Viele Wissenschaftler_innen glauben daran, dass eines Tages möglich sein wird, was bisher nur die Filmindustrie illustriert hat: Die Entwicklung von künstlichen Menschenwesen, die dem biologischen Homo Sapiens weit überlegen sind. Doch obwohl intelligente Roboter gegenwärtig nur auf der Leinwand realisiert werden können - die ethischen Fragen, die sich aus ihrer Existenz ergeben, sind durchaus real und relevant: Hat ein intelligentes Computerprogramm ein Recht auf Freiheit und Selbstbestimmung? Ein Film, der diese ethischen Fragen aufwirft und zudem eine hohe filmästhetische Qualität aufweist ist „Ex_Machina“ von Alexander Garland. In der folgenden Arbeit wird der Film medienpädagogisch analysiert und herausgestellt, inwiefern er für Jugendliche geeignet ist und ebenjene wichtigen ethischen Fragen thematisiert, welche für die heranwachsende Generation in ihrer immer technologischer werdenden Umwelt von großer Bedeutung sind.

Le fantasme de retour à la nature, entendu comme un retour à une matrice originelle a surtout pris la forme, en Occident, d'une recherche d'un paradis perdu ou d'un retour à un âge d'or. La première partie vise à illustrer la permanence de ce fantasme avec l'approche de quelques manifestations ayant traversé les âges. Ces expressions du fantasme de retour à la nature sont présentées en deux grandes thématiques : le rapport à l'altérité radicale avec les figures du barbare et du sauvage depuis la haute Antiquité jusqu'au premier voyage de Christophe Colomb dans le chapitre 1, puis la quête d'un monde meilleur avec les millénarismes chrétiens dans le chapitre 2. Le chapitre 3 est, quant à lui, consacré à l'évocation des traces préhistoriques de ce fantasme et, en particulier, aux conséquences de la fracture néolithique. La deuxième partie s'intéresse à l'identité du fantasme de retour à la nature et à sa fonction dans les imaginaires. En Occident, ce fantasme a donné naissance à un paradis terrestre permettant la synthèse de trois fantasmes fondamentaux : jeunesse éternelle, facilité et perfection. Cet aspect du fantasme est abordé dans le chapitre 5. La question de l'existence d'un imaginaire primordial est également approchée de même que les problèmes soulevés par l'élaboration d'une théorie générale de l'imaginaire, cette fois dans les chapitres 4 et 6. La troisième partie cherche à mettre au jour l'origine de ce fantasme : à savoir, sa généalogie évolutive. L'homme bénéficie d'un niveau de sécurité dont nul autre animal ne semble profiter. Homo sapiens doit ainsi son apparition et son essor à sa capacité à se soustraire à l'arbitraire du monde sauvage. Gain de l'évolution, cette liberté de l'être humain signifie son expulsion irréversible de la nature et pourrait être à l'origine du fantasme fondateur de retour à la nature. Le chapitre 7 s'intéresse plus particulièrement à la recherche de l'ailleurs, tandis que le chapitre 8 est focalisé sur les notions de transformation et de maîtrise du monde et le chapitre 9 sur la question de la liberté.

