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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
51

Recursive domains, indexed category theory and polymorphism

Taylor, P. January 1987 (has links)
No description available.
52

Carrier detection and patient studies in haemophilia B

Winship, P. R. January 1986 (has links)
No description available.
53

The influence of weak interactions on phase transformations and polymorphism in distributed n-aryl -formamides and -thioamides

Omondi, Bernard 22 December 2008 (has links)
A series of arylformamides and arylthioamides has been synthesized and analyzed using nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), powder and single crystal X-ray diffraction. The work involved the study of hydrogen bonding, weak intermolecular interactions, phase changes and co-crystallization in aryl - formamides and -thioamides resulting in the structure determination of twenty four crystals. Three sets of isomorphic compounds were identified from the 24 solid state structures: set one; 2,6-difluorophenylformamide (1a), 2,6- dichlorophenylformamide (2a) and 2-chloro-6-methylphenylformamide (4a); set two; 2,6-dimethylphenylthioamide (17) and 2-chloro-6- methylphenylthioamide (18) and set three; 2,6-diisopropylphenylformamide (6) and 2,6-diisopropylphenylthioamide (20). In the first two sets, 1a, 2a and 4a, and 17 and 18, there are similar regions of halogen interactions and hydrocarbon interactions with disorder in the chloro-methyl substituents in structures 4a and 18. As for compounds 6 and 20, both the chemical and geometrical effects (size and volume of the isopropyl substituents) play a role in their isomorphism. A mixture of 2,6-dichlorophenylformamide (2a) and 2,6- dimethylphenylformamide (3) yielded a co-crystal 22 in which there was one molecule in the asymmetric unit, same as co-crystal 23 [derived from 2,6- dichlorophenylthioamide (17) and 2,6-dimethylphenylthioamide (18)]. The molecules of the two co-crystals displayed disorder in the substituents on the 2 and 6 positions of the aryl ring as a result of the occurrence of chlorine and methyl groups in the same crystallographic sites. Co-crystal 22 adopted the structure of 2,6-dichlorophenylformamide 2a. Co-crystal 23 also had a ii structure similar to that of 2a and co-crystal 22. Co-crystal 24 derived from a mixture of 2,6-diisopropylphenylformamide (6) and 2,6-diisopropylphenylthioamide (20), and also had one molecule in the asymmetric unit which showed disorder in the position occupied by oxygen and sulfur atoms. The 24 structures studied exhibited a variety of motifs formed from weak intermolecular interactions. Investigation of these weak intermolecular interactions revealed four different categories1 for the arylformamides and only one category for the arylthioamides. The categories were different in their formation of N-H…O/S hydrogen bonds (in which adjacent molecules are related by 21-screw axes, glide planes or by translation) forming chains (as in category 1, 2 and 5), sheets (as in Category 3) or dimers and tetramers (as in category 4). The chains in categories 1, 2 and 5 are in the for form of spirals (molecules along the chain are related by 21-screw axes or glide planes) or stacks (molecules along the chains are related by translation). Compounds from the different categories had certain interactions that contributed most to the stabilizations of their crystals. Apart from the N-H…O/ S hydrogen bonds, π…π, C-H…π, C-F…π, C-H…F, C-H…Cl, C-H…O, Cl…Cl, Br…Br, Cl…O and Br…O interactions also had a role to play in the stabilization of the different structures. Lattice energies and the energies relating to different molecular arrangements were calculated using Gavezzottis’ OPIX program suit. This showed that the N-H…O/S hydrogen bonds and π…π interactions were the most important interactions amongst the 24 structures discussed in this work. The crystal structures, thermal behaviour and phase transformations of all arylformamides and arylthioamides have shown that a phase transformation was only observed when a halogen atom was one of the substituents and only for some of the formamides. 2,6-dichlorophenylformamide 2a and 2-chloro-6-methylphenylformamide 4a transform to a hightemperature form at 155 and 106 °C, respectively. The high-temperature forms 2b and 4b (grown by sublimation) are both monoclinic but not isomorphous, with one short axis of about 4.3 A°, and consist of chains of N– H…O hydrogen-bonded molecules stacked along the short axis, related by translation. 1a and 1b are related to the above polymorphs in their formation of N-H…O hydrogen bonding patterns. Finally, this contribution has analyzed the role of weak interactions on the structural and thermal properties of the compounds studied. In addition, a mechanism for the phase change in 2,6-dichlorophenylformamide has been proposed and rationalized through the examination of the structures themselves together with lattice energy calculations. (1. Category = different types of hydrogen bonding patterns formed by disubstituted phenyl -formamides and -thioamides discussed in this thesis).
54

Presence of the CYP2B6 516G>T polymorphism and increased plasma Efavirenz concentrations in South African HIV infected patients

