An ANP model to support decision-making in a Portuguese pharmaceutical supply chain

Dissertação para obtenção do Grau de Mestre em Engenharia e Gestão Industrial

Design of future distribution grids

Dissertação para obtenção do Grau de Mestre em Engenharia Electrotécnica e de Computadores

Quality of process modeling using BPMN: a model-driven approach

Dissertação para obtenção do Grau de Doutor em Engenharia Informática

A framework for efficient model transformations

The reported productivity gains while using models and model transformations to develop entire systems, after almost a decade of experience applying model-driven approaches for system development, are already undeniable benefits of this approach. However, the slowness of higher-level, rule based model transformation languages hinders the applicability of this approach to industrial scales. Lower-level, and efficient, languages can be used but productivity and easy maintenance seize to exist. The abstraction penalty problem is not new, it also exists for high-level, object oriented languages but everyone is using them now. Why is not everyone using rule based model transformation languages then? In this thesis, we propose a framework, comprised of a language and its respective environment, designed to tackle the most performance critical operation of high-level model transformation languages: the pattern matching. This framework shows that it is possible to mitigate the performance penalty while still using high-level model transformation languages.

New visualization model for large scale biosignals analysis

Benefits of long-term monitoring have drawn considerable attention in healthcare. Since the acquired data provides an important source of information to clinicians and researchers, the choice for long-term monitoring studies has become frequent. However, long-term monitoring can result in massive datasets, which makes the analysis of the acquired biosignals a challenge. In this case, visualization, which is a key point in signal analysis, presents several limitations and the annotations handling in which some machine learning algorithms depend on, turn out to be a complex task. In order to overcome these problems a novel web-based application for biosignals visualization and annotation in a fast and user friendly way was developed. This was possible through the study and implementation of a visualization model. The main process of this model, the visualization process, comprised the constitution of the domain problem, the abstraction design, the development of a multilevel visualization and the study and choice of the visualization techniques that better communicate the information carried by the data. In a second process, the visual encoding variables were the study target. Finally, the improved interaction exploration techniques were implemented where the annotation handling stands out. Three case studies are presented and discussed and a usability study supports the reliability of the implemented work.

Glia-Motoneuron dialogue in ALS onset and progression in SOD1G93A-mice model

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the pro-gressive loss of motoneurons (MN). Increasing evidence points glial cells as key players for ALS onset and progression. Indeed, MN-glia signalling pathways involving either neuroprotection or inflammation are likely to be altered in ALS. We aimed to study the molecules related with glial function and/or reactivity by evaluating glial markers and hemichannels, mainly present in astrocytes. We also studied molecules involved in mi-croglia-MN dialogue (CXCR3/CCL21; CX3CR1/CX3CL1; MFG-E8), as well as proliferation (Ki-67) and inflammatory-related molecules (TLR2/4, NLRP3; IL-18) and alarming/calming signals (HMGB1/autotaxin). We used lumbar spinal cord (SC) homogenates from mice expressing a mutant human-SOD1 protein (mSOD1) at presymptomatic and late-symptomatic ALS stages. SJL (WT) mice at same ages were used as controls. We observed decreased expression of genes associated with astrocytic (GFAP and S100B) and microglial (CD11b) markers in mSOD1 at the presymptomatic phase, as well as diminished levels of gap junction components pannexin1 and connexin43 and expression of Ki-67 and decreased autotax-in. In addition, microglial-MN communication was negatively affected in mSOD1 mice as well as in-flammatory response. Interestingly, we observed astrocytic (S100B) and microglial (CD11b) reactivity, increased proliferation (Ki-67) and increased autotaxin expression in symptomatic mSOD1 mice. In-creased MN-microglial dialogue (CXCR3/CCL21; CX3CR1/CX3CL1; MFG-E8) and hemichannel activ-ity, namely connexin43 and pannexin1, were also observed in mSOD1 at the symptomatic phase, along with an elevated inflammatory response as indicated by increased levels of HMGB1 and NLRP3. Our results suggest that decreased autotaxin expression is a feature of the presymptomatic stage, and precede the network of pro-inflammatory-related symptomatic determinants, including HMGB1, CCL21, CX3CL1, and NLRP3. The identification of the molecules and signaling pathways that are dif-ferentially activated along ALS progression will contribute for a better design of therapeutic strategies for disease onset and progression.

