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Bitalo, Daphne Nyachaki. "Implementation of molecular markers for triticale cultivar identification and marker-assisted selection." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71670.
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Thesis (MSc)--Stellenbosch University, 2012.Triticale is an amphidiploid that consists of wheat (A and B) and rye (R) genomes. This cereal is fast becoming important on a commercial basis and warrants further assessment for the better management and breeding of the hybrid. The assessment of the genetic diversity among the wheat and rye genomes within triticale can be obtained by using molecular markers developed in both donor genomes. Simple sequence repeats markers (SSRs) and amplified fragment length markers (AFLPs) have been previously used to assess the genetic diversity among triticale lines. SSRs are highly polymorphic markers that are abundant and which have been shown to be highly transferable between species in previous studies while AFLP markers are known to generate plenty of data as they cover so many loci. Thus, the aim of this study was to develop a marker system suitable to assess the genetic diversity and relationships of advanced breeding material (and cultivars) of the Stellenbosch University’s Plant Breeding Laboratory (SU-PBL). Therefore, both AFLP and SSR markers were initially analysed using eight triticale cultivars (with known pedigrees) to facilitate cultivar identification. Fourty-two AFLP primer combinations and 86 SSR markers were used to assess the genetic diversity among the Elite triticale cultivars. The AFLP primer combinations generated under average polymorphism information content (PIC) values. Furthermore, these markers generated neighbour-joining (NJ) and unweighted pair group method with arithmetic average (UPGMA) dendograms that displayed relationships that did not correspond with the available pedigree information. Therefore, this marker system was found not to be suitable. A set of 86 SSRs previously identified in both wheat and rye, was used to test the genetic diversity among the eight cultivars. The markers developed in wheat achieved 84% transferability while those developed in rye achieved 79.3% transferability. A subset of SSR markers was able to distinguish the cultivars, and correctly identify them by generating NJ and UPGMA dendograms that exhibited relationships that corroborated the available pedigree data. This panel of markers was therefore chosen as the most suitable for the assessment of the advanced breeding material. The panel of seven SSR markers was optimised for semi-automated analysis and was used to screen and detect the genetic diversity among 306 triticale entries in the F6, Senior and Elite phases of the SU-PBL triticale breeding programme. An average PIC value of 0.65 was detected and moderate genetic variation was observed. NJ and UPGMA dendograms generated showed no clear groupings. However, the panel of markers managed to accurately identify all cultivars within the breeding program. The marker panel developed in this study is being used to routinely distinguish among the advanced breeding material within the SU-PBL triticale breeding programme and as a tool in molecular-assisted backcross.
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Bashir, Rabia. "Developing markers from BAC-End sequences to improve marker assisted selection in soybean /." Available to subscribers only, 2007. http://proquest.umi.com/pqdweb?did=1456299651&sid=2&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Nordqvist, Sarah. "Biological Markers of Fertility." Doctoral thesis, Uppsala universitet, Obstetrik & gynekologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-234067.
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Infertility affects 15 % of couples, which corresponds to 60 - 80 million worldwide. The microenvironments in which the oocyte, embryo and fetus mature are vital to the establishment and development of a healthy pregnancy. Different biological systems, such as angiogenesis, the immune system and apoptosis need to be adequately regulated for pregnancy to occur and progress normally. The overall aim of this thesis was to investigate the impact of Histidine-rich glycoprotein (HRG) and Src homology 2 domain-containing adapter protein B (SHB) on human female fertility. HRG is a plasma protein that regulates angiogenesis, the immune system, coagulation/fibrinolysis and apoptosis, by building complexes with various ligands. The impact of HRG on fertility is studied here for the first time. HRG is present in follicular fluid, the Fallopian tube, endometrium, myometrium and placenta. HRG distribution within embryo nuclei depends on developmental stage. Blastocysts express and secrete HRG. The HRG C633T single nucleotide polymorphism (SNP) appears to affect the chance of pregnancy and, correspondingly, parameters associated with pregnancy in IVF. Additionally, this HRG genotype may increase the risk in IVF of only developing embryos unfit for transfer. SHB is an adaptor protein involved in intracellular signaling complexes that regulate angiogenesis, the immune system and cell proliferation/apoptosis. Shb knockout mice have altered oocyte/follicle maturation and impaired embryogenesis. The impact of three SHB polymorphisms (rs2025439, rs13298451 and rs7873102) on human fertility is studied for the first time. The SNP prevalences did not differ between infertile and fertile women. BMI, gonadotropin dosages, the percentage of immature oocytes, the number of fertilized oocytes, the percentage of good-quality embryos and the day of embryo transfer seems to be affected by SHB genotype. In conclusion, HRG and SHB appear to influence female fertility. They are potential biomarkers that might be used for predicting pregnancy chance in infertile women. Knowledge of these genotypes may improve patient counseling and individualization of treatment.
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Viriyasirikul, Pattama. "Aspect markers in Thai." Thesis, University of Essex, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274379.
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Cai, Na. "Molecular markers of stress." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:95826e79-6ef0-4148-8478-5778994f97fc.
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Using data from the China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE) Consortium study of major depressive disorder (MDD)on 11,670 Han Chinese women, this thesis describes an investigation on the etiology of MDD, a psychiatric disease that has eluded previous genetic studies as well as investigations of its mechanistic underpinnings. It asks: what happens during stress, how may it contribute to the risk of developing MDD, and why does it increase the risk of MDD in some people but not others. It presents three main findings. First, a GWAS on MDD conducted on 10,640 samples (5,303 cases and 5,337 controls) in the CONVERGE dataset found two genome wide significant associations with MDD, one lying at the 5' side of SIRT1, and the other in an intron of LHPP. Both signals have been replicated in a completely independent cohort of severe MDD cases and matched controls from Northern China, making them the first replicated association loci for MDD to date. Second, I found there are more copies of mtDNA in cases of MDD than controls and while the increase can be induced by stress, it is contingent on the depressed state. Further analyses of results from animal experiments showed stress increases mtDNA levels in a dose-dependent, reversible and tissue specific way that is mediated partly by stress steroids. Third, the total amount of heteroplasmy was found to increase with increasing mtDNA levels, and therefore is higher in cases of MDD than controls, consistent with a change in mitochondrial function observed in animal models of chronic stress. All three findings suggest stress causes changes in mtDNA, and this change may be larger in cases of MDD than controls. This difference between cases and controls may be due to differences in their regulation of mtDNA levels and sequence mutation during stress, and this may be genetically determined. This study provides a new perspective to the etiology of depression, suggesting it may have origins in metabolic regulation.
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Salmenkivi, Kaisa. "Tumor markers in pheochromocytomas." Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/laa/haart/vk/salmenkivi/.
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Hammett, Christopher John Keith. "Inflammatory markers and cardiovascular disease." Thesis, University of Auckland, 2010. http://hdl.handle.net/2292/14345.
