Development of process control strategies exploiting knowledge from systems biology: application to MDCK suspension cells

Madine Darby Canine Kidney (MDCK) cell lines have been extensively evaluated for their potential as host cells for influenza vaccine production. Recent studies allowed the cultivation of these cells in a fully defined medium and in suspension. However, reaching high cell densities in animal cell cultures still remains a challenge. To address this shortcoming, a combined methodology allied with knowledge from systems biology was reported to study the impact of the cell environment on the flux distribution. An optimization of the medium composition was proposed for both a batch and a continuous system in order to reach higher cell densities. To obtain insight into the metabolic activity of these cells, a detailed metabolic model previously developed by Wahl A. et. al was used. The experimental data of four cultivations of MDCK suspension cells, grown under different conditions and used in this work came from the Max Planck Institute, Magdeburg, Germany. Classical metabolic flux analysis (MFA) was used to estimate the intracellular flux distribution of each cultivation and then combined with partial least squares (PLS) method to establish a link between the estimated metabolic state and the cell environment. The validation of the MFA model was made and its consistency checked. The resulted PLS model explained almost 70% of the variance present in the flux distribution. The medium optimization for the continuous system and for the batch system resulted in higher biomass growth rates than the ones obtained experimentally, 0.034 h-1 and 0.030 h-1, respectively, thus reducing in almost 10 hours the duplication time. Additionally, the optimal medium obtained for the continuous system almost did not consider pyruvate. Overall the proposed methodology seems to be effective and both proposed medium optimizations seem to be promising to reach high cell densities.

An agent based architecture to support monitoring in plug and produce manufacturing systems using knowledge extraction

In recent years a set of production paradigms were proposed in order to capacitate manufacturers to meet the new market requirements, such as the shift in demand for highly customized products resulting in a shorter product life cycle, rather than the traditional mass production standardized consumables. These new paradigms advocate solutions capable of facing these requirements, empowering manufacturing systems with a high capacity to adapt along with elevated flexibility and robustness in order to deal with disturbances, like unexpected orders or malfunctions. Evolvable Production Systems propose a solution based on the usage of modularity and self-organization with a fine granularity level, supporting pluggability and in this way allowing companies to add and/or remove components during execution without any extra re-programming effort. However, current monitoring software was not designed to fully support these characteristics, being commonly based on centralized SCADA systems, incapable of re-adapting during execution to the unexpected plugging/unplugging of devices nor changes in the entire system’s topology. Considering these aspects, the work developed for this thesis encompasses a fully distributed agent-based architecture, capable of performing knowledge extraction at different levels of abstraction without sacrificing the capacity to add and/or remove monitoring entities, responsible for data extraction and analysis, during runtime.

A type system for value-dependent information flow analysis

Information systems are widespread and used by anyone with computing devices as well as corporations and governments. It is often the case that security leaks are introduced during the development of an application. Reasons for these security bugs are multiple but among them one can easily identify that it is very hard to define and enforce relevant security policies in modern software. This is because modern applications often rely on container sharing and multi-tenancy where, for instance, data can be stored in the same physical space but is logically mapped into different security compartments or data structures. In turn, these security compartments, to which data is classified into in security policies, can also be dynamic and depend on runtime data. In this thesis we introduce and develop the novel notion of dependent information flow types, and focus on the problem of ensuring data confidentiality in data-centric software. Dependent information flow types fit within the standard framework of dependent type theory, but, unlike usual dependent types, crucially allow the security level of a type, rather than just the structural data type itself, to depend on runtime values. Our dependent function and dependent sum information flow types provide a direct, natural and elegant way to express and enforce fine grained security policies on programs. Namely programs that manipulate structured data types in which the security level of a structure field may depend on values dynamically stored in other fields The main contribution of this work is an efficient analysis that allows programmers to verify, during the development phase, whether programs have information leaks, that is, it verifies whether programs protect the confidentiality of the information they manipulate. As such, we also implemented a prototype typechecker that can be found at http://ctp.di.fct.unl.pt/DIFTprototype/.

Learning domain-specific sentiment lexicons with applications to recommender systems

Search is now going beyond looking for factual information, and people wish to search for the opinions of others to help them in their own decision-making. Sentiment expressions or opinion expressions are used by users to express their opinion and embody important pieces of information, particularly in online commerce. The main problem that the present dissertation addresses is how to model text to find meaningful words that express a sentiment. In this context, I investigate the viability of automatically generating a sentiment lexicon for opinion retrieval and sentiment classification applications. For this research objective we propose to capture sentiment words that are derived from online users’ reviews. In this approach, we tackle a major challenge in sentiment analysis which is the detection of words that express subjective preference and domain-specific sentiment words such as jargon. To this aim we present a fully generative method that automatically learns a domain-specific lexicon and is fully independent of external sources. Sentiment lexicons can be applied in a broad set of applications, however popular recommendation algorithms have somehow been disconnected from sentiment analysis. Therefore, we present a study that explores the viability of applying sentiment analysis techniques to infer ratings in a recommendation algorithm. Furthermore, entities’ reputation is intrinsically associated with sentiment words that have a positive or negative relation with those entities. Hence, is provided a study that observes the viability of using a domain-specific lexicon to compute entities reputation. Finally, a recommendation system algorithm is improved with the use of sentiment-based ratings and entities reputation.

