Dissertations / Theses on the topic 'Potential damage'
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1
Angelidis, Nikolaos. "Damage sensing in CFRP composites using electrical potential techniques." Thesis, Cranfield University, 2004. http://dspace.lib.cranfield.ac.uk/handle/1826/127.
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This Thesis investigates the damage sensing capabilities of the electrical potential measurement technique in carbon fibre reinforced polymer composites. Impact damage was introduced in multidirectional laminates and its effect on potential distribution studied. It was found that delaminations and fibre breakages within the laminate can be detected and located by measuring potential changes on the external composite surface. The extent and size of potential changes were significantly affected by the position of the current electrodes in relation to the potential measurement probes. A numerical model was developed investigating the effect of different size delaminations, located in various positions within the lamina, on electrical potential distributions on the external ply, and a quantitative analysis of the numerical results is presented. The numerical simulations demonstrated that the measured potential changes on the external ply were in proportion to the delamination size. The numerical and experimental results were compared and the optimum configuration of current electrodes and potential probes for damage detection selected. The response of electrical potential to mechanical strain, in unidirectional and multidirectional samples was also investigated. It was found that the conductive medium, used for introducing the current, defines the piezo-resistance performance of the composite. A finite element model was developed able to predict the effect of inhomogeneous current introduction in unidirectional specimens on electrical potential and piezo-resistance. The effects of temperature and water absorption on potential measurements were also presented.
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Wang, Wenbin. "HDACi-induced DNA damage : identifying potential endpoints for safety assessment." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/98927/.
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Histone deacetylase inhibitors (HDACi) have been designed to alter the actions of epigenetic modifiers with the aim of 'reprogramming' the epigenome of diseased tissues back to their normal disease-free state. These inhibitors were designed to be non-DNA reactive and therefore considered safe from a genetic toxicology point of view. However, HDACi’s have been shown to induce DNA damage in healthy cells through unknown mechanisms, thereby posing significant risks to human health. Studies suggest that HDAC inhibitor-induced DNA damage is partly associated with changes in transcription and replication. Consequently, collisions between these events can result in the formation of DNA lesions and stable DNA:RNA hybrid structures (R-loops), which are implicated in the onset of cancer and various neurological diseases. Therefore, the aims of the current study were to better understand the mechanisms by which HDAC inhibitors may induce DNA damage and to identify potential endpoints for safety assessment: Chapter III: Efforts to study the effects of HDAC inhibition through a chemical approach proved unsuccessful in the yeast model organism but identified the HDAC mutant, rpd3Δ, showing histone hyper-acetylation compared to the wild type. Chapter IV: ChIP-chip was established for the TK6 lymphoblastoid cell line as a genome-wide tool for measuring the genotoxicity of HDAC inhibitors. Chapter V: Application of the ChIP-chip method showed that Trichostatin A-induced changes in histone H4 acetylation led to the re-distribution of transcription and replication on chromosome 17 in TK6 cells. This resulted in their co-localisation, suggestive of potential collisions. However, further efforts to determine this by mapping γH2AX and R-loop formation proved unsuccessful. Chapter VI: The yeast genetic mutant rpd3Δ was used to mimic the effects of treating with an HDAC inhibitor. The loss of RPD3 resulted in significantly higher levels of γH2A, predominantly at telomere regions. In conclusion, this thesis presents strong evidence to show that Trichostatin A promotes the co-localisation of transcription and replication, suggesting that there is a greater possibility of these processes colliding to form DNA damage.
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Martinez-Flores, Rene. "DAMAGE ASSESSMENT POTENTIAL OF A NOVEL SYSTEM IDENTIFICATION TECHNIQUE - EXPERIMENTAL VERIFICATION." Diss., Tucson, Arizona : University of Arizona, 2005. http://etd.library.arizona.edu/etd/GetFileServlet?file=file:///data1/pdf/etd/azu%5Fetd%5F1028%5F1%5Fm.pdf&type=application/pdf.
