Computational tools for strain optimization by tuning the optimal level of gene expression

In this work, a plug-in for the OptFlux Metabolic Engineering platform is presented, implementing methods that allow the identification of sets of genes to over/under express, relatively to their wild type levels. The optimization methods used are Simulated Annealing and Evolutionary Algorithms, working with a novel representation and operators. This overcomes the limitations of previous approaches based solely on gene knockouts, bringing new avenues for Biotechnology, fostering the discovery of genetic manipulations able to increase the production of certain compounds using a host microbe. The plug-in is made freely available together with appropriate documentation.Support of FCT and Programa COMPETE (ref. PTDC/EIA-EIA/ 115176/2009)

Who is Tracking Me on the Web?

Lately, online privacy is an issue that has been gaining the focus of the media because more and more companies have adopted business models which offer its customers free services and increasing its value by manipulating and possibly selling the information acquired by gathering the data from its users on the web. These methods are diverse and have benefited from the technology advancements in the internet browsers and the evolution of technologies such as HTLM5 and JavaScript. This dissertation aims to gather and analyze the information regarding the tracking that takes place in the Portuguese online market, this will be supported by a detailed state of the art of the technologies and methods used in the gathering of user information. To identify the major players in web tracking the study will analyze the websites which Portuguese users frequently visit and evaluate their prevalence and the methods used to gather the information. With the goal of identifying those entities. With this research, the author pretends to inform the public of who are the main entities involve in the process of collecting personal information, its methods used and how to prevent it. A Paper based on a subset of 300 websites using the same framework and analysis tool of this research was published for the symposium INForum 2016, which took place in September of 2016.A privacidade na internet têm sido um tópico que nos últimos anos tem vindo a ganhar atenção dos média. Cada vez mais empresas adotam modelos de negócios que oferecem serviços gratuitos aos utilizadores, gerando valor por tratar e possivelmente vender informação adquirida pela recolha de dados da utilização dos websites. Os métodos de recolha são variados e tiram proveito dos avanços tecnológicos dos browsers e das tecnologias à sua volta, por exemplo HTLM5 e JavaScript. Esta dissertação pretende reunir e analisar a informação relativa as tecnologias usadas para a recolha informação no mercado online português, vai ser suportado por um detalhado estado da arte das tecnologias e métodos usados na recolha de informação dos utilizadores. Para identificar as principais entidades envolvidas na perda de privacidade dos utilizadores, este estudo vai analisar os websites que os portugueses mais frequentam e avaliar a prevalência dessas entidades e os métodos por esses usados. Com esta investigação pretende-se informar as pessoas de quem são as principais entidades envolvidas nos processos de recolha de informação pessoal, os métodos usados e como o prevenir. Um artigo baseado num subconjunto de 300 websites utilizando a mesma framework e mesma ferramenta de analise foi publicado para o simpósio INForum 2016 que se realizou em setembro de 2016

Johnson & Johnson position in the pharmaceutical industry competitive landscape

This work project “Johnson & Johnson Place in the Pharmaceutical IndustryCompetitive Landscape” analyses Johnson & Johnson business within the pharmaceutical industry. Given the demand for JNJ products and the growth in revenues brought with COVID-19 due to the Janssen vaccine sales, we estimate a sales growth of 11.4% compared to last year. We will analyze the COVID-19 pandemic current and possible future implications for the industry and the company and compare it with other pharmaceutical companies which are COVID-19 vaccine producers. We will also investigate JNJ most relevant mergers and acquisitions as well as to examine the pharmaceutical industry and the current and future evolution of microeconomic indicators both in the US and the rest of the world. Our valuation of Johnson & Johnson yields a price target of 197.57$ which results in a return of 16.03% and therefore a BUY recommendatio

Optimization approaches for the in silico discovery of optimal targets for gene over/underexpression

