Synteza i właściwości oksiranowych pochodnych estrów kwasów fosfonowych

Wydział Chemii

Deficiencias minerales en bovinos para carne: diagnóstico, caracterización y control

La demanda de una producción de alimentos cada vez mayor a nivel mundial sumado a la tecnificación y al ritmo acelerado del progreso de las explotaciones agropecuarias actuales hacen que el ganado deba soportar elevadas presiones de producción aumentando los requerimientos de nutrientes. Este es el caso de los minerales considerados actualmente elementos esenciales para los animales, aunque tradicionalmente fueron definidos como los nutrientes pobres de la nutrición y alimentación animal. Actualmente se ha demostrado con evidencia clínica y productiva, el importante rol metabólico de los minerales en el animal sano y productivo, como también se ha definido qué elemento mineral y porcentaje del mismo es requerido para el normal funcionamiento del organismo. Los macro-minerales (calcio, magnesio, fósforo, sodio, potasio, cloro y azufre) y los oligo-minerales (cobre, zinc, hierro, selenio, cobalto, iodo, manganeso, molibdeno y cromo) son elementos esenciales y necesarios para transformar la proteína y la energía de los alimentos en componentes del organismo o en productos animales como leche, carne, crías, piel, lana. Además, ayudan al organismo a combatir las enfermedades, manteniendo al animal en buen estado de salud. Se ha considerado a los minerales como el tercer grupo limitante en la nutrición animal, siendo a su vez, el que mayor potencial y menor costo tiene para incrementar la producción del ganado. Los minerales desempeñan funciones tan importantes como ser constituyentes de la estructura ósea y dental, de tejidos blandos y líquidos corporales. Están involucrados en el funcionamiento celular, siendo activadores de más de trescientas enzimas, constituyentes esenciales de vitaminas, hormonas y pigmentos respiratorios y facilitando la actividad de los microorganismos del rumen. Cuando el aporte de minerales en la ración no es el adecuado en calidad y/o cantidad se originan las deficiencias minerales, encuadradas dentro de las enfermedades metabólicas o enfermedades de la producción. Estas han sido informadas en casi todo el mundo y son responsables de importantes pérdidas económicas en los rodeos de bovinos para carne. Las deficiencias y/o desequilibrios minerales pueden causar los siguientes trastornos en los animales: bajo porcentaje de parición, mayor número de servicios por concepción, abortos, retenciones placentarias, incremento del intervalo entre partos, baja producción de leche, menor peso al nacimiento y al destete, menor porcentaje de destete, menor ganancia de peso, mayor incidencia de enfermedades infecciosas, fracturas espontáneas, diarrea, deformación de huesos y mortandad. Así cobra importancia el diagnóstico mediante el análisis de la sangre de los animales, del pasto y el agua que consumen y la caracterización de estas deficiencias en primarias o secundarias con el objetivo de poder realizar un control de las mismas mediante un adecuado plan de suplementación mineral acorde a las necesidades de los distintos establecimientos agropecuarios.

Synthèse de sulfilimines et de sulfoximines catalysée par les métaux de transition