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Styers, Diane Marie. "Ozone Damage Potential to Loblolly Pine Ecosystems in Metropolitan Atlanta, Georgia." Digital Archive @ GSU, 2005. http://digitalarchive.gsu.edu/geosciences_theses/21.
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Atlanta is one of the largest metropolitan areas in the southeastern United States and is the only area in the region currently listed in “serious” 1-hour ozone nonattainment. Despite its exceedance history, impacts on Atlanta’s urban forests have not been the focus of any major studies. The purpose of this study was to examine air pollution damage to vegetation using a foliar-injury survey on Stone Mountain. The objectives of this project included 1) establishing that pollution transport from Atlanta to Stone Mountain occurs, 2) determining the magnitude of ozone concentrations near Stone Mountain and 3) assessing sensitive plant species on Stone Mountain for foliar injury. Results from this study confirm that Stone Mountain is located downwind from Atlanta. Ozone concentrations were sufficiently high to damage vegetation and these consistently peaked in July. Foliar injury was present on understory species on Stone Mountain, but was not observed on loblolly pine species.
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Pearson, Colin. "Investigating the mutagenic potential of clustered DNA damage in 'E. coli'." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425891.
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Prajapati, Seeran. "Potential drop detection of creep damage in the vicinity of welds." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337718046.
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McLaren, Tanya Thomson. "Identification of potential marker proteins of toxicant-induced damage to spermatogenesis." Thesis, University of Edinburgh, 1994. http://hdl.handle.net/1842/20011.
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Spermatogenesis involves a complex series of cell-cell interactions which are probably mediated by secreted proteins. The primary objective of the studies described in this thesis was therefore to identify specific proteins which change in relative abundance in the early stages of toxicant-induced damage to spermatogenesis and which might have potential use as markers of such damage. Identification of such proteins might pin-point the possible biochemical causes of the toxic effects on the testis, and also give insight into normal control mechanisms in spermatogenesis. The chemicals used in these studies were meta-dinitrobenzene (m-DNB), nitrobenzene (NB) and methoxyacetic acid (MAA). The effect of severe disruption of spermatogenesis, induced by short-term local testicular heating, was assessed in order to establish whether protein changes comparable to those seen following toxicant exposure could be identified. Within 4 hours of treatment, stage-specific changes in the incorporation of 35S-methionine into both secreted proteins and intracellular proteins were deserved. Analysis by 2-D SDS PAGE identified 8 proteins which were affected adversely following heat treatment, all of which had been affected by toxicant exposure. In conclusion, the studies presented in this thesis have identified proteins which have potential use as markers of early toxicant-induced damage to spermatogenesis. Studies to date in the rat have identified proteins in peripheral blood which derive from the Sertoli cells and germ cells and the expectation is that most if not all ST-secreted proteins will appear in blood. Therefore the logical next step will be to determine whether any of the proteins identified in the present studies are detectable in peripheral blood and whether the amounts change following toxicant exposure.
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Topping, Adam Partington. "Ruby laser-assisted depilation : the mode of action and potential ways of improving outcome." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246739.
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Collins, Sara A. "The potential of entomopathogenic nematodes to reduce damage by Hylobius abietis L." Thesis, Imperial College London, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265266.
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Ellard, David. "Psychological stress and neutrophil activation : the potential for tissue damage and disease." Thesis, Coventry University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271262.
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Bailey, D. A. "The effect of damage on the energy absorption potential of composite structures." Thesis, University of Nottingham, 2005. http://eprints.nottingham.ac.uk/13560/.