Metabolic engineering (ME) efforts have been recently boosted by the increase in the number of annotated genomes and by the development of several genome-scale metabolic models for microbes of interest in industrial biotechnology. Based on these efforts, strain optimization methods have been proposed to reach the best set of genetic changes to apply to selected host microbes, in order to create strains that are able to overproduce metabolites of industrial interest. Previous work in strain optimization has been mostly based in finding sets of gene (or reaction) deletions that lead to desired phenotypes in computational simulations. In this work, we focus on enlarging the set of possible genetic changes, considering gene over and underexpression. A gene is considered under (over) expressed if its expression value is constrained to be significantly lower (higher) than the one in the wild-type strain, used as a reference. A method is proposed to propagate relative gene expression values to flux constraints over related reactions, making use of the available transcriptional/ translational information. The algorithms chosen for the optimization tasks are metaheuristics such as eolutionary agorithm (EA) and smulated anealing (SA), based on previous successful work on gene knockout optimization. These methods were modified appropriately to accommodate the novel optimization tasks and were applied to study the optimization of succinic and lactic acid production using Escherichia coli as the host. The results are compared with previous ones obtained in gene knockout optimization, thus showing the usefulness of the approach. The methods proposed in this work were implemented in a novel plug-in for OptFlux, an open-source software framework for ME. Supplementary Material is available at www.liebertonline.com/cmb

O martírio contemporâneo à luz de Cl 1,24

A presente investigação teve como ponto de partida a análise ao versículo 24 da Carta aos Colossenses: «Agora, alegro-me nos sofrimentos que suporto por vós e completo na minha carne o que falta às tribulações de Cristo, pelo seu corpo que é a Igreja». Da mesma foi possível inferir que as traduções portuguesas não exprimem claramente o conteúdo do versículo, nem a exegese compreendeu, ao longo da história, o seu correto significado. Por isso, propomos a tradução: «Agora, alegro-me nos sofrimentos que suporto por vós e completo o que falta das tribulações de Cristo à minha carne pelo seu corpo, que é a Igreja». Assim sendo, a expressão «tribulações» não se refere apenas aos sofrimentos da Paixão, mas a toda a vida de Cristo. Da mesma forma, ao contrário do que postulam as teses exegéticas mais comuns, aquilo que o versículo afirma é a necessidade que cada cristão tem de se configurar mais a Cristo – e não de completar os sofrimentos ou Paixão de Cristo, uma vez que esta é plena e está completa. Neste sentido, podemos alargar a compreensão do termo mártir – aquele que testemunha Cristo – àqueles o que O imitam, o que abrange expressões como caridade, oração e morte. Assim, todo aquele que na sua vida imita Cristo configura-se a Ele, ou seja, completa em si mesmo o que lhe falta das tribulações de Cristo e testemunha-O igualmente. Este testemunho pode ser vislumbrado nos milhares de cristãos que ao longo da história, em especial nos séculos XX e XXI, foram perseguidos por causa da sua fé.This present research has had as its starting point the analysis of Colossians 1:24: «Now, I rejoice in what I am suffering for you, and I fill up in my flesh what is still lacking in regard to Christ’s afflictions, for the sake of his body, which is the Church». This has enabled us to infer that neither the Portuguese translations of the afore-mentioned text express the clear content of the verse, nor have the exegetes understood, throughout history, its full meaning. Hence, we propose the following translation: «Now I rejoice in the sufferings I withstand for you and I complete what the afflictions of Christ are lacking to my flesh through its body which is the Church». Therefore, the term «afflictions» does not refer exclusively to the sufferings of the Passion, but comprises the whole life of Christ. Again, contrary to most exegetes’ theses, the verse basically expresses the need every christian has of further configurating himself with Christ – and not the one of completing the sufferings or Passion of Christ, since this process is obviously fully completed. Subsequently, we can expand the understanding of the term martyr – every one who testifies Christ – to those who imitate Thee, a conduct which encompasses expressions such as charity, prayer and death. Hence, every one who imitates Christ throughout life configurates himself to Thee, e.g., to complete in oneself what one is lacking of the afflictions of Christ, in addition to testifying Thee. Such testimonies can be found in the lives of thousands of christians that, in the course of history, particularly in the 20th and the 21st centuries, have been persecuted for their faith

A software platform for evolutionary computation with pluggable parallelism and quality assurance