Les sulfilimines et les sulfoximines sont des motifs structuraux dont l’intérêt synthétique est grandissant, notamment du fait de leurs applications en chimie médicinale et en agrochimie. Les travaux rapportés dans cet ouvrage décrivent le développement de nouvelles méthodes de synthèse efficaces pour la production de ces unités atypiques. Ces méthodes sont basées sur la réactivité d’une source d’azote électrophile, vis-à-vis de thioéthers et de sulfoxydes. L’utilisation d’un complexe métallique introduit en quantité catalytique a permis de favoriser le processus réactionnel. En tirant bénéfice de l’expertise de notre groupe de recherche sur le développement de réactions d’amination stéréosélectives de liaisons C-H et d’aziridination de styrènes, nous avons d’abord étudié la réactivité des N-mésyloxycarbamates comme source d’azote électrophile. Après avoir optimisé sa synthèse sur grande échelle, ce réactif chiral a été utilisé dans des réactions d’amination de thioéthers et de sulfoxydes, catalysées par un dimère de rhodium (II) chiral. Un processus diastéréosélectif efficace a été mis au point, permettant de produire des sulfilimines et des sulfoximines chirales avec d’excellents rendements et sélectivités. Au cours de l’optimisation de cette méthode de synthèse, nous avons pu constater l’effet déterminant de certains additifs sur la réactivité et la sélectivité de la réaction. Une étude mécanistique a été entreprise afin de comprendre leur mode d’action. Il a été observé qu’une base de Lewis telle que le 4-diméthylaminopyridine (DMAP) pouvait se coordiner au dimère de rhodium(II) et modifier ses propriétés structurales et redox. Les résultats que nous avons obtenus suggèrent que l’espèce catalytique active est un dimère de rhodium de valence mixte Rh(II)/Rh(III). Nous avons également découvert que l’incorporation de sels de bispyridinium avait une influence cruciale sur la diastéréosélectivité de la réaction. D’autres expériences sur la nature du groupe partant du réactif N-sulfonyloxycarbamate nous ont permis de postuler qu’une espèce nitrénoïde de rhodium était l’intermédiaire clé du processus d’amination. De plus, l’exploitation des techniques de chimie en débit continu nous a permis de développer une méthode d’amination de thioéthers et de sulfoxydes très performante, en utilisant les azotures comme source d’azote électrophile. Basée sur la décompositon photochimique d’azotures en présence d’un complexe de fer (III) simple et commercialement disponible, nous avons été en mesure de produire des sulfilimines et des sulfoximines avec d’excellents rendements. Le temps de résidence du procédé d’amination a pu être sensiblement réduit par la conception d’un nouveau type de réacteur photochimique capillaire. Ces améliorations techniques ont permis de rendre la synthèse plus productive, ce qui constitue un élément important d’un point de vue industriel.

Análisis de la estática para la síntesis de furfural por destilación reactiva

Hoy día, se presta la atención a los derivados de furano y a los procesos catalíticos alrededor de éstos para la conversión de los azúcares contenidos en la biomasa lignocelulósica. En este sentido, el furfural también recibe una especial atención como potencial químico para la producción de bioproductos y biocombustibles. Debido a las dificultades presentadas en la separación del furfural en el proceso convencional, en este trabajo se presenta el análisis de la separación para obtener furfural de alta pureza a partir de xilosa deshidratada por destilación reactiva como proceso no convencional, aplicando la teoría básica de análisis estático para obtener la mejor información del proceso de destilación reactiva, obteniendo un esquema tecnológico que permite alcanzar una fracción molar de furfural de aproximadamente 0.9.

Physical Design Methodologies for Low Power and Reliable 3D ICs

As the semiconductor industry struggles to maintain its momentum down the path following the Moore's Law, three dimensional integrated circuit (3D IC) technology has emerged as a promising solution to achieve higher integration density, better performance, and lower power consumption. However, despite its significant improvement in electrical performance, 3D IC presents several serious physical design challenges. In this dissertation, we investigate physical design methodologies for 3D ICs with primary focus on two areas: low power 3D clock tree design, and reliability degradation modeling and management. Clock trees are essential parts for digital system which dissipate a large amount of power due to high capacitive loads. The majority of existing 3D clock tree designs focus on minimizing the total wire length, which produces sub-optimal results for power optimization. In this dissertation, we formulate a 3D clock tree design flow which directly optimizes for clock power. Besides, we also investigate the design methodology for clock gating a 3D clock tree, which uses shutdown gates to selectively turn off unnecessary clock activities. Different from the common assumption in 2D ICs that shutdown gates are cheap thus can be applied at every clock node, shutdown gates in 3D ICs introduce additional control TSVs, which compete with clock TSVs for placement resources. We explore the design methodologies to produce the optimal allocation and placement for clock and control TSVs so that the clock power is minimized. We show that the proposed synthesis flow saves significant clock power while accounting for available TSV placement area. Vertical integration also brings new reliability challenges including TSV's electromigration (EM) and several other reliability loss mechanisms caused by TSV-induced stress. These reliability loss models involve complex inter-dependencies between electrical and thermal conditions, which have not been investigated in the past. In this dissertation we set up an electrical/thermal/reliability co-simulation framework to capture the transient of reliability loss in 3D ICs. We further derive and validate an analytical reliability objective function that can be integrated into the 3D placement design flow. The reliability aware placement scheme enables co-design and co-optimization of both the electrical and reliability property, thus improves both the circuit's performance and its lifetime. Our electrical/reliability co-design scheme avoids unnecessary design cycles or application of ad-hoc fixes that lead to sub-optimal performance. Vertical integration also enables stacking DRAM on top of CPU, providing high bandwidth and short latency. However, non-uniform voltage fluctuation and local thermal hotspot in CPU layers are coupled into DRAM layers, causing a non-uniform bit-cell leakage (thereby bit flip) distribution. We propose a performance-power-resilience simulation framework to capture DRAM soft error in 3D multi-core CPU systems. In addition, a dynamic resilience management (DRM) scheme is investigated, which adaptively tunes CPU's operating points to adjust DRAM's voltage noise and thermal condition during runtime. The DRM uses dynamic frequency scaling to achieve a resilience borrow-in strategy, which effectively enhances DRAM's resilience without sacrificing performance. The proposed physical design methodologies should act as important building blocks for 3D ICs and push 3D ICs toward mainstream acceptance in the near future.