Integrated data model and DSL modifications

Companies are increasingly more and more dependent on distributed web-based software systems to support their businesses. This increases the need to maintain and extend software systems with up-to-date new features. Thus, the development process to introduce new features usually needs to be swift and agile, and the supporting software evolution process needs to be safe, fast, and efficient. However, this is usually a difficult and challenging task for a developer due to the lack of support offered by programming environments, frameworks, and database management systems. Changes needed at the code level, database model, and the actual data contained in the database must be planned and developed together and executed in a synchronized way. Even under a careful development discipline, the impact of changing an application data model is hard to predict. The lifetime of an application comprises changes and updates designed and tested using data, which is usually far from the real, production, data. So, coding DDL and DML SQL scripts to update database schema and data, is the usual (and hard) approach taken by developers. Such manual approach is error prone and disconnected from the real data in production, because developers may not know the exact impact of their changes. This work aims to improve the maintenance process in the context of Agile Platform by Outsystems. Our goal is to design and implement new data-model evolution features that ensure a safe support for change and a sound migration process. Our solution includes impact analysis mechanisms targeting the data model and the data itself. This provides, to developers, a safe, simple, and guided evolution process.

Genome-scale metabolic network reconstruction of Polaromonas sp. strain JS666: analysis of cDCE degradation rates and design of experiments for bioremediation improvement

Release of chloroethene compounds into the environment often results in groundwater contamination, which puts people at risk of exposure by drinking contaminated water. cDCE (cis-1,2-dichloroethene) accumulation on subsurface environments is a common environmental problem due to stagnation and partial degradation of other precursor chloroethene species. Polaromonas sp. strain JS666 apparently requires no exotic growth factors to be used as a bioaugmentation agent for aerobic cDCE degradation. Although being the only suitable microorganism found capable of such, further studies are needed for improving the intrinsic bioremediation rates and fully comprehend the metabolic processes involved. In order to do so, a metabolic model, iJS666, was reconstructed from genome annotation and available bibliographic data. FVA (Flux Variability Analysis) and FBA (Flux Balance Analysis) techniques were used to satisfactory validate the predictive capabilities of the iJS666 model. The iJS666 model was able to predict biomass growth for different previously tested conditions, allowed to design key experiments which should be done for further model improvement and, also, produced viable predictions for the use of biostimulant metabolites in the cDCE biodegradation.

Analysis and design of sinusoidal quadrature RC-oscillators

Modern telecommunication equipment requires components that operate in many different frequency bands and support multiple communication standards, to cope with the growing demand for higher data rate. Also, a growing number of standards are adopting the use of spectrum efficient digital modulations, such as quadrature amplitude modulation (QAM) and orthogonal frequency division multiplexing (OFDM). These modulation schemes require accurate quadrature oscillators, which makes the quadrature oscillator a key block in modern radio frequency (RF) transceivers. The wide tuning range characteristics of inductorless quadrature oscillators make them natural candidates, despite their higher phase noise, in comparison with LC-oscillators. This thesis presents a detailed study of inductorless sinusoidal quadrature oscillators. Three quadrature oscillators are investigated: the active coupling RC-oscillator, the novel capacitive coupling RCoscillator, and the two-integrator oscillator. The thesis includes a detailed analysis of the Van der Pol oscillator (VDPO). This is used as a base model oscillator for the analysis of the coupled oscillators. Hence, the three oscillators are approximated by the VDPO. From the nonlinear Van der Pol equations, the oscillators’ key parameters are obtained. It is analysed first the case without component mismatches and then the case with mismatches. The research is focused on determining the impact of the components’ mismatches on the oscillator key parameters: frequency, amplitude-, and quadrature-errors. Furthermore, the minimization of the errors by adjusting the circuit parameters is addressed. A novel quadrature RC-oscillator using capacitive coupling is proposed. The advantages of using the capacitive coupling are that it is noiseless, requires a small area, and has low power dissipation. The equations of the oscillation amplitude, frequency, quadrature-error, and amplitude mismatch are derived. The theoretical results are confirmed by simulation and by measurement of two prototypes fabricated in 130 nm standard complementary metal-oxide-semiconductor (CMOS) technology. The measurements reveal that the power increase due to the coupling is marginal, leading to a figure-of-merit of -154.8 dBc/Hz. These results are consistent with the noiseless feature of this coupling and are comparable to those of the best state-of-the-art RC-oscillators, in the GHz range, but with the lowest power consumption (about 9 mW). The results for the three oscillators show that the amplitude- and the quadrature-errors are proportional to the component mismatches and inversely proportional to the coupling strength. Thus, increasing the coupling strength decreases both the amplitude- and quadrature-errors. With proper coupling strength, a quadrature error below 1° and amplitude imbalance below 1% are obtained. Furthermore, the simulations show that increasing the coupling strength reduces the phase noise. Hence, there is no trade-off between phase noise and quadrature error. In the twointegrator oscillator study, it was found that the quadrature error can be eliminated by adjusting the transconductances to compensate the capacitance mismatch. However, to obtain outputs in perfect quadrature one must allow some amplitude error.

