Modeling and optimization of extracellular polysaccharides production by Enterobacter A47

Polysaccharides are gaining increasing attention as potential environmental friendly and sustainable building blocks in many fields of the (bio)chemical industry. The microbial production of polysaccharides is envisioned as a promising path, since higher biomass growth rates are possible and therefore higher productivities may be achieved compared to vegetable or animal polysaccharides sources. This Ph.D. thesis focuses on the modeling and optimization of a particular microbial polysaccharide, namely the production of extracellular polysaccharides (EPS) by the bacterial strain Enterobacter A47. Enterobacter A47 was found to be a metabolically versatile organism in terms of its adaptability to complex media, notably capable of achieving high growth rates in media containing glycerol byproduct from the biodiesel industry. However, the industrial implementation of this production process is still hampered due to a largely unoptimized process. Kinetic rates from the bioreactor operation are heavily dependent on operational parameters such as temperature, pH, stirring and aeration rate. The increase of culture broth viscosity is a common feature of this culture and has a major impact on the overall performance. This fact complicates the mathematical modeling of the process, limiting the possibility to understand, control and optimize productivity. In order to tackle this difficulty, data-driven mathematical methodologies such as Artificial Neural Networks can be employed to incorporate additional process data to complement the known mathematical description of the fermentation kinetics. In this Ph.D. thesis, we have adopted such an hybrid modeling framework that enabled the incorporation of temperature, pH and viscosity effects on the fermentation kinetics in order to improve the dynamical modeling and optimization of the process. A model-based optimization method was implemented that enabled to design bioreactor optimal control strategies in the sense of EPS productivity maximization. It is also critical to understand EPS synthesis at the level of the bacterial metabolism, since the production of EPS is a tightly regulated process. Methods of pathway analysis provide a means to unravel the fundamental pathways and their controls in bioprocesses. In the present Ph.D. thesis, a novel methodology called Principal Elementary Mode Analysis (PEMA) was developed and implemented that enabled to identify which cellular fluxes are activated under different conditions of temperature and pH. It is shown that differences in these two parameters affect the chemical composition of EPS, hence they are critical for the regulation of the product synthesis. In future studies, the knowledge provided by PEMA could foster the development of metabolically meaningful control strategies that target the EPS sugar content and oder product quality parameters.

Design of New Materials for Passive Vibration Control

The aim of this contribution is to extend the techniques of composite materials design to non-linear material behaviour and apply it for design of new materials for passive vibration control. As a first step a computational tool allowing determination of macroscopic optimized one-dimensional isolator behaviour was developed. Voigt, Maxwell, standard and more complex material models can be implemented. Objective function considers minimization of the initial reaction and/or displacement peak as well as minimization of the steady-state amplitude of reaction and/or displacement. The complex stiffness approach is used to formulate the governing equations in an efficient way. Material stiffness parameters are assumed as non-linear functions of the displacement. The numerical solution is performed in the complex space. The steady-state solution in the complex space is obtained by an iterative process based on the shooting method which imposes the conditions of periodicity with respect to the known value of the period. Extension of the shooting method to the complex space is presented and verified. Non-linear behaviour of material parameters is then optimized by generic probabilistic meta-algorithm, simulated annealing. Dependence of the global optimum on several combinations of leading parameters of the simulated annealing procedure, like neighbourhood definition and annealing schedule, is also studied and analyzed. Procedure is programmed in MATLAB environment.

Implementation progress of mental health services in Rwanda: Bugesera district case