Gounden, Verena 31 March 2011 (has links)
MMed, Chemical Pathology, Faculty of Health Sciences, University of the Witwatersrand / Introduction The 516G>T polymorphism in exon 4 of the CYP2B6 gene has been linked to increased plasma Efavirenz (EFV) levels. EFV levels can predict therapeutic efficacy and are related to the likelihood of developing adverse central nervous system (CNS) effects. The aims of this study were to a) determine the presence of the 516G>T and other possible CYP2B6 exon 4 polymorphisms in a South African group of HIV-infected individuals and b) to investigate the relationship between the EFV plasma concentrations, the CYP2B6 516G>T polymorphism and the occurrence of CNS related side effects in this group of patients. Methods Data from 80 patients are presented. Genetic polymorphisms in exon 4 of the CYP2B6 gene were identified using PCR amplification of this region followed by sequencing of the amplification products. EFV levels were analysed by Ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Assessment of the presence of CNS related side effects following EFV initiation were elicited with the use of a questionnaire together with physical examination. Results Plasma EFV concentrations displayed high inter-individual variability amongst subjects with levels ranging from 94 μg /l to 23227 μg/l. 23 % of patients were TT homozygous for the 516G>T polymorphism. These patients had significantly higher EFV levels vs. those with the wild (GG) genotype (p <0.05). Those who experienced no side effects had significantly lower EFV plasma concentrations vs. the group which experienced the most severe side effects (p< 0.05). iv Conclusion The significant association between the 516G>T polymorphism and plasma EFV concentrations has been demonstrated in a South African cohort. A rapid and sensitive method for the measurement of plasma EFV was developed and validated.
55

Adaptation of existing methods of genotyping platelet polymorphisms associated with cerebrovascular disease for use within the routine laboratory setting and determining the relative frequency in a cohort of stroke patients

Moodly, Sadhaseevan 09 November 2009 (has links)
M.Sc.(Med.), Faculty of Health Sciences, University of the Witwatersrand, 2008 / Introduction It is widely recognised that stroke is a multi-factorial disorder in which platelets play a crucial role in thrombus formation resulting in ischaemic stroke. Platelet adhesion and aggregation are initiated by the interaction of various platelet glycoproteins (GP’s) such as GPIbα, which binds to von Willebrand Factor and GPIIb/IIIa a fibrinogen receptor. Recent studies have shown that the GP’s are polymorphic and the polymorphisms described within GPIbα such as Kozak- 5T/C, the variable number of tandem repeats (VNTR) and the Human Platelet antigen 2 (HPA2), have been implicated in the development of stroke, while the PIA polymorphism of GPIIb/IIIa was found to contribute to “aspirin resistance”. Therefore, these polymorphisms may be potentially important for early detection and early intervention and thus setting the need to provide for a high volume genotype testing at health care centres. One of the most used techniques to determine platelet function is platelet aggregometry. However, the major disadvantages of platelet aggregation is that it is influenced by a number of environmental factors and its access is limited to tertiary health centres. Platelet aggregation measures the functional expression of platelets, which is known to deteriorate over time. It is for this reason that new methods at molecular level such as polymerase chain reaction (PCR) are needed to explore the role of genotypic expressions, which are not influenced by environmental factors. Currently, conventional PCR is used to detect platelet polymorphisms in the research settings and has limitations as a routine diagnostic test. Furthermore, it is time consuming and is prone to contamination. With the recent advances in real-time PCR it is possible to genotype large sample batches rapidly without compromising on the quality, accuracy and precision of results. This study aims to adapt conventional PCR methodology onto a real-time platform for detecting platelet polymorphisms that have been implicated in both stroke and aspirin resistance. Materials and methods A total of 60 caucasian patients classified as having ischaemic stroke by virtue of MRI and Doppler analysis from the Stroke Clinic at the Johannesburg Hospital were enrolled for this study. Healthy caucasian individuals (38), age and gender matched were enrolled as controls. DNA samples were extracted from all the subjects and the prevalence of the Kozak –5T/C, HPA-2, VNTR and GPIIIa PIA polymorphisms were determined first by using conventional PCR and then the real-time LightCycler TM PCR method. Results The frequency of the unfavourable alleles ( the PIA2 allele for the GPIIIa PIA polymorphism, the T allele for the Kozak –5T/C polymorphism, the B allele for the HPA-2 polymorphism and the C allele for the VNTR polymorphism) of the different GP’s were higher in the stroke patients when compared to the control subjects but did not reach statistical significance. There was complete statistical agreement between the results obtained for the conventional PCR as compared to the results obtained for real-time PCR except for the VNTR polymorphism, due to the difficulty in designing and the unavailability of probes for the real-time PCR assay. However, it is important to note that adapting the real-time PCR as a new methodology would greatly benefit both the patients and the clinicians by providing early detection and the possibility of early therapeutic intervention. Conclusion Therefore in conclusion, it is possible to perform not only conventional PCR for platelet polymorphism but also real-time PCR on a large scale without compromising on the quality, accuracy and precision on platelet polymorphisms that play a significant role in stroke and aspirin resistance. However, a larger population based study needs to be performed to confirm the findings.
56