A Bayesian optimization algorithm for the nurse scheduling problem

A Bayesian optimization algorithm for the nurse scheduling problem is presented, which involves choosing a suitable scheduling rule from a set for each nurse’s assignment. Unlike our previous work that used GAs to implement implicit learning, the learning in the proposed algorithm is explicit, i.e. eventually, we will be able to identify and mix building blocks directly. The Bayesian optimization algorithm is applied to implement such explicit learning by building a Bayesian network of the joint distribution of solutions. The conditional probability of each variable in the network is computed according to an initial set of promising solutions. Subsequently, each new instance for each variable is generated by using the corresponding conditional probabilities, until all variables have been generated, i.e. in our case, a new rule string has been obtained. Another set of rule strings will be generated in this way, some of which will replace previous strings based on fitness selection. If stopping conditions are not met, the conditional probabilities for all nodes in the Bayesian network are updated again using the current set of promising rule strings. Computational results from 52 real data instances demonstrate the success of this approach. It is also suggested that the learning mechanism in the proposed approach might be suitable for other scheduling problems.

Raman Spectroscopy and DFT calculations for the Electronic Structure Characterization of Conjugated Polymers

In the last three decades, there has been a broad academic and industrial interest in conjugated polymers as semiconducting materials for organic electronics. Their applications in polymer light-emitting diodes (PLEDs), polymer solar cells (PSCs), and organic field-effect transistors (OFETs) offer opportunities for the resolution of energy issues as well as the development of display and information technologies1. Conjugated polymers provide several advantages including low cost, light weight, good flexibility, as well as solubility which make them readily processed and easily printed, removing the conventional photolithography for patterning2. A large library of polymer semiconductors have been synthesized and investigated with different building blocks, such as acenes or thiophene and derivatives, which have been employed to design new materials according to individual demands for specific applications. To design ideal conjugated polymers for specific applications, some general principles should be taken into account, including (i) side chains (ii) molecular weights, (iii) band gap and HOMO and LUMO energy levels, and (iv) suited morphology.3-6 The aim of this study is to elucidate the impact that substitution exerts on the molecular and electronic structure of π-conjugated polymers with outstanding performances in organic electronic devices. Different configurations of the π-conjugated backbones are analyzed: (i) donor-acceptor configuration, (ii) 1D lineal or 2D branched conjugated backbones, and (iii) encapsulated polymers (see Figure 1). Our combined vibrational spectroscopy and DFT study shows that small changes in the substitution pattern and in the molecular configuration have a strong impact on the electronic characteristics of these polymers. We hope this study can advance useful structure-property relationships of conjugated polymers and guide the design of new materials for organic electronic applications.