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Background: Inflammation is now recognised to play a central part in the initiation, progression and clinical manifestation of atherosclerotic cardiovascular disease. Correspondingly, on a population level, circulating levels of a wide range of inflammatory markers have been shown to be predictive of future cardiovascular events, regardless of whether they are measured in asymptomatic people, patients with stable angina, or patients with acute coronary syndromes. These include both systemic markers of inflammation such as the white blood cell count (WBC), fibrinogen, and C-reactive protein (CRP), and locally produced mediators of inflammation such as the cellular adhesion molecule soluble intercellular adhesion molecule 1 (sICAM-1), the cell-surface protein soluble CD40 ligand (sCD40L), and the metalloproteinase pregnancy associated plasma protein-A (PAPP-A). Investigation of these inflammatory markers has given many useful insights into the mechanisms that underlie the development of atherosclerosis and atherosclerotic clinical events. However, although the association (on a population level) of raised inflammatory markers with increased atherosclerotic events is widely accepted, the clinical utility of these markers (their ability to provide meaningful additional information that will help individualise treatment strategies and lead to better clinical outcomes) remains a subject of vigorous debate. Consequently, the research presented in this thesis has two broad purposes: to determine the value of inflammatory markers in a particular clinical situation (the prediction of restenosis following percutaneous coronary intervention), and to examine whether vascular inflammation is a modifiable risk factor (whether marker levels can be lowered by health interventions such as drug therapy, exercise, or smoking cessation). Methods and results: a. Inflammatory markers and restenosis To investigate whether inflammatory markers are predictive of restenosis following PCI, inflammatory markers (CRP, sICAM-1, sCD40L and PAPP-A) were measured prior to and 48 hours, 1 week and 1 month after elective PCI, and angiographic follow-up was performed at 6 months, in 133 stable angina patients. PCI led to a significant rise in CRP, sCD40L and PAPP-A levels 48 hours post-procedure, but neither pre-PCI nor post-PCI inflammatory marker levels were predictive of restenosis. This lack of association could not be attributed to concurrent use of medications such as statins, thienopyridines or glycoprotein IIb/IIIa inhibitors, since 50% of patients were not on statins and no patients received thienopyridines or glycoprotein IIb/IIIa inhibitors during the study. b. The effects of lipid lowering agents on inflammatory marker levels The effects of lipid-modifying agents on inflammatory marker levels were tested in 215 participants with stable angina randomised to simvastatin or placebo, and a further 100 participants randomised to simvastatin or bezafibrate, over a treatment period of at least 2 years. In addition, the effect of statins on the inflammatory response to PCI was assessed in a subset of 92 patients by comparing inflammatory marker levels before and 48 hours, 1week, and 1 month after PCI in those randomised to simvastatin versus those randomised to placebo. Although simvastatin led to a reduction in CRP levels with long-term therapy, the effect was modest and variable compared to the predictable effect on cholesterol levels. Average CRP levels fell ~5%, compared to a 40% reduction in LDL cholesterol, and CRP levels increased in nearly a quarter of patients on simvastatin. In addition, simvastatin did not lower levels of any other inflammatory marker, and had no appreciable effect on the inflammatory response to PCI. Similarly, bezafibrate therapy did not lower levels of any inflammatory marker. c. The effect of exercise training on inflammatory marker levels. The effects of exercise training on inflammatory markers were assessed in two separate randomised controlled trials. The first trial involved CRP measurement in 63 healthy elderly participants randomised to either 6 months��� exercise training or to a control group. The second trial involved measurement of several inflammatory markers (WBC, fibrinogen, CRP, sCD40L, sICAM-1) in 152 healthy female smokers randomised to either 12 weeks��� exercise training or to a health education (control) group as part of a smoking cessation program. In both trials, exercise led to a significant improvement in fitness but had no effect on inflammatory marker levels. d. The effect of smoking cessation on inflammatory marker levels The smoking cessation trial also investigated the effect of abstinence from smoking on inflammatory marker levels. Forty-eight individuals (35%) achieved 6 weeks verified abstinence from smoking. Abstinence caused a significant decrease in WBC and fibrinogen levels but had no effect on other inflammatory markers (CRP, sICAM-1, and sCD40L). Conclusions: There are several important findings from this research. Firstly, inflammatory markers are not useful in the prediction of restenosis following PCI in stable angina. Secondly, neither simvastatin nor bezafibrate have major antiinflammatory effects in vivo. This brings into question the mechanism(s) by which statins lower CRP, and has implications for recent proposals in the literature advocating the clinical use of CRP to titrate statin therapy. Thirdly, smoking cessation leads to a reduction in WBC and fibrinogen levels (which may reflect changes in pulmonary inflammation), but neither exercise nor smoking cessation are associated with a broad reduction in inflammatory markers linked to cardiovascular risk. It is therefore unlikely the appreciable cardiovascular benefits of these interventions are due in any substantial part to antiinflammatory effects. It remains to be demonstrated whether there are interventions which can reliably lower inflammatory marker levels, whether this decreases cardiovascular risk, and whether measurement of inflammatory markers improves upon current management of cardiovascular disease and leads to actual clinical benefit.
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Gupta, Manu. "Autoimmune markers in autoimmune diabetes /." Stockholm, 2003. http://diss.kib.ki.se/2004/91-7349-756-8/.
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Ford, Kanti. "Early markers of pubertal change." Cincinnati, Ohio : University of Cincinnati, 2008. http://rave.ohiolink.edu/etdc/view.cgi?acc_num=ucin1212153560.
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Choi, In Ji. "Discourse markers in children's narratives." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.503958.
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Rantapää, Dahlqvist Solbritt. "Genetic markers in rheumatoid arthritis." Doctoral thesis, Umeå universitet, Reumatologi, 1985. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-101305.
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Genetic as well as environmental factors are believed to be of importance in the etiology of rheumatoid arthritis (RA). There are a number of previous studies of genetic markers in RA, but so far no genetic linkage and only a few associations have been found. Of the associations only one (with the HLA antigen DR4) appears to be well documented. In most previous association studies the patients have not been divided according to sex and family history of RA. In this investigation the HLA antigens A, B and DR and five serum protein systems (Bf, C3, Pi, Hp and Tf) were studied in patients with erosive rheumatoid arthritis (RA), from northern Sweden. Special attention was paid to variations in the strength of associations according to sex and family history of polyarthritis. The following results were found: The frequency of the HLA antigen B27 was significantly increased in the North-Swedish population (16.6%) and among patients with a family history of polyarthritis (42.6%). In agreement with previous investigations a significantly increased frequency of the DR4 antigen was found in the RA patients. In the properdin factor B (Bf) system the S phenotype was found to be significantly increased in male patients and in patients with a family history of polyarthritis, more severe form of RA and high titres of rheumatoid factor. No significant differences with respect to phenotype or gene frequencies were found in the C3 complement system. Thus, the association between RA and C3 found in previous investigations was not confirmed. A significant increase of rare alpha-1-antitrypsin (Pi) types (MS, MZ, MF and SZ) was found among RA patients. However, the increase concerned mainly Z heterozygotes and was more strongly pronounced among male patients. In the haptoglobin system a significant increase of the Hp^ gene and the Hp2-2 type was found among patients with a family history of polyarthritis, more pronounced among males. A significant increase of the transferrin gene and of the 2 type was found among male RA patients, more pronounced among patients with a family history of polyarthritis. In 6 out of 8 gene loci studied significant associations were found, which is in agreement with a multifactorial etiology of RA. The results were largely in agreement with the hypothesis that associations would be expected to be stronger in males and in patients with a family history of polyarthritis. A notable finding was the high frequency of first degree relatives (around 40%) with symmetric peripheral polyarthritis of which more than 70% had a diagnosis of RA verified by hospital records.Diss. (sammanfattning) Umeå : Umeå universitet, 1985, härtill 6 uppsatser.
digitalisering@umu
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Corbett, Christopher. "Novel markers of liver fibrosis." Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/5603/.
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With chronic liver disease rising, the need to stage of liver disease and fibrosis accurately is paramount as it helps guide therapy and informs prognosis. Liver biopsy is a flawed gold standard, associated with morbidity and mortality. Application of simple non-invasive tests to assess fibrosis could provide a safe way of identifying patients in greatest need of intervention and of monitoring response to therapy. I have shown in this thesis that transient elastography is an excellent tool for ruling out significant fibrosis in patients with chronic liver disease. It is easy to learn and successful scanning correlates well with histological liver fibrosis. I have also shown that Use of APRI with a cut off of >1.5-2 and Fib-4 >3.25 can provide prognostic value for overall and liver-related mortality in patients with viral hepatitis. Finally I have assessed a range of potential new biomarkers showing that combining measuring serum levels of the chemokine CXCL10 and the endothelial adhesion receptor VAP-1 can increase the correlation strength with fibrosis stage. Using morphometric analysis of liver fibrosis I show that the same markers can be linked to quantitatively measured fibrosis, removing subjective bias and reducing inter and intra-operator variance in histological assessment.
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Lewis, Nigel da Costa. "Surrogate markers in clinical trials." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620204.
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Slyvka, N. O., I. A. Plesh, L. D. Boreiko, and Olena Viktorivna Makarova. "Diagnostic markers of hepatorenal syndrome." Thesis, Программа 99-ї підсумкової науковової конференції професорсько-викладацького персоналу Вищого державного навчального закладу України "Буковинський державний медичний університет" 12, 14, 19 лютого 2018 року, 2018. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/13765.
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Sirobaba, L. "Negation markers vs language modus." Thesis, Sumy State University, 2015. http://essuir.sumdu.edu.ua/handle/123456789/39157.
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Brand, Elizabeth Gertruida. "Selectable markers for recombinant poxvirus." Thesis, University of Cape Town, 1993. http://hdl.handle.net/11427/25692.
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Gavicharla, Avinash. "Methylation Markers In Hepatocellular Carcinoma." Cleveland State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=csu1372005514.
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Miracle, W. Charles. "Discourse markers in Mandarin Chinese." The Ohio State University, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=osu1232114951.
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FORD, KANTI RANU M. D. "Early Markers of Pubertal Onset." University of Cincinnati / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212153560.
