Parkinson’s disease is the second most common age-related neurodegenerative disease after Alzheimer’s disease. The characteristic pathological feature of Parkinson’s disease is the loss of neurons in the substantia nigra pars compacta (SNpc), which leads to a striatal dopamine deficiency responsible for the major symptoms of Parkinson’s disease. These symptoms include tremor at rest, postural instability, bradykinesia and in the later stages of Parkinson’s disease, even psychosis. Presently, there is still no cure for Parkinson’s disease and all treatments are only symptomatic. Current research is therefore directed towards the prevention of further dopaminergic neurodegeneration, while the ultimate aim is the reversal of neurodegeneration. Monoamine oxidase (MAO) enzymes are responsible for the regulation and metabolism of monoamine neurotransmitters, such as dopamine. There are two MAO isoforms, MAO-A and MAO-B. Since MAO-B has greater activity in the basal ganglia, it is of particular importance in movement disorders, which include Parkinson’s disease. The selective inhibition of MAO-B, increases dopamine available for binding, and thus reduces Parkinson’s disease symptoms. MAO inhibitors also have neuroprotective potential and thus may slow down, halt and even reverse neurodegeneration in Parkinson’s disease. It is still unclear exactly how MAO inhibitors protect neurons, but one theory suggests that MAO inhibition decreases oxidative stress by reducing the formation of hydrogen peroxide, a metabolic by-product of MAO oxidation of monoamines. Normally, hydrogen peroxide is inactivated by glutathione (GSH), however, in Parkinson’s disease, GSH levels are low, resulting in the accumulation of hydrogen peroxide, which then becomes available for the Fenton reaction. In the Fenton reaction, Fe2+ reacts with hydrogen peroxide and generates an active free radical, the hydroxyl radical. This radical depletes cellular anti-oxidants, damage lipids, proteins and DNA. MAO inhibitors reduce the formation of hydrogen peroxide thus decreasing the formation of hydroxyl radicals and oxidative stress. The MAO inhibitory potential of natural and synthetic chalcones have been illustrated. For example, in 1987, Tanaka and co-workers determined that natural chalcones, such as isoliquiritigenin, have MAO inhibitory activity in rat mitochondria. In 2009, Chimenti and co-workers synthesized a series of 1,3-diphenyl-2-propen-1-ones which exhibited human MAO-B (hMAO-B) selective inhibitory activity. On the other hand, Robinson and co-workers (2013), synthesized novel furanochalcones which also had hMAO-B selective inhibitory activity. A reversible, competitive mode of binding was demonstrated by these compounds. Since the effect of heterocyclic substitution, other than furan on the MAO inhibitory properties of the chalcone scaffold remains unexplored, the aim of this study was to synthesize and evaluate further heterocyclic chalcone analogues as inhibitors of hMAO. RESULTS Design and synthesis: Heterocyclic chalcone analogues that incorporated pyrrole, 5- methylthiophene, 5-chlorothiophene and 2-methoxypyridine substitution were synthesized using the Claisen-Schmidt condensation reaction. All compounds were characterized with 1H-NMR, 13CNMR, IR, MS, and melting points were recorded. Purity was determined with HPLC analysis. MAO inhibition studies: The 50% inhibitory concentration (IC50) values and selectivity index (SI) of all compounds were determined using a fluorometric assay and kynuramine as substrate. Eight out of the ten synthesized compounds exhibited IC50 values < 1 μM, and can thus be considered as potent MAO-B inhibitors, while all compounds showed selectivity for the MAO-B isoform. Compound 10i was the most potent MAO-B inhibitor with an IC50 value of 0.067 μM and the highest SI of 240.7. The most potent MAO-A inhibitor, compound 10f, had an IC50 value of 3.805 μM. Some structure-activity relationships were derived, for example; it was concluded that heterocyclic substitution with 5-methyl-thiophene ring resulted in optimal hMAO-B inhibition, while pyrrole substitution was less favourable. Further investigation is however required as this is only a preliminary study. Reversibility studies: To determine the reversibility of binding, the recovery of enzymatic activity after dilution of the enzyme inhibitor complexes were determined for selected compounds. Results indicated that the most potent MAO-A inhibitor, the pyrrole derivative 10f, had a reversible mode of binding to both the hMAO-B and hMAO-A isoforms, since the enzyme activities were completely recovered by dilution of the inhibitor concentration. In contrast, enzyme activity was only partially recovered after dilution of the most potent MAO-B inhibitor 10i, indicating that this methylthiophene derivative possibly exhibited tight binding to the hMAO-B isoform, and the inhibition caused by this compound was not readily reversed by dilution. In order to determine whether the tight binding as exhibited by compound 10i was due to the thiophene or phenyl moieties, reversibility of binding was also determined for the pyrrole derivative 10e. The results showed that 10e had a reversible mode of binding to the hMAO-B isoform, and enzyme activity was completely recovered by dilution of the inhibitor. Based on these results, it was concluded that the tight binding as exhibited by compound 10i was due to the presence of the thiophene moiety. To confirm that compound 10i exhibited tight, and not irreversible binding, reversibility of binding was also determined by dialysis of enzyme-inhibitor mixtures. For this purpose hMAO-B and 10i, at a concentration of 4 × IC50, were preincubated for a period of 15 min and subsequently dialyzed for 24 h. The results of this study showed that 10i had a reversible mode of binding for MAO-B, since enzyme activity was recovered to a level of 83% after dialysis. Mode of inhibition: To determine the mode of inhibition of compound 10f, Lineweaver-Burk plots were constructed for the inhibition of hMAO-A and hMAO-B. The lines of the Lineweaver-Burk plots intersected at a single point at the y-axis, indicating that 10f had a competitive mode of binding to both hMAO-B and hMAO-A isoforms. MTT viability assay: To determine the toxicity of the chalcones for cultured cells, selected compounds were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay. The cytotoxicity of the test compounds were evaluated at concentrations of 1 and 10 μM, in HeLa cells. The results indicated that compound 10i was non-toxic at 1 and 10 μM, with 100% and 96% cell viability remaining after 24 h exposure of the compound to the cultured cells. Compound 10f, however, exhibited significant toxicity at 10 μM, with only 5% viable cells remaining. In contrast, compound 10e, with the same pyrrole moiety as 10f, was non-toxic at 1 μM and 10 μM, with 99% and 98%, cell viability remaining. It was concluded that the pyrrole moiety of 10f was not responsible for its higher degree of cytotoxicity, which suggests that the CF3 substituent may play a role in the higher degree of cytotoxicity observed for 10f. Further investigation is required to determine the mode of cytotoxicity, when cultured cells are exposed to 10f. Docking Studies: To complete this study and rationalise the results of the MAO inhibition studies, molecular modelling was carried out and all compounds were docked into the crystal structure of hMAO-B, by using the CDOCKER module of Discovery Studio. Some insights were obtained regarding the binding of compound 10i. This compound bound to MAO-B with the phenyl ring facing the FAD cofactor. This orientation allowed for the formation of pi-pi interaction with Tyr 398 as well as a pi-sigma interaction between the thiophene ring and Ile 199 (which is part of the gating switch of MAO-B). It is speculated that the tight binding component of hMAO-B inhibition by 10i may, at least in part, be attributed to the interaction of this compound with the gating switch amino acid, Ile 199. The docking results also showed that most compounds interacted with Tyr 326 or Tyr 398, while interactions with Cys 172, Gln 206, Ile 199 and Tyr 435 also occurred. In conclusion, novel heterocyclic chalcone analogues with promising MAO-B inhibitory activities were successfully synthesized and evaluated. / MSc (Pharmaceutical Chemistry) North-West University, Potchefstroom Campus, 2014