RESUMO: O Ministério da Saúde do Governo do Ruanda identifica a saúde mental como uma área de prioridade estratégica para a intervenção em resposta à alta carga dos transtornos mentais no Ruanda. Ao longo dos últimos 20 anos após o genocídio, o sector público reconstruiu sua Resposta Nacional de Saúde Mental com base no acesso equitativo aos cuidados, através do desenvolvimento de uma Política Nacional de Saúde Mental e novas estruturas de saúde mental. A política de Saúde Mental do Ruanda, revista em 2010, prima pela descentralização e integração dos serviços de saúde mental em todas as estruturas nacionais do sistema de saúde e ao nível da comunidade. O presente estudo de caso tem como objetivo avaliar a situação do sistema de saúde mental de um distrito típico de uma área rural no Ruanda, e sugerir melhorias, incluindo algumas estratégias para monitoras as mudanças. Os resultados do estudo permitirão ao Ruanda reforçar a sua capacidade para implementar o Plano Nacional de Saúde Mental ao nível dos distritos. O relatório também será útil para monitorar o progresso da implementação de serviços de saúde mental nos distritos, incluindo a prestação de serviços de base comunitária e a participação dos usuários, suas famílias e outros interessados na promoção, prevenção, assistência e reabilitação em saúde mental. Este estudo também procurou avaliar o progresso da implementação dos cuidados de saúde mental a nível descentralizado, com vista a compreender as implicações em termos de recursos desses processos. Foi realizada uma análise situacional num local do distrito, baseado em entrevistas com as principais partes interessadas responsáveis, usando o Instrumento de Avaliação de Sistemas de Saúde Mental da Organização Mundial da Saúde (WHO-AIMS). Os resultados sugerem que os recursos humanos para a saúde mental e serviços de base comunitária de saúde mental no distrito continuam a ser extremamente limitados. Os profissionais de saúde mental são adicionalmente limitados na sua capacidade para oferecer intervenções de emergência a pacientes psiquiátricos e garantir a continuidade do tratamento farmacológico a pacientes com condições crônicas. Para planejar efetivamente, de acordo com as necessidades da comunidade, sugerimos que o sistema de saúde mental deve envolver também os representantes das famílias e dos usuários no processo de planificação de modo a melhorar a sua contribuição no processo de implementação das atividades de saúde mental. Este estudo de caso do Distrito de Bugesera oferece a primeira análise de nível distrital dos serviços de saúde mental no Ruanda, e pode servir como uma mais-valia para a melhoria do sistema de saúde mental, incluindo a advocacia para a melhoria da qualidade dos cuidados de saúde mental a este nível, aumentando o financiamento para a implementação de serviços clínicos de saúde mental e os recursos humanos disponíveis para a prestação de cuidados de saúde mental, principalmente a nível dos cuidados primários.--------------------- ABSTRACT: To deal with the high burden of mental health disorders resulting from consequences of the 1994 genocide against Tutsis, the Rwanda Ministry of Health (MoH) considers mental health as a priority intervention. For the last 20 years, Ministry of Health focused on rebuilding a national and equity-oriented mental health program responding to the population needs in mental health. Mental health services are now decentralized and integrated in the national health system, from the community level up to the referral level. This study assessed the situation of mental health services in one rural district in Rwanda. It was aimed at assessing the progress of implementation of mental health care at the decentralized level, focusing on resource implications and processes. This study is based on interviews conducted with key stakeholders, using the World Health Organization's Assessment Instrument for Mental Health Systems (WHO-AIMS). Findings show that human resources for mental health care and community-based mental health services of the assessed district remain extremely limited. Mental health professionals face limitation regarding the ability to provide emergency management of psychiatric patients and to ensure continuity of psychopharmacological treatment of patients with chronic conditions. To improve the implementation process of mental health interventions and activities, a planning process based on community needs and the involvement of representatives of families and users in planning process should be considered. The Bugesera case study on the situation of mental health services can serve as a baseline for improvement of the mental health program in Rwanda, in terms of quality care services, infrastructure and equipment, human and financial resources.

Bioproduction of succinic acid from renewable feedstocks by Actinobacillus succinogenes 130Z

