Design and synthesis of novel quinolones directed to the Plasmodium falciparum bc1 protein complex

Tese de Doutoramento, Química, Especialização em Química Orgânica, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2016

Design gráfico para televisão

Dissertação para obtenção do grau de Mestre em Design de Comunicação apresentada na Universidade de Lisboa - Faculdade de Arquitetura.

Design, Fabrication, and Mechanical Property Analysis of 3D Nanoarchitected Materials

Recent developments in micro- and nanoscale 3D fabrication techniques have enabled the creation of materials with a controllable nanoarchitecture that can have structural features spanning 5 orders of magnitude from tens of nanometers to millimeters. These fabrication methods in conjunction with nanomaterial processing techniques permit a nearly unbounded design space through which new combinations of nanomaterials and architecture can be realized. In the course of this work, we designed, fabricated, and mechanically analyzed a wide range of nanoarchitected materials in the form of nanolattices made from polymer, composite, and hollow ceramic beams. Using a combination of two-photon lithography and atomic layer deposition, we fabricated samples with periodic and hierarchical architectures spanning densities over 4 orders of magnitude from ρ=0.3-300kg/m³ and with features as small as 5nm. Uniaxial compression and cyclic loading tests performed on different nanolattice topologies revealed a range of novel mechanical properties: the constituent nanoceramics used here have size-enhanced strengths that approach the theoretical limit of materials strength; hollow aluminum oxide (Al₂O₃) nanolattices exhibited ductile-like deformation and recovered nearly completely after compression to 50% strain when their wall thicknesses were reduced below 20nm due to the activation of shell buckling; hierarchical nanolattices exhibited enhanced recoverability and a near linear scaling of strength and stiffness with relative density, with E∝ρ^1.04 and σy∝ρ^1.17 for hollow Al₂O₃ samples; periodic rigid and non-rigid nanolattice topologies were tested and showed a nearly uniform scaling of strength and stiffness with relative density, marking a significant deviation from traditional theories on “bending” and “stretching” dominated cellular solids; and the mechanical behavior across all topologies was highly tunable and was observed to strongly correlate with the slenderness λ and the wall thickness-to-radius ratio t/a of the beams. These results demonstrate the potential of nanoarchitected materials to create new highly tunable mechanical metamaterials with previously unattainable properties.

APPLICATION OF AN IMPUTATION METHOD FOR GEOSPATIAL INVENTORY OF FOREST STRUCTURAL ATTRIBUTES ACROSS MULTIPLE SPATIAL SCALES IN THE LAKE STATES, U.S.A.

Credible spatial information characterizing the structure and site quality of forests is critical to sustainable forest management and planning, especially given the increasing demands and threats to forest products and services. Forest managers and planners are required to evaluate forest conditions over a broad range of scales, contingent on operational or reporting requirements. Traditionally, forest inventory estimates are generated via a design-based approach that involves generalizing sample plot measurements to characterize an unknown population across a larger area of interest. However, field plot measurements are costly and as a consequence spatial coverage is limited. Remote sensing technologies have shown remarkable success in augmenting limited sample plot data to generate stand- and landscape-level spatial predictions of forest inventory attributes. Further enhancement of forest inventory approaches that couple field measurements with cutting edge remotely sensed and geospatial datasets are essential to sustainable forest management. We evaluated a novel Random Forest based k Nearest Neighbors (RF-kNN) imputation approach to couple remote sensing and geospatial data with field inventory collected by different sampling methods to generate forest inventory information across large spatial extents. The forest inventory data collected by the FIA program of US Forest Service was integrated with optical remote sensing and other geospatial datasets to produce biomass distribution maps for a part of the Lake States and species-specific site index maps for the entire Lake State. Targeting small-area application of the state-of-art remote sensing, LiDAR (light detection and ranging) data was integrated with the field data collected by an inexpensive method, called variable plot sampling, in the Ford Forest of Michigan Tech to derive standing volume map in a cost-effective way. The outputs of the RF-kNN imputation were compared with independent validation datasets and extant map products based on different sampling and modeling strategies. The RF-kNN modeling approach was found to be very effective, especially for large-area estimation, and produced results statistically equivalent to the field observations or the estimates derived from secondary data sources. The models are useful to resource managers for operational and strategic purposes.