Electro-Optical/Infrared sensor turret integration on an aircraft - structural im-pact on LOCKHEED MARTIN C-130H and design methodology

The growing need to patrol and survey large maritime and terrestrial areas increased the need to integrate external sensors on aircraft in order to accomplish those patrols at increasingly higher altitudes, longer range and not depending upon vehicle type. The main focus of this work is to elaborate a practical, simple, effective and efficient methodology for the aircraft modification procedure resulting from the integration of an Elec-tro-Optical/Infra-Red (EO/IR) turret through a support structure. The importance of the devel-opment of a good methodology relies on the correct management of project variables as time, available resources and project complexity. The key is to deliver a proper tool for a project de-sign team that will be used to create a solution that fulfils all technical, non-technical and certi-fication requirements present in this field of transportation. The created methodology is inde-pendent of two main inputs: sensor model and aircraft model definition, and therefore it is in-tended to deliver the results for different projects besides the one that was presented in this work as a case study. This particular case study presents the development of a structure support for FLIR STAR SAPHIRE III turret integration on the front lower fuselage bulkhead (radome) of the LOCKHEED MARTIN C-130 H. Development of the case study focuses on the study of local structural analysis through the use of Finite Element Method (FEM). Development of this Dissertation resulted in a cooperation between Faculty of Science and Technology - Universidade Nova de Lisboa and the company OGMA - Indústria Aeronáutica de Portugal

Design of bio-inspired ionic liquids for protein stabilisation

Ionic Liquids (ILs) consist in organic salts that are liquid at/or near room temperature. Since ILs are entirely composed of ions, the formation of ion pairs is expected to be one essential feature for describing solvation in ILs. In recent years, protein - ionic liquid (P-IL) interactions have been the subject of intensive studies mainly because of their capability to promote folding/unfolding of proteins. However, the ion pairs and their lifetimes in ILs in P-IL thematic is dismissed, since the action of ILs is therefore the result of a subtle equilibrium between anion-cation interaction, ion-solvent and ion-protein interaction. The work developed in this thesis innovates in this thematic, once the design of ILs for protein stabilisation was bio-inspired in the high concentration of organic charged metabolites found in cell milieu. Although this perception is overlooked, those combined concentrations have been estimated to be ~300 mM among the macromolecules at concentrations exceeding 300 g/L (macromolecular crowding) and transient ion-pair can naturally occur with a potential specific biological role. Hence the main objective of this work is to develop new bio-ILs with a detectable ion-pair and understand its effects on protein structure and stability, under crowding environment, using advanced NMR techniques and calorimetric techniques. The choline-glutamate ([Ch][Glu]) IL was synthesized and characterized. The ion-pair was detected in water solutions using mainly the selective NOE NMR technique. Through the same technique, it was possible to detect a similar ion-pair promotion under synthetic and natural crowding environments. Using NMR spectroscopy (protein diffusion, HSQC experiments, and hydrogen-deuterium exchange) and differential scanning calorimetry (DSC), the model protein GB1 (production and purification in isotopic enrichment media) it was studied in the presence of [Ch][Glu] under macromolecular crowding conditions (PEG, BSA, lysozyme). Under dilute condition, it is possible to assert that the [Ch][Glu] induces a preferential hydration by weak and non-specific interactions, which leads to a significant stabilisation. On the other hand, under crowding environment, the [Ch][Glu] ion pair is promoted, destabilising the protein by favourable weak hydrophobic interactions , which disrupt the hydration layer of the protein. However, this capability can mitigates the effect of protein crowders. Overall, this work explored the ion-pair existence and its consequences on proteins in conditions similar to cell milieu. In this way, the charged metabolites found in cell can be understood as key for protein stabilisation.