Doel: Die studie het gepoog om vaders se persepsie en ervaring van uitdagings in hulle verhouding met hul leergestremde kind te verken en te beskryf. Agtergrond: Leergestremdheid is ’n baie algemene probleem by kinders en is bekend vir die negatiewe effek wat dit op die kind self en op die ouers van die kinders uitoefen. Dit blyk dat ’n leergestremde kind addisionele spanning op die ouers plaas. Hierdie studie fokus alleenlik op die vader van ’n leergestremde kind omrede die meeste studies slegs op die moeder-kind-verhouding fokus, aangesien die moeder as die primêre versorger van die kind beskou word. Die navorsingsmetode wat vir hierdie studie gebruik is, was ’n kwalitatiewe navorsingsontwerp. Die populasie het bestaan uit vaders met leergestremde kinders in die ouderdomsgroep van 13 tot 18 jaar en wat as gevolg van intrinsieke oorsake leergestremd is. Die data is aan die hand van semigestruktureerde onderhoude met vyf vaders, asook met ’n groepsgesprek bekom. Die doel was om die vaders se ervaring van hulle verhouding met hul leergestremde kind te ondersoek, waarna tematiese analises gebruik is om data saam te stel. Die elemente van kwalitatiewe verkennende en beskrywende teorie het as breër raamwerk vir die studie gedien. Bevindings: Die vaders het hulle verhouding met hul leergestremde kind as baie frustrerend beskryf en gesê dat hulle ook nie ’n goeie verhouding met hul kind het nie. Gevoelens van teleurstelling het primêr betrekking op die onvoldoende verwagtinge wat die vaders vir hulle kind koester. Hulle gevoel dat hulle geen ondersteuning van die skole en van die breër gemeenskap ontvang nie, het ook tot ’n negatiewe ervaring met die leergestremde kind gelei. / MA (Psychology), North-West University, Potchefstroom Campus, 2014