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This thesis describes work undertaken to investigate the effects of damage on the energy absorption potential of composite tubes. Tubes of various geometries and manufactured from either continuous filament random mat (CoFRM) or glass braid and polyester resin were subjected to various types of damage before testing. Damage types consisted of drilled holes, to simulate the use of drilling components for the need of assembly, impacts, to simulate damage that may occur through tool drops or items being kicked up during use and PET inserts to simulate delamination. Large glass CoFRM/polyester tubes with an outer diameter of 89.1mm and varying wall thicknesses were crushed quasi-statically at a speed of 5mmlmin. Small CoFRM and braided glass/polyester tubes with an outer diameter of 38.1mm and a 2mm wall thickness were tested quasi statically and dynamically at a speed of 5m1s. Tubes were tested undamaged and containing various sizes of holes, simulated delamination and impacts. Specific energy absorptions (SEA) and failure modes were compared. Threshold values of damage size have been found for each tube and test type, above which unstable failures and subsequent unpredictable reductions in energy absorptions occur. The small CoFRM tubes showed a decrease in SEA as the test rate increased and this was attributed to the rate dependency of the resin, causing greater fragmentation allowing fibres to bend more easily and without fracturing. The braided small tubes showed an increase in SEA as the test rate increased due to a change in the mode of failure attributed to a higher compressive strength at the increased rate. Relatively small hole sizes and impacts, of 5mm and 1.5J-3J, were seen to reduce the energy absorption of the materials tested at quasi-static test speeds. However, an increase in damage tolerance was identified as test rate increased and this was attributed to an increase in compressive strength and fracture toughness, and reduction in crush load, as the speed of test increased.
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Hirschfield, Gideon Morris. "C-reactive protein and enhancement of tissue damage : a potential therapeutic target." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445514/.
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Human C-reactive protein (CRP), the classical acute phase reactant, is a member of the pentraxin family of calcium dependent ligand binding proteins. When ligand bound, particularly to phosphocholine residues found in cell membranes, bacterial cell walls and lipoprotein particles, CRP activates the complement cascade through engagement of Clq. Prior studies have suggested an important role for CRP both epidemiologically and biologically in atherothrombosis and its consequences. In the largest study to date of the epidemiological association between CRP and future cardiac events in healthy individuals, we demonstrate in contrast to previous studies, that the additive value of this inflammatory marker is less than previously thought. Further study of the biology of this ancient molecule in a number of animal models of disease has failed to confirm a protective role for CRP in endotoxaemia, and despite evidence of upregulated production in a transgenic mouse strain prone to atherosclerosis, we have demonstrated no apparent effect of human CRP on atherogenesis. Finally we have clearly and robustly shown that decamerisation of pentameric CRP by a novel low molecular weight palindromic inhibitor effectively prevents the ligand binding properties of this protein. This has established a platform for pharmacological inhibition of CRP in myocardial infarction and stroke where the complement activation initiated by CRP binding to necrotic cells has been suggested to be pro-inflammatory and deleterious.
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Travis, Brandon. "The effects of bileaflet prosthesis pivot geometry on turbulence and blood damage potential." Diss., Georgia Institute of Technology, 2001. http://hdl.handle.net/1853/10024.
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Barker, Anthony David Purslove. "The damage potential of the root-lesion nematode Pratylenchus bolivianus in the UK." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312235.
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Upadhyaya, Sneha. "Development of an Improved and Internally-Consistent Framework for Evaluating Liquefaction Damage Potential." Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/95941.
