This study revolves around a family in which 4 male members have metabolic profiles similar to that of atypical 3–methylcrotonyl–CoA carboxylase (MCC) deficiency, an inborn error of leucine catabolism. This profile consists of high urinary 3–hydroxyisovaleric acid (3–HIVA) and trace amounts of 3–methylcrotonylglycine. One of the individuals also had clinical symptoms of chronic fatigue and muscle weakness, symptoms also related to MCC–deficiency. Further investigation showed that these individuals were negative for MCC–deficiency. The inheritance pattern of the abnormal metabolic profile seemed to indicate a link to the X–chromosome. In this study the single nucleotide polymorphism (SNP) and copy number variation (CNV) profiles of the X–chromosomes of participating members of the family were investigated for a possible link to the abnormal metabolic profile, using SNP6 DNA microarrays. The data generated by the SNP6 arrays was of good quality. The small sample size available for this study necessitated an unorthodox method for analysing the SNP6 data. No clear link between the SNP6 data and the abnormal metabolic profile was found. Selected SNP calls made by the SNP6 arrays were verified by sequencing. The origin of the elevated 3–HIVA detected in the urine of the male family members was also investigated. This was done by culturing fibroblasts from case individuals in culture medium supplemented with deuterium labelled leucine. The culture medium was analysed using GC–MS after an organic acid extraction. The resulting data seems to indicate at least two sources of 3–HIVA formation by the cells, one originating from leucine and another from a source other than leucine. The mevalonate shunt is one possible source of 3–HIVA, which does not originate from leucine catabolism. / Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2011.

This study revolves around a family in which 4 male members have metabolic profiles similar to that of atypical 3–methylcrotonyl–CoA carboxylase (MCC) deficiency, an inborn error of leucine catabolism. This profile consists of high urinary 3–hydroxyisovaleric acid (3–HIVA) and trace amounts of 3–methylcrotonylglycine. One of the individuals also had clinical symptoms of chronic fatigue and muscle weakness, symptoms also related to MCC–deficiency. Further investigation showed that these individuals were negative for MCC–deficiency. The inheritance pattern of the abnormal metabolic profile seemed to indicate a link to the X–chromosome. In this study the single nucleotide polymorphism (SNP) and copy number variation (CNV) profiles of the X–chromosomes of participating members of the family were investigated for a possible link to the abnormal metabolic profile, using SNP6 DNA microarrays. The data generated by the SNP6 arrays was of good quality. The small sample size available for this study necessitated an unorthodox method for analysing the SNP6 data. No clear link between the SNP6 data and the abnormal metabolic profile was found. Selected SNP calls made by the SNP6 arrays were verified by sequencing. The origin of the elevated 3–HIVA detected in the urine of the male family members was also investigated. This was done by culturing fibroblasts from case individuals in culture medium supplemented with deuterium labelled leucine. The culture medium was analysed using GC–MS after an organic acid extraction. The resulting data seems to indicate at least two sources of 3–HIVA formation by the cells, one originating from leucine and another from a source other than leucine. The mevalonate shunt is one possible source of 3–HIVA, which does not originate from leucine catabolism. / Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2011.

With the resource constrained nature of mobile devices and the resource abundant offerings of the cloud, several promising optimisation techniques have been proposed by the green computing research community. Prominent techniques and unique methods have been developed to offload resource/computation intensive tasks from mobile devices to the cloud. Most of the existing offloading techniques can only be applied to legacy mobile applications as they are motivated by existing systems. Consequently, they are realised with custom runtimes which incur overhead on the application. Moreover, existing approaches which can be applied to the software development phase, are difficult to implement (based on manual process) and also fall short of overall (mobile to cloud) efficiency in software qualityattributes or awareness of full-tier (mobile to cloud) implications. To address the above issues, the thesis proposes a model-driven architecturefor integration of software quality with green optimisation in Mobile Cloud Applications (MCAs), abbreviated as Mango architecture. The core aim of the architecture is to present an approach which easily integrates software quality attributes (SQAs) with the green optimisation objective of Mobile Cloud Computing (MCC). Also, as MCA is an application domain which spans through the mobile and cloud tiers; the Mango architecture, therefore, takesinto account the specification of SQAs across the mobile and cloud tiers, for overall efficiency. Furthermore, as a model-driven architecture, models can be built for computation intensive tasks and their SQAs, which in turn drives the development – for development efficiency. Thus, a modelling framework (called Mosaic) and a full-tier test framework (called Beftigre) were proposed to automate the architecture derivation and demonstrate the efficiency of Mango approach. By use of real world scenarios/applications, Mango has been demonstrated to enhance the MCA development process while achieving overall efficiency in terms of SQAs (including mobile performance and energy usage compared to existing counterparts).