Succinic acid (SA) is a highly versatile building block that is used in a wide range of industrial applications. The biological production of succinic acid has emerged in the last years as an efficient alternative to the chemical production based on fossil fuels. However, in order to fully replace the competing petro-based chemical process from which it has been produced so far, some challenges remain to be surpassed. In particular, one main obstacle would be to reduce its production costs, mostly associated to the use of refined sugars. The present work is focused on the development of a sustainable and cost-e↵ective microbial production process based on cheap and renewable resources, such as agroindustrial wastes. Hence, glycerol and carob pods were identified as promising feedstocks and used as inexpensive carbon sources for the bioproduction of succinic acid by Actinobacillus succinogenes 130Z, one of the best naturally producing strains. Even though glycerol is a highly available carbon source, as by-product of biodiesel production, its consumption by A. succinogenes is impaired due to a redox imbalance during cell growth. However, the use of an external electron acceptor such as dimethylsulfoxide (DMSO) may improve glycerol metabolism and succinic acid production by this strain. As such, DMSO was tested as a co-substrate for glycerol consumption and concentrations of DMSO between 1 and 4% (v/v) greatly promoted glycerol consumption and SA production by this biocatalyst. Aiming at obtaining higher succinic acid yield and production rate, batch and fed-batch experiments were performed under controlled cultivation conditions. Batch experiments resulted in a succinic acid yield on glycerol of 0.95 g SA/g GLY and a production rate of 2.13 g/L.h, with residual production of acetic and formic acids. In fed-batch experiment, the SA production rate reached 2.31 g/L.h, the highest value reported in the literature for A. succinogenes using glycerol as carbon source. DMSO dramatically improved the conversion of glycerol by A. succinogenes and may be used as a co-substrate, opening new perspectives for the use of glycerol by this biocatalyst. Carob pods, highly available in Portugal as a residue from the locust bean gum industry, contain a significant amount of fermentable sugars such as sucrose, glucose and fructose and were also used as substrate for succinic acid production. Sugar extraction from raw and roasted carobs was optimized varying solid/water ratio and extraction time, maximizing sugar recovery while minimizing the extraction of polyphenols. Kinetic studies of glucose, fructose and sucrose consumption by A. succinogenes as individual carbon sources till 30 g/L were first determined to assess possible metabolic diferences. Results showed no significant diferences related to sugar consumption and SA production between the diferent sugars. Carob pods water extracts were then used as carbon source during controlled batch cultivations. (...)

Predicting market movement with Artificial Neural Networks

This paper presents an application of an Artificial Neural Network (ANN) to the prediction of stock market direction in the US. Using a multilayer perceptron neural network and a backpropagation algorithm for the training process, the model aims at learning the hidden patterns in the daily movement of the S&P500 to correctly identify if the market will be in a Trend Following or Mean Reversion behavior. The ANN is able to produce a successful investment strategy which outperforms the buy and hold strategy, but presents instability in its overall results which compromises its practical application in real life investment decisions.

Cultural journalism in a digital environment : new models, practices and possibilities

Both culture coverage and digital journalism are contemporary phenomena that have undergone several transformations within a short period of time. Whenever the media enters a period of uncertainty such as the present one, there is an attempt to innovate in order to seek sustainability, skip the crisis or find a new public. This indicates that there are new trends to be understood and explored, i.e., how are media innovating in a digital environment? Not only does the professional debate about the future of journalism justify the need to explore the issue, but so do the academic approaches to cultural journalism. However, none of the studies so far have considered innovation as a motto or driver and tried to explain how the media are covering culture, achieving sustainability and engaging with the readers in a digital environment. This research examines how European media which specialize in culture or have an important cultural section are innovating in a digital environment. Specifically, we see how these innovation strategies are being taken in relation to the approach to culture and dominant cultural areas, editorial models, the use of digital tools for telling stories, overall brand positioning and extensions, engagement with the public and business models. We conducted a mixed methods study combining case studies of four media projects, which integrates qualitative web features and content analysis, with quantitative web content analysis. Two major general-interest journalistic brands which started as physical newspapers – The Guardian (London, UK) and Público (Lisbon, Portugal) – a magazine specialized in international affairs, culture and design – Monocle (London, UK) – and a native digital media project that was launched by a cultural organization – Notodo, by La Fábrica – were the four case studies chosen. Findings suggest, on one hand, that we are witnessing a paradigm shift in culture coverage in a digital environment, challenging traditional boundaries related to cultural themes and scope, angles, genres, content format and delivery, engagement and business models. Innovation in the four case studies lies especially along the product dimensions (format and content), brand positioning and process (business model and ways to engage with users). On the other hand, there are still perennial values that are crucial to innovation and sustainability, such as commitment to journalism, consistency (to the reader, to brand extensions and to the advertiser), intelligent differentiation and the capability of knowing what innovation means and how it can be applied, since this thesis also confirms that one formula doesn´t suit all. Changing minds, exceeding cultural inertia and optimizing the memory of the websites, looking at them as living, organic bodies, which continuously interact with the readers in many different ways, and not as a closed collection of articles, are still the main challenges for some media.