Les canaux semi-circulaires présentent un grand intérêt dans l'évolution. Des travaux récents ont montré que pour certains caractères, le génome humain est plus étroitement lié à celui du bonobo ou du chimpanzé que ces derniers entre eux. Dans ce contexte, il est important de comprendre le degré auquel les différences morphologiques et structurales entre ces trois espèces, reflètent les connaissances phylogéniques actuelles. Cette étude vise à comparer la variabilité anatomique des canaux semi-circulaires à partir de 260 examens tomodensitométriques d'homo sapiens, pan paniscus et pan troglodytes existants. Nous appliquons un modèle mathématique valide avec des examens micro tomodensitométriques et une quantification de l'erreur de mesure. Principalement, nous trouvons que les humains et les bonobos partagent plus de similarités entre eux qu'avec les chimpanzés par rapport a l'orientation tridimensionnelle de leurs canaux semi-circulaires, un résultat qui ne cadre pas avec les connaissances phylogénétiques actuelles. Une première hypothèse consiste en une évolution convergente dans laquelle les bonobos et les humains produisent indépendamment, des phénotypes semblables, peut-être en réponse aux pressions de sélection similaires éventuellement associées à des adaptations posturales. Une deuxième explication possible et plus parcimonieuse, c'est que la morphologie labyrinthique partagée entre le bonobo et l'homme représente la condition ancestrale à partir de laquelle les chimpanzés se sont déviés par la suite. La symétrie remarquable des CSC est le deuxième résultat majeur de cette étude pour ses implications dans la taphonomie. Il a le potentiel pour enquêter sur les fossiles altérés, déduire la probabilité de déformation post-mortem qui peut conduire à des difficultés dans la compréhension de la variation taxonomique, des relations phylogénétiques et de la morphologie fonctionnelle. / For some traits, the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. Therefore, it becomes crucial to understand whether morphological differences between humans, chimpanzees and bonobos reflect the well known phylogeny. Here we investigate intra and extra labyrinthine semicircular canals morphology using 260 computed tomography scans of homo sapiens, pan paniscus and pan troglodytes. We apply a mathematical model validated with micro-computed tomography scans and measurement error quantification. We find striking differences between, on the one hand, humans and bonobos and, on the other hand, chimpanzees concerning the 3D orientation of their semicircular canals. This finding does not fit with the phylogenetic knowledge. The first hypothesis is convergent evolution in which bonobos and humans produce independently similar phenotypes possibly in response to similar selection pressure maybe associated with postural adaptations. A second possible and more parsimonious explanation is that the bonobo-human labyrinthine shared morphology represents the ancestral condition with chimpanzees being subsequently derived. The remarkable symmetry of the SCC is the second major result of this study for its implications in taphonomy. It has the potential to investigate altered fossil, inferring the probability of post-mortem deformation which can lead to difficulties in understanding taxonomic variation, phylogenetic relationships, and functional morphology.

Current anti-malarial methods have been effective in reducing the number of malarial cases. However, these methods do not completely block the transmission of the parasite. Research has shown that repeated use of the current anti-malarial drugs, which include artemisinin-based drug combinations, might be toxic to humans. There have also been reports of an emergence of artemisinin-resistant parasites. Finding anti-malarial drugs through the drug discovery process takes a long time and failure results in a great financial loss. The failure of drug discovery projects can be partly attributed to the improper selection of drug targets. There is thus a need for an eff ective way of identifying and validating new potential malaria drug targets for entry into the drug discovery process. The availability of the genome sequences for the Plasmodium parasite, human host and the Anopheles mosquito vector has facilitated post-genomic studies on malaria. Proper utilizationof this data, in combination with computational biology and bioinformatics techniques, could aid in the in silico prioritization of drug targets. This study was aimed at extensively annotating the protein sequences from the Plasmodium parasites, H. sapiens and A. gambiae with data from di fferent online databases in order to create a resource for the prioritization of drug targets in malaria. Essentiality, assay feasibility, resistance, toxicity, structural information and druggability were the main target selection criteria which were used to collect data for protein annotations. The data was used to populate the Discovery resource (http://malport. bi.up.ac.za/) for the in silico prioritization of potential drug targets. A new version of the Discovery system, Discovery 2.0 (http://discovery.bi.up.ac.za/), has been developed using Java. The system contains