Este trabalho tem como objetivo apresentar as características e conceitos da aplicação de centros de controle de motores inteligente, demonstrando as vantagens da utilização de rede industrial no controle da produção, especificamente o protocolo DeviceNet, e reunir em um documento as informações sobre a utilização e aplicações de diferentes configurações de acionamento e comando de motores instalados em um CCM. Para isso, foram realizados estudos e simulações de acionamentos elétricos protegidos por relés de sobrecarga em diferentes configurações de ligações e tecnologias utilizadas em instalações elétricas industriais, alterando os equipamentos, montagens e sinais recebidos para comando e proteção das cargas, bem como, observando os dados referentes aos custos de engenharia, instalação e materiais. Para as quatro opções analisadas foram estimados os tempos de projeto, instalação e valores estimados dos produtos e serviços necessários, fornecendo uma tabela comparativa entre as opções estudadas, além de concluir que o uso de CCM inteligente conectado ao aplicativo de supervisão IntelliCENTER se apresentou como a melhor solução, pois agrega as melhores características técnicas dos painéis elétricos, bem como a disponibilidade de monitoramento e controle da produção, com a utilização da rede DeviceNet. Além dos valores envolvidos na aquisição e startup, também foram observados os possíveis ganhos operacionais do sistema inteligente, pois permite via sistema supervisório os diagnósticos instantâneos, alarmes e desligamentos que localizam os defeitos nos acionamentos controlados. / This work aims to present the intelligent motor control center characteristics and concepts by showing the advantages of the industrial network application in the manufacturing control, more specific the DeviceNet protocol and gather in one document the information about the application and how to use different configurations of drivers and motor control installed in a MCC. In order to gather this information several studies and simulation were made by changing the equipment, assembling and signals in electric drivers protected by overload relays with different technologies and kind of connections used in industrial installations and comparing the engineering, assembling, and material costs. For the four analyzed options of drivers, the project development time, installation, product costs and necessary services were estimated showing a comparative table between options. This study will prove that the intelligent MCC connected to the IntelliCENTER software is the best solution because uses the best technical solution and also have the ability to monitor and control manufacturing, using DeviceNet network. Besides the acquisition and start up values it was also observed the operational benefits of the intelligent system, showing alarms, instantaneous diagnostics, and problems in the components of the controlled starter, by means supervisory system.

Magister Pharmaceuticae - MPharm / Medicines (CMs) are widely available to the South African public. However, CMs have not yet been evaluated by the Medicines Control Council (MCC). The MCC has published new guidelines for the regulation of CMs, with which CM companies are required to comply. OBJECTIVE: Determine to what degree Western Herbal CM labelling complies with the MCC’s requirements. METHODS: Thirteen CM products containing recognised Western Herbal ingredients were selected from pharmacies in the northern suburbs of Johannesburg. Labelling information on the immediate and outer container labels, as well as the package inserts, was investigated. The relevant corresponding European Medicines Agency (EMA) monographs and MCC guidelines were used to assess compliance. RESULTS: None of the products complied with the product dosage section of the monographs. Furthermore, the products contained indications that were not present in the monographs. The products did not fully meet the MCC’s mandatory minimum labelling requirements, and they did not demonstrate total compliance with all of the MCC’s requirements for product labels and package inserts.

No description available.

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with rising global incidence. Merkel cell polyomavirus (MCV) was discovered in 2008 in 80% of MCC samples and since then a causal link between MCV and the majority of MCC cases has been established. microRNAs (miRNA, miR) are a family of small non-coding RNAs which play a key role in post-transcriptional regulation of gene expression and are considered significant players in disease and development in many species. Whilst the focus of MCV research has thus far been on the oncogenic MCV early proteins, large tumour (LT) and small tumour (sT) antigens, there is a knowledge gap regarding MCV miRNA and its functional significance in MCV pathogenesis. Given the emerging importance of viral miRNAs in virus-host interaction and pathogenesis, the aim of this doctoral research project was to investigate alterations in host cell transcripts induced by MCV miRNA and determine any functional significance these might have on virus-host cell interaction. RNA sequencing (RNA-Seq) in the presence and absence of MCV miRNA uncovered a multitude of downregulated cellular transcripts. Gene ontology analysis revealed that MCV miRNA targets transcripts associated with multiple cellular processes, however, regulation of immune response was overrepresented in our datasets. Validation of RNA-Seq data using MCV miRNA mimics and a synthetic, fully replicative MCV genome (MCVSyn) confirmed RNA-Seq data at mRNA and protein expression level for several targets, including the cytokine stimulating gene, SP100, and the neutrophil stimulator chemokine, CXCL8. Moreover, dual luciferase assays revealed that SP100 and MAPK10 (a member of mitogen-activated protein kinases (MAPK) family which is involved in regulation of CXCL8 expression) are directly and specifically targeted and downregulated by MCV miRNA. The MCV miRNA-dependent dysregulation of CXCL8 secretion is associated with impaired neutrophil migration, suggesting that the virus miRNA may be implicated in evasion of the host immune response.

