In silico constraint-based strain optimization methods: the quest for optimal cell factories

Shifting from chemical to biotechnological processes is one of the cornerstones of 21st century industry. The production of a great range of chemicals via biotechnological means is a key challenge on the way toward a bio-based economy. However, this shift is occurring at a pace slower than initially expected. The development of efficient cell factories that allow for competitive production yields is of paramount importance for this leap to happen. Constraint-based models of metabolism, together with in silico strain design algorithms, promise to reveal insights into the best genetic design strategies, a step further toward achieving that goal. In this work, a thorough analysis of the main in silico constraint-based strain design strategies and algorithms is presented, their application in real-world case studies is analyzed, and a path for the future is discussed.

Kinematic constraint equations

This chapter presents a general methodology for the formulation of the kinematic constraint equations at position, velocity and acceleration levels. Also a brief characterization of the different type of constraints is offered, namely the holonomic and nonholonomic constraints. The kinematic constraints described here are formulated using generalized coordinates. The chapter ends with a general approach to deal with the kinematic analysis of multibody systems.

Algorithms and tools for in silico design of cell factories

PhD thesis in Bioengineering

Generating timed trajectories foran autonomous robot

Tese de Doutoramento Programa Doutoral em Engenharia Electrónica e Computadores

Otimização com restrições de complementaridade: algoritmos e aplicações

Tese de Doutoramento em Engenharia Industrial e de Sistemas (PDEIS)

Project management under uncertainty: a study on solution methods

Project Management involves onetime endeavors that demand for getting it right the first time. On the other hand, project scheduling, being one of the most modeled project management process stages, still faces a wide gap from theory to practice. Demanding computational models and their consequent call for simplification, divert the implementation of such models in project management tools from the actual day to day project management process. Special focus is being made to the robustness of the generated project schedules facing the omnipresence of uncertainty. An "easy" way out is to add, more or less cleverly calculated, time buffers that always result in project duration increase and correspondingly, in cost. A better approach to deal with uncertainty seems to be to explore slack that might be present in a given project schedule, a fortiori when a non-optimal schedule is used. The combination of such approach to recent advances in modeling resource allocation and scheduling techniques to cope with the increasing flexibility in resources, as can be expressed in "Flexible Resource Constraint Project Scheduling Problem" (FRCPSP) formulations, should be a promising line of research to generate more adequate project management tools. In reality, this approach has been frequently used, by project managers in an ad-hoc way.

Estudo e conceção de um sistema de encaixe rápido e simples para próteses de membros inferiores

Dissertação de mestrado integrado em Engenharia Biomédica

Modelação de governo electrónico para países emergentes: O caso de São Tomé e Príncipe

Tese de Doutoramento em Tecnologias e Sistemas de Informação

O ensino da flauta de bisel em grupo como inovação pedagógica: Uma investigação-ação no 2.º Ciclo do Ensino Básico

Tese de Doutoramento em Estudos da Criança (Especialidade em Educação Musical)

Algorithms and computational tools for metabolic flux analysis

PhD thesis in Biomedical Engineering

Modelling and verifying smell-free architectures with the Archery language

Architectural (bad) smells are design decisions found in software architectures that degrade the ability of systems to evolve. This paper presents an approach to verify that a software architecture is smellfree using the Archery architectural description language. The language provides a core for modelling software architectures and an extension for specifying constraints. The approach consists in precisely specifying architectural smells as constraints, and then verifying that software architectures do not satisfy any of them. The constraint language is based on a propositional modal logic with recursion that includes: a converse operator for relations among architectural concepts, graded modalities for describing the cardinality in such relations, and nominals referencing architectural elements. Four architectural smells illustrate the approach.

Basic constraints between two vectors

This chapter deals with the characterization of the basic constraints between two vectors. This issue plays a crucial role in the formulation of constraint equations for mechanical joints. In particular, relations between two parallel and two perpendicular vectors are derived. Moreover, formulation for a vector that connects two generic points is presented. The material described here is developed under the framework of multibody systems formulation for spatial systems.

Kinematic joints constraints

"Series title: Springerbriefs in applied sciences and technology, ISSN 2191-530X"

Equations of motion for constrained systems

"Series title: Springerbriefs in applied sciences and technology, ISSN 2191-530X"

A critical evaluation of methods for the reconstruction of tissue-specific models

Under the framework of constraint based modeling, genome-scale metabolic models (GSMMs) have been used for several tasks, such as metabolic engineering and phenotype prediction. More recently, their application in health related research has spanned drug discovery, biomarker identification and host-pathogen interactions, targeting diseases such as cancer, Alzheimer, obesity or diabetes. In the last years, the development of novel techniques for genome sequencing and other high-throughput methods, together with advances in Bioinformatics, allowed the reconstruction of GSMMs for human cells. Considering the diversity of cell types and tissues present in the human body, it is imperative to develop tissue-specific metabolic models. Methods to automatically generate these models, based on generic human metabolic models and a plethora of omics data, have been proposed. However, their results have not yet been adequately and critically evaluated and compared. This work presents a survey of the most important tissue or cell type specific metabolic model reconstruction methods, which use literature, transcriptomics, proteomics and metabolomics data, together with a global template model. As a case study, we analyzed the consistency between several omics data sources and reconstructed distinct metabolic models of hepatocytes using different methods and data sources as inputs. The results show that omics data sources have a poor overlapping and, in some cases, are even contradictory. Additionally, the hepatocyte metabolic models generated are in many cases not able to perform metabolic functions known to be present in the liver tissue. We conclude that reliable methods for a priori omics data integration are required to support the reconstruction of complex models of human cells.