This paper proposes the Java Evolutionary Computation Library (JECoLi), an adaptable, flexible, extensible and reliable software framework implementing metaheuristic optimization algorithms, using the Java programming language. JECoLi aims to offer a solution suited for the integration of Evolutionary Computation (EC)-based approaches in larger applications, and for the rapid and efficient benchmarking of EC algorithms in specific problems. Its main contributions are (i) the implementation of pluggable parallelization modules, independent from the EC algorithms, allowing the programs to adapt to the available hardware resources in a transparent way, without changing the base code; (ii) a flexible platform for software quality assurance that allows creating tests for the implemented features and for user-defined extensions. The library is freely available as an open-source project.Fundação para a Ciência e a Tecnologia (FCT) - PTDC/EIA-EIA/115176/2009, Programa COMPET

Eucalyptus citriodora and Azadirachta indica oil activity in the control of Colletotrichum acutatum, in strawberry crop

A flor-preta é uma das doenças mais importantes do morangueiro e a busca por alternativas de controle tem sido uma constante, principalmente em áreas de cultivo orgânico. Assim, objetivou-se avaliar a eficiência, in vitro e in vivo, dos óleos de Eucalyptus citriodora e Azadirachta indica no controle de Colletotrichum acutatum em morangueiro. No experimento in vitro determinou-se a inibição do crescimento micelial quando o fungo foi submetido aos extratos nas concentrações de 0; 0,25; 0,5; 1,0 e 1,5%. No campo, avaliou-se o controle da doença com a aplicação dos óleos nas concentrações de 0, 0,5 e 1,0%, pulverizados em intervalos de 7, 15 e 30 dias, em plantas inoculadas com suspensão de 10(6) conídios/mL. As avaliações foram realizadas semanalmente, observando-se a ocorrência e tamanho de lesões no pedúnculo e nos frutos, abortamento floral, produtividade, e ocorrência natural da doença. In vitro todos os tratamentos apresentaram redução significativa do crescimento micelial do fungo quando comparados ao controle. No campo, apenas o óleo de nim apresentou efeito significativo, reduzindo o abortamento floral e a ocorrência de frutos doentes advindos de flores inoculadas. Porém, maior ocorrência natural de doença foi observada quando a dosagem de 1,0% foi aplicada semanalmente.Anthracnose is one of the most important diseases in strawberry crop, and the search for control alternatives has been frequent, especially in organic cultivation areas. Thus, the present study aimed to evaluate the in vitro and in vivo efficiency of Eucaliptus citriodora and Azadirachta indica oil on the control of Colletotrichum acutatum in strawberry. In the in vitro experiment, mycelial growth inhibition was determined when the fungus was subjected to extracts at the following concentrations: 0; 0.25; 0.5; 1.0; and 1.5%. In the field, the disease control was evaluated through oil spraying at 0, 0.5 and 1.0% concentrations at intervals of seven, fifteen and thirty days, in plants inoculated with 10(6) conidia/mL suspension. Evaluations were weekly performed, and parameters such as occurrences and size of lesions in the peduncle and in the fruits, flower abortion, productivity, and natural disease occurrences were observed. In vitro, all treatments showed significant reduction in the mycelial growth relative to control. In the field, only neem oil had a significant effect decreasing flower abortion and the occurrences of sick fruits originated from inoculated flowers. However, natural disease occurrence was higher when 1.0% was weekly sprayed

The cyclin D1 carboxyl regulatory domain controls the division and differentiation of hematopoietic cells

International audienceAbstractBackgroundThe family of D cyclins has a fundamental role in cell cycle progression, but its members (D1, D2, D3) are believed to have redundant functions. However, there is some evidence that contradicts the notion of mutual redundancy and therefore this concept is still a matter of debate.ResultsOur data show that the cyclin D1 is indispensable for normal hematopoiesis. Indeed, in the absence of D1, either in genetic deficient mice, or after acute ablation by RNA interference, cyclins D2 and D3 are also not expressed preventing hematopoietic cell division and differentiation at its earliest stage. This role does not depend on the cyclin box, but on the carboxyl regulatory domain of D1 coded by exons 4–5, since hematopoietic differentiation is also blocked by the conditional ablation of this region.ConclusionThese results demonstrate that not all functions of individual D cyclins are redundant and highlight a master role of cyclin D1 in hematopoiesis