Polymorphism and structural studies of isoniazid derivatives

Hean, Duane 21 May 2015 (has links)
A Dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science. 21 May 2015 / Crystal polymorphism is the capacity of a solid crystalline form to exist in more than one structural arrangement. In the pharmaceutical setting investigations into the polymorphic forms of potential drugs are of vital importance since different crystalline forms can affect bioavailability, mechanical, thermal, and chemical properties. One such example is isonicotinic acid-(1-phenylethylidene) hydrazide (IPH), a derivative of the popular drug isoniazid (used as first line treatment against Mycobacterium tuberculosis) was found to crystallise in six different polymorphic forms. Each crystal structure was determined using X-ray diffraction techniques and including the thermal phase relationships of the polymorphic compound were delineated. In addition to polymorph elucidation, isonicotinic acid-(1-phenylethylidene) hydrazide was modified with –OH and –NH2 at various aromatic positions, creating geometric pyridyl isomers. In-depth studies of these pyridyl isomers revealed a diverse range of supramolecular aggregates. Preliminary thermal screening suggests that only a small selection of these pyridyl isomers present potential polymorphic activity for further study.
57

Association of the blood biochemical index with CYP2E1 5¡¦flanking region Rsa I/Pst I gene polymorphism and alcohol consumption habit in Southern Taiwan aborigines

Kuo, Chia-ling 24 August 2005 (has links)
The microsomal ethanol oxidizing system (MEOS) is involved in metabolism of alcohol in the liver, the major component of MEOS is cytochrome P4502E1 (CYP2E1). CYP2E1 gene polymorphisms that alter its functions may be associated with alcohol susceptibility in individual. A RsaI/PstI restriction fragment length polymorphism (RFLP) has been reported in the 5¡¦-flanking region of CYP2E1 gene. The rare mutant allele (c2 allele) that lacks the Rsa I restriction site, but can cut with Pst I has been found to be associated with higher transcriptional activity, mRNA expression, protein levels and enzyme activity than the commom wild type-c1 allele. CYP2E1-dependent oxidative stress on the pathogenesis of alcohol-induced liver injury. The recent epidemiological studies have point out that there are a high prevalence of alcohol consumption in aborigines of Southern taiwan. Dr.Bosron presented an drinks wine the behavior receives the environment and the genetic factor influence, this kind of difference also receives the racial influence to be really big. This study focus on the aborigines with high alcohol drinks rate to examine the possible effect on drinks habit and gene polymorphism of CYP2E1 RsaI/PstI to blood biochemicial index. The experimental result found that male aborigines drinker in blood pressure, triglyceride, HDL cholesterol, uric acid and AST value more than male aborigines non-drinker. However the values are in T.cholesterol, LDL cholesterol, creatinine less than non-drinker. The female aborigines drinker in blood pressure, HDL cholesterol, uric acid, creatinine and AST value more than female aborigines non-drinker. However the values are in T.cholesterol and LDL cholesterol less than non-drinker. Nevertheless, male aborigines drinker and female aborigines non-drinker did not achieved diversity of statistical in function of CYP2E1 gene polymorphism to biochemical index. Male aborigines non-drinkers have c1/c2+c2/c2 in CYP2E1 gene polymorphism compare to c1/c1 also have higher WHR (0.93¡Ó0.05 vs. 0.90¡Ó0.06, p = 0.035) and ALT (30.0¡Ó22.0 IU/L vs. 21.5¡Ó11.0 IU/L , p = 0.012). To summary, male aborigines who have c2 allele in CYP2E1 gene polymorphism may relate to obese and Liver dysfuction.
58

Association of Fas Related Apoptosis Pathway Genes with the Risk and Prognosis for Oral Cancer