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Pinto, Diana Maria de Figueiredo. "Molecular markers for diabetic nephropathy." Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/15953.
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Mestrado em Bioquímica - Bioquímica ClínicaType 2 diabetes is one of the most common metabolic disorders in the world. Globally, the prevalence of this disorder is predicted to increase, along with the risk of developing diabetic related complications. One of those complications is diabetic nephropathy, defined by a progressive increase in proteinuria and a gradual decline in renal function. Approximately 25% to 30% of type 2 diabetic individuals develop this complication. However, its underlying genetic mechanisms remain unclear. Thus, the aim of this study is to contribute to the discovery of the genetic mechanisms involved in the development and progression of diabetic nephropathy, through the identification of relevant genetic variants in Portuguese type 2 diabetic individuals. The exomes of 36 Portuguese type 2 diabetic individuals were sequenced on the Ion ProtonTM Sequencer. From those individuals, 19 did not present diabetic nephropathy, being included in the control group, while the 17 individuals that presented the diabetic complication formed the case group. A statistical analysis was then performed to identify candidate common genetic variants, as well as genes accumulating rare variants that could be associated with diabetic nephropathy. From the search for common variants in the study population, the statistically significant (p-value ≤ 0.05) variants rs1051303 and rs1131620 in the LTBP4 gene, rs660339 in UCP2, rs2589156 in RPTOR, rs2304483 in the SLC12A3 gene and rs10169718 present in ARPC2, were considered as the most biologically relevant to the pathogenesis of diabetic nephropathy. The variants rs1051303 and rs1131620, as well as the variants rs660339 and rs2589156 were associated with protective effects in the development of the complication, while rs2304483 and rs10169718 were considered risk variants, being present in individuals with diagnosed diabetic nephropathy. In the rare variants approach, the genes with statistical significance (p-value ≤ 0.05) found, the STAB1 gene, accumulating 9 rare variants, and the CUX1 gene, accumulating 2 rare variants, were identified as the most relevant. Both genes were considered protective, with the accumulated rare variants mainly present in the group without the renal complication. The present study provides an initial analysis of the genetic evidence associated with the development and progression of diabetic nephropathy, and the results obtained may contribute to a deeper understanding of the genetic mechanisms associated with this diabetic complication.
A diabetes tipo 2 é um dos distúrbios metabólicos mais comuns no mundo. Globalmente, está previsto um aumento da sua prevalência, assim como um aumento do risco de desenvolver complicações associadas. Uma dessas complicações é a nefropatia diabética, definida pelo aumento progressivo de proteinúria e um declínio gradual da função renal. Aproximadamente 25% a 30% dos indivíduos com diabetes tipo 2 desenvolvem esta complicação. No entanto, os mecanismos genéticos associados permanecem por esclarecer. Posto isto, o objetivo deste estudo é contribuir para a identificação dos mecanismos envolvidos no desenvolvimento e progressão desta complicação, através da identificação de variantes genéticas relevantes, em indivíduos com diabetes tipo 2 na população portuguesa. Para isso, os exomas de 36 portugueses com diabetes tipo 2 foram sequenciados na plataforma Ion ProtonTM. Desses individuos, 19 não apresentavam nefropatia diabética, tendo sido incluídos no grupo de controlo, e os restantes 17 individuos, com a complicação diagnosticada, formaram o grupo dos casos. Uma análise estatística foi depois realizada para identificar, com base nas diferenças genéticas entre os dois grupos, variantes comuns, assim como genes que acumulam variantes raras candidatas, que podem explicar o risco acrescido ou diminuído para desenvolver a complicação. Na pesquisa das variantes comuns, as variantes rs1051303 e o rs1131620 no gene LTBP4, a variante rs660339 no UCP2, a variante rs2589156 no gene RPTOR, a variante rs2304483 no SLC12A3 e, por fim, a variante rs10169718 presente no gene ARPC2, foram, de todas aquelas consideradas estatisticamente significativas (p-value ≤ 0,05), as mais relevantes para a patogénese da nefropatia diabética. O rs1051303 e o rs1131620, assim como o rs660339 e o rs2589156, têm um efeito protetor, enquanto o rs2304483 e o rs10169718 foram considerados de risco, estando associados a indivíduos que sofrem da complicação referida. Pela abordagem utilizada para identificar as variantes raras, o gene STAB1, que acumula 9 variantes, e o gene CUX1, que acumula 2, foram, de todos os genes com significado estatístico (p-value ≤ 0,05), aqueles que se evidenciaram como sendo biologicamente relevantes. Ambos os genes foram considerados protetores, já que as suas variantes raras acumuladas estavam presentes maioritariamente nos indivíduos que não apresentam esta complicação renal. Este estudo providencia uma análise inicial das evidências genéticas associadas ao desenvolvimento e progressão da nefropatia diabética, podendo os seus reultados contribuir para uma melhor compreensão dos mecanismos genéticos que estão por detrás do seu surgimento.
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Oguejiofor, Kenneth Kenechukwu. "Prognostic markers in oropharyngeal cancers." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/prognostic-markers-in-oropharyngeal-cancers(fda96224-657d-4049-ae6c-50db33a5388a).html.
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Introduction: Human papillomavirus (HPV) is changing the prevalence, survival and treatment paradigms in oropharyngeal squamous cell carcinoma (OPSCC). Improved survival of patients with HPV positive compared to HPV negative OPSCC has led to trials of treatment de-escalation. Current HPV detection methods are imprecise, therefore standardised assessment of transcriptionally active HPV in OPSCC is required. Furthermore, the differences in immune characteristics and/or the hypoxia response/effects could explain observed differences in prognosis between HPV positive and negative OPSCC. Rigorous HPV detection and subsequent biomarker evaluation should provide additional information required before introduction of treatment de-escalation in broad patient groupings. Methods: The study cohort was 218 patients with OPSCC who received radiotherapy with curative intent. HPV status was determined on pre-treatment, formalin-fixed paraffin-embedded blocks using: 1) polymerase chain reaction (PCR); 2) in-situ hybridisation (ISH) and 3) immuno-histochemistry (IHC). QuantiGene multiplex assay was designed to detect mRNA of reference sequences of the common high-risk HPV types (16, 18, 33, 35, 45, 52 and 58). HPV detection methods were compared with mRNA quantification. Multimarker IHC of immune cell markers using chromogenic and fluorescent staining was performed, analysed and compared with single marker IHC using automated multispectral image analysis. A validated multiplex IHC method was used for a) chromogenic (CD3, CD4, CD8, and FoxP3) and b) fluorescent (CD8, CD68 and PD1/PD-L1) evaluation in tumour and stroma compartments. Single marker IHC was used to investigate tumour hypoxia markers (HIF-1α and CA-IX) in HPV positive and negative OPSCC. Results: p16 IHC and ISH were the most sensitive and specific, respectively, for classifying HPV status. The combination of the three tests had the highest positive/negative predictive values compared with QuantiGene mRNA detection. Multiplex validation showed that, for serial sections up to 6 μm apart, there were highly significant correlations (P<0.0001) between single and multiplex counts for both chromogenic and fluorescent IHC. Overall there was less variation in cell counts with fluorescent staining when compared to chromogenic staining. Multiplex IHC of TILs in HPV positive and negative OPSCC showed higher infiltration in both tumour and stromal areas of CD3+CD4+ and CD3+CD8+ T cells but not CD4+FoxP3 Tregs in HPV positive compared with HPV negative OPSCC. Only CD3+CD8+ stromal and not tumour area infiltration was associated with increased survival (P=0.02). PD-L1 expression was higher in HPV negative OPSCC and this was related to macrophage (CD68) expression of PD-L1. In HPV negative tumours infiltration with CD68+PD-L1 was associated with a good prognosis. HPV negative patients had higher expression of HIF-1α but not CA-IX. High expression of both markers was associated with a poor prognosis irrespective of HPV status. Conclusions: There are other prognostic factors operating in the larger subdivision of HPV positive and negative OPSCC. Precise HPV detection and inclusion of other prognostic factors is required before treatment de-escalation is used. Expression of immune inhibitory factors (PD1/PD-L1) alone without contextualisation with immune cell density is insufficient for patient prognostication and potential selection for therapy using immune checkpoint inhibitors. Hypoxia modification of radiotherapy should be explored in both HPV positive and negative OPSCC.
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Miracle, William Charles. "Discourse markers in Mandarin Chinese /." Connect to resource, 1991. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1232114951.
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Riordan, Edward A. "Imaging markers for osteoarthritis progression." Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/20347.
