamic system of multi-agent interaction, simulating a large-scale urban disaster scenario. Teams of rescue agents are charged with the tasks of minimizing civilian casualties and infrastructure damage while competing against limitations on time, communication, and awareness. This thesis provides the first known attempt of applying Genetic Programming (GP) to the development of behaviours necessary to perform well in the RCRSS. Specifically, this thesis studies the suitability of GP to evolve the operational behaviours required of each type of rescue agent in the RCRSS. The system developed is evaluated in terms of the consistency with which expected solutions are the target of convergence as well as by comparison to previous competition results. The results indicate that GP is capable of converging to some forms of expected behaviour, but that additional evolution in strategizing behaviours must be performed in order to become competitive. An enhancement to the standard GP algorithm is proposed which is shown to simplify the initial search space allowing evolution to occur much quicker. In addition, two forms of population are employed and compared in terms of their apparent effects on the evolution of control structures for intelligent rescue agents. The first is a single population in which each individual is comprised of three distinct trees for the respective control of three types of agents, the second is a set of three co-evolving subpopulations one for each type of agent. Multiple populations of cooperating individuals appear to achieve higher proficiencies in training, but testing on unseen instances raises the issue of overfitting.

Genetic Programming for Non-Photorealistic Rendering

This thesis focuses on developing an evolutionary art system using genetic programming. The main goal is to produce new forms of evolutionary art that filter existing images into new non-photorealistic (NPR) styles, by obtaining images that look like traditional media such as watercolor or pencil, as well as brand new effects. The approach permits GP to generate creative forms of NPR results. The GP language is extended with different techniques and methods inspired from NPR research such as colour mixing expressions, image processing filters and painting algorithm. Colour mixing is a major new contribution, as it enables many familiar and innovative NPR effects to arise. Another major innovation is that many GP functions process the canvas (rendered image), while is dynamically changing. Automatic fitness scoring uses aesthetic evaluation models and statistical analysis, and multi-objective fitness evaluation is used. Results showed a variety of NPR effects, as well as new, creative possibilities.

Feature Selection and Classification Using Age Layered Population Structure Genetic Programming

The curse of dimensionality is a major problem in the fields of machine learning, data mining and knowledge discovery. Exhaustive search for the most optimal subset of relevant features from a high dimensional dataset is NP hard. Sub–optimal population based stochastic algorithms such as GP and GA are good choices for searching through large search spaces, and are usually more feasible than exhaustive and deterministic search algorithms. On the other hand, population based stochastic algorithms often suffer from premature convergence on mediocre sub–optimal solutions. The Age Layered Population Structure (ALPS) is a novel metaheuristic for overcoming the problem of premature convergence in evolutionary algorithms, and for improving search in the fitness landscape. The ALPS paradigm uses an age–measure to control breeding and competition between individuals in the population. This thesis uses a modification of the ALPS GP strategy called Feature Selection ALPS (FSALPS) for feature subset selection and classification of varied supervised learning tasks. FSALPS uses a novel frequency count system to rank features in the GP population based on evolved feature frequencies. The ranked features are translated into probabilities, which are used to control evolutionary processes such as terminal–symbol selection for the construction of GP trees/sub-trees. The FSALPS metaheuristic continuously refines the feature subset selection process whiles simultaneously evolving efficient classifiers through a non–converging evolutionary process that favors selection of features with high discrimination of class labels. We investigated and compared the performance of canonical GP, ALPS and FSALPS on high–dimensional benchmark classification datasets, including a hyperspectral image. Using Tukey’s HSD ANOVA test at a 95% confidence interval, ALPS and FSALPS dominated canonical GP in evolving smaller but efficient trees with less bloat expressions. FSALPS significantly outperformed canonical GP and ALPS and some reported feature selection strategies in related literature on dimensionality reduction.

