UJI Navigation Network, Development of a pedestrian spatial network within the University Jaume I of Castellón (Spain)

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.

How reporting and controlling systems can be effectively designed to support the decision-making process: The case of a Software SME

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Petri net based development of globally-asynchronous locally-synchronous distributed embedded systems

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

Precast concrete wall-foundation connection. Development of a seismic dissipative connection

Seismic events are a major factor to consider in structural design of buildings in many countries. With the purpose of saving lives, most of the design codes lead to structural solutions that withstand large seismic actions without collapsing, but without taking into account a possible usage of the structures after the earthquake. As a result, it is necessary to consider the time needed to repair/retrofit the damaged structures (i.e. the downtime) since this period of inactivity may result in huge financial implications for the occupants of the buildings. In order to minimise the damages and simplify repair operations, structural solutions with rocking systems and negligible residual displacements have been developed during the last two decades. Systems with precast concrete rocking walls were studied with the aim of investigat- ing suitable and convenient structural alternatives to minimise the damage in case of an earthquake. Experimental, numerical and analytical analyses on post-tensioned solutions, with and without energy dissipation devices, were carried out in this research. The energy dissipation devices were made from steel angles that were further developed during the research. Different solutions for these devices were experimentally tested under cyclic loading and the results are presented. Numerical and analytical work on steel angles was also carried out. Regarding the concrete rocking wall systems, two concrete rocking wall systems were studied: post-tensioned walls and post-tensioned walls with energy dissipation devices. In the latter, the solution was to fix them externally to the wall, allowing their easy replacement after an earthquake. It is shown that the dissipaters are a viable solution for use in precast concrete rocking wall systems. A building case study is presented. The comparison between a traditional monolithic system and a hybrid solution was carried out, allowing the evaluation of the efficiency of the solution that was developed.

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.

Development of human central nervous system 3D in vitro models for preclinical research

Neurological disorders are a major concern in modern societies, with increasing prevalence mainly related with the higher life expectancy. Most of the current available therapeutic options can only control and ameliorate the patients’ symptoms, often be-coming refractory over time. Therapeutic breakthroughs and advances have been hampered by the lack of accurate central nervous system (CNS) models. The develop-ment of these models allows the study of the disease onset/progression mechanisms and the preclinical evaluation of novel therapeutics. This has traditionally relied on genetically engineered animal models that often diverge considerably from the human phenotype (developmentally, anatomically and physiologically) and 2D in vitro cell models, which fail to recapitulate the characteristics of the target tissue (cell-cell and cell-matrix interactions, cell polarity). The in vitro recapitulation of CNS phenotypic and functional features requires the implementation of advanced culture strategies that enable to mimic the in vivo struc-tural and molecular complexity. Models based on differentiation of human neural stem cells (hNSC) in 3D cultures have great potential as complementary tools in preclinical research, bridging the gap between human clinical studies and animal models. This thesis aimed at the development of novel human 3D in vitro CNS models by integrat-ing agitation-based culture systems and a wide array of characterization tools. Neural differentiation of hNSC as 3D neurospheres was explored in Chapter 2. Here, it was demonstrated that human midbrain-derived neural progenitor cells from fetal origin (hmNPC) can generate complex tissue-like structures containing functional dopaminergic neurons, as well as astrocytes and oligodendrocytes. Chapter 3 focused on the development of cellular characterization assays for cell aggregates based on light-sheet fluorescence imaging systems, which resulted in increased spatial resolu-tion both for fixed samples or live imaging. The applicability of the developed human 3D cell model for preclinical research was explored in Chapter 4, evaluating the poten-tial of a viral vector candidate for gene therapy. The efficacy and safety of helper-dependent CAV-2 (hd-CAV-2) for gene delivery in human neurons was evaluated, demonstrating increased neuronal tropism, efficient transgene expression and minimal toxicity. The potential of human 3D in vitro CNS models to mimic brain functions was further addressed in Chapter 5. Exploring the use of 13C-labeled substrates and Nucle-ar Magnetic Resonance (NMR) spectroscopy tools, neural metabolic signatures were evaluated showing lineage-specific metabolic specialization and establishment of neu-ron-astrocytic shuttles upon differentiation. Chapter 6 focused on transferring the knowledge and strategies described in the previous chapters for the implementation of a scalable and robust process for the 3D differentiation of hNSC derived from human induced pluripotent stem cells (hiPSC). Here, software-controlled perfusion stirred-tank bioreactors were used as technological system to sustain cell aggregation and dif-ferentiation. The work developed in this thesis provides practical and versatile new in vitro ap-proaches to model the human brain. Furthermore, the culture strategies described herein can be further extended to other sources of neural phenotypes, including pa-tient-derived hiPSC. The combination of this 3D culture strategy with the implemented characterization methods represents a powerful complementary tool applicable in the drug discovery, toxicology and disease modeling.