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Joint damage in osteoarthritis (OA) involves characteristic changes in multiple joint tissue types, with alterations in the shape of subchondral bone and composition of synovial fluid occurring concomitantly with cartilage damage. Systemic risk factors such as obesity and local biomechanical processes that determine joint loading have long been shown to predispose to the disease, and more recent evidence suggests that specific genetic loci and inflammatory processes may make contributions, but the exact mechanisms driving the initiation and progression of the disease are yet to be elucidated. Advances in imaging that allow visualisation of minute changes in structures such as cartilage composition and subchondral bone shape have enabled longitudinal tracking of early disease development. It is hoped that the identification of early imaging biomarkers for later disease will not only assist in clarifying disease pathogenesis, but facilitate the development of disease-modifying interventions by shortening the lead time for assessing their effectiveness. This thesis aimed to clarify the current information on the utility of imaging biomarkers in research into the pathogenesis and treatment of osteoarthritis, and investigate potential imaging markers in the two regions that contribute the most to the disease burden of osteoarthritis; the knee and the hand. It utilises data from three clinical studies; a cross-sectional survey on quality of life indices in patients with arthritis, and the ongoing KANON (Knee Anterior Cruciate Ligament Non-operative vs. Operative Treatment) and COMBO (Combined Conservative Therapies on Clinical Outcomes in Thumb Base Osteoarthritis) trials. The chapters are presented in mixed manuscript form and journal format owing to differing stages of publication, and are designed to be read independently. Chapter one presents an introduction to the current understanding of the pathogenesis of OA and the role of imaging in clinical research. Chapter two presents published data from a cross-sectional survey that included 1039 participants via an online platform and utilised the validated ICOAP (Measure of Intermittent and Constant Osteoarthritis Pain) and EQ5D scores. The data identified the knees and hands as the regions in which pain was the most common, and in which arthropathy was the most detrimental to activities of daily living. This regional distribution differed slightly from studies in which participants were drawn from clinician referral, rather than from a convenience sample, raising points on the potential advantages of online platforms, and framing the subsequent focus on research into imaging biomarkers for OA of the knees and hands. Chapter three provides a further introduction to magnetic resonance imaging (MRI) to provide a background for the subsequent two chapters, and consists of a published book chapter that focuses on MRI as an imaging modality that enables direct visualisation of changes in both structure and composition in different joint tissues through the modification of contrast and sequences. In chapter four, post-traumatic osteoarthritis is discussed in two published manuscripts in terms of its value in investigating disease pathogenesis through imaging. Traumatic joint injury, and anterior cruciate ligament (ACL) rupture in particular, is strongly linked to the subsequent development of osteoarthritis, so provides an opportunity to track pathological changes from a defined starting point, and therefore potentially identify early imaging markers for subsequent disease. Chapter five presents data from serial MRIs in the KANON trial, which included 121 individuals who had sustained an acute anterior cruciate ligament (ACL) rupture to a previously uninjured knee. In the trial, 62 participants were randomised to undergo early ACL reconstruction and structured rehabilitation, and 59 were allocated to undergo structured rehabilitation alone, with an optional delayed ACL reconstruction. MRIs of the knee were obtained for all participants at baseline, two years, and five years, and for a subgroup of 63 participants, additional MRIs were performed at 3, 6, and 12 months. The serial MR imaging has enabled the effects of concomitant injuries such as osteochondral fractures and meniscal tears to be tracked, as well as providing longitudinal measurements of changes in cartilage and subchondral bone that can then be correlated with clinical outcomes. Data on the regional changes in the area of bone covered by cartilage (cAB) as a potential biomarker for disease, and the effects of baseline injuries to other joint structures, are presented. In chapter six, data on radiographic markers in trapeziometacarpal (base of thumb) osteoarthritis are presented from the COMBO trial. It includes two manuscripts – one published and one in the process of review – that present data from the first 100 participants included in the COMBO trial. Radiographic markers have traditionally had a poor correlation with symptomatic and functional outcomes, so generalised estimating equations are used for bilateral data to minimize the influence of interpersonal confounding factors and account for the fact that within-person measurements are not independent. The radial subluxation ratio is investigated in the manuscripts as a marker for structural and functional osteoarthritis progression, and radiographic markers of disease severity are analysed in relation to pain and functional outcomes in symptomatic disease. In summary, magnetic resonance imaging and radiographic markers are investigated in relation to their utility as indicators of osteoarthritis progression, and in acting as outcomes for the assessment of potential interventions in clinical trials.
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Brooks, Nicole Lisa. "Apoptotic markers in ejaculated human spermatozoa." Thesis, University of the Western Cape, 2005. http://etd.uwc.ac.za/index.php?module=etd&.
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The role of male germ cell death in spermatogenesis is an important one as it removes dysfunctional or genetically damaged germ cells and is necessary to maintain an optimal germ cell to Sertoli cell ratio. The formation of the bloodtestis barrier requires the elimination of excessive germ cells and a surge of germ cell apoptosis occurs prior to puberty regulating the ratio of germ cells to Sertoli cells. The aim of this study was to evaluate the presence of four apoptotic markers on sperm from patients with various grades of fertility using flow cytometry. Furthermore, any correlations between the apoptotic marker assays and the standard semen analysis results were identified. This study compares early and late parameters of apoptosis with morphological features in spermatozoa in the same samples. The three sample groups were identified as: teratozoospermic [G-pattern] (n=26), teratozoospermic [P-pattern] (n=98) and oligoteratozoospermic [Ppattern] (n=36). Standard semen analysis was conducted on the semen samples according to the WHO guidelines. Four apoptotic marker assays using flow cytometry was applied in this study to examine the apoptotic alterations in ejaculate sperm. These assays included the Annexin-V staining for the determination of phosphatidylserine exposure, APO-Direct to identify DNA fragmentation, caspase-3 to detect expression of this active protease during early apoptosis and Fas expression. For the Annexin-V and caspase-3 assays, statistically significant differences (P<0.05) were evident between the three groups. No significant differences (P>
0.05) were found between the groups with respect to the APO-Direct assay. A significant difference (P<
0.05) was found when comparing the teratozoospermic [G-pattern] group and the oligoteratozoospermic [P-pattern] group for the Fas assay. A strong positive correlation was evident between the Fas and the caspase-3 assays in the teratozoospermic [G-pattern] group. For the teratozoospermic [P-pattern group] the following positive correlations existed between the APO-Direct and the Fas assays, APO-Direct and caspase-3 assays and between caspase-3 and Fas assays. The only strong positive correlation was between the caspase-3 and APO-Direct assays in the oligoteratozoospermic [P-pattern] group. The presence of spermatozoa showing microscopic features resembling apoptosis has been identified in ten human ejaculate samples per sample group. Electron microscopy was used to identify morphological features of apoptosis in these human sperm samples. Classical apoptosis as observed in diploid cells could be identified in sperm and these included: loose fibrillarmicrogranular chromatin network, presence of vacuoles in the nuclear chromatin, membranous bodies within the vacuoles of the chromatin, partially disrupted nuclear membranes, plasma membrane protuberances and apoptotic bodies containing cytoplasmic vacuoles and dense masses. This study has confirmed that semen samples with abnormal semen parameters exhibit the presence of apoptotic markers in sperm. The identification of apoptotic markers on the sperm suggests that abnormalities occur during their developmental process, however, the exact mechanism thereof remains unclear. These findings may suggest that certain apoptotic markers may be an indicator of abnormal sperm function and possibly indicative of male infertility.
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Mawlood, Shakhawan K. "Epigenetic markers in forensics and ageing." Thesis, University of Strathclyde, 2016. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=27051.