Development of Physics-based Models and Design Optimization of Power Electronic Conversion Systems

The main objective for physics based modeling of the power converter components is to design the whole converter with respect to physical and operational constraints. Therefore, all the elements and components of the energy conversion system are modeled numerically and combined together to achieve the whole system behavioral model. Previously proposed high frequency (HF) models of power converters are based on circuit models that are only related to the parasitic inner parameters of the power devices and the connections between the components. This dissertation aims to obtain appropriate physics-based models for power conversion systems, which not only can represent the steady state behavior of the components, but also can predict their high frequency characteristics. The developed physics-based model would represent the physical device with a high level of accuracy in predicting its operating condition. The proposed physics-based model enables us to accurately develop components such as; effective EMI filters, switching algorithms and circuit topologies [7]. One of the applications of the developed modeling technique is design of new sets of topologies for high-frequency, high efficiency converters for variable speed drives. The main advantage of the modeling method, presented in this dissertation, is the practical design of an inverter for high power applications with the ability to overcome the blocking voltage limitations of available power semiconductor devices. Another advantage is selection of the best matching topology with inherent reduction of switching losses which can be utilized to improve the overall efficiency. The physics-based modeling approach, in this dissertation, makes it possible to design any power electronic conversion system to meet electromagnetic standards and design constraints. This includes physical characteristics such as; decreasing the size and weight of the package, optimized interactions with the neighboring components and higher power density. In addition, the electromagnetic behaviors and signatures can be evaluated including the study of conducted and radiated EMI interactions in addition to the design of attenuation measures and enclosures.

Pressure Induced Structural Changes and Gas Diffusion Pathways in Monomeric Fluorescent Proteins

Fluorescent proteins (FPs) are extremely valuable biochemical markers which have found a wide range of applications in cellular and molecular biology research. The monomeric variants of red fluorescent proteins (RFPs), known as mFruits, have been especially valuable for in vivo applications in mammalian cell imaging. Fluorescent proteins consist of a chromophore caged in the beta-barrel protein scaffold. The photophysical properties of an FP is determined by its chromophore structure and its interactions with the protein barrel. Application of hydrostatic pressure on FPs results in the modification of the chromophore environment which allows a systematic study of the role of the protein-chromophore interactions on photophysical properties of FPs. Using Molecular Dynamics (MD) computer simulations, I investigated the pressure induced structural changes in the monomeric variants mCherry, mStrawberry, and Citrine. The results explain the molecular basis for experimentally observed pressure responses among FP variants. It is found that the barrel flexibility, hydrogen bonding interactions and chromophore planarity of the FPs can be correlated to their contrasting photophysical properties at vaious pressures. I also investigated the oxygen diffusion pathways in mOrange and mOrange2 which exhibit marked differences in oxygen sensitivities as well as photostability. Such computational identifications of structural changes and oxygen diffusion pathways are important in guiding mutagenesis efforts to design fluorescent proteins with improved photophysical properties.

Structural Health Monitoring Inside Concrete and Grout Using the Wireless Identification and Sensing Platform (WISP)

This research investigates the implementation of battery-less RFID sensing platforms inside lossy media, such as, concrete and grout. Both concrete and novel grouts can be used for nuclear plant decommissioning as part of the U.S. Department of Energy’s (DOE’s) cleanup projects. Our research examines the following: (1) material characterization, (2) analytical modeling of transmission and propagation losses inside lossy media, (3) maximum operational range of RFID wireless sensors embedded inside concrete and grout, and (4) best positioning of antennas for achieving longer communication range between RFID antennas and wireless sensors. Our research uses the battery-less Wireless Identification and Sensing Platform (WISP) which can be used to monitor temperature, and humidity inside complex materials. By using a commercial Agilent open-ended coaxial probe (HP8570B), the measurements of the dielectric permittivity of concrete and grout are performed. Subsequently, the measured complex permittivity is used to formulate analytical Debye models. Also, the transmission and propagation losses of a uniform plane wave inside grout are calculated. Our results show that wireless sensors will perform better in concrete than grout. In addition, the maximum axial and radial ranges for WISP are experimentally determined. Our work illustrates the feasibility of battery-less wireless sensors that are embedded inside concrete and grout. Also, our work provides information that can be used to optimize the power management, sampling rate, and antenna design of such sensors.

