Computational methods for prediction of T-cell epitopes - a framework for modelling, testing, and applications

Computational models complement laboratory experimentation for efficient identification of MHC-binding peptides and T-cell epitopes. Methods for prediction of MHC-binding peptides include binding motifs, quantitative matrices, artificial neural networks, hidden Markov models, and molecular modelling. Models derived by these methods have been successfully used for prediction of T-cell epitopes in cancer, autoimmunity, infectious disease, and allergy. For maximum benefit, the use of computer models must be treated as experiments analogous to standard laboratory procedures and performed according to strict standards. This requires careful selection of data for model building, and adequate testing and validation. A range of web-based databases and MHC-binding prediction programs are available. Although some available prediction programs for particular MHC alleles have reasonable accuracy, there is no guarantee that all models produce good quality predictions. In this article, we present and discuss a framework for modelling, testing, and applications of computational methods used in predictions of T-cell epitopes. (C) 2004 Elsevier Inc. All rights reserved.

Evaluation of computational methods for the reconstruction of HLA haplotypes

Human leukocyte antigen (HLA) haplotypes are frequently evaluated for population history inferences and association studies. However, the available typing techniques for the main HLA loci usually do not allow the determination of the allele phase and the constitution of a haplotype, which may be obtained by a very time-consuming and expensive family-based segregation study. Without the family-based study, computational inference by probabilistic models is necessary to obtain haplotypes. Several authors have used the expectation-maximization (EM) algorithm to determine HLA haplotypes, but high levels of erroneous inferences are expected because of the genetic distance among the main HLA loci and the presence of several recombination hotspots. In order to evaluate the efficiency of computational inference methods, 763 unrelated individuals stratified into three different datasets had their haplotypes manually defined in a family-based study of HLA-A, -B, -DRB1 and -DQB1 segregation, and these haplotypes were compared with the data obtained by the following three methods: the Expectation-Maximization (EM) and Excoffier-Laval-Balding (ELB) algorithms using the arlequin 3.11 software, and the PHASE method. When comparing the methods, we observed that all algorithms showed a poor performance for haplotype reconstruction with distant loci, estimating incorrect haplotypes for 38%-57% of the samples considering all algorithms and datasets. We suggest that computational haplotype inferences involving low-resolution HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1 haplotypes should be considered with caution.

Xmds: eXtensible multi-dimensional simulator

A software package that efficiently solves a comprehensive range of problems based on coupled complex nonlinear stochastic ODEs and PDEs is outlined. Its input and output syntax is formulated as a subset of XML, thus making a step towards a standard for specifying numerical simulations.

A multi-purpose rainfall simulator for field infiltration and erosion studies

This paper describes a rainfall simulator developed for field and laboratory studies that gives great flexibility in plot size covered, that is highly portable and able to be used on steep slopes, and that is economical in its water use. The simulator uses Veejet 80100 nozzles mounted on a manifold, with the nozzles controlled to sweep to and from across a plot width of 1.5 m. Effective rainfall intensity is controlled by the frequency with which the nozzles sweep. Spatial uniformity of rainfall on the plots is high, with coefficients of variation (CV) on the body of the plot being 8-10%. Use of the simulator for erosion and infiltration measurements is discussed.

Branching processes and computational collapse of discretized unimodal mappings

In computer simulations of smooth dynamical systems, the original phase space is replaced by machine arithmetic, which is a finite set. The resulting spatially discretized dynamical systems do not inherit all functional properties of the original systems, such as surjectivity and existence of absolutely continuous invariant measures. This can lead to computational collapse to fixed points or short cycles. The paper studies loss of such properties in spatial discretizations of dynamical systems induced by unimodal mappings of the unit interval. The problem reduces to studying set-valued negative semitrajectories of the discretized system. As the grid is refined, the asymptotic behavior of the cardinality structure of the semitrajectories follows probabilistic laws corresponding to a branching process. The transition probabilities of this process are explicitly calculated. These results are illustrated by the example of the discretized logistic mapping.