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Soil liquefaction continues to be one of the leading causes of ground failure during earthquakes, resulting in significant damage to infrastructure around the world. The study presented herein aims to develop improved methodologies for predicting liquefaction triggering and the consequent damage potential such that the impacts of liquefaction on natural and built environment can be minimized. Towards this end, several research tasks are undertaken, with the primary focus being the development of a framework that consistently and sufficiently accounts for the mechanics of liquefaction triggering and surface manifestation. The four main contributions of this study include: (1) development of a framework for selecting an optimal factor of safety (FS) threshold for decision making based on project-specific costs of mispredicting liquefaction triggering, wherein the existing stress-based "simplified" model is used to predict liquefaction triggering; (2) rigorous investigation of manifestation severity index (MSI) thresholds for distinguishing cases with and without manifestation as a function of the average inferred soil-type within a soil profile, which may be employed to more accurately estimate liquefaction damage potential at sites having high fines-content, high plasticity soils; (3) development of a new manifestation model, termed Ishihara-inspired Liquefaction Severity Number (LSNish), that more fully accounts for the effects of non-liquefiable crust thickness and the effects of contractive/dilative tendencies of soil on the occurrence and severity of manifestation; and (4) development of a framework for deriving a "true" liquefaction triggering curve that is consistent with a defined manifestation model such that factors influential to triggering and manifestation are handled more rationally and consistently. While this study represents significant conceptual advance in how risk due to liquefaction is evaluated, additional work will be needed to further improve and validate the methodologies presented herein.Doctor of Philosophy
Soil liquefaction continues to be one of the leading causes of ground failure during earthquakes, resulting in significant damage to infrastructure around the world (e.g., the 2010-2011 Canterbury earthquake sequence in New Zealand, 2010 Maule earthquake in Chile, and the 2011 Tohoku earthquake in Japan). Soil liquefaction refers to a condition wherein saturated sandy soil loses strength as a result of earthquake shaking. Surface manifestations of liquefaction include features that are visible at the ground surface such as sand boils, ejecta, cracks, and settlement. The severity of manifestation is often used as a proxy for damage potential of liquefaction. The overarching objective of this dissertation is to develop improved models for predicting triggering (i.e., occurrence) and surface manifestation of liquefaction such that the impacts of liquefaction on the natural and built environment can be minimized. Towards this end, this dissertation makes the following main contributions: (1) development of an approach for selecting an appropriate factor of safety (FS) against liquefaction for decision making based on project-specific consequences, or costs of mispredicting liquefaction; (2) development of an approach that allows better interpretations of predictions of manifestation severity made by the existing models in profiles having high fines-content, high plasticity soil strata (e.g., clayey and silty soils), given that the models perform poorly in such conditions; (3) development of a new model for predicting the severity of manifestation that more fully accounts for factors controlling manifestation; and (4) development of a framework for predicting liquefaction triggering and surface manifestation such that the distinct factors influential to each phenomenon are handled more rationally and consistently.
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Besley, Stephen C. "Studies of the use of derivatised polycations as potential drug delivery systems to DNA." Thesis, University of Leicester, 1991. http://hdl.handle.net/2381/33974.
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The major target of ionising radiation has been determined as cellular DNA. Damage to DNA, as detected at 77K under conditions of direct damage by ESR, is localised on the bases thymine and guanine. This damage leads to single and double strand breaks, precursors of cell death and mutagenesis. In an attempt to intercept the damage at the bases, before formation of strand breaks, the use of polycations as potential drug delivery systems to DNA has been examined. Magnetic resonance techniques have been used to establish that polyamines used are present almost completely as polyammonium cations at pH 7 and to probe the interactions of a number of polycations with DNA. Sodium-NMR was used to investigate the affinity of polyamines, poly- aminothiols and transition-metal complexes for DNA, via sodium ion displacement from the DNA region. It was found that small metal complexes displace a greater number of sodium ions than polyamines of similar charge. Application of the counterion condensation theory led to a model of the counterions existing within a cylinder around the DNA of approximate radius 20A. The mode of interaction of polyammonium cations was studied using proton magnetic resonance. Linewidths, related to the transverse relaxation rate, give information on the motion of compounds close to DNA. Comparison of linewidths in the presence and absence of DNA revealed no significant broadening. This was interpreted as indicative of a loose, electrostatic interaction, not significantly hindering motion of the cations close to DNA, suggesting rapid motion of polyammonium ions along the DNA. The radioprotection of DNA by various transition-metal complexes was studied using ESR. Certain compounds exhibited protection via electron transfer, resulting in a decreased radical yield.
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Llano, Jorge. "Modern Computational Physical Chemistry : An Introduction to Biomolecular Radiation Damage and Phototoxicity." Doctoral thesis, Uppsala University, Department of Cell and Molecular Biology, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4224.
