The multistage life cycle of malaria-causing P. falciparum is complex, making prevention and treatment difficult. As a result of resistance to many antimalarial drugs, novel compounds with unexplored targets are constantly sought after for the purpose of treating the symptoms of malaria. Here, novel compounds were screened for antiplasmodial activity against the symptom-causing asexual intraerythrocytic malaria-causing parasites. Unfortunately, many novel compounds in the drug discovery pipeline and drugs in clinical use possess underlying pharmacological issues that makes administration challenging. These include low aqueous solubility and short half-life which negatively impact bioavailability resulting in toxicity. This, in turn, increases patient non-compliance and the emergence of drug-resistant strains. Nanoparticles (NP) have the ability to mask drugs from the external environment while increasing circulation time and often alleviate many issues at once. Furthermore, the selected drugs do not need to be modified. Drug conjugation NPs with a targeting ligand and stimuli-responsive linkers have been extensively researched in many diseases, however, none have been reported for malaria clinically. Here, the first acid-labile targeted NP (tNP) that exploits the biology of infected erythrocytes and the specialised food vacuole (FV) of P. falciparum is interrogated for ability to decrease toxicity while retaining antimalarial activity. This dissertation describes the effect of tNPs on the efficacy and toxicity of selected compounds. In vitro haemolysis and cytotoxicity assays revealed that the tNPs are biocompatible to erythrocytes and HepG2 cells. The data also shows that tNPs decrease the toxicity of drugs and the chosen novel compound against human cells. A decrease in antiplasmodial activity was observed in vitro for the tNPs when compared to the novel compound and drugs on their own. However, this was due to the biogenesis of the FV and a shortened window of release. Nonetheless, the NP backbone was not active against P. falciparum intraerythrocytic parasites whereas tNPs were, showing activity due to released drug. The targeting ligand was also not specific for antiplasmodial activity. Although a significant loss in activity is observed, the results presented here suggests that these novel acid-labile tNPs serve as an attractive starting point for targeted treatment of malaria with an improved patient tolerance. Furthermore, novel compounds with issues can be selected without having to be modified or completely discarded. Therefore, increasing the chances of finding a variety of compounds that can be used to treat malaria while keeping patients safe. / Dissertation (MSc (Biochemistry))--University of Pretoria, 2020. / NRF / Biochemistry / MSc (Biochemistry) / Unrestricted

A common task in many database applications is the migration of legacy data from multiple sources into a new one. This requires identifying semantically related elements of the source and target systems and the creation of mapping expressions to transform instances of those elements from the source format to the target format. Currently, data migration is typically done manually, a tedious and timeconsuming process, which is difficult to scale to a high number of data sources. In this paper, we describe QuickMig, a new semi-automatic approach to determining semantic correspondences between schema elements for data migration applications. QuickMig advances the state of the art with a set of new techniques exploiting sample instances, domain ontologies, and reuse of existing mappings to detect not only element correspondences but also their mapping expressions. QuickMig further includes new mechanisms to effectively incorporate domain knowledge of users into the matching process. The results from a comprehensive evaluation using real-world schemas and data indicate the high quality and practicability of the overall approach.

Conventionally geographic data produced and disseminated by the national mapping agencies are used for studying various urban issues. These data are not commonly available or accessible, but also are criticized for being expensive. However, this trend is changing along with the rise of Volunteered Geographic Information (VGI). VGI, known as user generated content, is the geographic data collected and disseminated by individuals at a voluntary basis. So far, a huge amount of geographic data has been collected due to the increasing number of contributors and volunteers. More importantly, they are free and accessible to anyone.   There are many formats of VGI such as Wikimapia, Flickr, GeoNames and OpenStreetMap (OSM). OSM is a new mapping project contributed by volunteers via a wiki-like collaboration, which is aimed to create free, editable map of the entire world. This thesis adopts OSM as the main data source to uncover the hidden patterns around the urban systems. We investigated some fundamental issues such as city rank size law and the measurement of urban sprawl. These issues were conventionally studied using Census or satellite imagery data.   We define the concept of natural cities in order to assess city size distribution. Natural cities are generated in a bottom up manner via the agglomeration of individual street nodes. This clustering process is dependent on one parameter called clustering resolution. Different clustering resolutions could derive different levels of natural cities. In this respect, they show little bias compared to city boundaries imposed by Census bureau or extracted from satellite imagery. Based on the investigation, we made two findings about rank size distributions. The first one is that all the natural cities in US follow strictly Zipf’s law regardless of the clustering resolutions, which is different from other studies only investigating a few largest cities. The second one is that Zipf’s law is not universal at the state level, e.g., Zipf’s law for natural cities within individual states does not hold valid.   This thesis continues to detect the sprawling based on natural cities. Urban sprawl devours large amount of open space each year and subsequently leads to many environmental problems. To curb urban sprawl with proper policies, a major problem is how to objectively measure it. In this thesis, a new approach is proposed to measure urban sprawl based on street nodes. This approach is based on the fact that street nodes are significantly correlated with population in cities. Specifically, it is reported that street nodes have a linear relationship with city sizes with correlation coefficient up to 0.97. This linear regression line, known as sprawl ruler, can partition all cities into the sprawling, compact and normal cities. This study verifies this approach with some US census data and US natural cities. Based on the verification, this thesis further applies it to three European countries: France, Germany and UK, and consequently categorizes all natural cities into three classes: sprawling, compact and normal. This categorization provides a new insight into the sprawling detection and sets a uniform standard for cross comparing sprawling level across an entire country. / QC 20101206

