The thesis deals with possible ways of coping with the consequences of miscarriage. The theoretical part first defines the topic of pregnancy from a medical and psychological point of view. It also includes the definition of miscarriage types. Furthermore, an overview of the experience of the child's loss in the early stages of pregnancy is elaborated, impacts on the psyche of the woman and manifestations in her behavior are considered. The process of grieving by individual authors is considered in the context of the early loss of the child. The issue of termination of pregnancy is also seen from the perspective of trauma theory. Possible protective and risk factors accompanying the loss-making process are discussed. Last but not least, the following professional psychological, medical and lay care for a woman after the loss of a child is mentioned. The empirical part of the thesis deals with the affection of the whole phenomenon of child loss during the early stages of pregnancy. Emphasis is placed on the mapping of protective and risk factors with which women had their own experience. The empirical part is based mainly on interviews with women with experience of loss of a child and with professionals who work in this field. Data evaluation was based on grounded theory principles. Keywords:...

Disertační práce se zabývá vyšetřováním kvalitativních vlastností diferenčních rovnic se zpožděním, které vznikly diskretizací příslušných diferenciálních rovnic se zpožděním pomocí tzv. $\Theta$-metody. Cílem je analyzovat asymptotické vlastnosti numerického řešení těchto rovnic a formulovat jeho horní odhady. Studována je rovněž stabilita vybraných numerických diskretizací. Práce obsahuje také srovnání s dosud známými výsledky a několik příkladů ilustrujících hlavní dosažené výsledky.

Greenhouse gas emissions are increasing every year, and in Sweden the construction industrystands for one fifth of the total emissions. One way for construction companies to push formore sustainable development is through voluntary sustainability certifications. As the numberof certified projects continues to rise, how to manage these projects during the early stagesbecomes an increasingly important question. Therefore, the purpose of this report has been toexplore and identify factors of success, connected to the management of certified constructionprojects during early project stages, in a relatively unexplored Swedish context. Data was collected through a literature review and seventeen semi-structured interviews withindustry professionals, and the following thematic analysis resulted in a refined list of factorsto consider during early project stages for successful certification. By applying critical successfactor (CSF) as theoretical framework, fifteen critical success factors were identified andcompared with those from previous research. Integrating the certification, planning for it duringearly stages, certification reconciliation meetings and a driven and competent specialist areexamples of identified CSFs from this list. Conclusions drawn in this report are that the Swedish context does not differ much fromprevious research, as most success factors had previously been identified by others.Furthermore, the results of this report indicate that the sustainability specialist, coordinator orconsultant is an increasingly important role for certified projects, and that they need trust,mandate and space to coordinate the work with the certification. Lastly, contributions havebeen made to the field of research on certified construction projects by providing a list ofsuccess factors with examples and data from Swedish industry professionals. This list canadditionally be considered by industry professionals when undertaking certified constructionprojects. Some issues concerning the application of CSF as framework have also beendiscussed in this report, which researchers in the field can consider for their future researchendeavors. / Utsläppen av växthusgaser ökar varje år och i Sverige står byggbranschen för en femtedel avde totala utsläppen. Ett sätt för byggföretag att driva på för en mer hållbar utveckling är genomfrivilliga hållbarhetscertifieringar. I takt med att antalet certifierade projekt ökar, blir hur manhanterar dessa projekt under de tidiga stadierna en allt viktigare fråga. Syftet med denna uppsatshar därför varit att utforska och identifiera framgångsfaktorer kopplade till ledningen avcertifierade byggprojekt under tidiga projektskeden, i en relativt outforskad svensk kontext. Data insamlades med en litteraturstudie och sjutton semistrukturerade intervjuer med personerfrån byggindustrin, och den följande tematiska analysen resulterade i en lista över faktorer attbeakta under tidiga projektstadier för framgångsrik certifiering. Genom att använda criticalsuccess factor (CSF) som teoretiskt ramverk identifierades femton kritiska framgångsfaktorersom jämfördes med dem nämnda i tidigare forskning. Integrering av certifieringen, planeringför den i tidiga skeden, certifieringsavstämningsmöten och en driven, kompetent specialist ärexempel på identifierade kritiska framgångsfaktorer från denna lista. Slutsatser som dras i denna uppsats är att den svenska kontexten inte skiljer sig mycket fråntidigare forskning, då de flesta framgångsfaktorer redan identifierats av andra. Vidare indikerarresultaten i denna uppsats att hållbarhetsspecialisten, koordinatorn eller konsulten är en alltviktigare roll i certifierade projekt, och att de behöver förtroende, mandat och utrymme för attsamordna arbetet med certifieringen. Den här uppsatsen har bidragit till forskningsområdet omcertifierade byggprojekt genom att tillhandahålla en lista över framgångsfaktorer med exempeloch data från personer inom den svenska byggindustrin. Denna lista kan dessutom användasav personer inom branschen framöver, när de tar sig an certifierade byggprojekt. Vissa problemsom rör tillämpningen av CSF som ramverk har också diskuterats i denna uppsats, som forskareinom området kan överväga för sin framtida forskning.