new and automatically updated data as well as improved functionalities. The new data in Discovery 2.0 includes UniProt accessions, gene ontology annotations from the UniProt-GOA project, pathways from Reactome and Malaria Parasite Metabolic Pathways databases, protein-protein interactions data from. IntAct as well as druggability data from the DrugEBIlity resource hosted by ChEMBL. Users can access the data by searching with a protein identi er, UniProt accession, protein name or through the advanced search which lets users filter protein sequences based on different protein properties. The results are organized in a tabbed environment, with each tab displaying different protein annotation data. A sample investigation using a previously proposed malarial target, S-adenosyl-Lhomocysteine hydrolase, was carried out to demonstrate the diff erent categories of data available in Discovery 2.0 as well as to test if the available data is su fficient for assessment and prioritization of drug targets. The study showed that using the annotation data in Discovery 2.0, a protein can be assessed, in a species comparative manner, on the potential of being a drug target based on the selection criteria mentioned here. However, supporting data from literature is also needed to further validate the findings. / Dissertation (MSc)--University of Pretoria, 2012. / Biochemistry / unrestricted

No início do século XX, poucas décadas depois do início da eletrificação das casas, o conceito de uma residência automatizada já era utilizado como símbolo de um futuro livre das tarefas domésticas. No entanto, mesmo com o desenvolvimento de tecnologias de suporte, a automação de residências nunca contemplou uma ampla disseminação e uso. Este trabalho realiza uma análise social, econômica, tecnológica, cultural e de saúde da sociedade, desde o início do século XX até os dias atuais, para entender o comportamento humano relativo ao ambiente residencial e identificar as possíveis causas que não favoreceram a implantação de sistemas de controle e automação nestes ambientes. Ele ainda propõe uma arquitetura de sistemas eletrônicos e computacionais para o ambiente residencial, baseada em um conjunto de requerimentos e de abstrações coerentes com o contexto socioeconômico vigente e factível diante das atuais disponibilidades tecnológicas, a fim de direcionar os esforços na área e fomentar o desenvolvimento de aplicações. Adicionalmente, é apresentada uma plataforma de desenvolvimento hardware, firmware e software , denominada Home Sapiens, cuja concepção, projeto e desenvolvimento foram feitos no contexto desta tese. Baseada em nós de controle distribuídos, ela permite o acesso aos dados provenientes de sensores, a geração de informações de contexto, a identificação de serviços e a manipulação das características do ambiente residencial segundo regras de decisão, planejamento e métodos de aprendizado baseados em técnicas de Inteligência Artificial / In the early twentieth century, a few decades after the beginning of the electrification of houses, the concept of an automated home was used as a symbol of a future free of domestic chores. However, even with the development of supporting technologies, the automation of homes never contemplated a wide dissemination and use. This paper presents an analysis social, economic, technological, cultural and health of society, from the early twentieth century to the present day, to understand human behavior on the residential environment and to identify possible causes that did not favor deployment of control systems and automation in these environments. It also proposes an architecture of computer and electronic systems for the residential environment, based on a set of applications and abstractions consistent with the current socioeconomic context and feasible under the available technology in order to direct efforts in the area and promote the development of applications. Additionally, the implementation of a framework hardware, firmware and software called Home Sapiens is presented, whose conception, design and development were made in the context of this thesis. Based on distributed control nodes, it provides access to data from sensors, the generation of information of context, the identification of services and handling characteristics of the residential environment in accordance with rules of decision, planning and learning methods based on Artificial Intelligence.

Utilizing the lexicon of the French experimental thinkers Gilles Deleuze and Felix Guattari, research is engaged which indicates that their insights are compatible with and augmentative to the field of Conflict Studies. Specifically, four recognized conflict management approaches, which include the concepts of negotiation, the transformation of the conflict, narrative, and the transformation of the conflicted parties, are populated via an emerging Deleuze and Guattari inspired modus operandi. This process has resulted in an original new term, Conflict Inhabitation, which proposes that the conflicted parties recognize, to their mutual benefit, the centrality of difference to possibility and the acknowledgement of existence as dynamically becoming. This adventure is contextualized utilizing a Personal Narrative Autoethnographic Methodology which systematically engages the intensity of what it means to reside as a person in midst of the human induced Global Warming Climate Change experience during the Anthropocene Epoch. / Graduate

