Developing personalized cancer therapies based on cancer genomics methodologies forms the basis for future cancer therapeutics. A genomics platform was developed based on canine cancer to produce a proof-of-concept for personalized genomics led therapeutic choices but also developing personalized therapeutics for canine cancer patients themselves. The platform identified the genetic state of a canine cancer patient within two drugable pathways; p53 and HSP90/IRF1. The former gene was wild-type p53 thus directing the use of p53 activating molecules. The latter mutations in both HSP90 and IRF1 suggested an investigation into HSP90 and interferon signalling molecules as drug leads. Drugs that target both of these pathways were subsequently used to measure drug effects in cell line models but also to identify novel biomarkers of drug responses. My study focused on the effect of the HSP90-inhibitor Ganetespib had on its client proteins, particularly IRF-1. Briefly my results indicated the following:(i) Ganetespib downregulated IRF-1 protein levels in A375 cell lines and this attenuation was not mediated by either MDM2 or CHIP (E3 ligase). IFNγ- induced IRF-1 was also observed to be downregulated when Ganetespib was used in combination therapy.(ii) Insitu proximity ligation assay showed induced HSC70 upregulation upon HSP90 inhibition by Ganetespib and HSC70/MDM2 complexes were seen to be stabilized compared to the usage of MDM2/p53 inhibitor-nutlin. I hypothesize that MDM2/HSC70 complex might chaperon IRF-1 into lysosome for degradation via chaperon mediated autophagy pathway. (iii) My results also indicate that Ganetespib can downregulate IFN γ- induced PDL-1 expression in melanoma cell lines. Pre-sensitizing the cells with Ganetespib prior to the addition of IFNγ could attenuate PDL-1 to basal levels. (iv) My results also showed that the downregulation of PDL-1 by Ganetespib is an IRF-1 dependent mechanism. Therefore, my results suggest that HSP90 represents an important emerging target for cancer therapy because its inactivation results in the simultaneous blockade of multiple signalling pathways and can also sensitize tumor cells to other anticancer agents. Targeting HSP90 could also help to disrupt PD1/PDL- 1 interaction and activate immune system to recognise tumor cells. I conclude that HSP90 and IRF-1 play a critical role in types II interferon pathways and these findings establish a novel basis for the design of future Ganetespib-based combinatorial approaches to improve patient outcomes in this disease. These approaches finally demonstrate that cancer genomics can stratify choice of cancer drugs used on patients but also provide evidence that cancer patient samples can be used for the specific stratification of cancer drug choice based on cancer genomics data.