Tax Crimes Abstract The diploma thesis deals with tax crimes. The aim is to create a systematic overview and evaluation of the current criminal law of tax crimes in the legal order of the Czech Republic. The initial chapter focuses on the general definition of terms, including developmental stages of tax crimes, which mentions the reintroduction of criminality in the preparation of tax evasion, charge and similar mandatory payments in the Criminal Code in specific cases. The next chapter is devoted to a historical evolution into the development of tax crime legislation. The third chapter analyzes the legislative framework of the criminal law regulation of tax crimes in the Czech legal system. As part of the analysis of the crime tax fraud is explained how carousel fraud abusing the tax system within the EU works, as it is one of the most exploited tax evasions in the field of value added tax. This chapter also pays attention to the principle of nemo tenetur ipsum accusare in connection with taxation of income that originated from criminal activities. The next chapter deals with the prevention of tax evasion, with an emphasis on reverse-charge, which is based on the principle that the obligation to declare value added tax is transferred from the provider to its recipient. I follow up with the criminal...

För att skapa bättre förutsättningar att nå Parisavtalet och EU:s mål om klimatneutralitet har Europeiska kommissionen antagit Taxonomiförordningen, som kan beskrivas som ett klassificeringssystem för miljömässigt hållbara investeringar. Eftersom bygg- och fastighetssektorn bidrar till en stor andel av de globala koldioxidutsläppen finns ett kapitel i Taxonomiförordningens delegerande akt Climate Delegated Act med tekniska granskningskriterier som riktar sig särskilt mot bygg- och fastighetsverksamheter. I den delegerande akten fastställs tekniska granskningskriterier för sex miljömål. Från och med räkenskapsår 2022 ska bolag som omfattas av förordningen redovisa hur stor andel av bolagets ekonomiska aktiviteter som linjerar med EU-taxonomin. Det fanns få tidigare studier om implementering av EU:s taxonomi i bygg- och fastighetssektorn, men dessa pekar på att det råder en stor osäkerhet kring hur taxonomin ska implementeras och hur kriterierna ska tolkas. Syftet med examensarbetet var att bidra till ökad kunskap om vad införandet av EU-taxonomin innebär och hur den kan komma att påverka en byggentreprenörs verksamhet i Sverige. Utmaningar för en byggentreprenör identifierades på två olika nivåer: projekt- och företagsnivå. Därtill undersöktes hur EU-taxonomin kan förändra en byggentreprenörens hållbarhetsarbete i nyproduktionsprojekt, som idag främst sker genom miljöcertifiering. För att besvara forskningsfrågorna utfördes en litteraturstudie, en intervjustudie samt en projektutvärdering. Litteraturstudien resulterade i en introduktion till EU-taxonomin och dess uppbyggnad samt tolkningar, åsikter och kritik från tidigare forskning. Vidare genomfördes en genomlysning av hur BREEAM-SE v6.0 och Miljöbyggnad 4.0 implementerat EU-taxonomin. Utmaningar och påverkan på en byggentreprenörs hållbarhetsarbete undersöktes baserat på en projektutvärdering av 13 av NCC Building Swedens miljöcertifierade nybyggnadsprojekt samt en intervjustudie med två NCC-anställda med arbetsuppgifter som berör implementering av EU-taxonomin på företaget. Trots att EU-taxonomin syftar till att öka jämförbarheten mellan företags miljömässiga hållbarhetsarbete och klargöra definitionen av vad som kan anses miljömässigt hållbart visade resultaten att EU-taxonomins tekniska granskningskriterier i hög grad ger utrymme för tolkning vilket skapar utmaningar på både företags- och projektnivå. Utmaningarna rörde begreppsförvirring, omfattning samt av vem och i vilket skede ett kriterium bör hanteras för att linjera med EU-taxonomin. Resultaten indikerade också att en stor utmaning för byggentreprenören kommer att vara att hantera tekniska granskningskriterier som ligger utanför en byggentreprenörs rådighet. I ett nybyggnadsprojekt är flera aktörer delaktiga och