The Transformer, an attention-based deep learning architecture, has shown promising capabilities in both Natural Language Processing and Computer Vision. Recently, it has also been applied to time series classification, which has traditionally used statistical methods or the Gated Recurrent Unit (GRU). The aim of this project was to apply multivariate time series classification to evaluate Transformer-based models, in comparison with the traditional GRUs. The evaluation was done within the problem of startup success prediction at a venture and private equity firm called EQT. Four different Machine Learning (ML) models – the Univariate GRU, Multivariate GRU, Transformer Encoder, and an already existing implementation, the Time Series Transformer (TST) – were benchmarked using two public datasets and the EQT dataset which utilized an investor-centric data split. The results suggest that the TST is the best-performing model on EQT’s dataset within the scope of this project, with a 47% increase in performance – measured by the Area Under the Curve (AUC) metric – compared to the Univariate GRU, and a 12% increase compared to the Multivariate GRU. It was also the best, and third-best, performing model on the two public datasets. Additionally, the model also demonstrated the highest training stability out of all four models, and 15 times shorter training times than the Univariate GRU. The TST also presented several potential qualitative advantages such as utilizing its embeddings for downstream tasks, an unsupervised learning technique, higher explainability, and improved multi-modal compatibility. The project results, therefore, suggest that the TST is a viable alternative to the GRU architecture for multivariate time series classification within the investment domain. With its performance, stability, and added benefits, the TST is certainly worth considering for time series modeling tasks. / Transformern är en attention-baserad arkitektur skapad för djupinlärning som har demonsterat lovande kapacitet inom både naturlig språkbehandling och datorseende. Nyligen har det även tillämpats på tidsserieklassificering, som traditionellt har använt statistiska metoder eller GRU. Syftet med detta projekt var att tillämpa multivariat tidsserieklassificering för att utvärdera transformer-baserade modeller, i jämförelse med de traditionella GRUerna. Jämförelsen gjordes inom problemet med att klassificera vilka startup-företag som är potentiellt framgångsrika eller inte, och gjordes på ett risk- och privatkapitalbolag som heter EQT. Fyra olika maskininlärningsmodeller – Univariat GRU, Multivariat GRU, Transformer Encoder och en redan existerande implementering, TST – jämfördes med hjälp av två offentliga datamängder och EQT-datamängden som använde sig av en investerarcentrerad datauppdelning. Resultaten tyder på att TST är den modellen som presterar bäst på EQT:s datauppsättning inom ramen för detta projekt, med en 47% ökning i prestanda – mätt med AUC – jämfört med den univariata GRUn och en ökning på 12% jämfört med den multivariata GRUn. Det var också den bäst och tredje bäst presterande modellen på de två offentliga datamängderna. Modellen visade även den högsta träningsstabiliteten av alla fyra modellerna och 15 gånger kortare träningstider än den univariata GRUn. TST visade även flera potentiella kvalitativa fördelar som att använda dess inbäddningar för nedströmsuppgifter, en oövervakad inlärningsteknik, högre förklarabarhet och förbättrad multimodal kompatibilitet. Projektresultaten tyder därför på att TST är ett gångbart alternativ till GRUarkitekturen för multivariat tidsserieklassificering inom investeringsdomänen. Med sin prestanda, stabilitet och extra fördelar är TST verkligen värt att överväga för tidsseriemodelleringsproblem.

Kindling epileptogenesis has been associated with a number of different forms of neuroplasticity in the hippocampus, including mossy fibre sprouting and an increase in both intracellular calcium and zinc. The purpose of this thesis was to determine whether interfering with the influx of calcium via the voltage gated calcium channels would interfere with kindling- induced plasticity. Both kindled and control rats were injected with either 5 or 25mg/kg of the L-type voltage gated calcium channel blocker, nifedipine, or a control vehicle, DMSO (dimethylsulfoxide). The kindled groups received a kindling stimulation twice a day for 11 days. It was revealed that both doses of nifedipine significantly increased afterdischarge duration (p<0.001) and furthermore, both doses of nifedipine were capable of significantly interfering with the rate of kindling (p<0.001). Three weeks following the last kindling stimulation, rats were perfused and brain tissue was processed according to the Timm method. The density of Timm granules, an indication of the level of intracellular zinc in the mossy fibre pathway, was quantified. The results of this analysis revealed that 25mg/kg of nifedipine is capable of significantly reducing the amount of intracellular zinc in both the IML (p<0.04) and the CA3 (p<0.01) region of the mossy fibre pathway, regardless of whether the rats had received kindling stimulations or not. These results provide support for the notion that nifedipine (5 or 25mg/kg) is an effective anticonvulsant agent. These results also suggest that, at a sufficient dose (25mg/kg), nifedipine can reduce the amount of intracellular zinc in the mossy fibre pathway in both kindled and non-kindled animals, suggesting that nifedipine may be a useful therapeutic agent for pathologies that have been associated with zinc-induced neurotoxicity. / Thesis / Master of Science (MSc)