Dynamic combinatorial chemistry (DCC) is a powerful tool to identify new ligands for biological targets. In the technique, library synthesis and hit identification are neatly combined into a single step. A labile functionality between fragments allows the biological target to self-select binders from a dynamic combinatorial library (DCL) of interconverting building blocks. The scope of suitable reversible reactions that proceed under thermodynamic control in physiological conditions has been gradually expanded over the last decades, however DCC has thus far failed to gain traction as a technique appropriate for drug discovery in the pharmaceutical industry. The constraints placed on library size by validated analytical techniques, and the effort-intensive reality of this academically elegant concept have not allowed DCC to develop into a broad-platform technique to compete with the high-throughput screening campaigns favoured by medicinal chemists. This thesis seeks to develop DCL analysis techniques, in an effort to increase the library size and accelerate the analysis of DCC experiments. Using a 19F-labelled core scaffold, we constructed a DCL that could be monitored non-invasively by 19F NMR. Building on NMR techniques developed by fragment screening and non-biological DCC campaigns, the method was developed to circumvent the undesired equilibrium-perturbing side effects arising from sample-consuming analytical methods. The N-acylhydrazone (NAH) DCL equilibrated rapidly at pH 6.2 using 4-amino-L-phenylalanine (4-APA) as a novel, physiologically benign, nucleophilic catalyst. The DCL was designed to target b-ketoacyl-ACP synthase III (FabH), an essential bacterial enzyme and antibiotic target. From the 5-membered DCL, a single combination was identified as a privileged structure by our 19F NMR method. The result correlated well with an in vitro assay, validating 19F NMR as a tool for DCL screening. During the 19F NMR study we identified an established antimicrobial compound, 4,5- dichloro-1,2-dithiole-3-one (HR45), to have potential as a core scaffold from which to develop future DCLs targeting FabH. Despite the potentially tractable chemistry of HR45 for DCC, lack of knowledge around the inhibitory mechanism of the compound prevented us from proceeding. Thus, we used mass spectrometry, NMR and molecular modelling to show that HR45 acts by forming a covalent adduct with S. aureus FabH. The 5-chloro substituent directs attack from the nucleophilic thiol side chain of the essential active site cysteine-112 residue via a Michael-type addition elimination mechanism. Although interesting, this mechanism disfavoured the use of HR45 as a core scaffold for NAH exchange in a DCC campaign. Electrospray ionisation mass spectrometry (ESI-MS) is a powerful technique that allows for larger DCLs by eliminating the size-limitations imposed by the need for spectral or chromatographic resolution of DCL members. We developed a 4-APAcatalysed NAH library targeting the pyridoxal 5’-phosphate (PLP) dependent enzyme 7,8-diaminopelargonic acid synthase (BioA), an essential enzyme in the biotin biosynthesis pathway. We exploited the aldehyde moiety of PLP to form an NAH DCL with a panel of hydrazides, and used the BioA isozymes from M. tuberculosis (Mtb) and E. coli to template the library. A combination of buffer exchange and denaturing ESI-MS allowed us to conduct a DCC experiment with a 29-member DCL. Hits from the DCC experiment correlated well with differential scanning fluorimetry (DSF) results. Of these hits, 5 compounds were selected for further study. In vivo activity was displayed by 2 compounds against E. coli and the ESKAPE pathogen A. baumannii. The identification of compounds with antibacterial activity from a DCL further validates ESI-MS as a platform technology for drug discovery.

The vast supply of different smartphone makes and models, along  with their  accompanying operating  systems,  increase the  demand  for  an  all-in-one  development  solution.   Quite a  few  approaches  to  solving  this  problem  have  cropped  up over the years, ranging from purely web-oriented solutions to something more akin to a native application.   React Native and Progressive Web App development are two different approaches,  both new and promising,  on this spectrum.   This thesis evaluates these approaches in a standardized way using the  ISO  25010 Product  Quality  Model to  gain  insight  into these  types  of  cross-platform  development  as  well  as  how well  such  an  evaluation  works  in  this  context.   The  results show that, while not a perfect fit, a standardized evaluation brings forward less obvious aspects of the development process and contributes with a helpful structure to the evaluation process.

This master thesis aimed to develop a prototype of a hardware platform which allowed digital communication as well as DC power to be transmitted over one pair of wires. The prototype was used as a pre-study for Axis Communications AB that wanted a bit rate high enough to transmit digital audio, as well as enough power to supply a set of speakers. The prototype included one circuit to send power and data (master), as well as two receivers (slaves). With this configuration data rates of up to 17 Mbps were achieved as well as an output power of 90 W from master. The data was transmitted on a RS-485 bus type, which was AC coupled to a 48 V DC bias. Because of the AC coupling, the bit stream needed to alternate, therefore Manchester encoded data, or similar, was recommended. The receiver cards included a buck converter to supply the circuits with a stable 5 V DC. The converters needed at least 10 V supply voltage to function, which gave a theoretical max range in cabling when accounting for voltage drop in the cables. For a 0.75 mm² power cord at max allowed current, this range was 500 metres per wire.