No description available.

The perception is that inborn errors of metabolism (IEM) are rare, but the reality is that more than 600 lEMs are now recognized. The organic aciduria, 3-methylcrotonyl-CoA carboxylase (MCC) deficiency arises when 3-methylcrotonyl-Coenzyme A (CoA) carboxylase that participates in the fourth step of the leucine catabolism is defective. Tandem mass spectrometry (MS/MS) based screening programmes in North America, Europe and Australia, showed that MCC deficiency is the most frequent organic aciduria detected, with an average frequency of 1:50 000. Therefore MCC deficiency is considered an emerging disease in these regions. The incidence of MCC deficiency in the Republic of South Africa (RSA) is not yet known. However, one 48 year old male Caucasian individual (HGS) was diagnosed suffering from mild MCC deficiency, since elevated levels of 3-hydroxyisovaleric acid, 3- hydroxyisovalerylcarnitine, 3-methylcrotonylglycine was present in his urine. Several groups are currently working on various aspects of this emerging disease with the focus on the molecular characterisation of MCC deficiency. In the RSA no molecular based diagnostic method which complements MS/MS screening programmes have yet been implemented. Therefore, the aim of this study was to implement the necessary techniques for the molecular characterisation of MCC deficiency, the determination of the sequence of the open reading frame (ORF) of mccA and mccB subunits to determine which mutation(s) are present in the South African MCC deficient patient. For the implementation of the molecular characterisation, a two-pronged approached was used to characterize MCC of a MCC non-deficient individual (CFC). This approach included the reverse transcriptase polymerase chain reaction (RT-PCR) amplification of the ORFs of the associated genes [mccA (19 exons) and mccB (17 exons] and the PCR amplification of selected (genomic deoxyribonucleic acid (gDNA) regions (exons mccA8, mccA11 , mccB5, mccB6 and mccB5-intron 5-6 exon 6 (mccB5-6) which have been found to have mutations associated with MCC deficiency in Caucasians. The sequence analyses produced surprising results of the amplified ORFs (CFCmccA and CFCmccB) of the MCC non-deficient individual CFC. A non-synonymous single nucleotide polymorphism (SNP) (1391C→A, H464P) associated with MCC deficiency (Gallardo et al., 2001) was identified in the CFCmccA subunit. Another SNP (1368G→A, A456A) recently listed in GenBank was observed in the amplified CFCmccB ORF. No significant novel variations or described mutations were identified in the amplified genomic regions mccA8, mccA11 ,mccB5, mccB6 and mccB5-6. The implemented molecular approach was used to characterise MCC of our MCC deficient patient (HGS). The patient did not have any mutation in the four selected exons mccA8, mccA11, mccB5, mccB6 or the genomic region mccB5-6. The RT-PCR amplification of both ORFs (HGSmccA and HGSmccB) resulted in multiple amplicons. Gel extracted amplicons of the expected size were sequenced. Of the 36 exons, 34 exons were sequenced. This includes all 19 exons of HGSmccA and 15 of 17 exons of HGSmccB (exons 1-6 and exons 9-17). The non-synonymous SNP (1391C→A, H464P) detected in CFCmccA (MCC non-deficient individual), seems to be present in the HGSmccA subunit of the MCC deficient individual, HGS. The HGSmccB amplicons could not be entirely sequenced. However, the region exon 1-6 and 9-17 was sequenced but no described or novel mutations were identified. The lack of sequence data of region exon 7-8 led to an incomplete molecular characterisation of the MCC deficiency in HGS. In conclusion, the basic methods and techniques for the molecular characterisation of MCC deficient patients have been implemented locally. A few additional sequencing primers need to be designed to cover mccB7 and mccB8 as well as the entire coding and non-coding strands of each MCC gene (mccA and mccB). The primers for RT-PCR of both mccA and mccB need to be further refined to ensure better specificity. / Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2007.

The intersection of homosexuality and faith values, a very controversial topic in the United States, has generated both social accommodation as well as “culture war.” In the past forty years this nation has witnessed the establishment of predominantly gay congregations, gay “welcoming” and “affirming” mainstream congregations, as well as virulently anti-gay religious organizations. This study investigates the origins and evolving history of gay and gay-affirming religious traditions in America with an emphasis on Atlanta and Georgia. Primarily an oral history, this project draws from eighty-two interviews as well as primary and secondary documents to construct this history. Several conclusions unfold: 1) Southern culture, though uniquely religious, has been more accommodating of gays and lesbians than heretofore appreciated; 2) citizens of Atlanta and the state of Georgia have been primary historical producers of gay and gay-affirming religious culture and institutions in America; 3) gay religious history pre-dates the Stonewall Rebellion, thus troubling and adding nuance to the traditional metanarrative of LGBTQ history; and 4) the paths of and to gay-affirming religious activism and institution building follows several distinct patterns.