<p>Phospho-MurNAc-pentapeptide translocase (MraY) is a conserved membrane-spanning enzyme involved in the biosynthesis of bacterial cell walls. MraY generates lipid I by transferring the phospho-MurNAc-pentapeptide to the lipid carrier undecaprenyl-phosphate. MraY is a primary target for antibiotic development because it is essential in peptidoglycan synthesis and targeted by 5 classes of natural product antibiotics. The structure of this enzyme will provide insight into the catalytic mechanism and a platform for future antibiotic development. MraY genes from 19 bacteria were cloned, expressed, purified and assayed for biochemical stability. After initial crystallization screening, I found that MraY from Aquifex aeolicus (MraYAA) produced diffracting crystals. Recombinant MraYAA is functional and shows inhibition by the natural inhibitor capuramycin. After extensive optimization of crystallization conditions, we extended the resolution limit of the crystal to 3.3 Å. The crystal structure, the first structure of the polyprenyl-phosphate N-acetyl hexosamine 1-phosphate transferase (PNPT) superfamily, reveals the architecture of MraYAA and together with functional studies, allow us to identify the location of Mg2+ at the active site and the putative binding sites of both substrates. My crystallographic studies provide insights into the mechanism of how MraY attaches a building block of peptidoglycan to the carrier lipid.</p><p>Voltage-gated Na+ (NaV) channels initiate action potentials in neurons and cardiac myocytes. NaV channels are composed of a transmembrane domain responsible for voltage-dependent Na+ conduction and a cytosolic C-terminal domain (CTD) that regulates channel function through interactions with many auxiliary proteins including members of the fibroblast growth factor homologous factor (FHF) family and calmodulin (CaM). Through the collaboration between our lab and Geoffrey Pitt's lab, we report the first crystal structure of the ternary complex of the human NaV1.5 CTD, FGF13, and Ca2+-free CaM at 2.2 Å. Combined with functional experiments based on structural insights, we present a platform to understand roles of these auxiliary proteins in NaV channel regulation and the molecular basis of mutations that lead to neuronal and cardiac diseases. Furthermore, we identify a critical interaction that contributes to the specificity between individual NaV CTD isoforms and distinctive FHFs.</p> / Dissertation

No description available.

This work focuses on using forward and adjoint transport in a hybrid application of 3-D deterministic (PENTRAN) and Monte Carlo (MCNP5) codes to model a series of neutron detector blocks. These blocks, or “channels,” contain a unique set of moderators with 4 atm He-3 proportional detectors tuned to detect and profile a gross energy spectrum of a passing neutron (SNM) source. Ganging the units together as a large area system enables one to apply time gating the source-detector response to maximize signal to noise responses from a passing source with minimal background; multiple units may be positioned as a collective synthetic aperture detector array to be used as a way of performing real time neutron spectroscopy for detecting special nuclear materials in moving vehicles.

The effects of Gated Communities (GCs) were analysed. According to the literature, these urban artefacts are negative for society. They are blamed to provoking social segregation, social exclusion and undermining democracy. In a Latin American context the consequences could be worse. Latin America has the highest level of social inequality in the world and the rapid growth of GCs is making this inequality more visible. This study implemented the concept of Social Capital, in order to understand the urban problems in this urban geography. The study is based in Machala, a mid-sized city in Ecuador. It was found that GCs’ residents lack of trust of outsiders, residents are more distant from disadvantage groups, social networks are being homogenised and there is a stigmatisation of life outside the community’s walls. This study seeks to create awareness on the type of urban growth in Machala by exploring the consequences of fragmentation, privatisation and segregation via GCs.