Design of products to honor people post mortem

The cemeterial units, are places of social practices of everyday life and worship and the tomb where nostalgia can be externalized and the memory of the deceased revered. In Western societies we can find a category of artifacts meant to evoke the memory or honor the dead. In this paper we we mention three examples of products that enabled a reflection on the concepts that gave rise to their ways, and that risks to fit them into a new "material culture", in that it may have created a break with the traditional system codes and standards shared by companies, and its manifestations in relation to the physical creation of this category of products. This work offers a reflection on the Design Products.What probably makes it special is the field where it is located: the design of products in one post mortem memory. Usually made of granite rock or marble, have the form of plate or tablet, open book or rolled sheet. On one side have a photograph of the person who intend to honor and inscriptions. The thought of inherent design of this work put on one side the intricate set of emotions that this type of product can generate, and other components more affordable, and concerning the form, function and object interactions with users and with use environments. In the definition of the problem it was regarded as mandatory requirements: differentiation, added value and durability as key objectives.The first two should be manifested in the various components / product attributes. The aesthetic and material/structural durability of product necessarily imply the introduction of qualifying terms and quantitative weights, which positively influence the generation and evaluation of concepts based on the set of 10 principles for the project that originated a matrix as a tool to aid designing products. The concrete definition of a target audience was equally important. At this stage, the collaboration of other experts in the fields of psychology and sociology as disciplines with particular ability to understand individuals and social phenomena respectively was crucial. It was concluded that a product design to honor someone post mortem, should abandon the more traditional habits and customs to focus on identifying new audiences. Although at present it can be considered a niche market, it is believed that in the future may grow as well as their interest in this type of products.

Engineering design of an integrated sustainable process system for cassava biobased materials

Cassava contributes significantly to biobased material development. Conventional approaches for its bio-derivative-production and application cause significant wastes, tailored material development challenges, with negative environmental impact and application limitations. Transforming cassava into sustainable value-added resources requires redesigning new approaches. Harnessing unexplored material source, and downstream process innovations can mitigate challenges. The ultimate goal proposed an integrated sustainable process system for cassava biomaterial development and potential application. An improved simultaneous release recovery cyanogenesis (SRRC) methodology, incorporating intact bitter cassava, was developed and standardized. Films were formulated, characterised, their mass transport behaviour, simulating real-distribution-chain conditions quantified, and optimised for desirable properties. Integrated process design system, for sustainable waste-elimination and biomaterial development, was developed. Films and bioderivatives for desired MAP, fast-delivery nutraceutical excipients and antifungal active coating applications were demonstrated. SRRC-processed intact bitter cassava produced significantly higher yield safe bio-derivatives than peeled, guaranteeing 16% waste-elimination. Process standardization transformed entire root into higher yield and clarified colour bio-derivatives and efficient material balance at optimal global desirability. Solvent mass through temperature-humidity-stressed films induced structural changes, and influenced water vapour and oxygen permeability. Sevenunit integrated-process design led to cost-effectiveness, energy-efficient and green cassava processing and biomaterials with zero-environment footprints. Desirable optimised bio-derivatives and films demonstrated application in desirable in-package O2/CO2, mouldgrowth inhibition, faster tablet excipient nutraceutical dissolutions and releases, and thymolencapsulated smooth antifungal coatings. Novel material resources, non-root peeling, zero-waste-elimination, and desirable standardised methodology present promising process integration tools for sustainable cassava biobased system development. Emerging design outcomes have potential applications to mitigate cyanide challenges and provide bio-derivative development pathways. Process system leads to zero-waste, with potential to reshape current style one-way processes into circular designs modelled on nature's effective approaches. Indigenous cassava components as natural material reinforcements, and SRRC processing approach has initiated a process with potential wider deployment in broad product research development. This research contributes to scientific knowledge in material science and engineering process design.