No início do século XX, poucas décadas depois do início da eletrificação das casas, o conceito de uma residência automatizada já era utilizado como símbolo de um futuro livre das tarefas domésticas. No entanto, mesmo com o desenvolvimento de tecnologias de suporte, a automação de residências nunca contemplou uma ampla disseminação e uso. Este trabalho realiza uma análise social, econômica, tecnológica, cultural e de saúde da sociedade, desde o início do século XX até os dias atuais, para entender o comportamento humano relativo ao ambiente residencial e identificar as possíveis causas que não favoreceram a implantação de sistemas de controle e automação nestes ambientes. Ele ainda propõe uma arquitetura de sistemas eletrônicos e computacionais para o ambiente residencial, baseada em um conjunto de requerimentos e de abstrações coerentes com o contexto socioeconômico vigente e factível diante das atuais disponibilidades tecnológicas, a fim de direcionar os esforços na área e fomentar o desenvolvimento de aplicações. Adicionalmente, é apresentada uma plataforma de desenvolvimento hardware, firmware e software , denominada Home Sapiens, cuja concepção, projeto e desenvolvimento foram feitos no contexto desta tese. Baseada em nós de controle distribuídos, ela permite o acesso aos dados provenientes de sensores, a geração de informações de contexto, a identificação de serviços e a manipulação das características do ambiente residencial segundo regras de decisão, planejamento e métodos de aprendizado baseados em técnicas de Inteligência Artificial / In the early twentieth century, a few decades after the beginning of the electrification of houses, the concept of an automated home was used as a symbol of a future free of domestic chores. However, even with the development of supporting technologies, the automation of homes never contemplated a wide dissemination and use. This paper presents an analysis social, economic, technological, cultural and health of society, from the early twentieth century to the present day, to understand human behavior on the residential environment and to identify possible causes that did not favor deployment of control systems and automation in these environments. It also proposes an architecture of computer and electronic systems for the residential environment, based on a set of applications and abstractions consistent with the current socioeconomic context and feasible under the available technology in order to direct efforts in the area and promote the development of applications. Additionally, the implementation of a framework hardware, firmware and software called Home Sapiens is presented, whose conception, design and development were made in the context of this thesis. Based on distributed control nodes, it provides access to data from sensors, the generation of information of context, the identification of services and handling characteristics of the residential environment in accordance with rules of decision, planning and learning methods based on Artificial Intelligence.

ABCB1, a member of the ATP binding cassette (ABC) transporter family, hydrolyses ATP as energy source for the translocation of substrate chemicals across the cell membrane. ABCB1-like transporters are found in all studied species. Typically, these transporters are abundant in tissues that separate compartments of the body such as the blood-brain barrier. Among the ABC transporters the ABCB1-like transporter proteins are of particular interest because they accept a broad variety of substrates and are therefore able to confer multidrug resistance (MDR) and multixenobiotic resistance (MXR) in wildlife, respectively. Inhibitors of the ABCB1-like transporter function can cause chemosensitisation, i.e. accumulation and increased sensitivity of organisms towards potentially harmful (natural/man-made) ABCB1-like substrate chemicals. In zebrafish (Danio rerio) Abcb4 was identified as functionally homologous to ABCB1. The aim of this study was to further characterise Danio rerio Abcb4 and to provide a database to approach the question to what extent ABCB1-like transporter related functions/effects are of ecotoxicological relevance. Main objectives are whether and how known ABCB1 ATPase stimulators and inhibitors interact with Abcb4 ATPase activity; to what extent ABCB1 ATPase assay data are transferable to Abcb4 ATPase assay data; and whether and how environmental chemicals interact with Danio rerio Abcb4 ATPase activity. In this study we established a test system – the ATPase assay with recombinant Danio rerio Abcb4 – to study the interaction of chemicals with the ATPase activity of the transporter protein. To relate obtained data to data for the well-known Homo sapiens ABCB1 and because available data for Homo sapiens ABCB1 were not in all cases suitable for a comparison, the ATPase assay with recombinant ABCB1 was adapted accordingly. Chemicals were tested up to concentrations in the