The master thesis: Inter-application communication in IPTV client was conducted at the Business Multimedia Unit in Ericsson. In the IPTV client side, there is a need to control another IPTV client remotely with a low latency. This functionality can be used in playing game and remote operation in IPTV. The current solution is that clients communicate through the portal (Ericsson’s Web based IPTV system) in remote location with high latency. The focus of this thesis work is designing, building and evaluating a communication mechanism among IPTV clients in a LAN. The major contribution of this thesis is analysis and design of a solution. The comparison between an implemented solution in this project and other possible solutions is also included in this thesis. The purpose of the solution is to improve the configuration and performance of Ericsson IPTV clients. In the thesis, a prototype of inter-application communication between IPTV clients was designed. The prototype includes a proxy server (Based on Node.js), UPnP applications (Based on open source UPnP stacks), communication components in portal system and an Android client. The prototype has achieved the goals of setting up fast and convenient communication in Ericsson IPTV client side, without using the IPTV server. UPnP applications allow two devices in a LAN find each other with no need to configure IP and port. A local proxy server, a couple of communication components in portal and an Android application are used to set up communication in a LAN. Also different solutions have been analyzed and designed in the project. And some related technologies have been investigated and introduced. Measurement and test shows that the communication between IPTV clients in a LAN is fast enough to replace the way of communication through the server. Security analysis shows some possible drawbacks, like the security vulnerability and compatibility. The security can be improved by some future work, part of which is proposed and designed in the thesis. Analysis also shows the advantages and disadvantages of on different service discovery technologies.

Context information is information that describes the user's context. The goal of the Adaptive Context Aware Services (ACAS) project is to enable applications to use context information in order to adapt their behaviour to the user and his environment without requiring the user to manually change/manage parameters. While the concept of linking context aware entities together to form a logical "context network" was introduced earlier in the project, some questions regarding context information discovery and the discovery of context aware entities were previously unanswered. The goal of this thesis was to design and evaluate such a context network allowing entities todiscover each other and exchange information regarding their services and context information. For this purpose, a "Context Entity Registrar" has been developed allowing entities to register, thus they can easily be found by other entities who can query this registrar. During the design of this proposed solution, a special focus has been given to the performance of the registrar, especially how it scales when answering a large number of requests, in order to validate the design's potential as a solution to context aware entity discovery. Measurements have shown that this proposed solution scales well, making it a key element of a context network. Discovery of other entities and of context information play an important role to determine the performances of a context aware implementation. This masters thesis addresses first the issue of the architecture of the context network and then some tests to measure the performances of the proposed solution. / Context information är information som beskriver användarens omgivning. Adaptive Context Aware Services (ACAS) projektet har som mål att möjliggöra applikationer att använda kontext information för att anpassa sitt beteende till användaren och dess miljö, utan att kräva att användaren ska sätta eller hantera alla parametrar manuellt. ACAS projektet har tidigare infört konceptet "context network" som förbinder context aware enheter. Det finns dock kvar några obesvarade frågor angående upptäckt av context information och av context aware enheter.Trots att sättet att länka ihop kontextmedvetna enheter för att forma ett logiskt 'kontext nätverk' introducerades tidigare i projektet, finns det kvar några obesvarade frågor angående upptäckt av kontext information och upptäckt av kontextmedvetna enheter. Examensarbetets mål är att utforma och utvärdera ett sådant kontextnätverk som ger enheterna möjlighet att upptäcka varandra och utbyta information om tjänster och context information. Därför utvecklades "Context Entity Registrar" så att enheterna kan registrera sig för att kunna bli upptäckta av andra enheter som kan göra förfrågningar till detta register. Under designen av denna föreslagna lösning har särskild fokus lagts på registrens prestanda, speciellt avseende skalbarhet med avseende på antalet förfrågningar for att validera designens potential som lösning för kontextmedveten upptäckt av enheter. Mätningar har visat att lösningen skalar bra vilket gör kontext registret till ett nyckelelement i ett kontextnätverk. Upptäkten av andra enheter och av kontextinformation har en viktig roll i att bestämma en kontextmedveten implementations prestanda. Detta examensarbete kommer först att behandla kontextnätverkets arkitektur och därefter några testerna för att mäta prestanda i den föreslagna lösningen.

