Endocrine disrupting chemicals (EDCs) are ubiquitous in the environment and their presence in water bodies is documented. They discharge into surface water (SW) unmonitored, posing a threat to both aquatic and terrestrial lives. This is a challenge as not all populations have access to treated drinking water (TDW). The EDC contaminated serves as a route of exposure, together with ineffective treatment plants. Given the complexity of the endocrine system, EDCs may mimic or antagonise natural hormones or disrupt their synthesis, metabolism and excretion. The associated health effects include testicular dysgenesis syndrome, metabolic disorders and cancers. Policy and internationally standardised test methods are however sti ll limited. This study therefore aimed to assess the suitability of two assays used for screening estrogenic activity and one for androgenic activity in different water sources. The study consisted of two phases. In phase 1, water sample (tap, surface and treated wastewater) were collected from a catchment area in Pretoria. The samples and a spiked MilliQ laboratory water sample were extracted with solid phase extraction (SPE) and sent to Germany for distribution to participating laboratories. Samples (n=24) from six different countries were received to test for androgenic activity in the MDA-kb2 reporter gene assay. In phase 2, SW and TDW samples were collected from April 2015 until March 2016. The samples were filtered, extracted using SPE and assayed with the YES assay, T47D-KBluc reporter gene assay for estrogenic activity and MDA-kb2 reporter gene assay for androgenic activity. In phase 1, androgenic activity was detected in 4 out of 24 (21%) samples and ranged from 0.23 ± 0.040 ng/L to 0.008 ± 0.001 ng/L DHTEqs. In phase 2, estrogenic activity was detected in 16 out of 24 (67%) SW samples in the T47DKBluc reporter gene assay and ranged from 0.31 ± 0.05 pg/L to 10.51 ± 5.74 pg/L EEqs. It was below the detection limit (dl) in the YES assay. Androgenic activity was detected in 4 out of 24 (17%) SW samples, ranging from 0.0033 ± 0.0050 ng/L to 0.090 ± 0.040 ng/L DHTEqs. Androgenic and estrogenic activity was higher i n pretreatment samples compared to post-treatment in both treatment plants. In phase 1, the MDA-kb2 reporter gene assay was successfully applied to water samples from different sources. Androgenic activity was highest in treated wastewater. In phase 2, treatment plants proved to be effective in removing estrogens detected in the SW samples, as the TDW samples were below the dl. Estrogenic activity is within the ranges reported in other studies. Positive samples were below the 0.7 ng/L proposed trigger value for health risk assessments. Detected androgenic activity was lower in TDW samples compared to the SW samples supplying the two treatment plants indicating that they were both effective in removing the androgenic activity detected. Few studies have reported androgenic activity in tap water. This study strengthens the argument for using a battery of assays when monitoring endocrine activity as EDCs occur at low concentrations in mixtures. / Dissertation (MSc)--University of Pretoria, 2017. / School of Health Systems and Public Health (SHSPH) / MSc / Unrestricted

Molecular dynamics (MD) is a powerful tool that can be applied to protein folding and protein structure. MD allows for the calculation of movement, and final position, of atoms in a biomolecule. These movements can be used to investigate the pathways that allow proteins to fold into energetically favorable structures. While MD is very useful, it still has its limitations. Most notable, computing power and time are of constant concern. Protein structure is inherently important due to the direct link between the structure of a protein and its function. One of the four levels of protein structure, the secondary structure, is the first level to accommodate for the three-dimensional shape of a protein. The main driving force behind secondary structure is hydrogen bonding, which occurs between the carboxyl oxygen and the amine hydrogen of the backbone of a peptide. Determining a greater link between hydrogen bond patterns and types of secondary structure can provide more insight on how proteins fold. Because molecular dynamics allows for an atomic level view of the dynamics behind protein folding/unfolding, it becomes very useful in observing the effects of particular hydrogen bond patterns on the folding pathway and final structure formed of a protein. Using molecular dynamic simulations, a series of experiments in an attempt to alter structure, hydrogen bonding, and folding patterns, can be performed. This information can be used to better understand the driving force of secondary structure, and use the knowledge gained to manipulate these simulations to force folding events, and with that, desired secondary structure features.