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This PhD project describes the development of two novel forensic approaches the use of trace DNA isolation and profiling from fired gun cartridges, and the development and application of epigenetic analyses of the autosomal and mitochondrial genomes in order to estimate age. In the first part of the work two novel swabs (forensiX) and a standard cotton swab (EUROTUBE/Deltalab) were compared for the collection of forensic samples. Additionally, the effect of long-term storage of these samples was assessed. The forensiX swabs generally produced a higher (two- to four-fold) DNA yield compared to standard swab (around 750 pg and 250 pg, respectively, from 0.5 μL of saliva). These findings demonstrate the importance of ‘active drying’ performance in the preservation of DNA and swab selection. Using the forensiX swabs, we subsequently produced data that indicated that DNA samples deposited on cartridges during loading can survive firing from eight different types of gun. It has been shown that the methylation status of certain human DNA loci correlates with ageing. Blood sample DNA from a cohort of 82 women aged 18 to 91 years was obtained. We used Illumina MiSeq next generation sequencing platform to investigate the promoter regions of 23 genes suggested to have age-correlated methylation levels. Methylation levels at three CpGs located in the ASPA, ITGA2B and PDE4C genes showed an epigenetic signature of ageing with only a 6 year error range from chronological age. The methylation of mitochondrial DNA (mtDNA) is a new and incompletely described phenomenon with unknown biological control and significance. We describe the bisulphite sequencing of mtDNA from the same cohort of individuals. We detected low and variable levels of mtDNA methylation at 54 of 133 CpG sites interrogated. Regression analysis of methylation levels at two CpG sites (M1215 and M1313) located within the 12S ribosomal RNA gene showed an inverse relationship with age. We wished to create a fast and simple forensic tool (compared to next generation sequencing) for practical age estimation. The EpiTect Methyl II PCR system (QIAGEN) was used to compare methylation levels of CpG islands of the promoter regions of 4 age related genes (NPTX2, KCNQ1DN, GRIA2 and TRIM58). The data obtained from DNA methylation quantification showed successful estimation of subject age (11 year accuracy). This thesis describes practical steps to obtain forensic DNA samples while also applying novel techniques to explore the use of epigenetic profiling as a means to age prediction. The data generated suggest that the analysis of methylation patterns of both specific autosomal and mitochondrial gene sequences from biological evidence left at crime scene may help build up an accurate picture of an offender’s age and may help investigators obtain better descriptive information about a contributor from DNA, regardless of database inclusion.
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Nikitina-Zake, Liene. "Immunogenetic markers in immune-mediated diseases /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-718-5/.
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Weigelt, Britta. "Molecular markers of breast cancer metastasis." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2005. http://dare.uva.nl/document/88848.
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Hijazi, Ziad. "New Risk Markers in Atrial Fibrillation." Doctoral thesis, Uppsala universitet, Institutionen för medicinska vetenskaper, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-198833.
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Atrial fibrillation (AF) confers an independent increased risk of stroke and death. The stroke risk is very heterogeneous and current risk stratification models based on clinical variables, such as the CHADS2 and CHA2DS2VASc score, only offer a modest discriminating value. The aims of this thesis were to study cardiac biomarkers, cardiac troponin and natriuretic peptides e.g. N-terminal prohormone-B-type natriuretic peptide (NT-proBNP), and describe levels in AF patients, investigate the association with stroke or systemic embolism, cardiovascular event, major bleeding and mortality, and to assess how levels of cardiac biomarkers change over time. Cardiac troponin was analyzed with contemporary assays and high sensitivity assays. The study populations consisted of patients with atrial fibrillation and one risk factor for stroke included in the RE-LY (n=6189) and the ARISTOTLE (n=14892) biomarker substudies. Median follow-up time was 2.2 years and 1.9 years, respectively. In a subset of participants (n=2514) data from repeated measurements was available at three months. Cardiac troponin was detectable in 57.0% with the contemporary assay and 99.4% with the high sensitivity assay. NT-proBNP was elevated in approximately three quarters of the participants. In Cox models adjusted for established risk factors the cardiac biomarkers levels was independently associated with stroke or systemic embolism, cardiovascular events, and mortality. Only cardiac troponin was associated with major bleeding. In ROC analyses the prediction of stroke or systemic embolism, cardiovascular events, and mortality increased significantly by addition of cardiac troponin or NT-proBNP to the models. Persistent detectable cardiac troponin (contemporary assay) and elevated NT-proBNP levels were found in a large number of participants. Persistent detectable or elevated levels conferred significantly higher risk for stroke or systemic embolism, cardiovascular events, and mortality. By using both cardiac biomarkers simultaneously the risk stratification improved even further for all outcomes. In conclusion the analyses for the first time display that elevation of troponin I and NT-proBNP are common in patients with AF and independently related to increased risks of stroke, cardiovascular events and mortality. Persistent elevation of troponin and NT-proBNP indicate a worse prognosis than transient elevations or no elevations of either marker. The cardiac biomarkers added substantial improvements to existing risk stratification models.
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Rippin, Julian John. "Pterins as markers of immune activation." Thesis, Imperial College London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338590.
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Ackerman, Hans Christian. "Disease association mapping : methods and markers." Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249649.
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Tanner, Lydia Nathania. "Functional imaging markers for tumour characterisation." Thesis, University of Oxford, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555356.
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There is rapidly increasing interest in functional imaging for the diagnosis and monitoring of disease. In particular, Dynamic Contrast Enhanced (DCE) Mag- netic Resonance Imaging (MRI) is of enormous, and growing importance in medical imaging, fundamentally because it provides a powerful tool for assessing tumour vasculature. Furthermore it has been proposed as a means of moni- toring disease progression and for identifying potential markers for predicting patient response to therapy. In principle, DCE-MRI data can be quantified us- ing pharmacokinetic models, enabling extraction of physiologically meaningful parameters. Although the combination of DCE-MRI sequencing and pharmacokinetic mod- elling promises quantitative analysis of response, as well as providing the clinician with parametric information (such as Ktrans and kep), there are a number of fun- damental problems to be addressed. When we applied the published models to clinical colorectal cancer MRI data sets, we observe that many voxels within the tumour volume fail to produce identifiable pharmacokinetic information. We ad- dress the root causes of this problem as a necessary precursor to moving beyond calculating average pharmacokinetic values for a region of interest to observing and quantifying tumour heterogeneity. We find a high dependence of the pharmacokinetic model on uncorrected motion in the MR images, and on estimation of the pre-contrast Tl tissue relaxation time. We quantify the effects of each of these, and derive a more reliable means of generating concentration curves, necessary as a precursor to pharmacokinetic modelling. Next, we look at the standard two compartment model for DCE-MRI. While the functional form of the compartment model is known, computation of the amount of contrast agent depends critically upon knowing the arterial input function. We demonstrate a high dependence of the pharmacokinetic model on the choice of arterial input function. We quantify the effects of model and population- averaged parameter choice and find that the standard image based methods used for individual arterial input function extraction, based on identifying an artery or reference region, are unsuitable on clinical data whose temporal resolution is low. We propose an alternative method to extract the plasma concentration from the tissue of interest. We assess the new method on both simulated and clinical data; the results show a more robust estimation of the pharmacokinetic parameters. The literature suggests DCE-MRI has applications in predicting the response of tumours to neoadjuvant chemoradiotherapy. For colorectal cancer, only 70% of patients demonstrate response to therapy with 10-20% responding completely. By clustering parameters across patients to infer blood flow patterns common for different subsets of tumour, we attempt to find a suitable description of.
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Lim, Ee Tuan. "Neurodegenerative markers : insights into multiple sclerosis." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1444993/.
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Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) characterised pathologically by inflammation, demyelination and variable degrees of axonal loss and gliosis. Remyelination, axonal and synaptic plasticity have been identified as mechanisms underlying functional recovery. MS typically follows a chronic course, in the sense that new episodes or steady progression are the rule. Currently radiological surrogates of inflammation, demyelination and axonal loss are available, but these correlate only modestly with the development of cumulative disability. In this thesis, potential brain specific protein (BSP) markers for these pathological processes are identified and compared to existing magnetic resonance (MR) markers. OBJECTIVES: Levels of the nervous system proteins S100B (astrocytic activation), glial fibrillary acidic protein (GFAP astrogliosis), neurofilaments (axonal marker) and ferritin (microglial activation) and other inflammatory markers (i.e. anti-myelin antibodies) were measured. These values were correlated with both histopathological measurements in post-mortem specimens and MR imaging measures in patients with MS. Histology and immunochemistry of tissue sections characterised normal and pathological CNS and localized the extent of demyelinating plaques.
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Chau, Raymond Tsz-hong. "Linguistic markers of deception: um andlike." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46631112.
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McClelland, Carol Margaret. "Surrogate markers to determine drug activity." Thesis, University of Kent, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413298.
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Allam, Mohamed Mostfa El-Said. "Evaluation of urinary markers in leukaemia." Thesis, University of Leeds, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.236697.
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Satterthwaite, Gemma. "Discovery of diagnostic markers for atherosclerosis." Thesis, University of Sheffield, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274961.
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Silva, K. D. Renuka R. "Markers of chylomicron metabolism in man." Thesis, University of Reading, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394221.
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Allen, Marcus Christopher. "Biochemical markers of pulmonary oxygen toxicity." Thesis, University of Aberdeen, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.277226.