byggentreprenören är ofta i beställarens händer vad gäller exempelvis val av produkter och utformning. Gällande vissa kriterier är byggentreprenören även i händerna på myndigheters arbete, främst det som sker i den kommunala planprocessen. Samverkan bedömdes därav vara en kritisk faktor för den byggentreprenör som avser att uppfylla EU-taxonomin i ett projekt. Aktörers beroende av varandra innebär svårigheter men kan reducera klimatpåverkan i det långa loppet. Samverkan inom byggentreprenörers är också viktigt då EU-taxonomin berör många avdelningar. Vidare indikerade studien att EU-taxonomin kommer att medföra en stor administrativ börda och att flera av EU-taxonomins kriterier är kostnadsdrivande. De tekniska granskningskriterier som, enligt examensarbetets resultat, kommer att vara mest utmanande för en byggentreprenör i nyproduktionsprojekt är de kriterier som berör klimatrisk- och sårbarhetsanalyser och implementering av anpassningslösningar; en byggnads flexibilitet, demonterbarhet, resurseffektivitet och anpassningsbarhet; samt kriteriet kopplat byggkomponenter- och material innehållande formaldehyd och cancerframkallande ämnen. Projektutvärderingen visade att de nybyggnadsprojekt som var miljöcertifierade med BREEAM-SE 2017 i högre grad linjerade med EU-taxonomin än projekt som miljöcertifierats enligt Miljöbyggnad 3. Det indikerar att personer och företag som tidigare arbetat med BREEAM-SE har bättre kunskapsmässiga förutsättningar att uppfylla EU-taxonomin än de som arbetat med Miljöbyggnad eller inte alls arbetat med miljöcertifiering. Studiens resultat pekar på två möjliga scenarier där EU-taxonomin antingen kommer att komplettera miljöcertifieringar som incitament till gröna fördelaktiga lån eller ersätta miljöcertifieringarna helt. I det senare fallet finns risk för ett mindre ambitiöst miljömässigt hållbarhetsarbete då både BREEAM-SE och Miljöbyggnad mäter miljöprestanda inom fler områden och ställer högre krav än EU-taxonomins tekniska granskningskriterier. Vidare har miljöcertifieringarna, till skillnad från EU-taxonomin, betygsnivåer som motiverar projektteamet att göra mer för ett högre betyg. Hur EU-taxonomin kommer att påverka en byggentreprenörs hållbarhetsarbete på projektnivå, som idag främst sker genom miljöcertifiering, beror på hur banker och investerare kommer att bedöma och värdesätta linjering, eller icke-linjering, med EU-taxonomin. / To accomplish the goals of The Paris Agreement and The European Green Deal, the European Commission launched The Taxonomy Regulation, which can briefly be described as a classification system for environmentally sustainable economic activities. Since the construction and real estate industry annually contributes to a large proportion of global carbon dioxide emissions, one chapter in The Taxonomy Regulation’s delegated act Climate Delegated Act was assigned to industry. The Climate Delegated Act provides so-called technical screening criteria for six environmental objectives. As of the fiscal year 2022, all companies affected by the directive on "non-financial sustainability reporting" must report the percentage of the company’s EU taxonomy-aligned financial activities. There was limited previous research regarding the EU taxonomy, but the found literature indicated a vast uncertainty about how the taxonomy should be implemented and how the criteria should be interpreted. The purpose of this study, a Master’s Thesis paper, was to contribute to increased knowledge of establishing the EU taxonomy and how it will affect a Swedish construction company’s operations. Challenges a construction company may face because of the EU taxonomy were studied and identified at the project and organizational levels. This study also intended to investigate how the EU taxonomy relates to a construction company’s current work with environmental sustainability in new construction projects where sustainability assessment methods, such as BREEAM-SE or Miljöbyggnad, today play an essential role. The study is based on a literature study, an interview study and a project evaluation. A literature