At the intersection of digital identities and new language and social practice online is the concept of searchable talk (ST). ST describes the process of tagging discourse in a social networking service (SNS) with a hashtag (#), allowing it to be searchable by others. Although originating in Twitter, ST has expanded into other SNS, and is used therein not only to mark language-based posts, but also multimodal posts and images. While scholars have elucidated the structure and function of ST, their studies have primarily examined ST within language-based posts; few have researched ST with respect to images and other types of multimodal environments. In addition, ST has primarily been explored in its SNS of origin, Twitter. This project directly addresses these gaps by adopting a social semiotic approach to ST in three SNS with very different technological affordances, Twitter, Tumblr, and Pinterest. Through a multimodal discourse analysis (Kress, 2009) combining both linguistic and other visual methods, I ask how visual and linguistic choices operate semiotically across SNS environments with different affordances and constraints. Specifically, I uncover the multiple meanings of Beyoncé across a data set of 300 tweets, posts, and pins composed from entering #Beyoncé in the search engine of each SNS. I argue that 13 meaning-based identity categories emerge for Beyoncé, and link these meanings to their visual and linguistic expressions. I then compare these findings across modes and across platforms. Ultimately, I assert that this cross-platform approach elucidates Beyoncé as a cultural object subject to reinterpretation where #Beyoncé means much more than just “Beyoncé.” That is, when considering its multiple roles and meanings, #Beyoncé becomes a site of visual and linguistic indexicality in a process of entextualization. In this process, it is SNS users’ reinterpretations – linguistically and visually – that realize racist, sexist, and hegemonic Discourses, as well as those of emancipation and resistance.

Un grand nombre de traitements sont aujourd'hui disponibles pour la cancérologie, dont l'objectif est d'éliminer tous les tissus cancéreux en minimisant les dommages occasionnés sur les tissus sains. La chimio-embolisation est considérée comme un régime de traitement localisé, préconisé pour certains cancers. Cependant, le ciblage des tumeurs profondément enfouies par chimio-embolisation est actuellement limité en raison de la taille des cathéters. Compte tenu des échelles envisagées, l'utilisation des microrobots magnétiquement guidés est l'une des approches les plus prometteuses. L'objectif de cette thèse consiste à développer les outils permettant à des microrobots endovasculaires (ou transporteurs magnétiques), de naviguer dans le corps humain, en utilisant les gradients magnétiques d'un appareil IRM clinique amélioré. Pour cela, une compréhension approfondie de l'environnement d'évolution du microrobot est une étape au préalable, en vue d'établir des stratégies de navigation adéquates. La variation des paramètres physiologiques de l'humain et l'utilisation d'un scanner IRM nécessitent d'une part, une robustesse du contrôleur vis-à-vis des erreurs de modélisation, et d'autre part, l'anticipation du comportement du système. A cet effet, la commande prédictive, trouve ici toute son efficacité pour résoudre les problèmes de poursuite. En outre, une plateforme d'instrumentation a été conçue au sein du laboratoire en vue de démontrer les concepts proposés, et de valider les stratégies de navigation prédictives développées dans nos travaux. Puis, dans un deuxième temps, nous avons intégré ces approches dans une plateforme d'IRM clinique. / Today, many cancer treatments are available, whose goal is to kill the cancerous tissue and to minimize damage to healthy tissue. Chemoemobilization is considered as a targeting treatment recommended for some cancers. However, targeting tumor deeply buried using chemoemobilization is currently limited due to the size of the microcatheters. Taking into account the scales considered, the use of magnetically guided microrobots is one of the most promoting approaches. The objective of this thesis is to develop tools for endovascular microrobots (or carriers), navigate in the human body using magnetic gradients of an improved clinical MRI. For this, understanding microrobot evolution environment is a first step, in order to develop appropriate navigation strategies. The variation of the human physiological parameters and the use of MRI scanner require a robustness of the controller to the modeling errors, and the anticipation of the system behavior. For this, predictive control is fully effective to solve the tracking problem. In addition, an instrumentation platform was designed to demonstrate the proposed concepts and to validate the predictive navigation strategies developed in our work. Then, in a second step, we investigated these approaches in clinical MRI platform.