The function of most proteins is regulated by post-translational modifications, of which phosphorylation in particular has been shown to be ubiquitous and of paramount importance to cell signaling. Two enzyme families, protein kinases and phosphatases, regulate phosphorylation, and aberrant activities of family members have been implicated in many diseases such as cancer and neurological disorders. Thus, understanding the function of these enzymes in living cells is important for understanding their biology and for designing new therapies, but a challenging task due to their highly conserved architecture. The major focus of the dissertation is on the development of a new approach to selectively turn-on multiple specific kinases and/or phosphatases using orthogonal ligands as chemical inducers of dimerization (CIDs). Specific kinases or phosphatases were dissected at particular sites into two inactive fragments or split-proteins. The split fragments are attached to interacting protein pairs of CID systems, such that upon addition of the specific ligand they heterodimerize with subsequent reassembly of the split-protein and concomitant activity. We demonstrated the in vitro and in cellulo feasibility of this approach using three orthogonal CIDs, rapamycin, abscisic acid, and gibberellic acid, to turn-on members of the tyrosine kinase group such as Lyn and Src, and of the tyrosine phosphatase group such as PTP1B and SHP1. We have also developed a new synthetic photocleavable di-trimethoprim CID that allows for ligand-gated turn-on of desired kinases in live cells. The new CID can be cleaved or turned-off by UV irradiation which results in a turn-off of kinase activity. Small molecule controlled split-proteins allow for developing logic gates and we demonstrate that the systems we have developed can be used to construct 7 out of the 10 basic, circuit-type Boolean phosphorylation-based logic gates in living cells. These post-translational logic gates may have interesting applications in synthetic biology. Finally, we present an initial approach to use redesigned kinases and redesigned ligands as potential scaffolds for developing new CIDs. Thus, we provide and extend new methodologies that potentially allow for posttranslational control over the activity of user defined split-kinases and split-phosphatases for interrogating and redesigning signaling pathways. The last section of this work focuses on understanding small-molecule selectivity toward protein kinases. We systematically analyzed different reported kinase screens to further understand the reliability of large scale data in the kinome field as the design of selective inhibitors is one the most useful approaches for understanding the function of enzymes or the development of drugs in a natural setting such as a primary cell or an organism.

Thesis is submitted in partial fulfilment for the degree of Master of Urban Design to the Faculty of Engineering and the Built Environment, at the University of the Witwatersrand, Johannesburg, 2017 / Influenced by the thinking of the Garden City movement, gated and so-called lifestyle security estates have become overwhelmingly popular in many cities across the world. With demand fuelled by a combination of security concerns and a belief that such schemes provides enhanced efficiency and comfortability, these estates have come under severe scrutiny with regards to its apparent spatial and socio-economic impacts on the city structure as a whole. However, despite the severe criticism and awareness, these types of developments have showed very little signs of decline - thus perhaps illustrating a real economic rationale in the desire of people to reside in environments with higher perceptions of safety and control. Cities respond to this by clearly delineating urban development boundaries and even in some cases publish design principles that promote integration and inclusion. These more than often become contested by means of political- and private sector influences resulting in the perpetual realities of estate development and no real prohibiting actions and remedial recourse. Given these realities, what then does the future hold for our city landscape? Could we possibly reposition ourselves now to better the outcome later? Using Steyn City and Dainfern in the Fourways area, as two mega development case studies, this academic inquiry seeks to reflect on the status quo of estate developments and creatively find internal possible clues within the very structuring elements of such schemes that could potentially unlock and ‘un-gate’ developments and in the process improve access to opportunities in the city. This could surely not only provide new insights as to what the potential future can be, but it also provides the opportunity to redefine the ‘right to the city’ and opportunity in already deprived and isolated localities. / XL2018

A partir de questionamentos associados à proliferação de condomínios horizontais e loteamentos fechados em Vinhedo (gated communities nos E.U.A), procurou-se evidenciar através de indicadores pautados no conceito de sustentabilidade urbana, o que se tem de realmente sustentável quando da introdução destes empreendimentos na paisagem. Para isso foram consideradas duas dimensões: a sustentabilidade social urbana e a sustentabilidade ambiental urbana, cada qual com dois indicadores; mobilidade e acessibilidade a áreas verdes ou/lazer públicas intramuros, cobertura vegetal arbórea e impermeabilização dos solos, sendo estes últimos analisados entre 1962 e 2012, tanto intra como extramuros. Esta proposta visou demonstrar que o modelo ou padrão de habitação urbana baseada em loteamentos fechados e condomínios horizontais amplia em Vinhedo a possibilidade de alcance da sustentabilidade ambiental urbana, ao mesmo tempo em que reduz a possibilidade de alcance da sustentabilidade social urbana, uma vez que sua lógica de implantação desconsidera importantes funções sociais a serem desempenhadas pela cidade, dessa forma, o alcance da sustentabilidade urbana considerada como um todo se torna parcial. / From questions associated with the proliferation of horizontal condominiums and closed subdivisions in Vinhedo (gated communities), it was tried to highlight by indicators guided the concept of urban sustainability, which has really sustainable when the introduction of these enterprises in the landscape. For this we considered two dimensions: urban social sustainability and urban environmental sustainability, each with two indicators; mobility and accessibility to green areas or / public recreational intramural, arboreal coverage and soil sealing, the latter being analyzed between 1962 and 2012, both intra and extramural. This proposal aimed to demonstrate that the model or pattern of urban housing based on closed subdivisions and horizontal condominiums in Vinhedo expands the possibility of reach of urban environmental sustainability, while reducing the possibility of reaching the urban social sustainability, once its logic implementation ignores important social functions to be performed by the city, thereby achieving urban sustainability considered as a whole becomes partial.