Bibliography: pages 80-84. / In this investigation an ex-post facto research method was used to gather the curiosity scores and academic science achievement results of approximately 200 pupils in one black and two predominantly white schools in Cape Town suburbs. Curiosity scores were also obtained for 150 pupils from five other high schools who submitted projects for the annual Young Scientists Exhibition (EXPO) in June 1988. The data was collected by means of two instruments devised and validated by Maw & Maw (1964) and by author-designed tests of curiosity, after refinement using a pilot study. The scores were analysed by means of t-tests, X2- (chi-square) tests and correlations. It was found that: 1) No significant differences existed samples of black and white junior between the high school science pupils on measures of curiosity. 2) No overall significant difference was found between high achieving and low achieving science pupils on the curiosity tests given to both the standard 6 and standard 7 pupils in the three chosen schools. 3) A highly significant difference on measures of curiosity was found between the group of Expo pupils (voluntary young scientists), and the ordinary groups of science pupils from the three different schools. 4) Significant correlations were found between the science pupils' inherent curiosity levels and their achievement in general science in several instances.

Cattle price discovery is a process of determining the price in the market through the interactions of cattle buyers (packers) and sellers (ranchers). Locating the price discovery center or market, and estimating price interactions among the regional fed cattle markets and also among feeder cattle markets can help define a relevant fed cattle procurement market. This research identifies that the U.S. cattle markets is discovered in the futures markets, feeder cattle futures and fed futures.

Exploration has been a common literary topic throughout the history of humans. However, much of this historical tradition bas possessed a fairly narrow Ill focus, emphasizing the drama and heroics of an individual explorer or concentrating on a description of a particular exploration. There has been little attempt at understanding the process of exploration and placing this important process in context with the historic and geographic phenomena that both affect and are affected by it. In this thesis, the author has broken the process of exploration down into a theoretical structure that is presented in a holistic model. This model has then been applied to the history of 15th century Portuguese exploration to test its applicability and usefulness.

No discreet study of the Spanish voyages of discovery and exploration to the northwest coast of North American during the 1770's has been published in English. The purpose of this thesis is to examine the Spanish expeditions of 1774, 1775, and 1779, directed by New Spain's Viceroy Antonio Maria Burareli y Ursua (1771-1779).

Indiana University-Purdue University Indianapolis (IUPUI) / Protein-protein interactions are fundamental in cell signaling and cancer progression. An increasing prevalent idea in cancer therapy is the development of small molecules to disrupt protein-protein interactions. Small molecules impart their action by binding to pockets on the protein surface of their physiological target. At protein-protein interactions, these pockets are often too large and tight to be disrupted by conventional design techniques. Residues that contribute a disproportionate amount of energy at these interfaces are known as hot spots. The successful disruption of protein-protein interactions with small molecules is attributed to the ability of small molecules to mimic and engage these hot spots. Here, the role of hot spots is explored in existing inhibitors and compared with the native protein ligand to explore how hot spot residues can be leveraged in protein-protein interactions. Few studies have explored the use of interface residues for the identification of hit compounds from structure-based virtual screening. The tight uPAR•uPA interaction offers a platform to test methods that leverage hot spots on both the protein receptor and ligand. A method is described that enriches for small molecules that both engage hot spots on the protein receptor uPAR and mimic hot spots on its protein ligand uPA. In addition, differences in chemical diversity in mimicking ligand hot spots is explored. In addition to uPAR•uPA, there are additional opportunities at unperturbed protein-protein interactions implicated in cancer. Projects such as TCGA, which systematically catalog the hallmarks of cancer across multiple platforms, provide opportunities to identify novel protein-protein interactions that are paramount to cancer progression. To that end, a census of cancer-specific binding sites in the human proteome are identified to provide opportunities for drug discovery at the system level. Finally, tumor genomic, protein-protein interaction, and protein structural data is integrated to create chemogenomic libraries for phenotypic screening to uncover novel GBM targets and generate starting points for the development of GBM therapeutic agents. / 2020-10-03