study, an interview study and a project evaluation were carried out to answer the research questions. The literature study resulted in an introduction to the EU taxonomy and its structure as well as presents interpretations, opinions and criticism from previous research. The literature study also investigated how BREEAM-SE v6.0 and Miljöbyggnad 4.0 have implemented the EU taxonomy. Challenges and the EU taxonomy’s impact on a construction company’s work with environmental sustainability were investigated based on a project evaluation of 13 NCC Sweden Building new construction projects which were certified with either BREEAM-SE 2017 or Miljöbyggnad 3. Lastly, two NCC employees were interviewed to add more knowledge about the organizational perspective of the EU taxonomy implementation. The EU taxonomy aims to clarify the definition of environmental sustainability and increase the ability to compare companies’ and countries’ work with sustainability, but this study concludes that construction companies who want to align with the EU taxonomy will face several challenges. Firstly, the EU taxonomy’s technical screening criteria include much room for interpretation, creating challenges at the project and organizational levels. There is confusion about the scope and regarding by whom and at what stage several of the criteria should be dealt with. A significant challenge for a construction company will be dealing with criteria that are considered beyond a construction company’s or the project team’s control. Several stakeholders are involved in a new construction project, and the construction company is often not a part of the early stages. Decisions affecting the construction company’s taxonomy alignment may be taken without their involvement. Therefore, cooperation and collaboration are critical factors for a construction company that intends to fulfill the EU taxonomy in a project. The dependence on each other implies a vast challenge, but at the same time, it will probably lead to broader and more open collaboration which will reduce the environmental impact in the long term. Collaboration will also be necessary within the construction company as the EU taxonomy affects several departments. Furthermore, the study indicated that the EU taxonomy will imply a large administrative burden and several criteria are costly. The most challenging technical screening criteria for a construction company in a new construction project in Sweden are the criteria that concern the climate risk and vulnerability assessment and implementation of adaption solutions; a building’s adaptation, flexibility, resource efficiency and dismantlability; as well as the criteria about building components and materials containing formaldehyde, carcinogenic volatile organic compounds and more. The project evaluation clearly showed that projects certified with BREEAM-SE aligned to a greater degree with the EU taxonomy. Therefore, employees and companies used to working with BREEAM will have prerequisites for taxonomy alignment compared to those used to working with Miljöbyggnad or no sustainability assessment method at all. Both BREEAM-SE and Miljöbyggnad evaluate a building’s environmental sustainability performance based on more aspects and have higher requirements than the EU taxonomy. It is still unclear whether the EU taxonomy will complement or replace the sustainability assessment methods as the incitement for green beneficial financing. If the EU taxonomy becomes the new and only incitement, there is most likely a risk of less ambitious work with environmental sustainability at the project level. Furthermore, BREEAM-SE and Miljöbyggnad have rating levels that motivate the project always to make an effort. The study showed that the EU taxonomy is not a successful tool yet, but there is a strong belief in its potential. The extent to which the EU taxonomy will affect a construction company’s work with sustainability depends on how banks and investors will value EU taxonomy alignment.

No description available.

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