Hydrophobic coatings find application in various sectors of the economy including to electronics, textiles, optical devices, and in scientific and commercial equipment. These different applications demand that different hydrophobic coatings posses a range of properties that may include smoothness or roughness, thicknesses on the order of a monolayer or a micron, robustness or the ability to dissolve quickly, transparency or opacity, water resistance or water permeability, electrical conductivity, oleophobicity, etc. However, whatever the final/desired properties, deposition via dry-deposition processes offers significant advantages, including greater reproducibility, increased environmental friendliness, and cost effectiveness on an industrial scale. Herein I explore the chemical vapor deposition of silanes and the characterization of a commercial, hydrophobic coating to better prepare and understand hydrophobic coatings on different materials. One of the characterization techniques I used frequently in these studies is X-ray photoelectron spectroscopy (XPS). Accordingly, in Chapter 2 of this thesis I discuss this technique vis-à-vis the chemical shifts it detects, which reflect the oxidation states of materials being probed. In particular, I discuss a recommendation made over a decade ago by Gion Calzaferri for 'fixing' the problem of oxidation numbers as applied to organic materials and show how XPS confirms his suggestion. In Chapter 3 I introduce hydrogen as an etch/cleaning gas for silicon wafers. I first show that, like argon and oxygen plasmas, hydrogen plasmas will effectively clean silicon wafers. However, I then show that hydrogen plasma treatment leads to a silicon surface that is chemically different than those prepared with the other plasmas and that undergoes silanization to a greater extent -- the resulting surfaces have higher water contact angles and thicknesses. In Chapter 4 I study the deposition of a potential barrier layer for water, which was prepared from an aza silane: N-n-butyl-aza-2,2-dimethoxysilacyclopentane (1) in a molecular layer deposition (MLD)-like process using either water or ammonium hydroxide as the second half reactant. This molecule has the interesting property of undergoing self-limiting growth, where the termination of this growth is accelerated by use of an ammonium hydroxide catalyst. Interestingly, films of 1 are considerably thicker on nylon than on silicon, which is explained by nylon acting as a water reservoir in the reaction. In Chapter 5 I show the careful characterization of the hydrophobic coating on an Apple iPod nano, which was probed by ToF-SIMS, wetting, and XPS. I could identify that the coating is only applied to the touchscreen of the device. SIMS suggested that the fluorinated coating contains oxygen, which should add to its biodegradability. Finally, in Chapter 6 I make recommendation for future work in these areas.

Previous literature has indicated a relationship between poverty, participation in extracurricular activities, and developmental outcomes. The current study aimed to investigate and develop a deeper understanding of extracurricular activities (ECAs) and their impacts on adolescent development using two self-report tools, the YES 2.0 and the Delinquent Attitude Scale (DAS). The researcher surveyed 174 high school seniors from students attending schools in poverty areas and students attending schools not located in poverty areas in Mississippi, examining disparities in ECA opportunities, barriers to participation, and the positive and negative impacts of ECAs on development. Additional data were collected from school administrators, allowing the researcher to compare ECA participation among students attending schools in poverty areas and students attending schools not located in poverty areas and the barriers that impact this participation. Results showed that students attending schools in poverty areas were less likely to participate in ECAs than those students attending schools not located in poverty areas. Lack of awareness about programs was the most common barrier reported by students. To address this, it is recommended that schools emphasize recruiting for ECAs and involve students at younger ages. Regarding the impact of ECAs on development, participation in ECAs was found to have a positive impact on certain developmental areas, regardless of poverty area. Negative outcomes were minimal in all poverty areas. However, excessive participation in ECAs adversely affected grades among students attending schools in poverty areas. Overall, this study highlights the importance of addressing disparities in ECA opportunities and barriers to participation and the potential positive impact of ECAs on adolescent development.