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The realm of molecular physical chemistry ranges from the structure of matter and the fundamental atomic and molecular interactions to the macroscopic properties and processes arising from the average microscopic behaviour.
Herein, the conventional electrodic problem is recast into the simpler molecular problem of finding the electrochemical, real chemical, and chemical potentials of the species involved in redox half-reactions. This molecular approach is followed to define the three types of absolute chemical potentials of species in solution and to estimate their standard values. This is achieved by applying the scaling laws of statistical mechanics to the collective behaviour of atoms and molecules, whose motion, interactions, and properties are described by first principles quantum chemistry. For atomic and molecular species, calculation of these quantities is within the computational implementations of wave function, density functional, and self-consistent reaction field theories. Since electrons and nuclei are the elementary particles in the realm of chemistry, an internally consistent set of absolute standard values within chemical accuracy is supplied for all three chemical potentials of electrons and protons in aqueous solution. As a result, problems in referencing chemical data are circumvented, and a uniform thermochemical treatment of electron, proton, and proton-coupled electron transfer reactions in solution is enabled.
The formalism is applied to the primary and secondary radiation damage to DNA bases, e.g., absorption of UV light to yield electronically excited states, formation of radical ions, and transformation of nucleobases into mutagenic lesions as OH radical adducts and 8-oxoguanine. Based on serine phosphate as a model compound, some insight into the direct DNA strand break mechanism is given.
Psoralens, also called furocoumarins, are a family of sensitizers exhibiting cytostatic and photodynamic actions, and hence, they are used in photochemotherapy. Molecular design of more efficient photosensitizers can contribute to enhance the photophysical and photochemical properties of psoralens and to reduce the phototoxic reactions. The mechanisms of photosensitization of furocoumarins connected to their dark toxicity are examined quantum chemically.
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Chern, Shuh-Gi. "Probabilistic analysis of pore pressure induced damage potential for structures subjected to earthquake motions." Diss., Georgia Institute of Technology, 1986. http://hdl.handle.net/1853/21224.
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Christian, Marc. "Biomarkers of Physiological Damage and their Potential for Work-Related Musculoskeletal Disorder Risk Assessment." Diss., Virginia Tech, 2014. http://hdl.handle.net/10919/25877.
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Work-related musculoskeletal disorders (WMSDs) continue to present a substantial personal and economic burden. Biomarkers, in providing objective measures of physiological changes, may offer advantages over current tools for WMSD risk assessment. Existing work has identified biomarkers of cartilage and muscle damage, and demonstrated responsiveness to various forms of physical activity and biomechanical loading. Here, three studies were complete to further assess the occupational relevance/utility of three selected biomarkers: Cartilage Oligomeric Matrix Protein (COMP), Interleukin-6 (IL6), and Creatine Kinase (CK). First, the effects of age, obesity, gender, and diurnal variation was investigated. Significant effects of time, age, and gender were evident, as well as some interactive effects, for COMP and CK, but not IL6. Second, biomarker levels were compared between individuals in occupations having relatively high and low WMSD risk. IL6 levels were greater in the high-risk group, while COMP levels demonstrated an oscillatory pattern, and CK levels did not vary between groups. Third, physical demands were imposed on the lumbar spine during a repetitive flexion/extension task, under conditions with different loading and frequency. IL6 levels varied significantly over time and between added load levels, while CK levels varied over time and was influenced by load and frequency. These studies demonstrate important features of biomarkers; that personal confounding factors need to be considered, that select biomarkers may be sensitive to occupational risk factor exposure, and particularly to task parameters in lifting activities involving the lower back. Further, these studies reveal important information concerning the relevance of the selected biomarkers, favorable time points for biomarker collection, and approximate biomarker levels expected between occupations and exposure to common risk factors. These results support the use of biomarkers in occupational settings for assessing exposure and WMSD risk imposed by common risk factors. Sensitivity to exposure levels is an important precursor to risk prediction, however prospective work is needed to verify predictive validity.Ph. D.
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De, Faria Newton. "A non-invasive visual evoked cortical potential test for detection of early glaucoma damage /." Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.