A test of basic psychological needs theory in young soccer players: Time-lagged design at the individual and team levels

Within the framework of basic psychological needs theory (Deci & Ryan, 2000), multilevel structural equation modeling (MSEM) with a time-lagged design was used to test a mediation model examining the relationship between perceptions of coaches’ interpersonal styles (autonomy supportive and controlling), athletes’ basic psychological needs (satisfaction and thwarting), and indicators of well-being (subjective vitality) and ill-being (burnout), estimating separately between and within effects. The participants were 597 Spanish male soccer players aged between 11 and 14 years (M = 12.57, SD = 0.54) from 40 teams who completed a questionnaire package at two time points in a competitive season. Results revealed that at the individual level, athletes’ perceptions of autonomy support positively predicted athletes’ need satisfaction (autonomy, competence, and relatedness), whereas athletes’ perceptions of controlling style positively predicted athletes’ need thwarting (autonomy, competence, and relatedness). In turn, all three athletes’ need satisfaction dimensions predicted athletes’ subjective vitality and burnout (positively and negatively, respectively), whereas competence thwarting negatively predicted subjective vitality and competence and relatedness positively predicted burnout. At the team level, team perceptions of autonomy supportive style positively predicted team autonomy and relatedness satisfaction. Mediation effects only appeared at the individual level.

Determinants of the Design and Use of PMS in Portuguese Government Agencies: A Complementary Theoretical Approach

Performance measurement is seen as a main pillar of public management reforms. However, prior research did not mitigate the level of ambiguity on PMS development and use and many questions left unanswered. Our findings provide knowledge on the design and use of PMS in the public sector answer- ing to calls for a complementary approach among institutional and contingency factors. The authors find that the design of PMS and the use of performance information for external purposes are increased to legitimate the organizational’ work and to obtain external support. Moreover, structural variables such as type of agency and management autonomy are also determinants on the organizational responses. Finally, the authors find some coupling between the design of PMS and outcomes. So, both contingent and institutional approaches play an important role on the empirical model.

Agronomic, morphogenic and structural characteristics of Marandu grass in silvopastoral systems composed of babassu palm and grass monoculture.

This study evaluated the agronomic, morphogenic and structural characteristics of palisadegrass (Urochloa brizantha) in silvopastoral systems (SSP?s) composed of babassu palms (Attalea speciosa) and grass monoculture in the Pre-Amazon region of the state of Maranhão, Brazil. The study followed a completely randomized design, with the arrangement in split plots with six replicates for the evaluation of agronomic characteristics and 30 repetitions for the morphogenic and structural characteristics. The plots were divided into pasture environments with different palm densities (monoculture, 80, 131, 160 palms.ha-¹), and the subplots were divided into the different seasons (rainy and dry).

Design, production and testing of innovative key components of HEV/BEV powertrains

Through modelling activity, experimental campaigns, test bench and on-field validation, a complete powertrain for a BEV has been designed, assembled and used in a motorsport competition. The activity can be split in three main subjects, representing the three key components of an BEV vehicle. First of all a model of the entire powertrain has been developed in order to understand how the various design choices will influence the race lap-time. The data obtained was then used to design, build and test a first battery pack. After bench tests and track tests, it was understood that by using all the cell charac-teristics, without breaking the rules limitations, higher energy and power densities could have been achieved. An updated battery pack was then designed, produced and raced with at Motostudent 2018 re-sulting in a third place at debut. The second topic of this PhD was the design of novel inverter topologies. Three inverters have been de-signed, two of them using Gallium Nitride devices, a promising semiconductor technology that can achieve high switching speeds while maintaining low switching losses. High switching frequency is crucial to reduce the DC-Bus capacitor and then increase the power density of 3 phase inverters. The third in-verter uses classic Silicon devices but employs a ZVS (Zero Voltage Switching) topology. Despite the in-creased complexity of both the hardware and the control software, it can offer reduced switching losses by using conventional and established silicon mosfet technology. Finally, the mechanical parts of a three phase permanent magnet motor have been designed with the aim to employ it in UniBo Motorsport’s 2020 Formula Student car.