The emergence of product certification systems as trade barriers

This paper addresses the growing difficulties automobile manufacturers face within their after sales business: an increasing number of trade obstacles set up by import countries discriminates against the foreign suppliers and impedes the international sales of genuine parts. The purpose of the study is to explore the emergence of trade restrictive product certification systems, which affect spare parts exports of automobile manufacturers. The methodology used includes review of the literature and an empirical study based on qualitative interviews with representatives of major stakeholders of the automotive after sales business. Relevant key drivers, which initiate the introduction of technical regulations in importing countries, are identified and analysed to evaluate their effect on the emerging trade policy. The analysis of the key drivers outlines that several interacting components, such as the global competitiveness of the country, macroeconomic and microeconomic factors, and certain country-specific variables induce trade restrictive product certification systems. The findings allow for an early detection of the emergence of product certification systems and provide a means to early recognise the risks and opportunities for the sales of automotive spare parts in the automakers’ target markets. This allows the manufacturers to react immediately and adapt in time to the upcoming changes.

ELECTROPHORETIC ANALYSIS OF 11 ENZYMES IN NATURAL POPULATIONS OFROOT, 1926 (DIPTERA: CULICIDAE) IN THE AMAZON REGION

Of eleven proteins analyzed in four Amazonian populations, the esterases showed the greatest variation, with five activity zones. EST1, EST2 and EST5 showed variation in each of the populations studied. EST1 and EST2 are each controlled by two, and EST5 by four, codomi-nant alleles. LAP presented six activity zones, with codominant variation in LAP5and LAP6.oc—GPDH was monomorphic with one activity band on starch gel and two on polyacrylamide gel. 1DH presented two activity zones, with variation in the IDHl region. PGM had a single activity zone, with variation in all populations. The Ariquemes populations showed five alleles and the other populations three, all of then codominant. Three activity zones with two codominant alleles were observed for ODH. Aldehyde Oxidase showed two activity zones, with variation in AOl only in the Ariquemes and Porto Velho/Samuel populations. 6-PGDH showed only one activity zone and variation only in the Ariquemes population. The remaing systems - XDH, G-6-PDH and GDH. was monomorphic.

Silica nanoparticles as dexamethasone delivery systems able to induce the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells

Bioactive glasses, especially silica-based materials, are reported to pres- ent osteoconductive and osteoinductive properties, fundamental char- acteristics in bone regeneration [1,2]. Additionally, dexamethasone (Dex) is one of the bioactive agents able to induce the osteogenic differ- entiation of mesenchymal stem cells by increasing the alkaline phos- phatase activity, and the expression levels of Osteocalcin and Bone Sialoprotein [3]. Herein, we synthesised silica (SiO2) nanoparticles (that present inherent bioactivity and ability to act as a sustained drug delivery system), and coated their surface using poly-L-lysine (PLL) and hyaluronic acid (HA) using the layer-by-layer processing technique. Further on, we studied the influence of these new SiO2-polyelectrolyte coated nanoparticles as Dex sustained delivery systems. The SiO2 nanoparticles were loaded with Dex (SiO2-Dex) and coated with PLL and HA (SiO2-Dex-PLL-HA). Their Dex release profile was evaluated and a more sustained release was obtained with the SiO2-Dex-PLL-HA. All the particles were cultured with human bone marrow-derived mes- enchymal stem cells (hBMSCs) under osteogenic differentiation culture conditions. hBMSCs adhered, proliferated and differentiated towards the osteogenic lineage in the presence of SiO2 (DLS 174nm), SiO2-Dex (DLS 175nm) and SiO2-Dex-PLL-HA (DLS 679nm). The presence of these materials induced the overexpression of osteogenic transcripts, namely of Osteocalcin, Bone Sialoprotein and Runx2. Scanning Elec- tron Microscopy/Electron Dispersive Spectroscopy analysis demon- strated that hBMSCs synthesised calcium phosphates when cultured with SiO2-Dex and SiO2-Dex-PLL-HA nanoparticles. These results indi- cate the potential use of these SiO2-polyelectrolytes coated nanoparti- cles as dexamethasone delivery systems capable of promoting osteogenic differentiation of hBMSCs.