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Yang, Sile. "Functional Characterisation and Therapeutic Potential of the Zinc Finger Protein ZNF827." Thesis, The University of Sydney, 2019. http://hdl.handle.net/2123/21100.
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The ends of linear eukaryotic chromosomes resemble double strand breaks, susceptible to the vigilant cellular DNA damage response machinery. Telomeres are specialised nucleoprotein structures found at the ends of human chromosomes that function as a protective cap safeguarding the integrity of the genome. In normal human somatic cells, telomeres shorten with each replicative cell division. Eventually, shortened telomeres trigger cellular senescence and apoptosis. Cancer cells overcome this proliferative barrier by acquiring a telomere maintenance mechanism. Alternative Lengthening of Telomeres (ALT) is a homologous recombination (HR) mediated telomere maintenance mechanism utilised by approximately 10-15% of all cancers. ALT status in certain cancer subtypes, such as osteosarcomas and astrocytomas, often predicts aggressive nature and poor prognosis. Therefore, the ALT pathway presents an attractive avenue for developing novel cancer therapeutics. To date, ALT specific therapeutic targets are lacking. Our lab has previously identified the zinc finger protein ZNF827 as a promising molecular target in the ALT pathway. ZNF827 recruits the nucleosome remodelling and histone deacetylase (NuRD) complex to ALT telomeres, and collaboratively facilitates multifaceted functions to promote HR-mediated telomere synthesis. However, the precise molecular mechanisms underlying the important roles of ZNF827 at ALT telomeres have not been fully elucidated. Prior to the study by our lab, ZNF827 was a protein of unknown function. This thesis has focused on the functional characterisation of ZNF827, with an ultimate goal of validating it as a therapeutic target in cancers utilising the ALT pathway. We have characterised ZNF827 from several perspectives. First, we have explored the biological functions of ZNF827 as a transcription factor and discovered novel roles of ZNF827 in cellular processes including embryonic development and immune response. Second, we have gained new insights into the recruitment of ZNF827 to ALT telomeres, characterised structurally and functionally the interaction interface between ZNF827 and the NuRD complex, and implicated ZNF827 SUMOylation in promoting ALT activity. We have also discovered that ZNF827 is novel ssDNA binding protein implicated in HR-directed repair of replication-associated DNA damage at telomeres as well as genome-wide, and that its role as a DNA damage response and repair protein is likely to be mediated through the ATR-mediated DNA signalling pathway. Finally, we have provided preliminary evidence that supports synthetic lethality between ZNF827 inhibition and the topoisomerase I inhibitor topotecan, implicating ZNF827 as a potential molecular target for ATR inhibition. Taken together, our findings have substantially expanded our knowledge on the zinc finger protein ZNF827 and provided further support for its therapeutic potential in the development of novel cancer therapies.
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Morley, Ana Maria Susana. "A study of the potential for infrared radiation to cause photochemical damage to the lens." Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428017.
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Altshuler, Kara Denise Best 1965. "Alkylation damage in mammalian cells : an analysis of the mutagenic potential of O4-methylthymine adducts." Thesis, Massachusetts Institute of Technology, 1994. http://hdl.handle.net/1721.1/38001.
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Carroll, Kaitlin R. "Targeted T Cell Ablation in Autoimmune Disease:The Therapeutic Potential of DNA Damage Response Molecule Manipulation." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1544100593082292.
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Tang, Swee May. "The influence of forest clearcutting patterns on the potential for debris flows and wind damage /." Thesis, Connect to this title online; UW restricted, 1995. http://hdl.handle.net/1773/5465.
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Duvvury, Rolan Shawn. "Potential negative effects of wind turbines on the ear." Thesis, Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/44927.