Design of biobased additives for tuning the properties of biopolymers

This work mainly arises from the necessity to support the rapid introduction of different biobased polymers that the industrial sector has been facing lately. Indeed, while considerable efforts are being made to find environmentally and economically sustainable materials, less attention is paid to their need to be properly compounded to fulfil increasingly rigorous technical and quality requirements. Therefore, there is a strong demand for the development of a novel generation of compatible additives able to improve the properties of biobased polymers while respecting sustainability. With this in mind, a new class of biobased plasticizers is herein proposed. Five different ketal-diesters were selectively synthesized starting from levulinic acid, a promising renewable chemical platform. These molecules were added to poly(vinyl chloride) as model polymer to test their plasticizing effectiveness. Complete morphological, thermal and viscoelastic characterizations showed a clear correlation between the structural features of the ketal-esters and the properties of the material. In addition, no significant leaching was found in both hydrophilic and lipophilic environments. Importantly, the proposed ketal-diesters performed comparably and, in some cases, even better than commercial plasticizers. The same molecules were then added to bacterial poly(3-hydroxybutyrate), a semicrystalline polyester characterized by poor thermal and mechanical properties. Morphology assessments showed no phase separation and the plasticizing effectiveness was confirmed by thermal and viscoelastic analyses, while leaching tests showed low extraction values. Readily usable fractions with controlled structure and tailored properties were obtained from highly heterogeneous industrial grade Kraft lignin. These fractions were then added to poly(vinyl alcohol). Promising preliminary results in terms of compatibility were achieved, with thermograms showing only one glass transition temperature. Finally, a fully biobased glycerol-trilevulinate was successfully synthesized by means of a mild and solvent-free route. Its plasticizing effectiveness was evaluated on poly(vinyl chloride), showing a significant decrease of the glass transition temperature of the material.

Computational resources for structural and metagenomic characterization of functions in bacteria and bacterial communities. Antimicrobial resistance, pathways for xenobiotic degradation and relationship between gut microbiome and ageing.

Prokaryotic organisms are one of the most successful forms of life, they are present in all known ecosystems. The deluge diversity of bacteria reflects their ability to colonise every environment. Also, human beings host trillions of microorganisms in their body districts, including skin, mucosae, and gut. This symbiosis is active for all other terrestrial and marine animals, as well as plants. With the term holobiont we refer, with a single word, to the systems including both the host and its symbiotic microbial species. The coevolution of bacteria within their ecological niches reflects the adaptation of both host and guest species, and it is shaped by complex interactions that are pivotal for determining the host state. Nowadays, thanks to the current sequencing technologies, Next Generation Sequencing, we have unprecedented tools for investigating the bacterial life by studying the prokaryotic genome sequences. NGS revolution has been sustained by the advancements in computational performance, in terms of speed, storage capacity, algorithm development and hardware costs decreasing following the Moore’s Law. Bioinformaticians and computational biologists design and implement ad hoc tools able to analyse high-throughput data and extract valuable biological information. Metagenomics requires the integration of life and computational sciences and it is uncovering the deluge diversity of the bacterial world. The present thesis work focuses mainly on the analysis of prokaryotic genomes under different aspects. Being supervised by two groups at the University of Bologna, the Biocomputing group and the group of Microbial Ecology of Health, I investigated three different topics: i) antimicrobial resistance, particularly with respect to missense point mutations involved in the resistant phenotype, ii) bacterial mechanisms involved in xenobiotic degradation via the computational analysis of metagenomic samples, and iii) the variation of the human gut microbiota through ageing, in elderly and longevous individuals.