Improving quality of medical service with mobile health software

An increasing number of m-Health applications are being developed benefiting health service delivery. In this paper, a new methodology based on the principle of calm computing applied to diagnostic and therapeutic procedure reporting is proposed. A mobile application was designed for the physicians of one of the Portuguese major hospitals, which takes advantage of a multi-agent interoperability platform, the Agency for the Integration, Diffusion and Archive (AIDA). This application allows the visualization of inpatients and outpatients medical reports in a quicker and safer manner, in addition to offer a remote access to information. This project shows the advantages in the use of mobile software in a medical environment but the first step is always to build or use an interoperability platform, flexible, adaptable and pervasive. The platform offers a comprehensive set of services that restricts the development of mobile software almost exclusively to the mobile user interface design. The technology was tested and assessed in a real context by intensivists.

Cationic Liposomes as antigenic delivery systems: development of an immunoprotective strategy against Candida albicans

Tese de Doutoramento Biologia Molecular e Ambiental - Especialidade em Biologia Celular e Saúde

Development of a new 3D OpenFOAM® solver to model the cooling stage in profile extrusion

[Excerpt] The advantages resulting from the use of numerical modelling tools to support the design of processing equipment are almost consensual. The design of calibration systems in profile extrusion is not an exception . H owever , the complex geome tries and heat exchange phenomena involved in this process require the use of numerical solvers able to model the heat exchange in more than one domain ( calibrator and polymer), the compatibilization of the heat transfer at the profile - calibrator interface and with the ability to deal with complex geometries. The combination of all these features is usually hard to find in commercial software. Moreover , the dimension of the meshes required to ob tain accurate results, result in computational times prohibitive for industrial application. (...)

Development of a methodology to incorporate risk and uncertainty in electricity power planning

Dissertação de mestrado em Engenharia Industrial

Development of an intelligent earthwork optimization system

Tese de Doutoramento em Engenharia Civil.

Development of active bio-based multilayer systems: encapsulation of cinnamaldehyde and their physicochemical characterization

[Excerpt] In this work, different multilayer structures, using a polyhydroxybutyrate-co-valerate film with a valerate content of 8% (PHBV8) as support, were developed aiming the development of active bio-based multilayer systems. An interlayer based on zein nanofibers with and without cinnamaldehyde were electrospun in the PHBV8 film and three multilayer systems were developed: 1) without an outer layer; 2) using a PHBV8 film as outer layer; and 3) using an alginate-based film as outer layer. Their physico-chemical properties were evaluated through: water vapour and oxygen permeabilities and colour measurements, Fourier Transform Infrared Spectroscopy (FTIR) and thermal analyses. Results showed that the presence of different outer layers affected the water vapour permeability and transparency of the multilayer films. (...)

Development of nanohydrogels as a vehicle for the release of bioactive compounds in food matrices

PhD in Chemical and Biological Engineering

Electroquímica de sustancias de interés en los sistemas agroalimentario y de sanidad animal. Desarrollo de biosensores electroquímicos. Aplicaciones analíticas.Electrochemistry of substances of interest in agroalimentary and animal health systems. Development of electrochemical biosensors. Analytical applications.