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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

This dissertation examines the activities and texts of four groups of activists who use culture jamming as a tactic to challenge dominant ideologies as they advocate for progressive social, cultural and economic change. Culture jamming, as defined here, is a practice whereby texts critical of the status quo are created through the appropriation and/or mimicry of the aesthetics and/or language that are a part of popular, or at least widely experienced, culture. Exploring the work of the Yes Men, the Adbusters Media Foundation, the Billboard Liberation Front and the Illegal Art exhibit, I argue that through their culture jamming these activists take critical theory into practice as a part of their goal is to raise the critical consciousness of the public. Confronting the issues of globalization, consumerism, and the political economy of the media in the United States, these culture jammers aim to highlight aspects of domination and oppression in their view results primarily from the corporate control of culture and politics. Using theories of ideology and hegemony developed by Karl Marx, Antonio Gramsci, Stuart Hall, and Raymond Williams to guide my analysis, I trace how each of these groups develop, present, and promote their critique. I steer clear of discussing the effectiveness of these culture jammers, focusing instead on the actions they take and theorizing some of the possible challenges and limitations they face in light of their own experiences. Differing requirements of cultural capital and deeper contextual information for most, if not all, of these culture jamming activities can make them especially complex forms of activism. What becomes clear is that culture jamming may be a tactic best suited to the maintenance of an activist community of people who already hold a critical position, as the jammer’s challenges to dominant culture and ideologies can be lost because of the form of the critique, or marginalized or otherwise ignored by the mainstream media. / text

In this comparative study of the two regions, Catalonia and Scotland, the party manifestos of the nationalistic parties will be compared, through an ideological point of view. In 2014 media gave attention to the two referendums, that the countries held quite close to each other. Europe were waiting with tension on the first elections results. The Scottish people voted no to independence from the United Kingdom. The Catalan people still went to the polls with high anticipation for independence for Catalonia, eventhough Spain had called the referendum illegal due to being against the constitution.   In order to make a comparison between, the Scottish National Party and the coalition party Junts pel Sí, an ideological analysis has been made. The aim with the study is to see similarities and differences between the two regions’ nationalistic movements and also to tell them apart from other nationalistic movements, by defining the ideological type. The results show that they are both quite nationalistic in their nature, meaning that they both would prefer independence. However, the Scottish National Party is less striving for independence and seek more to have greater influence in the parliament at Westminster. The Catalan nationalistic coalition party, on the other hand, strongly wants  independence. They desire a liberal democracy with an open Catalan market to the world, by international partnerships, and memberships with important international organs like the EU.   Eventhough much might speak for the nationalistic movements’ similarities, many interesting and diverse differences were found. These discoveries are important because all nationalistic movements aren’t the same and shouldn’t be seen as such.