Many countries, including South Africa, are facing the reality of insufficient water supplies to meet their present and future water demands due to decreasing freshwater availability and increasing demand. Increased populations and climate changes further exacerbate the problem. South Africa is considered the thirtieth driest country in the world with limited supplies of water which are unevenly distributed. Thus there is a need for alternative water sources to augment the freshwater supply. Wastewater reuse has been identified worldwide as a viable option to augment water supplies. While technologies are available to ensure proper treatment of wastewater to even potable standards, many countries have experienced public resistance to wastewater reuse due to negative perceptions of consumers. For wastewater reuse initiatives to be successful public acceptance is imperative. The aim of this study was to assess perceptions of consumers in the Vaal Triangle on wastewater reuse. This is the first study conducted in the Vaal Triangle on wastewater reuse hence this information can be valuable in future when wastewater reuse projects are implemented A questionnaire to measure perceptions of consumers on wastewater reuse was developed based on previous studies and distributed to people residing in the Vaal Triangle area. A response rate of 74% (515 completed questionnaires) was obtained from 700 distributed questionnaires. The results showed that socio-demographic factors such as age, race, qualification and level of employment affect the perceptions of consumers on wastewater reuse. Additionally, knowledge of wastewater reuse and water scarcity had a positive effect on consumer‟s perceptions. Some of the major reasons why consumers are not receptive to wastewater reuse are health concerns, lack of trust in the implementing agencies, poor management of the plants and safety of chemicals used to treat the water. Lack of knowledge on wastewater reuse was raised as a major concern in the study. All these concerns need to be addressed to ensure success of wastewater reuse projects within the area. Limitations within the study were identified and recommendations for future research were made. / MBA, North-West University, Potchefstroom Campus, 2015

Parkinson’s disease (PD) is an age related neurodegenerative disorder that presents with both motor and non-motor symptoms. The most common pathological characteristic of PD is the loss of the pigmented dopaminergic neurons of the substantia nigra pars compacta (SNpc), with the appearance of intracellular inclusions known as Lewy bodies in the affected neurons. The loss of the SNpc neurons results in a deficiency of dopamine in the nigrostriatal pathway of the brain, and it is this deficiency that is responsible for the motor symptoms of PD. Monoamine oxidase B (MAO-B) is predominantly found in the striatum and is responsible for the oxidative metabolism of dopamine. The first-line treatment of PD is dopamine replacement therapy with levodopa, the metabolic precursor of dopamine. Rapid metabolism of levodopa at central and peripheral level, however, hampers its therapeutic potential. MAO-B inhibition enhances striatal dopamine activity by means of inhibiting dopamine metabolism, and MAO-B inhibitors are thus used in the treatment of PD, particularly in combination with levodopa. The aim of this study was to design new potent, reversible MAO inhibitors with selectivity towards MAO-B for the symptomatic treatment of PD. Recent studies have shown that C5-substituted phthalide derivatives are highly potent inhibitors of human MAO-B. Phthalide derivatives were also found to be potent inhibitors of human MAO-A. The structural similarity between phthalide and 3-coumaranone suggests that 3-coumaranone may be a useful scaffold for the design of reversible MAO-B inhibitors. In the present study, 3-coumaranone derivatives were thus synthesised and evaluated as potential MAO-A and MAO-B inhibitors. By reacting 6-hydroxy-3-coumaranone with the appropriate alkylbromide in N,N-dimethylformamide in the presence of potassium carbonate, a series of twenty 3-coumaranone derivatives were synthesised. The structures of the compounds were verified with NMR spectroscopy and mass spectrometry. The purities of the compounds were determined by HPLC analyses. To determine the inhibition potencies, the recombinant human MAO-A and MAO-B enzymes were used, and the inhibition potencies were expressed as IC50 values. The results indicated that the 3-coumaranone derivatives are highly potent MAO-B inhibitors. For example, 9 of the 3-coumaranone derivatives inhibited MAO-B with IC50 values < 0.05 μM, with the most potent inhibitor exhibiting an IC50 value of 0.004 μM. Although the 3-coumaranone derivatives are selective MAO-B inhibitors, some compounds were also potent MAO-A inhibitors with the most potent inhibitor exhibiting an IC50 value of 0.586 μM. The reversibility of MAO-B inhibition by a representative inhibitor was examined by measuring the degree to which the enzyme activity recovers after dialysis of the enzyme-inhibitor complex. Since MAO-B activity was almost completely recovered after dialysis, it may be concluded that the 3-coumaranone derivatives bind reversibly to MAO-B. Lineweaver-Burk plots were constructed to show that the representative 3-coumaranone derivative is a competitive inhibitor of MAO-B. To conclude, the 3-coumaranone derivatives are potent, selective, reversible and competitive inhibitors of MAO-B. These compounds may find application in the treatment of neurodegenerative disorders such as PD. Potent MAO-A inhibitors were also discovered, which suggests that 3-coumaranone derivatives may serve as leads for the design of drugs for the treatment of depression. In addition, 3-coumaranone derivatives which inhibited both MAO-A and MAO-B, may have potential application in the therapy of both PD and depressive illness. / MSc (Pharmaceutical Chemistry), North-West University, Potchefstroom Campus, 2015