range of their water solubilities to modulate basal and stimulator co-treated Abcb4 and/or ABCB1 ATPase activities. ATPase stimulators are often transported substrates. However, lipophilic compounds stimulating the transporter ATPase activity are not or little transported by transporter action. Therefore, experiments revealing whether compounds are translocated by transporters chemical interference with the transporter protein will not be indicated. Chemicals inhibiting the stimulator (here verapamil) co-treated ATPase activity compete with the verapamil to stimulate ATPase activity or are non-competitive inhibitors. When tested individually, these chemicals can be stimulators or inhibitors of basal ATPase activity, or do not interact with basal ATPase activity. ATPase inhibitors mitigate ATPase activity and ABCB1-like transporter mediated translocation of substrate chemicals. Obtained ATPase assay data were analysed with regard to concentrations at half-maximal effects (EC50s) and effect strengths (percent modulation). ATPase assays with recombinant Abcb4 (at 27 °C) are comparable to ABCB1 ATPase assay data obtained at 37 °C. Danio rerio Abcb4 seems less temperature-sensitive than ABCB1. Calculated activation energies for Abcb4 ATPase activities (40.75 kJ/mol for basal ATPase activity) were up to half as high as those for ABCB1 ATPase activities (81.61 kJ/mol for basal ATPase activity). Larger activation energies were previously proposed to be indicative for larger conformational rearrangements and hence possibly smaller rearrangements take place in Abcb4 compared to ABCB1. Known standard modulators of Homo sapiens ABCB1 ATPase activity interacted specifically with Danio rerio Abcb4 ATPase actitiy. The EC50s of the tested chemicals – 16 of 17 tested chemiacals interacted with the ABCB1 and the Abcb4 ATPase activity – ranged from 0.09 to 296 µM for ABCB1 and from 0.14 to 171 µM for Abcb4. Qualitative ATPase assay data for ABCB1, as interaction or not, seems transferable to Danio rerio Abcb4. Furthermore, when aligning amino acid sequences of mammalian ABCB1 transporter proteins and Danio rerio Abcb4 and comparing ABCB1 residues known to bind to (lipophilic) chemicals no obvious hints were found that chemical binding to Abcb4 is certainly different from ABCB1. Twenty-five of 33 studied environmental chemicals modulated the Abcb4 ATPase activity as stimulators and/or inhibitors. Stimulation of basal Abcb4 ATPase activity was lower for environmental chemicals than for known standard modulators. EC50s of environmental chemicals ranged from below 10 to 357 µM. Effects by environmental chemicals on Abcb4 ATPase activity with EC50s close to their water solubilities may be rather unspecific. The results of this work underline that Abcb4 function is of ecotoxicological importance as on the one hand several environmental chemicals were identified to inhibit Abcb4 ATPase activity – likely acting as chemosensitisers, while on the other hand chemicals stimulating basal ATPase activity suggest that these chemicals are possibly transported. A number of environmental chemicals also inhibited the basal Abcb4 ATPase activity. Especially non-transported inhibitors of the basal Abcb4 ATPase activity would be of ecotoxicological relevance as organisms (here Danio rerio) exposed to these chemicals would not be protected by Abcb4 mediated multixenobiotic resistance and were moreover threatened by chemosensitisation. Future studies should systematically elucidate under which circumstances chemicals are apparently net transported by ABCB1-like transporters and relate these findings to concentrations of environmental chemicals and ABCB1-like transporter protein abundance in wildlife.

ABCB1, a member of the ATP binding cassette (ABC) transporter family, hydrolyses ATP as energy source for the translocation of substrate chemicals across the cell membrane. ABCB1-like transporters are found in all studied species. Typically, these transporters are abundant in tissues that separate compartments of the body such as the blood-brain barrier. Among the ABC transporters the ABCB1-like transporter proteins are of particular interest because they accept a broad variety of substrates and are therefore able to confer multidrug resistance (MDR) and multixenobiotic resistance (MXR) in wildlife, respectively. Inhibitors of the ABCB1-like transporter function can cause chemosensitisation, i.e. accumulation and increased sensitivity of organisms towards potentially harmful (natural/man-made) ABCB1-like substrate chemicals. In zebrafish (Danio rerio) Abcb4 was identified as functionally homologous to ABCB1. The aim of this study was to further characterise Danio rerio Abcb4 and to provide a database to approach the question to what extent ABCB1-like transporter related functions/effects are of ecotoxicological relevance. Main objectives are whether and how known ABCB1 ATPase stimulators and inhibitors interact with Abcb4 ATPase activity; to what extent ABCB1 ATPase assay data are transferable to Abcb4 ATPase assay data; and whether and how environmental chemicals interact with Danio rerio Abcb4 ATPase activity. In this study we established a test system – the ATPase assay with recombinant