Reports of endocrine disrupting potential of common environmental chemicals and the effects on reproductive health are well documented in literature. It has been suggested that deteriorating male reproductive health could be due to in utero exposures to these chemicals. The effects mediated through endocrine disrupting chemicals (EDCs) are on the fetus and may therefore be trans-generational. Ultimately, these chemicals land up in aquatic systems and affect wildlife and humans. Humans are exposed to these chemicals through multiple routes including atmosphere, water, occupational, domestic and food consumption. South Africa (SA) is an important livestock producer with about 13.8 million cattle within the feedlot industry contributing up to 80% of the total beef production. Veterinary growth stimulants (VGS) are used by beef producers to enhance growth in cattle. In SA, the following five VGS have been approved for use in beef products under the Register Act 36 of 1947, estradiol, progesterone and testosterone (natural), α'-zearalanol and trenbolone (synthetic). These VGS and their metabolites are environmentally stable compounds. The excretions from the animals are not treated and land up in the local aquatic systems, indirectly posing a health risk. In SA no research has been done on VGS associated with feedlot activities. The aim of this study was to investigate the effects of a mixture of VGS, as possible EDCs on the reproductive health and thyroid function in male rats in utero, during lactation and life-time exposure. The (anti)estrogenic and (anti)androgenic activity in water from specific feedlots was determined by using a battery of screening bio-assays. Water samples were collected over a period of a year and assessed for EDC activity in the recombinant yeast screen (YES), the T47D-KBluc (estrogenic) and the MDA-Kb2 (androgenic) bioassays. The OECD (Organization for Economic Co-operation and Development) 415 protocol, (1983) for a one-generation reproduction toxicity study, was modified to accommodate one control and three experimental groups. The experimental groups were orally gavaged with mixtures of: zilpaterol, diethylstilbestrol (DES) and α-zearalanol (Group 2; estogenic); with β'-trenbolone and methyltestosterone (MT) (Group 3; androgenic); a combination of compounds (Group 4; estrogenic and androgenic) and the Control group received cottonseed oil only. The bio-assay results indicated that water samples analysed from selected feedlots contained compounds with estrogenic activity. The shorter anogenital distance (AGD) (Group 3), decreased seminal vesicle mass (Group 4), decreased prostate mass (Group 4), increased lumen diameter (Group 3 and 4), lowered sperm concentration (Group 3), and increased T4 (Group 2 and 3) differed significantly from the control. The body weight of the males in Group 2 in the F2 generation was significantly lower than the control. The F2 females in Group 2, 3 and 4 were also significantly lower than the control. The reduced AGD, decreased seminal vesicle and increased T4 (thyroxine) might be the result of an estrogenic effect. The reduced sperm concentration might be the result of in utero and lactation exposure to these VGS. The bio-assays confirmed estrogenic activity in the feedlot water sources. The reproductive toxicology study findings confirm the hypothesis that VGS can act as EDCs and could therefore be responsible for negative reproductive effects and thyroid function. More research is needed to investigate the effects of VGS mixtures at different concentrations on male reproductive health, thyroid function and their offspring. AFRIKAANS : Goed gedokumenteerde literatuur dui aan dat chemikalieë wat algemeen in die omgewing gevind word, die potensiaal het om die manlike voortplantingstelsel aan te tas. Dit word gespekuleer dat in utero blootstelling verantwoordelik kan wees vir hierdie agteruitgang. Die fetus en daarop- volgende geslagte se gesondheid kan ook beÏnvloed word deur chemikalieë. Hierdie chemikalieë het die potensiaal om die watersisteme te bereik en gevolglik dier en menslike gesondheid te beÏnvloed. Blootstelling kan plaasvind deur verskeie roetes wat die atmosfeer, water, werksomstandighede, huishoudelike produkte en gekontamineerde voedsel insluit. Suid-Afrika (SA) is 'n belangrike produsent van vleisprodukte met omtrent 13.8 miljoen beeste wat bydra tot 80% van die vleisproduksie. Veterinêre-groei-stimulante (VGS) word gebruik om die vleisproduksie te verbeter. Vyf groei stimulante naamlik estradiol, progesteroon, testosteroon (natuurlike), α-zearalanol en trenboloon (sinteties) is goedgekeur onder die Wet 36 van 1947, vir groei produksie van beeste. Hierdie VGS en hul metaboliete is stabiel in die natuur. Die fekale en urinere uitskeidingsprodukte van die diere word nie behandel nie en eindig op in ons waterstelsels. Geen navorsing is nog in SA