Sun, Chih-Pei 27 July 2006 (has links)
One of the physiological functions of apoptosis is to eliminate cells that have sustained genetic aberrations, thereby preventing damaged cell from attaining uncontrolled cell proliferation or transformation into carcinoma. The apoptotic response is mediated by many apoptotic genes including Fas, survivin, caspases etc. through either the extrinsic pathway (death receptor pathway) or the intrinsic pathway (mitochondrial pathway). In this dissertation, we carried out a hospital-based case-control study to investigate the association between seven Fas related apoptosis pathway genes (Fas, FasL, survivin, XIAP, caspase-3, caspase-8 and caspase-9) and the risk for oral squamous cell carcinoma (OSCC). In this study, 279 newly diagnosed OSCC patients and 469 frequency-matched controls were recruited at Kaohsiung Veterans General Hospital from 2003 to 2006. Total eight various polymorphisms in seven genes mentioned above were examined by PCR-RFLP and our results showed that only FasL ¡V844TT genotype (P=0.047) was associated with the risk of OSCC. However, a trend of increased risk of OSCC was found in people with the increasing putative high-risk genotypes of Fas related apoptosis pathway genes (P for linear trend, 0.034). From our results of the gene-environment interaction analyses, three important observations were listed below: (1) the polymorphism of both FasL T-844C and survivin codon Lys129Glu were risk factors for Fukienese (P=0.023 and P=0.014, respectively), but not for other ethnicities examined. (2) For non-smokers, survivin codon Lys129Glu and caspase-3 A21926C polymorphisms had significant protect (P=0.047 and P=0.024, respectively). (3) For betel quid (BQ) chewers, caspase-9 codon Arg221Gln polymorphism was an important risk factor (P=0.048). Together, the results suggested that gene polymorphisms of Fas related apoptosis pathway were associated with the risk of OSCC. In order to evaluate the relationship between p53 and caspase-3 protein expression levels or clinicopathologic characteristics and survival outcome in OSCC, we examined the protein expression profilings of caspase-3 and p53 in those patients with buccal mucosa squamous cell carcinoma (BMSCC). Total 117 primary buccal carcinoma specimens were collected at KSVGH between 1990 and 2005 and their paraffin-embedded tissues were sectioned and subjected for immunohistochemistry examination. The overall cumulative survival rate was 62% for 5-years, 39% for 10-years and 18% for 14-years, respectively. Ours results showed that the survival rate of BMSCC was significantly correlated with all clinicopathological characteristics including cell differentiation, pathological stage, tumor size, lymph node metastasis, post-operative RT, post-operative CT and BQ chewing status. Most importantly, the high caspase-3 protein level in cytoplasm was an unfavorable prognostic factor in the univariate or the multivariate analysis. In conclusion, the join effect of genetic polymorphisms of Fas related apoptosis pathway genes and gene-environment combined effect may play important roles in the OSCC risk. In addition, high caspase-3 protein expression in cytoplasm may be used as a prognostic marker for patients with BMSCC.
59

Die Wirkung des BDNF-Polymorphismus auf trankraniell induzierte Neuroplastizität / Effects of BDNF Polymorphism on transcranial induced neuroplasticity

Bourakkadi Zarrouki, Driss 11 February 2013 (has links)
No description available.
60

Functional analysis of single nucleotide polymorphisms in the proximal promoter regions of the multidrug transporter genes MRP1/ABCC1 and MRP4/ABCC4

Chan,Yuen Man 28 September 2007 (has links)
The ATP-binding cassette (ABC) transporter superfamily consists of 49 members, to which both Multidrug Resistance Protein 1 (MRP1/gene symbol: ABCC1) and MRP4 (ABCC4) belong. Single nucleotide polymorphisms (SNPs) in drug metabolizing genes have been shown to affect individual responses to drugs and toxins. However, the role of SNPs in modulating the activity of drug transporters, such as MRP1 and MRP4, is poorly characterized. The overall goal of my thesis was to determine the effects of SNPs in the promoter regions of human ABCC1 and ABCC4. For MRP1/ABCC1, two proximal promoter SNPs (-275A>G, -260G>C) were identified in the literature and recreated in vitro, and the activity of the mutant ABCC1 promoter constructs was measured in five human cell lines using a dual luciferase assay. The activity of the -275A>G promoter was comparable to the wild-type ABCC1 promoter. On the other hand, the -260G>C substitution decreased ABCC1 promoter activity in HepG2, MCF-7 and HeLa (40 - 60%) cells. A 1706 bp fragment containing the 5’-flanking and untranslated regions of ABCC4 were isolated from two bacterial artificial chromosome clones and six serially deleted ABCC4 promoter reporter constructs generated. Luciferase assays of the basal promoter constructs of ABCC4 in HEK293T cells revealed the presence of one or more negative regulatory regions between -1706 and -876, between -876 and -641, and one or more positive regulatory regions between -641 and -356, and between -356 and -17. Also, the ABCC4 promoter displayed differential activity in MDCKI and LLC-PK1 cells than in HEK293T cells. One SNP (-523G>C) was identified from an online database and its activity tested. However, -523G>C SNP did not cause any significant change in the ABCC4 promoter activity in both HEK293T and HepG2 cells (80 – 130%). In summary, the data obtained suggest that the promoter SNPs studied may affect the transcriptional activity of ABCC1 or ABCC4, but it seems likely that this is not true in all cell types. / Thesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2007-09-28 10:03:16.119

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