Feature Selection and Classification Using Age Layered Population Structure Genetic Programming

The curse of dimensionality is a major problem in the fields of machine learning, data mining and knowledge discovery. Exhaustive search for the most optimal subset of relevant features from a high dimensional dataset is NP hard. Sub–optimal population based stochastic algorithms such as GP and GA are good choices for searching through large search spaces, and are usually more feasible than exhaustive and determinis- tic search algorithms. On the other hand, population based stochastic algorithms often suffer from premature convergence on mediocre sub–optimal solutions. The Age Layered Population Structure (ALPS) is a novel meta–heuristic for overcoming the problem of premature convergence in evolutionary algorithms, and for improving search in the fitness landscape. The ALPS paradigm uses an age–measure to control breeding and competition between individuals in the population. This thesis uses a modification of the ALPS GP strategy called Feature Selection ALPS (FSALPS) for feature subset selection and classification of varied supervised learning tasks. FSALPS uses a novel frequency count system to rank features in the GP population based on evolved feature frequencies. The ranked features are translated into probabilities, which are used to control evolutionary processes such as terminal–symbol selection for the construction of GP trees/sub-trees. The FSALPS meta–heuristic continuously refines the feature subset selection process whiles simultaneously evolving efficient classifiers through a non–converging evolutionary process that favors selection of features with high discrimination of class labels. We investigated and compared the performance of canonical GP, ALPS and FSALPS on high–dimensional benchmark classification datasets, including a hyperspectral image. Using Tukey’s HSD ANOVA test at a 95% confidence interval, ALPS and FSALPS dominated canonical GP in evolving smaller but efficient trees with less bloat expressions. FSALPS significantly outperformed canonical GP and ALPS and some reported feature selection strategies in related literature on dimensionality reduction.

Genetic Programming meets Model-Driven Development

Genetic programming is known to provide good solutions for many problems like the evolution of network protocols and distributed algorithms. In such cases it is most likely a hardwired module of a design framework that assists the engineer to optimize specific aspects of the system to be developed. It provides its results in a fixed format through an internal interface. In this paper we show how the utility of genetic programming can be increased remarkably by isolating it as a component and integrating it into the model-driven software development process. Our genetic programming framework produces XMI-encoded UML models that can easily be loaded into widely available modeling tools which in turn posses code generation as well as additional analysis and test capabilities. We use the evolution of a distributed election algorithm as an example to illustrate how genetic programming can be combined with model-driven development. This example clearly illustrates the advantages of our approach – the generation of source code in different programming languages.

Evolving Distributed Algorithms with Genetic Programming

Distributed systems are one of the most vital components of the economy. The most prominent example is probably the internet, a constituent element of our knowledge society. During the recent years, the number of novel network types has steadily increased. Amongst others, sensor networks, distributed systems composed of tiny computational devices with scarce resources, have emerged. The further development and heterogeneous connection of such systems imposes new requirements on the software development process. Mobile and wireless networks, for instance, have to organize themselves autonomously and must be able to react to changes in the environment and to failing nodes alike. Researching new approaches for the design of distributed algorithms may lead to methods with which these requirements can be met efficiently. In this thesis, one such method is developed, tested, and discussed in respect of its practical utility. Our new design approach for distributed algorithms is based on Genetic Programming, a member of the family of evolutionary algorithms. Evolutionary algorithms are metaheuristic optimization methods which copy principles from natural evolution. They use a population of solution candidates which they try to refine step by step in order to attain optimal values for predefined objective functions. The synthesis of an algorithm with our approach starts with an analysis step in which the wanted global behavior of the distributed system is specified. From this specification, objective functions are derived which steer a Genetic Programming process where the solution candidates are distributed programs. The objective functions rate how close these programs approximate the goal behavior in multiple randomized network simulations. The evolutionary process step by step selects the most promising solution candidates and modifies and combines them with mutation and crossover operators. This way, a description of the global behavior of a distributed system is translated automatically to programs which, if executed locally on the nodes of the system, exhibit this behavior. In our work, we test six different ways for representing distributed programs, comprising adaptations and extensions of well-known Genetic Programming methods (SGP, eSGP, and LGP), one bio-inspired approach (Fraglets), and two new program representations called Rule-based Genetic Programming (RBGP, eRBGP) designed by us. We breed programs in these representations for three well-known example problems in distributed systems: election algorithms, the distributed mutual exclusion at a critical section, and the distributed computation of the greatest common divisor of a set of numbers. Synthesizing distributed programs the evolutionary way does not necessarily lead to the envisaged results. In a detailed analysis, we discuss the problematic features which make this form of Genetic Programming particularly hard. The two Rule-based Genetic Programming approaches have been developed especially in order to mitigate these difficulties. In our experiments, at least one of them (eRBGP) turned out to be a very efficient approach and in most cases, was superior to the other representations.