gedoen om die potensiële bydraes wat voerkrale tot die besoedeling van water lewer, te bestudeer nie. Die doel van die studie was om die gesamentlike effekte van mengsels VGS as moontlike endokrien-ontwrigtende chemicalieë (EOC) op die manlike voortplantingstelsel en tiroïdhormone van mannetjiesrotte na in utero-, gedurende laktasie- en na 'n leeftyd-blootstelling te bepaal. Die (anti)estrogeniese en (anti)androgeniese aktiwiteit in water vanaf spesifieke voerkrale is met behulp van 'n reeks biologiese seltoetse bepaal. Watermonsters is geanaliseer met die gisseltoets (YES)(estrogenies), die T47D-KBluc (estrogenies) en die MDA-Kb2 (androgenies). Die OECD 415 protokol (1983) vir een generasie reproduktiewe toksologie toets was aangepas om een kontrole en drie eksperimentele groepe te huisves. Die eksperimentele groepe rotte is oraal gedoseer met 'n mengsel van zilpaterol, dietielstilbestrol (DES) en α-zearalanol (Groep 2); β-trenboloon en metieltestosteroon (Groep 3); 'n kombinasie van al bogenoemde (Groep 4); en 'n kontrole groep wat katoensaad olie VGS ontvang het nie. Estrogeniese aktiwiteit en sitotoksisiteit was teenwoordig in die water vanaf die voerkrale. Die verkorte anogenitale afstand (AGD) (Groep 3), kleiner seminale vesikel (SV) massa (Groep 4), kleiner prostaat massa (Groep 4), groter lumen deursneë (Groep 3 en 4), laer spermtelling (Groep 3), verhoogde T4 (Groep 2 en 3), het almal statisties-betekenisvol van die kontrole groep verskil. In die F2 generasie het die liggaamsmassas van die mannetjies in Groep 2 en liggaamsmassas van die wyfies in Groepe 2, 3 , 4, almal statisties-betekenisvol laer as die kontrole Groep. Die verkorte AGD, kleiner SV en verhoogde T4 kan moonlik wees as gevolg van 'n estrogeniese effek en die verlaagde sperm konsentrasie weens 'n in utero en laktasie blootstelling. Die biologiese seltoetse het die teenwoordigheid van estrogeniese aktiwiteit in voerkrale se water bevestig. Die gevolge van die blootstelling van EOC mengsels op voortplantings-parameters bevestig die moontlikheid van EOC effek geassosieer met VGS. Verdere navorsing is nodig om die dosisresponsverhoudings van verskillende VGS te ondersoek. Copyright / Dissertation (MSc)--University of Pretoria, 2011. / School of Health Systems and Public Health (SHSPH) / Unrestricted

Le carcinome hépatocellulaire (CHC) est la première néoplasie létale du foie, représentant 80 à 90% des cas. Actuellement, la majeure partie des patients bénéficient de solutions thérapeutiques avec des efficacités très modestes. La haute variété étiologique, l’hétérogénéité des tumeurs ainsi que l’absence de médiateurs oncogéniques clés connus dans le développement de cette pathologie sont responsables du manque d’options thérapeutiques. À partir d’un crible génétique du kinome humain, nous avons identifié la tyrosine kinase Yes comme un acteur majeur de la prolifération des cellules de CHC. Yes appartient à la famille des kinases Src qui contrôlent de nombreux processus cellulaires notamment la prolifération, la motilité et la survie. La sur-expression ou activation anormale de Yes est retrouvée dans de nombreux cancers et est souvent associée à un mauvais pronostic. Nous avons démontré par des expériences in vitro et in vivo l’activité pro-proliférative de Yes ainsi que son potentiel oncogénique. Notamment, dans un modèle murin de carcinogenèse hépatique induit par le diéthylnitrosamine, la déplétion génétique de Yes abolit totalement la formation de tumeurs. Grâce aux profils transcriptionnels obtenus dans plusieurs modèles cellulaires de CHC, nous avons découvert que l’activité de Yes est associée à une augmentation des signatures géniques des régulateurs transcriptionnels YAP et TAZ ainsi que du facteur transcriptionnel c-Myc. Ces observations ont abouti à identifier YAP, TAZ et c-Myc comme des nouveaux substrats de la tyrosine kinase Yes. Nous avons montré que la phosphorylation par Yes de YAP et TAZ médie leur recrutement dans le noyau ce qui conduit à une hausse de leur activité transcriptionnelle. Nous avons d’ailleurs confirmé l’importance de YAP et TAZ dans les propriétés prolifératives de Yes, notamment dans différents modèles murins de carcinogenèse hépatique. De manière intéressante, nous avons observé que près de 50% de CHCs humains présentent une activation anormale des kinases Src qui corrèle avec la phosphorylation