Abrir mão do conceito de centralidade, da proximidade aos centros comerciais, de serviços e culturais para morar em locais mais distantes provoca maiores deslocamentos para o trabalho, estudo e demais atividades rotineiras. Porém, percebe-se que a ocorrência de bairros residenciais nos arredores das metrópoles é um fenômeno mundial, como as gated communities nos Estados Unidos da América e os LOTEAMENTOS RESIDENCIAIS FECHADOS no Brasil, que podem oferecer condições de moradias mais espaçosas, dotadas de áreas livres e jardins, condições de segurança e privacidade, com menor preço da terra, demandadas sobretudo pelas camadas de renda mais altas da população. Esta rotina de deslocamentos pelo público que mora em um município e trabalha e/ou estuda em outro provoca o que se denomina de MOVIMENTO PENDULAR. A incidência do fluxo de MOVIMENTOS PENDULARES na população de alta renda foi atestada a partir de tabulações realizadas pelo autor utilizando o Microdados da Amostra dos Censos Demográficos (MICRODADOS), elaborado pelo Instituto Brasileiro de Geografia e Estatística (IBGE). O objetivo da dissertação é a elaboração e hierarquização de ATRIBUTOS que mais influenciam na motivação deste público, em abrir mão do conceito de centralidade e ir residir nestes empreendimentos. Os atributos foram hierarquizados de acordo com o método Analytic Hierarchy Process (AHP) por especialistas que atuam neste segmento de mercado imobiliário nos municípios de Barueri, Santana de Parnaíba, Cotia e Arujá. Os ATRIBUTOS hierarquizados consideram que a LOCALIZAÇÃO e as CARACTERÍSTICAS DO LOTEAMENTO RESIDENCIAL FECHADO, bem como as necessidades e preferências do público alvo, que estão associadas conforme o estágio nos CICLOS de VIDA FAMILIAR e PROFISSIONAL, podem condicionar estratégias competitivas quanto à seleção de terrenos para desenvolvimento de empreendimentos dessa tipologia. / Giving up the idea of centrality, that is, living near commercial, service and cultural centers to go live in distant places results in longer journeys to work, study and other routine activities. However, it can be noticed that residential neighborhoods in the outskirts of the big cities is a worldwide phenomenon, like the gated communities in the United States and the LOTEAMENTOS RESIDENCIAIS FECHADOS in Brazil, with their spacious houses, free areas and gardens, security and privacy, at a lower cost for the plots which are sought mainly by the higher income population. Such routine of coming and going by the people living in a given municipality and working and / or studying in another brings about the so-called Pendulum Movement. The incidence of the Pendulum Movement flow among the high-income population was attested by tabulations carried out by the author using Microdata from the Demografic Census Sample (MICRODADOS) prepared by the Brazilian Institute of Geography and Statistics (IBGE). The thesis objective is the development and ranking of ATTRIBUTES that most influence the motivation of the public in abdicating the concept of centrality and going live in these residential. The ATTRIBUTES were ranked according to the Analytic Hierarchy Process (AHP) by specialists working in this segment of the real state market in the municipalities of Barueri, Santana de Parnaíba, Cotia and Arujá. The above ranked ATTRIBUTES consider that LOCATION and CHARACTERISTICS OF LOTEAMENTO RESIDENCIAL FECHADO, as well as the needs and the preferences of the target public associated according to their stage in the FAMILY and PROFESSIONAL LIFE CYCLES might determine the competitive strategies regarding the site selection to develop ventures of this typology.