Prevalencia de enfermedad celiaca en Latinoamérica: revisión sistemática de la literatura y meta-análisis

Introducción: La enfermedad celiaca (EC) es una enfermedad autoinmune (EA) intestinal desencadenada por la ingesta de gluten. Por la falta de información de la presencia de EC en Latinoamérica (LA), nosotros investigamos la prevalencia de la enfermedad en esta región utilizando una revisión sistemática de la literatura y un meta-análisis. Métodos y resultados: Este trabajo fue realizado en dos fases: La primera, fue un estudio de corte transversal de 300 individuos Colombianos. La segunda, fue una revisión sistemática y una meta-regresión siguiendo las guías PRSIMA. Nuestros resultados ponen de manifiesto una falta de anti-transglutaminasa tisular (tTG) e IgA anti-endomisio (EMA) en la población Colombiana. En la revisión sistemática, 72 artículos cumplían con los criterios de selección, la prevalencia estimada de EC en LA fue de 0,46% a 0,64%, mientras que la prevalencia en familiares de primer grado fue de 5,5 a 5,6%, y en los pacientes con diabetes mellitus tipo 1 fue de 4,6% a 8,7% Conclusión: Nuestro estudio muestra que la prevalencia de EC en pacientes sanos de LA es similar a la notificada en la población europea.

Generic systolic array for genetic algorithms

The authors present a systolic design for a simple GA mechanism which provides high throughput and unidirectional pipelining by exploiting the inherent parallelism in the genetic operators. The design computes in O(N+G) time steps using O(N2) cells where N is the population size and G is the chromosome length. The area of the device is independent of the chromosome length and so can be easily scaled by replicating the arrays or by employing fine-grain migration. The array is generic in the sense that it does not rely on the fitness function and can be used as an accelerator for any GA application using uniform crossover between pairs of chromosomes. The design can also be used in hybrid systems as an add-on to complement existing designs and methods for fitness function acceleration and island-style population management

Genetic analysis of complex demographic scenarios: Spatially expanding populations of the cane toad, Bufo marinus

Inferring the spatial expansion dynamics of invading species from molecular data is notoriously difficult due to the complexity of the processes involved. For these demographic scenarios, genetic data obtained from highly variable markers may be profitably combined with specific sampling schemes and information from other sources using a Bayesian approach. The geographic range of the introduced toad Bufo marinus is still expanding in eastern and northern Australia, in each case from isolates established around 1960. A large amount of demographic and historical information is available on both expansion areas. In each area, samples were collected along a transect representing populations of different ages and genotyped at 10 microsatellite loci. Five demographic models of expansion, differing in the dispersal pattern for migrants and founders and in the number of founders, were considered. Because the demographic history is complex, we used an approximate Bayesian method, based on a rejection-regression algorithm. to formally test the relative likelihoods of the five models of expansion and to infer demographic parameters. A stepwise migration-foundation model with founder events was statistically better supported than other four models in both expansion areas. Posterior distributions supported different dynamics of expansion in the studied areas. Populations in the eastern expansion area have a lower stable effective population size and have been founded by a smaller number of individuals than those in the northern expansion area. Once demographically stabilized, populations exchange a substantial number of effective migrants per generation in both expansion areas, and such exchanges are larger in northern than in eastern Australia. The effective number of migrants appears to be considerably lower than that of founders in both expansion areas. We found our inferences to be relatively robust to various assumptions on marker. demographic, and historical features. The method presented here is the only robust, model-based method available so far, which allows inferring complex population dynamics over a short time scale. It also provides the basis for investigating the interplay between population dynamics, drift, and selection in invasive species.