Selective eating (SE) refers to an individual narrowing their range of preferred foods, resulting in a restricted food intake, high levels of rigidity and food refusal (Bryant-Waugh, 2000). SE is encompassed in the new Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V) (American Psychiatric Association, 2013) category avoidant restrictive food intake disorder (ARFID). Such difficulties are common in children with an autism spectrum disorder (ASD) (Raiten & Massaro, 1986) and neuropsychological differences have been found in children with ASD (Hill, 2004). This research aimed to be the first to investigate whether a distinct neuropsychological profile exists in children and adolescents with SE and furthermore, whether aspects of the profile vary depending on whether the child or adolescent displays elevated autistic traits. A case series of 10 children between the ages of 8 to 13 years old were recruited. A well-established neuropsychological test battery, the Ravello Profile (Rose, Frampton & Lask, 2012), was modified and administered to assess visuospatial processing, central coherence, executive functions (including cognitive flexibility, inhibition and planning) and theory of mind abilities. The results demonstrated a high degree of variability across the group in terms of visuospatial processing and theory of mind, weak central coherence across all participants and otherwise relatively intact abilities in executive function domains. There were no substantive findings in relation to those children with elevated autistic traits although a trend toward visuospatial processing differences did emerge. This exploratory case series was the first attempt to describe a neuropsychological profile in SE, however the small sample size and high variability in the data meant that a distinct neuropsychological profile did not emerge. The results did however provide an initial indication of possible trends in strengths and weaknesses across neuropsychological domains in SE. These findings have implications for the assessment and treatment of SE difficulties.

Memoria para optar al titulo de Ingeniero Civil / De acuerdo a parámetros internacionales Chile presenta escasez hídrica en gran parte de su territorio, y la demanda por este recurso sigue en aumento. Existen diversos modos de enfrentar este problema y uno de ellos es la reutilización de agua, dentro del cual se encuentra la recuperación y reuso de aguas grises, tema ampliamente explorado en países desarrollados en las últimas décadas. El presente Trabajo de Título tiene como objetivo principal aportar una herramienta para mejorar la eficiencia del uso del agua potable en Chile, introduciendo el tema de reutilización de aguas grises, como un medio para disminuir la demanda de agua. Este trabajo consta de investigación, experimentación y aplicación; en particular, esta última parte corresponde al diseño de una planta de tratamiento de aguas grises. Durante la elaboración de este trabajo se efectuó investigación de estudios internacionales en: caracterización de las aguas, tratamientos, usos posibles, riesgos entre otros. Se realizó también la primera caracterización de aguas grises conocida en el país, constituida por muestras de dos casas de las ciudades de Calama y Vallenar, cuyos resultados concuerdan plenamente con los de caracterizaciones internacionales. El proyecto de tratamiento propuesto se insertó en un proyecto hotelero en Calama, se procuró que éste fuese aplicable a diversos casos. Durante el diseño del sistema de tratamiento se efectuó una simulación de éste en laboratorio, a fin de comprobar su efectividad de purificación. Los resultados del análisis de calidad de agua, obtenida de la simulación, fueron positivos en relación a normas internacionales y la norma NCh 1333, a excepción del sodio, esto debido a la alta concentración en el agua potable de Calama. El análisis de costos entregó que el sistema diseñado es económicamente factible de realizar, dependiendo del precio del agua potable y de la etapa de recolección, esto último dado que las conducciones paralelas requeridas están en función de la configuración del recinto, por lo que su costo está directamente relacionado a la distribución de cada caso.