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This study has investigated potential biochemical markers of pulmonary oxygen toxicity (POT). Toxicity was investigated in male Sprague Dawley rats exposed to oxygen partial pressures ranging from 0.21-2.5 bars. It is known that prolonged exposure to 1 bar of oxygen damages pulmonary endothelial cells and so the biochemical functions of these cells have been studied. Control isolated perfused rat lungs were able to clear and/or metabolise a wide range of substances including 5-HT, PGE2, bradykinin, and angiotensin 1, all endothelial cell functions. As expected 5-HT clearance was compromised in isolated perfused rat lung obtained from rats exposed to 1 bar of oxygen, confirming endothelial cell damage. However the clearance of 5-HT by lungs obtained from rats exposed to 2.5 bars was normal, implying that the site of toxicity is different at these partial pressures. In addition enhancement of toxicity by vitamin E deficiency was not associated with endothelial cell damage at 2.5 bar. At the molecular level oxygen free radicals are thought to be the causative agents of POT. The radicals are reputed to damage lipids, but a process of peroxidation. One of the lipid fragment products of ω6 polyunsaturated fatty acids is n-pentane, a compound which is excreted on the breath. Monitoring of this compound during exposure to 0.21, 1.0, 2.5 bars of oxygen even in vitamin E deficient rats did not show a rise in pentane expiration in response to oxygen exposure. This implies that peroxidation of ω6 polyunsaturated fatty acids did not take place, although other lipids may have been peroxidised. In conclusion the site of POT may depend on the partial pressure of oxygen. Endothelial cell damage is probably absent during exposure to 2.5 bars of oxygen. In addition n-pentane monitoring, a reputed marker of POT, failed to reveal lipid perodixation during exposure to hyperoxia.
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Al-Mohammad, Abdallah. "Hibernating myocardium : prevalence and surrogate markers." Thesis, University of Aberdeen, 2017. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=235453.
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The aims of this thesis are to determine: 1. The true prevalence of hibernating myocardium in patients with severely impaired left ventricular contraction. (Chapter 3) 2. The viability status of the left ventricular wall aneurysm as defined by positron emission tomography. (Chapter 4) 3. The relationship between the incidence of hibernating myocardium and the coronary artery flow grade determined angiographically. (Chapter 5) 4. The relationship between the presence of Q waves (with or without preserved R wave) on the surface electrocardiogram and the presence of scar in the myocardium as diagnosed by positron emission tomography. (Chapter 6) 5. The relationship between the incidence of hibernating myocardium and QT dispersion on the surface electrocardiogram. (Chapter 7) 6. Looking for other markers of hibernation by PET. (Chapters 8 and 9) I proposed to look at the relationship between continuing metabolic activity in 10 akinetic or severely hypokinetic segments as an alternative method and thus as a new definition of pre-operative determination of hibernating myocardium. This is the topic in Chapter 8. Following the completion of question number 3, and the observed role of collateral circulation, I proposed to look into the role of TIMI 0-1 and collaterals grade 2-3 in maintaining viability and their role as a marker of hibernating myocardium. This won support in the form of a research grant from the British Heart Foundation in 1998. This was the topic of my last project, which was added to the thesis after its initial completion on the 23rd of December 2000. This is the topic of Chapter 9. 7. Following the delayed submission of the Thesis in 2015, I was asked to add Chapter 11 which summarised both my contribution since the Thesis was concluded into the topic of Hibernating myocardium; and the knowledge progression into the detection of the phenomenon and its clinical usefulness to bring the Thesis up to date. Methods: The patients were those with coronary artery disease and impaired left ventricular contraction recruited into a series of studies of the presence of hibernating myocardium using positron emission tomography, as the method of choice to preoperatively detect this phenomenon. The patients were either recruited from the cardiac catheterization laboratory or from the cohort of patients presenting with myocardial infarction to the cardiology unit at Aberdeen Royal Infirmary. All the studies were approved by the Grampian Research Ethics Committee. In some of the studies, cardiac magnetic resonance imaging was used for simple assessment of the myocardial contraction and thickening in the study reported in Chapter 9. Results and Conclusions: 1. Hiberanting myocardium affects over 50% of the patients with severe left ventricular systolic impairment with coronary artery disease. (Chapter 3). 2. None of the aneurysmal segments are viable. (Chapter 4) 3. Compared to the areas supplied by arteries with Thrpmbolysis In Myocardial Infarction (TIMI) flow grades 2-3, the areas supplied by almost occluded coronary arteries (TIMI 0-1 flow grades) are significantly more likely to have both evidence of scarred myocardium (highly significantly statistical difference p < 0.0001) and evidence of hibernating myocardium, just reaching statistical significance (p < 0.05). (Chapter 5) 4. The specificity of Q waves on the electrocardiogram (ECG) as markers for 11 myocardial scarring is 79%, with a low sensitivity of 41%. (Chapter 6) 5. Maintaining R waves following a pathological Q wave on the ECG is not helpful for predicting the presence of hibernating myocardium. (Chapter 6) 6. The presence or absence of hibernating myocardium did not impact on native QT dispersion, rate corrected QTc dispersion or on the maximum adjacent QT dispersion on the ECG. (Chapter 7). 7. A new definition of hibernating myocardium is proposed, helping to detect it preoperatively through the demonstration of metabolism – mechanical mismatch defect using a single radio-pharmaceutical. (Chapter 8) 8. As a marker of the classical perfusion –metabolism mismatch defect, the new proposed metabolism-mechanical mismatch defect by PET is sensitive (92%) and specific (97%), with excellent positive and negative predictive accuracies (96% and 93%, respectively). (Chapter 8) 9. While collaterals grade 2-3 supplying territories with blocked arteries and flow grades TIMI 0-1 may be sensitive markers (83%) of hibernating myocardium; they lack specificity (20%), and the differences between the two small groups completing the study did not reach statistical significance. (Chapter 9).
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Burke, Nathaniel Caleb. "Assessment of redox markers in cattle." Thesis, Virginia Tech, 2007. http://hdl.handle.net/10919/34587.
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Metabolic redox status may have important implications to cattle health and production. Antioxidants and biomarkers of oxidative stress were evaluated in cattle under three phases of management. Each phase stood alone as a treatment model, and managerial aspects during the phase were evaluated as potential moderators of redox balance. Yearling heifers were used to assess the impact of fescue toxicosis and heat stress on selected markers in study 1. Intravaginal temperatures, ADG, serum prolactin, plasma malondialdehyde, and whole blood Se, along with peripheral blood mononuclear cell glutathione peroxidase, glutathione reductase, and reduced:oxidized glutathione were determined during summer grazing. Results suggested that endophyte consumption does not promote oxidative stress in cattle. Heat stress may alter glutathione redox of white blood cells. In study 2, effects of gradual weaning strategies (anti-suckle nose clip and fenceline wean) and transport were evaluated in calves. Calf weights, Se and malondialdehyde in plasma, along with glutathione peroxidase and glutathione reductase in leukocytes were measured at -7, 0, 1, and 7 days surrounding weaning and transport. Little benefit of gradual weaning was detected, and oxidative stress may have been negligible. In study 3, the influences of grain- and forage-based diets were compared in finishing steers pre- and post-harvest. Total antioxidant capacity and malondialdehyde concentration of plasma, along with serum alpha-tocopherol, beta-carotene, and gamma-tocopherol were measured. Antioxidants and lipid oxidation were assessed in beef. Forages promoting plasma antioxidant capacity may protect cattle against oxidative stress. Antioxidants derived from forages inhibit lipid oxidation in pasture-finished beef.Master of Science
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Olckers, Lorna. "Judging essays : factors that influence markers." Master's thesis, University of Cape Town, 2006. http://hdl.handle.net/11427/12423.
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Includes bibliographical references (leaves 92-95).This thesis is an exploration of assessment with particular focus on the marking of essay assignments and the validity or soundness of that process.
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Israngkun, na Ayudthaya Porn Paul. "Potential biochemical markers for infantile autism /." The Ohio State University, 1986. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487322984315317.
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Maissa, Cecile A. "Biochemical markers and contact lens wear." Thesis, Aston University, 1999. http://publications.aston.ac.uk/9627/.