Synapsing variable length crossover: An algorithm for crossing and comparing variable length genomes

The Synapsing Variable Length Crossover (SVLC) algorithm provides a biologically inspired method for performing meaningful crossover between variable length genomes. In addition to providing a rationale for variable length crossover it also provides a genotypic similarity metric for variable length genomes enabling standard niche formation techniques to be used with variable length genomes. Unlike other variable length crossover techniques which consider genomes to be rigid inflexible arrays and where some or all of the crossover points are randomly selected, the SVLC algorithm considers genomes to be flexible and chooses non-random crossover points based on the common parental sequence similarity. The SVLC Algorithm recurrently "glues" or synapses homogenous genetic sub-sequences together. This is done in such a way that common parental sequences are automatically preserved in the offspring with only the genetic differences being exchanged or removed, independent of the length of such differences. In a variable length test problem the SVLC algorithm is shown to outperform current variable length crossover techniques. The SVLC algorithm is also shown to work in a more realistic robot neural network controller evolution application.

Genetic least squares for system identification

The recursive least-squares algorithm with a forgetting factor has been extensively applied and studied for the on-line parameter estimation of linear dynamic systems. This paper explores the use of genetic algorithms to improve the performance of the recursive least-squares algorithm in the parameter estimation of time-varying systems. Simulation results show that the hybrid recursive algorithm (GARLS), combining recursive least-squares with genetic algorithms, can achieve better results than the standard recursive least-squares algorithm using only a forgetting factor.

Application of the entropy technique and genetic algorithms to construction site layout planning of medium-size projects

Genetic algorithms (GAs) have been introduced into site layout planning as reported in a number of studies. In these studies, the objective functions were defined so as to employ the GAs in searching for the optimal site layout. However, few studies have been carried out to investigate the actual closeness of relationships between site facilities; it is these relationships that ultimately govern the site layout. This study has determined that the underlying factors of site layout planning for medium-size projects include work flow, personnel flow, safety and environment, and personal preferences. By finding the weightings on these factors and the corresponding closeness indices between each facility, a closeness relationship has been deduced. Two contemporary mathematical approaches - fuzzy logic theory and an entropy measure - were adopted in finding these results in order to minimize the uncertainty and vagueness of the collected data and improve the quality of the information. GAs were then applied to searching for the optimal site layout in a medium-size government project using the GeneHunter software. The objective function involved minimizing the total travel distance. An optimal layout was obtained within a short time. This reveals that the application of GA to site layout planning is highly promising and efficient.

Pharmacogenetics of Warfarin: Development of a Dosing Algorithm for Brazilian Patients

A dosing algorithm including genetic (VKORC1 and CYP2C9 genotypes) and nongenetic factors (age, weight, therapeutic indication, and cotreatment with amiodarone or simvastatin) explained 51% of the variance in stable weekly warfarin doses in 390 patients attending an anticoagulant clinic in a Brazilian public hospital. The VKORC1 3673G>A genotype was the most important predictor of warfarin dose, with a partial R(2) value of 23.9%. Replacing the VKORC1 3673G>A genotype with VKORC1 diplotype did not increase the algorithm`s predictive power. We suggest that three other single-nucleotide polymorphisms (SNPs) (5808T>G, 6853G>C, and 9041G>A) that are in strong linkage disequilibrium (LD) with 3673G>A would be equally good predictors of the warfarin dose requirement. The algorithm`s predictive power was similar across the self-identified ""race/color"" subsets. ""Race/color"" was not associated with stable warfarin dose in the multiple regression model, although the required warfarin dose was significantly lower (P = 0.006) in white (29 +/- 13 mg/week, n = 196) than in black patients (35 +/- 15 mg/week, n = 76).