L’objet de cette recherche concerne le développement de l’expertise enseignante chez les enseignantes et les enseignants d’histoire au secondaire. Une recension des écrits nous a permis d’identifier des aspects qui contribuent au développement professionnel comme les réseaux professionnels, la formation continue ou congrès, le mentorat, des lectures d’ouvrages spécialisés, des collègues de travail et l’expérience. L’objectif de recherche était d’identifier, auprès d’enseignantes et d’enseignants d’histoire au secondaire, quels sont les aspects et les expériences professionnelles qui ont contribué au développement de leur expertise professionnelle. Cette recherche, dite qualitative/interprétative de type exploratoire, repose sur la stratégie du récit de vie. Les participants sont quatre enseignants d’histoire au secondaire considérés comme experts. L’entrevue semi-dirigée a permis de colliger des données qualitatives quant aux aspects et aux expériences professionnelles ayant contribué au développement de leur expertise enseignante. Les résultats de recherche indiquent que les aspects ciblés au départ ont influencé à divers degrés le cheminement des experts participants. D’autres aspects ont émergé comme étant marquants dans le développement professionnel comme la passion ou l’intérêt pour l’enseignement de l’histoire, la qualité des relations tant avec les élèves qu’avec les collègues et la capacité de réfléchir sur sa pratique. Toutefois, trois aspects favorisent plus particulièrement le développement de l’expertise soit l’expérience, les compétences professionnelles en enseignement qui regroupent la préparation de cours, la réflexion sur sa pratique et la relation maitre/élève puis les collègues de travail. Cette recherche est utile parce qu’elle apporte un éclairage sur les aspects contribuant au développement de l’expertise enseignante et peut ouvrir la voie vers une autre étude qui mettrait en évidence les différences entre les voies empruntées pour développer cette dernière.

The role of universities in regional development has changed over the last two decades. Current discussion in literature confronts universities with challenges related to an emergence of a third role, that should universities perform in regional innovation systems. It concerns regionally-oriented activities, through which universities are becoming the leaders of regional economic and social development. This concept is applied to a comparative case study of two different Czech regions, South Bohemia Region and Moravian - Silesian Region. The objective is to verify, if different regional circumstances leads to a different form and intensity of networking between academic and private sector, or whether the main factor influencing the role of the two Czech universities is a specific national context. Key words: universities, partnership with private sector, regional innovation systems, third role

Diploma thesis "Talk show Uvolněte se, prosím and its political guests (qualitative and quantitative analysis of politicians' attendance in the show)" deals with the topic of convergence of entertainment and politics, hence politics and the media as such. The theoretical part of the thesis deals with the wider context of the issue - presentation of the politicians on television, interconnection of politics and humor, and the role of talk shows in political communication. The theoretical part presents the issue of political celebrities as one of the factors that affect communication between the politicians and the citizens. The practical part deals with the qualitative and quantitative analysis of the political guests' performance in the czech version of American talk shows Uvolněte se, prosím.

Název diplomové práce v anglickém jazyce, resumé, klíčová slova Employment of people with a disability This thesis sets out to introduce legislation in the employment of disabled persons in the Czech legal system. The thesis is devided into seven parts. The first part deals with the history of the relationship of disabled persons and the society as it recorded the oldest Greek and Roman sources of law as well as sources in our country. It describes several measures that have been introduced to make the lives of the poor and the sick better until 1948 . The second part provides an overview of the most important international sources and sources of the European Union. It describes the protection that these sources provide to basic human rights, the principle of equality and non-discrimination and to regulate the rights and status of persons with disabilities. In the third part the basic principle enabling people with disabilities to full participation in society is analyzed in detail - the principle of equal treatment and non- discrimination. In this part is described the importance of these concepts and their national legislation in the Charter of Fundamental Rights and Freedoms, anti- discrimination laws, labor and employment law. The fourth part describes the employment of persons with disabilities as...