An effective on-the-job training model-to facilitate strategy execution

Strategy execution has been a heated topic in the management world in recent years. However, according to a survey done by the Conference Board (2014), the chief executives are so concerned about the execution in their companies and have rated it as the No.1 or No.2 most challenging issue. Many of them choose to invest in training with a purpose to harvest the most for strategy execution. Therefore, this research is trying to find out a model to design training programs that can at most contribute to the success of strategy execution with three real-life training cases done by BTS Consulting Service. It was found that strategy execution could be greatly supported by training programs that take into consideration the four factors, namely Alignment, Mindset to Change, Capability and Organization Support. Main implications of the findings are presented and discussed. Key

A spatial multicriteria model for urban accessibility mapping

Accessibility is nowadays an important issue for the development of cities. It is seen as a priority in order toguarantee equal access to fundamental rights, to improve the quality of life of citizens and to ensure that everyone, regardless of age, mobility or ability, have equal access to all the resources and benefits cities have to offer. Consequently, factors closely related to the accessibility have gained a higher relevance for identifying and assessing the location of urban facilities. The main goal of the paper is to present an accessibility evaluation model applied in Santarém, in Brazil, a city located midway between the larger cities of Belem and Manaus. The research instruments, sampling method and data analysis proposed for mapping urban accessibility are described. Daily activities were used to identify and group key destinations. The model was implemented within a geographic information system and integrates the individualâ s perspective through the definition of each key destination weight, reflecting their significance for daily activities in the urban area. Accessibility to key destinations was mapped over 24 districts of the city of Santarém. The results of this model application can support city administration decision-making for new investments in order to improve urban quality of life.

A GIS extension model to calculate urban heat island intensity based on urban geometry

This paper presents a simulation model, which was incorporated into a Geographic Information System (GIS), in order to calculate the maximum intensity of urban heat islands based on urban geometry data. The method-ology of this study stands on a theoretical-numerical basis (Okeâ s model), followed by the study and selection of existing GIS tools, the design of the calculation model, the incorporation of the resulting algorithm into the GIS platform and the application of the tool, developed as exemplification. The developed tool will help researchers to simulate UHI in different urban scenarios.

Assessment of the effectiveness of steel fibre reinforcement for the punching resistance of flat slabs by experimental research and design approach

The present paper deals with the experimental assessment of the effectiveness of steel fibre reinforcement in terms of punching resistance of centrically loaded flat slabs, and to the development of an analytical model capable of predicting the punching behaviour of this type of structures. For this purpose, eight slabs of 2550 x 2550 x 150 mm3 dimensions were tested up to failure, by investigating the influence of the content of steel fibres (0, 60, 75 and 90 kg/m3) and concrete strength class (50 and 70 MPa). Two reference slabs without fibre reinforcement, one for each concrete strength class, and one slab for each fibre content and each strength class compose the experimental program. All slabs were flexurally reinforced with a grid of ribbed steel bars in a percentage to assure punching failure mode for the reference slabs. Hooked ends steel fibres provided the unique shear reinforcement. The results have revealed that steel fibres are very effective in converting brittle punching failure into ductile flexural failure, by increasing both the ultimate load and deflection, as long as adequate fibre reinforcement is assured. An analytical model was developed based on the most recent concepts proposed by the fib Mode Code 2010 for predicting the punching resistance of flat slabs and for the characterization of the behaviour of fibre reinforced concrete. The most refined version of this model was capable of predicting the punching resistance of the tested slabs with excellent accuracy and coefficient of variation of about 5%.