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The project objective was to develop a reliable selection procedure to match contact lens materials with individual wearers by the identification of a biochemical marker for assessment of in-eye performance of contact lenses. There is a need for such a procedure as one of the main reasons for contact lens wearers ceasing wearing contact lenses is poor end of day comfort i.e. the lenses become intolerable to the wearer as the day progresses. The selection of an optimal material for individual wearers has the potential benefit to reduce drop Qut, hence increasing the overall contact lens population, and to improve contact lens comfort for established wearers. Using novel analytical methods and statistical techniques, we were able to investigate the interactions between the composition of the tear film and of the biofilm deposited on the contact lenses and contact lens performance. The investigations were limited to studying the lipid components of the tear film; the lipid layer, which plays a key role in preventing evaporation and stabilising the tear film, has been reported to be significantly thinner and of different mixing characteristics during contact lens wear. Different lipid families were found to influence symptomatology, in vivo tear film structure and stability as well as ocular integrity. Whereas the symptomatology was affected by both the tear film lipid composition and the nature of the lipid deposition, the structure of the tear film and its stability were mainly influenced by the tear film lipid composition. The ocular integrity also appeared to be influenced by the nature of the lipid deposition. Potential markers within the lipid species have been identified and could be applied as follows: When required in order to identify a problematic wearer or to match the contact lens material to the contact lens wearer, tear samples collected by the clinician could be dispatched to an analytical laboratory where lipid analysis could be carried out by HPLC. A colorimetric kit based on the lipid markers could also be developed and used by clinician directly in the practice; such a kit would involve tear sampling and classification according to the colour into "Problem", "Border line" and "Good" contact lens wearers groups. A test kit would also have wider scope for marketing in other areas such as general dry-eye pathology.
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Bruford, Michael William. "Hypervariable markers in the chicken genome." Thesis, University of Leicester, 1992. http://hdl.handle.net/2381/34286.
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This thesis describes the characterization of minisatellite sequences in the chicken genome. A DNA fingerprinting protocol was established using four types of minisatellite probe in chickens. Segregation analysis was carried out on three pedigrees. Linkage was higher than in several other avian species, with groups of up to four cosegregating bands being detected. Although some overlap among probes occurred, the probes detected mostly independent sets of loci. Two commercial egg-laying lines were analyzed in detail. The mean band sharing coefficient was 0.5 - 0.6 and band frequencies in the lines were bimodally distributed. In an Investigation of rare breed populations, within population coefficients were found to be around 0.9 and between population values were around 0.15. These populations were highly inbred, and require genetic management. The charomid cloning system was used to isolate chicken minisatellites. Library 1 (11 - 21 kb size fraction) yielded 35,000 clones and Library 2 (2-7 kb) yielded 115,000 clones. 1,710 and 4,275 clones for Libraries 1 and 2 respectively, were transferred into microtitre wells and replicated on to nylon membranes. For Library 1, the total number of positively hybridizing minisatellites was 28 (1.64% of clones). For Library 2, the total number of positives was 113 (2.64%). 55 cloned fragments were tested against four unrelated chickens: 30 revealed variable single locus patterns. The mean number of alleles detected with clones isolated from Library 1 was 4.8 + 1.8 (s.d.), mean number of heterozygotes out of 4 was 2.3 + 1.4. The mean number of alleles detected with clones isolated from Library 2 was 3.8 + 1.5, and the mean number of heterozygotes out of four was 1.9 + 1.2. Detailed characterization was made of fifteen probes. Probes were tested against four families of 13, 13, 10 and 17 offspring. Informative segregations were produced in 51% of parent-offspring comparisons. No allelic mutation was observed, therefore the mean mutation rate was less than 0.003 per gamete (95% confidence maximum). Three probes were linked on an autosome, and one was Z chromosome linked. Heterozygosity and allelic variability were measured in 67 individuals. Mean heterozygosity ranged between 50% and 84%. Heterozygosity values were slightly lower than those found using the same system in humans (Armour et al. 1990), but very similar to those found in peafowl (Hanotte et al. 1991). There was no significant difference in the level of variability revealed by probes from the two libraries, though the mean number of heterozygous individuals among the different sample sets and mean percentage heterozygosity were generally higher for Library 1 than Library 2. Genetic variability within, and genetic distance among commercial egg-layer and broiler lines were analysed using distance matrices and parsimony. Both egg-layers and broiler lines showed similar levels of within-line variability and extremely large allele frequency differences. Genetic distance among lines were very high, reflecting the small population sample size. Maximum parsimony techniques failed to cluster individuals according to their population of origin. The proportion of the probe sequence made up of DNA flanking the minisatellite, and size differences within an individual when digested with different restriction enzymes, was tested using a panel of unrelated individuals digested separately with AluI and HaeIII. DNA samples were also digested with ten restriction enzymes. Variability, allele size and pattern clarity were analyzed for each probe/enzyme combination. For nine of these (60%), MboI, the cloning enzyme, gave the most interpretable pattern with the smallest allele size. However, occasionally, such as with cGgaMS134, AluI or HaeIII produced more informative low molecular weight patterns.
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Bont, Judith Maria de. "Biological Markers in Pediatric Brain Tumors." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/13263.
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Nees, Mary Barton. "Markers: Key Themes for Soul Survival." Digital Commons @ East Tennessee State University, 2017. https://www.amzn.com/1945975369/.
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This seven-chapter book, highlighted like a trail guide with Markers, will ease you into most basic, repeated themes found in the ancient texts. What is called the Old and New Testaments is a remarkable collection. It is intimidating for sure, but wise, prophetic, thorough and particular, with echoes that repeat into every culture. Through story and turn-arounds you will see how some very different individuals, in different times found their way into God’s real and sustaining peace. They listened to and reckoned with what God offers for soul survival. There’s hope here if you'll take it.https://dc.etsu.edu/alumni_books/1033/thumbnail.jpg
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Swagell, Christopher Dean. "Molecular markers of obesity and diabetes." Thesis, Queensland University of Technology, 2007. https://eprints.qut.edu.au/35762/1/Christopher_Swagell_Thesis.pdf.
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Recently it has been shown that the consumption of a diet high in saturated fat is associated with impaired insulin sensitivity and increased incidence of type 2 diabetes. In contrast, diets that are high in monounsaturated fatty acids (MUFAs) or polyunsaturated fatty acids (PUFAs), especially very long chain n-3 fatty acids (FAs), are protective against disease. However, the molecular mechanisms by which saturated FAs induce the insulin resistance and hyperglycaemia associated with metabolic syndrome and type 2 diabetes are not clearly defined.
It is possible that saturated FAs may act through alternative mechanisms compared to MUFA and PUFA to regulate of hepatic gene expression and metabolism. It is proposed that, like MUFA and PUFA, saturated FAs regulate the transcription of target genes. To test this hypothesis, hepatic gene expression analysis was undertaken in a human hepatoma cell line, Huh-7, after exposure to the saturated FA, palmitate. These experiments showed that palmitate is an effective regulator of gene expression for a wide variety of genes. A total of 162 genes were differentially expressed in response to palmitate. These changes not only affected the expression of genes related to nutrient transport and metabolism, they also extend to other cellular functions including, cytoskeletal architecture, cell growth, protein synthesis and oxidative stress response. In addition, this thesis has shown that palmitate exposure altered the expression patterns of several genes that have previously been identified in the literature as markers of risk of disease development, including CVD, hypertension, obesity and type 2 diabetes. The altered gene expression patterns associated with an increased risk of disease include apolipoprotein-B100 (apo-B100), apo-CIII, plasminogen activator inhibitor 1, insulin-like growth factor-I and insulin-like growth factor binding protein 3. This thesis reports the first observation that palmitate directly signals in cultured human hepatocytes to regulate expression of genes involved in energy metabolism as well as other important genes.
Prolonged exposure to long-chain saturated FAs reduces glucose phosphorylation and glycogen synthesis in the liver. Decreased glucose metabolism leads to elevated rates of lipolysis, resulting in increased release of free FAs. Free FAs have a negative effect on insulin action on the liver, which in turn results in increased gluconeogenesis and systemic dyslipidaemia. It has been postulated that disruption of glucose transport and insulin secretion by prolonged excessive FA availability might be a non-genetic factor that has contributed to the staggering rise in prevalence of type 2 diabetes. As glucokinase (GK) is a key regulatory enzyme of hepatic glucose metabolism, changes in its activity may alter flux through the glycolytic and de novo lipogenic pathways and result in hyperglycaemia and ultimately insulin resistance. This thesis investigated the effects of saturated FA on the promoter activity of the glycolytic enzyme, GK, and various transcription factors that may influence the regulation of GK gene expression. These experiments have shown that the saturated FA, palmitate, is capable of decreasing GK promoter activity. In addition, quantitative real-time PCR has shown that palmitate incubation may also regulate GK gene expression through a known FA sensitive transcription factor, sterol regulatory element binding protein-1c (SREBP-1c), which upregulates GK transcription.