Synthetic Circuits for Feedback and Detection in Bacteria

Synthetic biology, by co-opting molecular machinery from existing organisms, can be used as a tool for building new genetic systems from scratch, for understanding natural networks through perturbation, or for hybrid circuits that piggy-back on existing cellular infrastructure. Although the toolbox for genetic circuits has greatly expanded in recent years, it is still difficult to separate the circuit function from its specific molecular implementation. In this thesis, we discuss the function-driven design of two synthetic circuit modules, and use mathematical models to understand the fundamental limits of circuit topology versus operating regimes as determined by the specific molecular implementation. First, we describe a protein concentration tracker circuit that sets the concentration of an output protein relative to the concentration of a reference protein. The functionality of this circuit relies on a single negative feedback loop that is implemented via small programmable protein scaffold domains. We build a mass-action model to understand the relevant timescales of the tracking behavior and how the input/output ratios and circuit gain might be tuned with circuit components. Second, we design an event detector circuit with permanent genetic memory that can record order and timing between two chemical events. This circuit was implemented using bacteriophage integrases that recombine specific segments of DNA in response to chemical inputs. We simulate expected population-level outcomes using a stochastic Markov-chain model, and investigate how inferences on past events can be made from differences between single-cell and population-level responses. Additionally, we present some preliminary investigations on spatial patterning using the event detector circuit as well as the design of stationary phase promoters for growth-phase dependent activation. These results advance our understanding of synthetic gene circuits, and contribute towards the use of circuit modules as building blocks for larger and more complex synthetic networks.

Sintonia automática de controladores PID: uma abordagem neuro - genética

Dissertação de dout. em Electrónica e Computação, Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2004

Trajetória profissional de professoras do ensino médio : sentidos e usos de tecnologias digitais na sala de aula

Tese (doutorado)—Universidade de Brasília, Instituto de Psicologia, Programa de Pós-Graduação em Processos de Desenvolvimento Humano e Saúde, 2016.

Feasibility study and flow scheduling optimization of a multi-product pipeline system

The first goal of this study is to analyse a real-world multiproduct onshore pipeline system in order to verify its hydraulic configuration and operational feasibility by constructing a simulation model step by step from its elementary building blocks that permits to copy the operation of the real system as precisely as possible. The second goal is to develop this simulation model into a user-friendly tool that one could use to find an “optimal” or “best” product batch schedule for a one year time period. Such a batch schedule could change dynamically as perturbations occur during operation that influence the behaviour of the entire system. The result of the simulation, the ‘best’ batch schedule is the one that minimizes the operational costs in the system. The costs involved in the simulation are inventory costs, interface costs, pumping costs, and penalty costs assigned to any unforeseen situations. The key factor to determine the performance of the simulation model is the way time is represented. In our model an event based discrete time representation is selected as most appropriate for our purposes. This means that the time horizon is divided into intervals of unequal lengths based on events that change the state of the system. These events are the arrival/departure of the tanker ships, the openings and closures of loading/unloading valves of storage tanks at both terminals, and the arrivals/departures of trains/trucks at the Delivery Terminal. In the feasibility study we analyse the system’s operational performance with different Head Terminal storage capacity configurations. For these alternative configurations we evaluated the effect of different tanker ship delay magnitudes on the number of critical events and product interfaces generated, on the duration of pipeline stoppages, the satisfaction of the product demand and on the operative costs. Based on the results and the bottlenecks identified, we propose modifications in the original setup.

The actinin family of actin crosslinking proteins: natural functions and potential applications in synthetic biology

Actinin and spectrin proteins are members of the Spectrin Family of Actin Crosslinking Proteins. The importance of these proteins in the cytoskeleton is demonstrated by the fact that they are common targets for disease causing mutations. In their most prominent roles, actinin and spectrin are responsible for stabilising and maintaining the muscle architecture during contraction, and providing shape and elasticity to the red blood cell in circulation, respectively. To carry out such roles, actinin and spectrin must possess important mechanical and physical properties. These attributes are desirable when choosing a building block for protein-based nanoconstruction. In this study, I assess the contribution of several disease-associated mutations in the actinin-1 actin binding domain that have recently been linked to a rare platelet disorder, congenital macrothrombocytopenia. I investigate the suitability of both actinin and spectrin proteins as potential building blocks for nanoscale structures, and I evaluate a fusion-based assembly strategy to bring about self-assembly of protein nanostructures. I report that the actinin-1 mutant proteins display increased actin binding compared to WT actinin-1 proteins. I find that both actinin and spectrin proteins exhibit enormous potential as nano-building blocks in terms of their stability and ability to self-assemble, and I successfully design and create homodimeric and heterodimeric bivalent building blocks using the fusion-based assembly strategy. Overall, this study has gathered helpful information that will contribute to furthering the advancement of actinin and spectrin knowledge in terms of their natural functions, and potential unnatural functions in protein nanotechnology.

Cognitive Assessment System (CAS): Psychometric studies with Portuguese children from 7 to 15 years.