Computational differentiation of N-terminal signal peptides and transmembrane helices

Signal peptides and transmembrane helices both contain a stretch of hydrophobic amino acids. This common feature makes it difficult for signal peptide and transmembrane helix predictors to correctly assign identity to stretches of hydrophobic residues near the N-terminal methionine of a protein sequence. The inability to reliably distinguish between N-terminal transmembrane helix and signal peptide is an error with serious consequences for the prediction of protein secretory status or transmembrane topology. In this study, we report a new method for differentiating protein N-terminal signal peptides and transmembrane helices. Based on the sequence features extracted from hydrophobic regions (amino acid frequency, hydrophobicity, and the start position), we set up discriminant functions and examined them on non-redundant datasets with jackknife tests. This method can incorporate other signal peptide prediction methods and achieve higher prediction accuracy. For Gram-negative bacterial proteins, 95.7% of N-terminal signal peptides and transmembrane helices can be correctly predicted (coefficient 0.90). Given a sensitivity of 90%, transmembrane helices can be identified from signal peptides with a precision of 99% (coefficient 0.92). For eukaryotic proteins, 94.2% of N-terminal signal peptides and transmembrane helices can be correctly predicted with coefficient 0.83. Given a sensitivity of 90%, transmembrane helices can be identified from signal peptides with a precision of 87% (coefficient 0.85). The method can be used to complement current transmembrane protein prediction and signal peptide prediction methods to improve their prediction accuracies. (C) 2003 Elsevier Inc. All rights reserved.

Contratos bilaterais em mercados multi-agente de energia eléctrica: protocolo de ofertas alternadas

A liberalização do sector eléctrico, e a consequente criação de mercados de energia eléctrica regulados e liberalizados, mudou a forma de comercialização da electricidade. Em particular, permitiu a entrada de empresas nas actividades de produção e comercialização, aumentando a competitividade e assegurando a liberdade de escolha dos consumidores, para decidir o fornecedor de electricidade que pretenderem. A competitividade no sector eléctrico aumentou a necessidade das empresas que o integram a proporem preços mais aliciantes (do que os preços propostos pelos concorrentes), e contribuiu para o desenvolvimento de estratégias de mercado que atraiam mais clientes e aumentem a eficiência energética e económica. A comercialização de electricidade pode ser realizada em mercados organizados ou através de contratação directa entre comercializadores e consumidores, utilizando os contratos bilaterais físicos. Estes contratos permitem a negociação dos preços de electricidade entre os comercializadores e os consumidores. Actualmente, existem várias ferramentas computacionais para fazer a simulação de mercados de energia eléctrica. Os simuladores existentes permitem simulações de transacções em bolsas de energia, negociação de preços através de contratos bilaterais, e análises técnicas a redes de energia. No entanto, devido à complexidade dos sistemas eléctricos, esses simuladores apresentam algumas limitações. Esta dissertação apresenta um simulador de contratos bilaterais em mercados de energia eléctrica, sendo dando ênfase a um protocolo de ofertas alternadas, desenvolvido através da tecnologia multi-agente. Em termos sucintos, um protocolo de ofertas alternadas é um protocolo de interacção que define as regras da negociação entre um agente vendedor (por exemplo um retalhista) e um agente comprador (por exemplo um consumidor final). Aplicou-se o simulador na resolução de um caso prático, baseado em dados reais. Os resultados obtidos permitem concluir que o simulador, apesar de simplificado, pode ser uma ferramenta importante na ajuda à tomada de decisões inerentes à negociação de contratos bilaterais em mercados de electricidade.

Computational evaluation of hydraulic system behaviour with entrapped air under rapid pressurization

The pressurization of hydraulic systems containing entrapped air is considered a critical condition for the infrastructure's security due to transient pressure variations often occurred. The objective of the present study is the computational evaluation of trends observed in variation of maximum surge pressure resulting from rapid pressurizations. The comparison of the results with those obtained in previous studies is also undertaken. A brief state of art in this domain is presented. This research work is applied to an experimental system having entrapped air in the top of a vertical pipe section. The evaluation is developed through the elastic model based on the method of characteristics, considering a moving liquid boundary, with the results being compared with those achieved with the rigid liquid column model.