Smart platform towards batteries analysis based on internet-of-things

This paper presents a new approach of pre-defined profiles, based in different voltage and current values, to control the charging and discharging processes of batteries in order to assess their performance. This new approach was implemented in a prototype that was specially developed for such purpose. This prototype is a smart power electronics platform that allows to perform batteries analysis and to control the charging and discharging processes through a web application using pre-defined profiles. This platform was developed aiming to test different batteries technologies. Considering the relevance of the energy storage area based in batteries, especially for the batteries applied to electric mobility systems, this platform allows to perform controlled tests to the batteries, in order to analyze the batteries performance under different scenarios of operation. Besides the results obtained with the batteries, this work also intends to produce results that can contribute to an involvement in the strengthening of the Internet-of-Things.

Business intelligence in banking: A literature analysis from 2002 to 2013 using Text Mining and latent Dirichlet allocation

telligence applications for the banking industry. Searches were performed in relevant journals resulting in 219 articles published between 2002 and 2013. To analyze such a large number of manuscripts, text mining techniques were used in pursuit for relevant terms on both business intelligence and banking domains. Moreover, the latent Dirichlet allocation modeling was used in or- der to group articles in several relevant topics. The analysis was conducted using a dictionary of terms belonging to both banking and business intelli- gence domains. Such procedure allowed for the identification of relationships between terms and topics grouping articles, enabling to emerge hypotheses regarding research directions. To confirm such hypotheses, relevant articles were collected and scrutinized, allowing to validate the text mining proce- dure. The results show that credit in banking is clearly the main application trend, particularly predicting risk and thus supporting credit approval or de- nial. There is also a relevant interest in bankruptcy and fraud prediction. Customer retention seems to be associated, although weakly, with targeting, justifying bank offers to reduce churn. In addition, a large number of ar- ticles focused more on business intelligence techniques and its applications, using the banking industry just for evaluation, thus, not clearly acclaiming for benefits in the banking business. By identifying these current research topics, this study also highlights opportunities for future research.

Analysis of output properties of the Peroxiredoxin/Thioredoxin/Thioredoxin reductase system

Dissertação de mestrado em Bioinformática

Strategic planning of electricity systems: Integrating renewable energies

Tese de Doutoramento - Programa Doutoral em Engenharia Industrial e Sistemas (PDEIS)

A new empirical system for rock slope stability analysis in exploitation stage

An empirical system was developed to obtain a quality index for rock slopes in road infrastructures, named Slope Quality Index (SQI), and it was applied to a set of real slopes.The SQI is supported in nine factors affecting slope stability that contemplate the evaluation of different parameters. Consequently, each factor is classified by the degree of importance and influence by assigned weights. These weights were established through a statistical analysis of replies to a survey that was distributed to several experienced professionals in the field. The proposed SQI varies between1 and 5, corresponding to slopes in very good and very bad condition state, respectively. Besides the advantage linked to a quantitative and qualitative evaluation of slopes, theSQI also allows identifying the most critical factors on the slope stability, which is a fundamental issue for an efficient management of the slope network in the road infrastructure, namely in the planning of conservation and maintenance operations.

Analysis of portuguese residential buildings’ needs and proposed solutions

The Portuguese housing sector experienced a significant growth throughout the 20th century, particularly in the last quarter, after the democratic revolution in 1974. In fact, the number of buildings built between 1970 and 1990 is more than one third of the buildings actually existing in Portugal. Therefore most of them were built before the publication of the first regulation concerning the energy efficiency in buildings. Regarding this scenario, it would be expected that rehabilitation activities would represent most of the current construction activities. However, given some remaining barriers from old social policies, this situation is not observed; actually building retrofitting is the least significant sector, accentuating the degradation level of major part of the Portuguese housing stock. Several studies show that the main problems are found in the buildings envelope elements, such as roofs and façades. Based on this context, the aim of this paper is to introduce some examples of building retrofitting systems that, adapted to the Portuguese main needs and requirements may represent sustainable solutions to overcome the identified needs of Portuguese buildings' envelope.

Effect of NaCl additive on solute-solvent interactions in aqueous polyethylene glycol-sodium sulfate two-phase systems

Abstract Partition behavior of eight small organic compounds and six proteins was examined in poly(ethylene glycol)-8000-sodium sulfate aqueous two-phase systems containing 0.215 M NaCl and 0.5 M osmolyte (sorbitol, sucrose, TMAO) and poly(ethylene glycol)-10000-sodium sulfate-0.215 M NaCl system, all in 0.01 M sodium phosphate buffer, pH 6.8. The differences between the solvent properties of the coexisting phases (solvent dipolarity/polarizability, hydrogen bond donor acidity, and hydrogen bond acceptor basicity) were characterized with solvatochromic dyes using the solvatochromic comparison method. Differences between the electrostatic properties of the phases were determined by analysis of partitioning of sodium salts of dinitrophenylated (DNP-) amino acids with aliphatic alkyl side-chain. The partition coefficients of all compounds examined (including proteins) were described in terms of solute-solvent interactions. The results obtained in the study show that solute-solvent interactions of nonionic organic compounds and proteins in polyethylene glycol-sodium sulfate aqueous two-phase system change in the presence of NaCl additive.