The Cognitive Assessment System (CAS) is a new measure of cognitive abilities based on the Planning, Attention, Simultaneous and Successive (PASS) Theory. This theory is derived from research in neuropsychological and cognitive Psychology with particular emphasis on the work of Luria (1973). According to Naglieri (1999) and Naglieri and Das (1997), the PASS cognitive processes are the basic building blocks of human intellectual functioning. Planning processes provide cognitive control, utilization of processes and knowledge, intentionality, and self-regulation to achieve a desired goal; Attention processes provide focused, selective cognitive activity and resistance to distraction; and, Simultaneous and Successive processes are the two forms of operating on information. The PASS theory has had a strong empirical base prior to the publication of the CAS (see Das, Naglieri & Kirby, 1994), and its research foundation remains strong (see Naglieri, 1999; Naglieri & Das, 1997). The four basic psychological processes can be used to (1) gain an understanding of how well a child thinks; (2) discover the child’s strengths and needs, which can then be used for effective differential diagnosis; (3) conduct fair assessment; and (4) select or design appropriate interventions. Compared to the traditional intelligence tests, including IQ tests, the Cognitive Assessment System (CAS) has the great advantage of relying on a modern theory of cognitive functioning, linking theory with practice.

Unlocking the Potential of Women in the Rural Development Process of Republic of Srpska: The Role of Extension Service

In Bosnia Herzegovina the development of clear policy objectives and endorsement of a long-term, coherent and mutual agricultural and rural development policy have also been affected by structural problems: a lack of reliable information on population and other relevant issues, the absence of an adequate land registry system and cadastre. Moreover in BiH the agricultural and rural sectors are characterized by many factors that have typically affected transition countries such as land fragmentation, lack of agricultural mechanization and outdated production technologies, and rural aging, high unemployment and out-migration. In such a framework the condition and role of women in rural areas suffered for the lack of gender disaggregated data and a consequent poor information that lead to the exclusion of gender related questions in the agenda of public institutions and to the absence of targeted policy interventions. The aim of the research is to investigate the role and condition of women in the rural development process of Republic of Srpska and to analyze the capacity of extension services to stimulate their empowerment. Specific research questions include the status of women in the rural areas of Republic of Srpska, the role of government in fostering the empowerment of rural women, and the role of the extension service in supporting rural women. The methodology - inspired by the case study method developed by R. Yin - is designed along the three specific research questions that are used as building blocks. Each of the three research questions is investigated with a combination of methodological tools - including surveys, experts interviews and focus groups - aimed to overcome the lack of data and knowledge that characterize the research objectives.

Peptide-based low molecular weight gelators for the preparation of self-assembled materials

Low molecular weight gelators (LMWGs) based on pseudo-peptides are here studied for the preparation of supramolecular materials. These compounds can self-assemble through non-covalent interactions such as hydrogen bonds and π-π stacking, forming fibres and gels. A wide variety of materials can be prepared starting from these building blocks, which can be tuned and functionalised depending on the application. In this work, derivatives of the three aromatic amino acids L-Phenylalanine, L-Tyrosine and L-DOPA (3,4-dihydroxiphenylalanine) were synthesised and tested as gelators for water or organic solvents. First, the optimal gelating conditions were studied for each compound, varying concentration, solvent and trigger. Then the materials were characterised in terms of mechanical properties and morphology. Water remediation from dye pollution was the first focus of this work. Organogels were studied as absorbent of dyes from contaminated water. Hydrogels functionalised with TiO2 nanoparticles and graphene platelets were proposed as efficient materials for the photo-degradation of dyes. An efficient method for the incorporation of graphene inside hydrogels using the gelator itself as dispersant was proposed. In these materials a high storage modulus coexists with good self-healing and biocompatibility. The incorporation of a mineral phase inside the gel matrix was then investigated, leading to the preparation of composite organic/inorganic materials. In a first study, the growth of calcium carbonate crystals was achieved inside the hydrogel, which preserved its structure after crystal formation. Then the self-assembled fibres made of LMWGs were used for the first time instead of the polymeric ones as reinforcement inside calcium phosphate cements (CPCs) for bone regeneration. Gel-to-crystal transitions occurring with time in a metastable gel were also examined. The formation of organic crystals in gels can be achieved in multicomponent systems, in which a second gelator constitutes the independent gel network. Finally, some compounds unable to gelate were tested as underwater adhesives.