Danio rerio Abcb4 – to study the interaction of chemicals with the ATPase activity of the transporter protein. To relate obtained data to data for the well-known Homo sapiens ABCB1 and because available data for Homo sapiens ABCB1 were not in all cases suitable for a comparison, the ATPase assay with recombinant ABCB1 was adapted accordingly. Chemicals were tested up to concentrations in the range of their water solubilities to modulate basal and stimulator co-treated Abcb4 and/or ABCB1 ATPase activities. ATPase stimulators are often transported substrates. However, lipophilic compounds stimulating the transporter ATPase activity are not or little transported by transporter action. Therefore, experiments revealing whether compounds are translocated by transporters chemical interference with the transporter protein will not be indicated. Chemicals inhibiting the stimulator (here verapamil) co-treated ATPase activity compete with the verapamil to stimulate ATPase activity or are non-competitive inhibitors. When tested individually, these chemicals can be stimulators or inhibitors of basal ATPase activity, or do not interact with basal ATPase activity. ATPase inhibitors mitigate ATPase activity and ABCB1-like transporter mediated translocation of substrate chemicals. Obtained ATPase assay data were analysed with regard to concentrations at half-maximal effects (EC50s) and effect strengths (percent modulation). ATPase assays with recombinant Abcb4 (at 27 °C) are comparable to ABCB1 ATPase assay data obtained at 37 °C. Danio rerio Abcb4 seems less temperature-sensitive than ABCB1. Calculated activation energies for Abcb4 ATPase activities (40.75 kJ/mol for basal ATPase activity) were up to half as high as those for ABCB1 ATPase activities (81.61 kJ/mol for basal ATPase activity). Larger activation energies were previously proposed to be indicative for larger conformational rearrangements and hence possibly smaller rearrangements take place in Abcb4 compared to ABCB1. Known standard modulators of Homo sapiens ABCB1 ATPase activity interacted specifically with Danio rerio Abcb4 ATPase actitiy. The EC50s of the tested chemicals – 16 of 17 tested chemiacals interacted with the ABCB1 and the Abcb4 ATPase activity – ranged from 0.09 to 296 µM for ABCB1 and from 0.14 to 171 µM for Abcb4. Qualitative ATPase assay data for ABCB1, as interaction or not, seems transferable to Danio rerio Abcb4. Furthermore, when aligning amino acid sequences of mammalian ABCB1 transporter proteins and Danio rerio Abcb4 and comparing ABCB1 residues known to bind to (lipophilic) chemicals no obvious hints were found that chemical binding to Abcb4 is certainly different from ABCB1. Twenty-five of 33 studied environmental chemicals modulated the Abcb4 ATPase activity as stimulators and/or inhibitors. Stimulation of basal Abcb4 ATPase activity was lower for environmental chemicals than for known standard modulators. EC50s of environmental chemicals ranged from below 10 to 357 µM. Effects by environmental chemicals on Abcb4 ATPase activity with EC50s close to their water solubilities may be rather unspecific. The results of this work underline that Abcb4 function is of ecotoxicological importance as on the one hand several environmental chemicals were identified to inhibit Abcb4 ATPase activity – likely acting as chemosensitisers, while on the other hand chemicals stimulating basal ATPase activity suggest that these chemicals are possibly transported. A number of environmental chemicals also inhibited the basal Abcb4 ATPase activity. Especially non-transported inhibitors of the basal Abcb4 ATPase activity would be of ecotoxicological relevance as organisms (here Danio rerio) exposed to these chemicals would not be protected by Abcb4 mediated multixenobiotic resistance and were moreover threatened by chemosensitisation. Future studies should systematically elucidate under which circumstances chemicals are apparently net transported by ABCB1-like transporters and relate these findings to concentrations of environmental chemicals and ABCB1-like transporter protein abundance in wildlife.

Retrogenes are functional genes that are created through retroposition, whereby mature mRNA is reverse-transcribed and re-integrated into the genome. In this study, the following objectives were accomplished: (i) intrachromosomal- and interchromosomal-retroposed genes were located in H. sapiens, (ii) interchromosomal-retroposed genes were located in M. musculus, D. melanogaster, and C. elegans. To date, this is the first assay for intrachromosomal-retroposed genes in H. sapiens and interchromosomal-retroposed genes in C. elegans. Biases discovered include excess interchromosomal generation of retrogenes by chromosome X in H. sapiens, M. musculus, and D. melanogaster. Selection pressure created by the inactivation of the X chromosome during male meiosis appears to be at least partially responsible for this phenomenon. In addition, excess interchromosomal recruitment of retrogenes by chromosome X was observed in H. sapiens. The driving force appears to be an interplay between selection for female-beneficial genes and selection for male-beneficial genes. No other chromosome biases were discovered.