Se estudiarán los mecanismos de reacción electroquímica de las micotoxinas (metabolitos tóxicos generados por hongos) citrinina (CIT), patulina (PAT) y moniliformina (MON), de los antioxidantes naturales alfa, beta, gama y delta tocoferoles, de los flavonoides fisetina (FIS), morina (MOR), luteolina (LUT), rutina (RUT), buteina (BUT), naringenina (NAR) y miricetina (MIR) y de las hormonas esteroides estradiol (EDIOL), estrona (EONA) y estriol (ETRIOL). Por otra parte, se implementarán técnicas electroanalíticas para la detección y cuantificación de estos sustratos en muestras de matrices naturales que los contengan. Se realizará el diseño y caracterización de biosensores enzimáticos a partir de peroxidasas y/o fosfatasa alcalina para la determinación de la micotoxina CIT y de los flavonoides y, por otro, de inmunosensores para las micotoxinas ocratoxina A (OTA) y PAT y hormonas. Para el anclaje de enzimas y/o anticuerpos, se estudiarán las propiedades de electrodos modificados por monocapas autoensambladas, nanotubos de carbono y partículas magnéticas. Se usarán las técnicas de voltamperometría cíclica, de onda cuadrada y de redisolución con acumulación adsortiva, espectroscopías de impedancia electroquímica, electrólisis a potencial controlado, uv-vis e IR, microbalanza de cristal de cuarzo y microscopías de alta resolución (SEM, TEM, AFM). La importancia de este proyecto apunta a la obtención de nuevos datos electroquímicos de los sustratos indicados y conocimientos relacionados con la aplicación de electrodos modificados en la preparación de biosensores y en el desarrollo de técnicas alternativas para la determinación de los analitos mencionados precedentemente. Electrochemical reaction mechanisms of mycotoxins (toxic metabolites generated by fungi) citrinin (CIT), Patulin (PAT) and moniliformin (MON), natural antioxidants alpha, beta, gamma and delta tocopherols, flavonoids fisetin (FIS), morin (MOR), luteolin (LUT), rutin (RUT), butein (BUT), naringenin (NAR), miricetin (MIR) and steroid hormones estradiol (EDIOL), estrone (EONA) and estriole (ETRIOL) will be explored. On the other hand, electroanalytical techniques for the detection and quantification of these substrates in samples of natural matrices will be implemented. The design and characterization of enzymatic biosensors from peroxidases and/or from alkaline phosphatase for the determination of CIT and flavonoids, and also of inmunosensors for ochratoxin A (OTA) and PAT and hormones will be performed. For the anchor of enzymes and/or antibody, properties of electrodes modified by self assembled monolayers, carbon nanotubes and magnetic particles will be explored. Cyclic, square wave and adsorptive stripping voltammetries, electrochemical impedance spectroscopy, controlled potential electrolysis, uv-vis and IR, quartz crystal microbalance and high-resolution microcopies (SEM, TEM, AFM) will be used. The importance of this project is aimed at obtaining new electrochemical data for the indicated substrates and knowledge on the application of modified electrodes in preparation of biosensors and in the development of alternative techniques for the determination of the above-mentioned analytes.

Development of sensing systems for environmental monitoring

This project focused on the investigation and the development of a chemical sensing system for the determination of chromium Cr6+ and a bio-reactor followed by electrochemical detection at a glassy carbon electrode, for the determination of organochlorine compounds. The conjugation of Cr6+ with 1,5-diphenylcarbazide was studied at various types of electrodes such as glassy carbon, ultra-trace epoxy-graphite, chemically or un-modified carbon-paste and dropping-mercury. The cyclic voltammetric behaviour of the complex was also investigated. In addition, the possibility of developing a chemical sensor, Le. an electrochemical probe capable of sensing Cr6+ through its complexation with 1,5-diphenylacarbazide was studied. The conjugations of l-chloro-2,4-dinitrobenzene, 2,4-dichloronitrobenzene and ethacrynic, which are electrophilic organochlorine compounds, with reduced glutathione, were studied in order to test the bioreactor developed, based on the immobilisation of glutathione s-transferase. This was carried out at different types of electrodes such as glassy-carbon, gold, silver, platinum, epoxy-graphite, hangingmercury, and ferrocene-modified rotating-disc electrodes.