Veículos aéreos não-tripulados (VANTs) são relativamente recentes no meio acadêmico, onde muitas tecnologias e algoritmos vêm sendo pesquisados e desenvolvidos. A engenharia de software apliacada a este âmbito possui poucas abordagens em relação a sistemas autônomos e inteligentes, enquanto que sistemas multi-agentes e a programação orientada a agentes vêm sendo cada vez mais utilizadas. Este trabalho foca na aplicação do paradigma da programação orientada a agentes para o controle de VANTs, de modo a conceber um framework e utilizar arquitetura, teoria e ferramentas orientados a agentes como forma de prover uma abstração mais sofisticada para a programação de comportamentos inteligentes em VANTs. Na pesquisa, propõem-se o modelo UAVAS – Unmanned Aerial Vehicles AgentSpeak que é um framework de programação de comportamentos para VANTs que possui um modelo de abstração de veículos aéreos tripulados para veículos aéreos não-tripulados. Ao final, a pesquisa foi avaliada e validada por meio de resultados obtidos em simulações com a infraestrutura implementada. Dois estudos de caso foram realizados, um com ênfase nas comunicações inter-VANTs e cooperação de time, e outro com ênfase nas verificações dos mapeamentos de sinais com o envio de dados da infraestrutura. Para cada um dos casos, simuladores específicos foram criados no intuito de observar as características pertinentes de cada estudo de caso. / Unmanned aerial vehicles (UAVs) are relatively new in civilian context, where many technologies and algorithms have been the focus at much research and development. Software engineering applied to this field has few approaches in relation to autonomous systems and intelligent behavior development, while multi-agent system and agent-oriented programming are being increasingly used. This work focuses on applying the paradigm of agent-oriented programming for the control of UAVs, in order to design a framework and use architecture, theory and agent oriented tools as a way to provide a more sophisticated abstraction for programming intelligent behaviors in UAVs . The main contribution of this work is an architecture that allows the use of the Jason platform to program multiagent system which can control teams of autonomous unmanned aerial vehicles. In this research, we propose the UAVAS - Unmanned Aerial Vehicles AgentSpeak model, which is a framework to program intelligent behaviors to UAVs and owns an abstraction model of manned aircraft to unmanned aerial vehicles. At the end, the survey was evaluated and validated by means of results from simulations in the implemented infrastructure. Two case studies were performed, with emphasis on inter-UAV communication and cooperation of team, and the another one focusing on mapping verifications of data signals sent to the infrastructure. For each case, specific simulators have been created in order to observe the relevant characteristics of each case study.

COSTA, Philipp Bernardino. Uma abordagem para offloading em múltiplas plataformas móveis. 2014. 104 f. Dissertação (Mestrado em ciência da computação)- Universidade Federal do Ceará, Fortaleza-CE, 2014. / Submitted by Elineudson Ribeiro (elineudsonr@gmail.com) on 2016-07-12T15:14:02Z No. of bitstreams: 1 2014_dis_pbcosta.pdf: 2579064 bytes, checksum: 96c47daf2c7ccea16a7e2f6945cb1a7a (MD5) / Approved for entry into archive by Rocilda Sales (rocilda@ufc.br) on 2016-07-20T13:52:31Z (GMT) No. of bitstreams: 1 2014_dis_pbcosta.pdf: 2579064 bytes, checksum: 96c47daf2c7ccea16a7e2f6945cb1a7a (MD5) / Made available in DSpace on 2016-07-20T13:52:31Z (GMT). No. of bitstreams: 1 2014_dis_pbcosta.pdf: 2579064 bytes, checksum: 96c47daf2c7ccea16a7e2f6945cb1a7a (MD5) Previous issue date: 2014 / The mobile devices, like smartphones and tablets, have evolved considerably in last years in computational terms. Despite advances in their hardware, these devices have energy constraints regarded to their poor computing performance. Therefore, on this context, a new paradigm called Mobile Cloud Computing (MCC) has emerged. MCC studies new ways to extend the computational and energy resources, on mobile devices using the offloading techniques. A literature survey about MCC, has shown that there is no support heterogeneity on reported studies. In response, we propose a framework called MpOS (Multi-platform Offloading System), which supports the offloading technique in mobile application development, for two mobile platforms (Android and Windows Phone). Two case studies were developed with MpOS solution in order to evaluate the framework for each mobile platform. These case studies show how the offloading technique works on several perspectives. In BenchImage experiment, the offloading performance was analyzed, concerning to its execution on a remote execution site (a cloudlet on local network and public cloud in the Internet). The Collision application promotes the analysis of the offloading technique performance on real-time application, also using different serialization systems. In both experiments, results show some situations where it was better to run locally on smarphone, than performing the offloading operation and vice versa. / Os dispositivos móveis, especificamente os smartphones e os tablets, evoluíram bastante em termos computacionais nos últimos anos, e estão cada vez mais presentes no cotidiano das pessoas. Apesar dos avanços tecnológicos, a principal limitação desses dispositivos está relacionada com a questão energética e com seu baixo desempenho computacional, quando comparado com um notebook ou computador de mesa. Com base nesse contexto, surgiu o paradigma do Mobile Cloud Computing (MCC), o qual estuda formas de estender os recursos computacionais e energéticos dos dispositivos móveis através da utilização das técnicas de offloading. A partir do levantamento bibliográfico dos frameworks em MCC verificou-se, para o problema da heterogeneidade em plataformas móveis, ausência de soluções de offloading. Diante deste problema, esta dissertação apresenta um framework denominado de MpOS (Multiplataform Offloading System), que suporta a técnica de offloading, em relação ao desenvolvimento de aplicações para diferentes plataformas móveis, sendo desenvolvido inicialmente para as plataformas Android e Windows Phone. Para validação foram desenvolvidas para cada plataforma móvel, duas aplicações móveis, denominadas de BenchImage e Collision, que demonstram o funcionamento da técnica de offloading em diversos cenários. No caso do experimento realizado com BenchImage foi analisado o desempenho da aplicação móvel, em relação à execução local, no cloudlet server e em uma nuvem pública na Internet, enquanto no experimento do Collision (um aplicativo de tempo real) foi analisado o desempenho do offloading, utilizando também diferentes sistemas de serialização de dados. Em ambos os experimentos houve situações que era mais vantajoso executar localmente no smartphone, do que realizar a operação de offloading e vice-versa, por causa de diversos fatores associados com a qualidade da rede e com volume de processamento exigido nesta operação.