Computational evaluation of hydraulic system behaviour with entrapped air under rapid pressurization

The pressurization of hydraulic systems containing entrapped air is considered a critical condition for the infrastructure's security due to transient pressure variations often occurred. The objective of the present study is the computational evaluation of trends observed in variation of maximum surge pressure resulting from rapid pressurizations. The comparison of the results with those obtained in previous studies is also undertaken. A brief state of art in this domain is presented. This research work is applied to an experimental system having entrapped air in the top of a vertical pipe section. The evaluation is developed through the elastic model based on the method of characteristics, considering a moving liquid boundary, with the results being compared with those achieved with the rigid liquid column model.

A congestion management and transmission price simulator for competitive electricity markets

In a liberalized electricity market, the Transmission System Operator (TSO) plays a crucial role in power system operation. Among many other tasks, TSO detects congestion situations and allocates the payments of electricity transmission. This paper presents a software tool for congestion management and transmission price determination in electricity markets. The congestion management is based on a reformulated Optimal Power Flow (OPF), whose main goal is to obtain a feasible solution for the re-dispatch minimizing the changes in the dispatch proposed by the market operator. The transmission price computation considers the physical impact caused by the market agents in the transmission network. The final tariff includes existing system costs and also costs due to the initial congestion situation and losses costs. The paper includes a case study for the IEEE 30 bus power system.

Balancing market integration in MASCEM electricity market simulator

With the restructuring of the energy sector in industrialized countries there is an increased complexity in market players’ interactions along with emerging problems and new issues to be addressed. Decision support tools that facilitate the study and understanding of these markets are extremely useful to provide players with competitive advantage. In this context arises MASCEM, a multi-agent simulator for competitive electricity markets. It is essential to reinforce MASCEM with the ability to recreate electricity markets reality in the fullest possible extent, making it able to simulate as many types of markets models and players as possible. This paper presents the development of the Balancing Market in MASCEM. A key module to the study of competitive electricity markets, as it has well defined and distinct characteristics previously implemented.

Electric vehicles in urban areas: test cases using a scenario simulator

Electric vehicles introduction will affect cities environment and urban mobility policies. Network system operators will have to consider the electric vehicles in planning and operation activities due to electric vehicles’ dependency on the electricity grid. The present paper presents test cases using an Electric Vehicle Scenario Simulator (EVeSSi) being developed by the authors. The test cases include two scenarios considering a 33 bus network with up to 2000 electric vehicles in the urban area. The scenarios consider a penetration of 10% of electric vehicles (200 of 2000), 30% (600) and 100% (2000). The first scenario will evaluate network impacts and the second scenario will evaluate CO2 emissions and fuel consumption.

Electric vehicle scenario simulator tool for smart grid operators

This paper presents a simulator for electric vehicles in the context of smart grids and distribution networks. It aims to support network operator´s planning and operations but can be used by other entities for related studies. The paper describes the parameters supported by the current version of the Electric Vehicle Scenario Simulator (EVeSSi) tool and its current algorithm. EVeSSi enables the definition of electric vehicles scenarios on distribution networks using a built-in movement engine. The scenarios created with EVeSSi can be used by external tools (e.g., power flow) for specific analysis, for instance grid impacts. Two scenarios are briefly presented for illustration of the simulator capabilities.

Transmission price simulator in a liberalized electricity market

This paper presents a software tool (SIM_CMTP) that solves congestion situations and evaluates the taxes to be paid to the transmission system by market agents. SIM_CMTP provides users with a set of alternative methods for cost allocation and enables the definition of specific rules, according to each market and/or situation needs. With these characteristics, SIM_CMTP can be used as an operation aid for Transmission System Operator (TSO) or Independent System Operator (ISO). Due to its openness, it can also be used as a decision-making support tool for evaluating different options of market rules in competitive market environment, guarantying the economic sustainability of the transmission system.