To parallel the investigations into the mechanisms of FA molecular signalling, further studies of the effect of FAs on metabolic pathway flux were performed. Although certain FAs reduce SREBP-1c transcription in vitro, it is unclear whether this will result in decreased GK activity in vivo where positive effectors of SREBP-1c such as insulin are also present. Under these conditions, it is uncertain if the inhibitory effects of FAs would be overcome by insulin. The effects of a combination of FAs, insulin and glucose on glucose phosphorylation and metabolism in cultured primary rat hepatocytes at concentrations that mimic those in the portal circulation after a meal was examined. It was found that total GK activity was unaffected by an increased concentration of insulin, but palmitate and eicosapentaenoic acid significantly lowered total GK activity in the presence of insulin. Despite the fact that total GK enzyme activity was reduced in response to FA incubation, GK enzyme translocation from the inactive, nuclear bound, to active, cytoplasmic state was unaffected. Interestingly, none of the FAs tested inhibited glucose phosphorylation or the rate of glycolysis when insulin is present. These results suggest that in the presence of insulin the levels of the active, unbound cytoplasmic GK are sufficient to buffer a slight decrease in GK enzyme activity and decreased promoter activity caused by FA exposure. Although a high fat diet has been associated with impaired hepatic glucose metabolism, there is no evidence from this thesis that FAs themselves directly modulate flux through the glycolytic pathway in isolated primary hepatocytes when insulin is also present.
Therefore, although FA affected expression of a wide range of genes, including GK, this did not affect glycolytic flux in the presence of insulin. However, it may be possible that a saturated FA-induced decrease in GK enzyme activity when combined with the onset of insulin resistance may promote the dys-regulation of glucose homeostasis and the subsequent development of hyperglycaemia, metabolic syndrome and type 2 diabetes.
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Mangiacotti, M. "DETERMINATION OF IRRADIATION MARKERS IN FOODS." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/232733.
Full textAbstract:
Today’s food industry is faced with several important challenges, including food product deterioration and the constant increase of diseases related to the presence of pathogenic microorganisms in food products. Thus, adequate and effective food preservation strategies are even more important. Food irradiation is a technological process that can improve the microbiological quality of foodstuffs and extend the period in which it can be safely consumed. The radiation treatment, carried out under conditions of Good Manufacturing Practice, is considered as an effective, widely applicable food processing method judged to be safe on extensive available evidence. This technology can reduce the risk of food poisoning, control food spoilage and extend the shelf-life of foods without detriment to health and with minimal effect on nutritional or sensory quality. Due to its numerous positive effects, including those of a commercial nature, food irradiation has assumed a highly important role in the field of food preservation, and increasingly large numbers of foodstuffs are subjected to this treatment each year. For some time now, countries equipped with adequate food irradiation facilities have used this technology at well defined doses for the preservation of various foodstuffs. Because of the divergent opinions expressed by many consumers' organizations, the European Union has issued two directives (1999/2/EC and 1999/3/EC), which have been implemented in Italy by Legislative Decree No. 94 of 30 January 2001. Those directives aims at harmonizing the rules concerning the treatment and trade of irradiated foods in EU countries. With the open market, each country is obliged to accommodate the presence in its internal market of irradiated food commodities treated in other EU states or in extra-European countries. To further safeguard the consumer, the EU legislation provides for official annual checks at the product marketing stage, with the purpose of identifying improperly labeled or unauthorized products. Thus far, only limited food categories has been studied and subjected to interlaboratory validation by analytical detection methods for irradiated food identification. To meet the specific requirements of the laws and to increase acceptance of this type of food preservation technology, we have extended the field of application of both screening (PSL) and confirmatory (ESR, TL) physical methods to check compliance with labeling of irradiated foodstuffs. Therefore for consumer protection and information, following the invitation from the European Commission to improve and develop more reliable analytical standards, research work was focused on new applications of these physical methods. Relevant contributions have been made to the extension of the current field of application, with the development of promising analytical procedure able to estimate the actual dose administered to treated foods. The first goal was achieved investigating, even at low doses (0.1 kGy), the luminescence yield of oysters, considered a great delicacy in many parts of the world, and validating its identification with two physical techniques: PSL as screening method and TL as a confirmatory one. Besides oysters other seafood, including bivalve mollusks, i.e. brown Venus shells, clams, and mussels, all of which are widely consumed and likely to be treated with irradiation were studied with Electron Spin Resonance (ESR) spectroscopy.
It is well known that irradiation by ionising radiation leads to the formation of many radical species which, if stable, could be detected in calcified tissue such as mollusks' shell. Identification of four irradiated species of bivalve mollusks, i.e. brown Venus shells (Callista chione), clams (Tapes semidecussatus), mussels (Mytilus galloprovincialis) and oysters (Ostrea edulis) was performed. ESR could definitely identify irradiated seashells due to the presence of long-lived free radicals, primarily CO2-, CO33-, SO2- and SO3- radical anions. The presence of other organic free radicals, believed to originate from conchiolin, a scleroprotein present in the shells, was also ascertained. The use of one of these radicals as a marker for irradiation of brown Venus shells and clams can be envisaged. In addition to detection procedures a reliable dosimetric protocol for the reconstruction of the administered dose in irradiated oysters was proposed. Finally the results of a study on official checks by an accredited laboratory aimed at both evaluating the performances of detection methods and the presence of irradiated food on the Italian market, are discussed. Non-compliances found are due to both incorrect labelling and irradiation in non approved facilities in extra European countries. In summary, two physical methods, electron spin resonance (ESR) spectroscopy and thermoluminescence (TL) were studied most extensively and applied on a wide range of foods with successful results, whereas limitations of current standards were also assessed. The development and application of analytical methods for correct identification of irradiated samples from non-irradiated samples, along with protocols for dose evaluation, have become important for several purposes: upholding regulatory controls, checking compliance against labeling requirements, facilitating international trade, and reinforcing consumer confidence. Therefore the research on new detection methods represents a key area and more studies in this field should be encouraged.
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Jung, Renata. "Identification of Molecular Markers for Marker-Assisted Selection of Malting Quality and Associated Traits in Barley." Diss., North Dakota State University, 2015. http://hdl.handle.net/10365/25241.
Full textAbstract:
Barley (Hordeum vulgare L.) is one of the most important cereal crops in North Dakota, which ranks second amongst all states for barley production in the United States. Barley is used for the production of malt, which is used for brewing beer. The malting and brewing industries set strict standards for malt quality; yet, determining malt quality of experimental barley lines is very expensive. For this reason, quality is typically determined at the latter stages of the breeding program, resulting in rejection of many genotypes after large investments for agronomic performance, disease resistance, and end-use quality evaluations have occurred. High quality malt cultivars must possess numerous genetically controlled characteristics. This limits the effectiveness of phenotypic selection for malt quality. The use of marker-assisted selection (MAS) may enable breeders to eliminate lines with undesirable traits earlier in the breeding process, reducing costs, and improving genetic gain. In spite of the large number of mapped QTLs, few examples exist in the literature in which QTL analysis and MAS have been applied to the genetic improvement of malting barley. This research was initiated to identify robust marker-trait associations for malting quality, disease resistance, and agronomic traits utilizing genome-wide association mapping of selected NDSU two-rowed lines. Our research successfully identified numerous marker-trait associations for the traits evaluated to be used for MAS to improve the North Dakota State University barley breeding program.American Malting Barley Association
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Algouzi, S. "Discourse markers in Saudi English and British English : a comparative investigation of the use of English discourse markers." Thesis, University of Salford, 2015. http://usir.salford.ac.uk/34008/.
Full textAbstract:
Based on two corpora, one of Saudi learners and the other of native English speakers, this thesis investigates qualitatively and quantitatively the use of English discourse markers in the speech of advanced Saudi learners of English in the third and fourth years of undergraduate study of English and compares it to the use of discourse markers by native speakers of English. Three of the most frequently occurring discourse markers in the spoken language, namely so, you know and like, are analysed. Qualitatively, the results from the Saudi learners’ corpus show that the three discourse markers under investigation serve a variety of discourse functions. In particular, they show that native speakers of English use so and like more frequently than Saudi learners. You know is used more frequently by Saudis. These results introduce to the research field of discourse markers a new conceptualization of how non-native Saudi English language learners use discourse markers in their speech. Even though the results from the Saudi learners’ corpus show that the three discourse markers are used with a variety of discourse functions, the analysis of the textbooks shows that of the three discourse markers, so is the only one introduced. This makes it difficult to make a strong claim about the connection of the local pedagogy and the use of the discourse markers. Saudi English learners are possibly able to acquire them through their exposure to the media and through their interaction in English with their peers.