et activation de YAP. Enfin, nous avons observé in vitro et in vivo que Yes stabilise c-Myc. En effet, l’expression transgénique de Yes constitutivement actif dans des hépatocytes entraine la stabilisation de c-Myc à des stades précoces du développement tumoral et une induction de plusieurs de ses gènes cibles à des stades plus tardifs. En plus de leur synergie d’action, cette étude propose que la tyrosine Yes intervient dans les propriétés oncogéniques de c-Myc. Finalement, nous avons découvert que la kinase Yes joue un rôle dans la progression de la stéatose hépatique. En effet, la progression de la pathologie est abolie à la suite de la déplétion de Yes ou suivant l’inhibition pharmacologique des kinases Src. De plus, la survie des cellules tumorales face à leur élimination par le système immunitaire semble être favorisé par la signalisation Yes qui induit l’expression des points de contrôle immuns PD-L1/2. En conclusion nous avons découvert et caractérisé trois nouveaux effecteurs clés de la signalisation oncogénique de la tyrosine kinase Yes dans le CHC. D’ailleurs, la signature génique induite par Yes permet de prédire la survie des patients atteints de CHC. Ces données fournissent de robustes évidences qui placent la tyrosine kinase Yes comme une cible thérapeutique de choix pour la maladie du CHC. / Hepatocellular carcinoma (HCC) is the first lethal neoplasia of the liver, representing 80 to 90% of cases. Currently, for most patients the therapeutic option only provides modest efficiencies. The high etiological variety and heterogeneity of the tumors as well as the absence of known key oncogenic mediator in the development of this pathology is mainly responsible for the lack of therapeutic option. Based on a genetic screen of the human kinome, we identified the tyrosine kinase Yes as a major player in the proliferation of HCC cells. Yes belongs to the family of Src kinases which control many cellular processes including proliferation, motility and survival. The over-expression or abnormal activation of Yes is detected in many cancers and is often associated with poor prognosis. We have demonstrated in vitro and in vivo the pro-proliferative activity of Yes as well as its oncogenic potential. In particular, in a mouse model of hepatic carcinogenesis induced by diethylnitrosamine, the genetic depletion of Yes completely abolishes the formation of tumors. Thanks to the transcriptional profiles obtained in several cellular models of CHC, we discovered that the activity of Yes is associated with an increase in the gene signatures of the transcriptional regulators YAP and TAZ as well as of the transcriptional factor c-Myc. These observations led to the identification of YAP, TAZ and c-Myc as new substrates for the tyrosine kinase Yes. We have shown that the phosphorylation of YAP and TAZ by Yes mediates their recruitment into the nucleus associated with an increase in their transcriptional activity. We have also confirmed the importance of YAP and TAZ in the proliferative properties of Yes in various mouse models of hepatocarcinogenesis. Interestingly, we observed that nearly 50% of human CHCs exhibit an abnormal activation of Src kinases that correlates with phosphorylation and activation of YAP. Moreover, in vitro and in vivo experiments revealed that Yes stabilizes c-Myc. Indeed, the transgenic expression of constitutively active Yes into hepatocytes leads to the accumulation of c-Myc protein at early stages of tumor development and to the induction of several of its target genes at later stages. In addition to their synergistic action, this study suggests that Yes is involved in the oncogenic properties of c-Myc. Finally, we discovered that Yes kinase plays a role in the progression of fatty liver diseases. Indeed, the progression of the pathology is abolished following the depletion of Yes or the pharmacological inhibition of Src kinases. In addition, the survival of Yes-active tumor cells is associated with the induction of PD-L1/2 immune checkpoints that protect cells from immune elimination. In conclusion, we have discovered and characterized three new key effectors of the oncogenic tyrosine kinase Yes in HCC. Interestingly, the gene signature induced by Yes can predict the survival of patients with HCC. These data provide strong evidence for targeting the tyrosine kinase Yes in HCC.