A Plataforma de Stewart é um dos exemplos mais populares dos manipuladores do tipo paralelo, disponibilizando 6 graus de liberdade, apresentando ao mesmo tempo propriedades superiores de precisão e relação peso/carga, quando comparadas com mecanismos do tipo serial, o que a converte em uma opção atrativa para ser aplicada como simulador de movimentos. Neste contexto, o presente trabalho estuda o controle de seguimento de trajetória de um Manipulador Plataforma Stewart (MPS) com atuadores hidráulicos para ser aplicado como simulador de movimentos de navios. O estudo envolve a análise da cinemática, dinâmica, e controle do manipulador, incluindo a modelagem matemática dos cilindros hidráulicos usados como atuadores. Atenção especial é dispendida à formulação da dinâmica do MPS no espaço de juntas, procurando demonstrar a propriedade de antissimmetría das Matrizes de Inércia e Coriolis. O controle proposto foi validado como estável pelo critério de Lyapunov, e, leva em consideração tanto o sistema mecânico da Plataforma de Stewart, quanto o sistema de acionamento hidráulico dos atuadores. Através de simulações de controle usando trajetórias similares às do movimento de um navio, comprovou-se que o sistema proposto consegue disponibilizar fielmente os movimentos de uma embarcação. / The Stewart Platform is one of the most representative examples of parallel manipulators. It has six degrees of freedoms, and superior precision and load/weight ratio when compared to serial manipulators, properties that make them suitable and attractive options for motion simulation applications. In this sense, this work focuses on robust tracking control design for a high load capacity hydraulically driven Stewart Platform manipulator, capable of vessel motion simulations. The kinematic, dynamic and control analysis of the manipulator are presented, as well as a mathematical model of the hydraulic cylinders used as actuators. Especial attention is given to the derivation of the manipulator dynamics formulation, the skew symmetric property of the Inertia and Coriolis matrices is carefully proven in both Cartesian and joint state spaces. The proposed controller takes into consideration the manipulator mechanical dynamics and the actuators hydraulic dynamics. Furthermore, the Lyapunov criteria is used to guarantee control closed loop stability. The control performance is verified by means of computer simulations.

The master´s thesis deals with mechanical design of mechanism ensuring moving of cab of simulator in shape of mechanism with Parallel kinematics structure including design of hydraulic drive circuit. The diploma thesis contains also calculation of forces in linear hydraulic motors, calculation of working speed of these motors and drawing documentation.