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This thesis presents investigations on the potential negative effects of wind turbine noise on the human ear from a sound point source (i.e. wind farm). In Chapter 2, the tectorial membrane, which is a crucial gelatinous structural matrix located within the cochlea of the inner ear, is considered to have a similar constitutive stress-strain relationship to that of an elastomer (rubber) in tension. The tectorial membrane appears to stretch when subjected to constant heavy sound stimulation. The tectorial membrane is modeled as a simply-supported beam with an external load Pext applied at midspan. A virtual work approach is used to balance the external work at midspan Pextδz of the tectorial membrane with the internal strain energy from its hysteresis loops. These hysteresis loops quantify the amount of damage that the tectorial membrane undergoes due to an applied external loading. Normalized damage tables are presented at the end of the chapter to suggest safe distances away from the wind turbines to limit damage to the tectorial membrane. Chapter 3 considers a hypothetical autonomous village constructed in South Pretoria, South Africa. This village accommodates approximately 2000 people (~500 families) and receives electricity for hot water from a nearby 2.5 MW wind farm. The design process for the village is discussed from an architectural and design standpoint. The wind farm specifications, specifically the number of 2.5 MW wind turbines needed to provide electricity for hot water, are established. Results from Chapter 2 are used to suggest minimum safe distances between the wind farm and the autonomous village in the context of limiting damage to the tectorial membrane.
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Matito, Sánchez Cecilia. "Polyphenolic fractions from wine by-products as potential antitumoral and/or protective agents against UV damage." Doctoral thesis, Universitat de Barcelona, 2006. http://hdl.handle.net/10803/989.
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Cancer is one of the leading causes of death in countries throughout the world. Increase in the production of Reactive Oxygen Species (ROS) has been implicated in many human disease processes, including aging and carcinogenesis. Detoxification of ROS in the cell is provided by both enzymatic and non-enzymatic systems, which constitute the antioxidant defence systems and is crucial to the survival of organisms. The cancer inhibitory propierties of antioxidant compounds such as polyphenols have been well established in experimental and epidemiological studies, showing the intake of these antioxidants within our diet can carry out an effective protective action toward the oxidative stress created in the body by imbalance between ROS and its endogenous defence mechanism. However, the molecular mechanisms responsibles for these effects are not so well known and more studies are needed to provide clear evidence of their protective effects.The aim of this study is to determine and compare the posible antitumoral properties of several polyphenolic fractions, obtained from the extraction and fractionation of wine by-products consisting of grape skins, seeds and stems. These polyphenolic fractions have high antiradical potential and are mainly composed by flavanol monomers with or without gallate groups, glycosylated flavonols and mostly procyanidin oligomers. The effect of these fractions is analysed on cancer cells at cellular and metabolic levels. Moreover, as solar radiation in the UV range is the major source of adverse reactions in the skin and is one of the most efficient environmental carcinogen known, the possible capacity of these fractions to protect against cellular damage induced by ultraviolet radiation is evaluated and compared.
The results obtained in this study let us to confirm the polyphenolic fractions studied are very specific antiproliferative agents with very low cytotoxicity to non-proliferative normal cells, such as peripherial blood lymphocites (PBLs). Moreover, treatment with these fractions results in intracellular metabolic changes, restricting the ability of tumoral cells to proliferate and inhibiting glycolysis, being higher for the fraction rich in ECG containing oligomeric flavanols.
Like for the study of antitumoral effect at cellular and metabolic levels, the results obtained in the analysis of the protective capacity of these polyphenolic fractions against UV-induced damage, confirm them as potential natural chemopreventive agents.
Briefly, the results obtained in this study let us to conclude the polyphenolic fractions rich in procyanidin oligomers and gallate esters are the most efficient as antitumoral agents, active at both cellular and metabolic levels with low cytotoxicity. Additionally, polymerization and percentge of galloylation are also important in the efficacy of the polyphenolic fractions as protectors against damage induced by ultraviolet radiation, suggesting they may be useful for the prevention and treatment of a variety of solar UV light-induced human skin disorders.
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Horicks, Florence. "INVESTIGATION OF POTENTIAL ACTION MECHANISMS OF GONADOTROPIN-RELEASING HORMONE ANALOGUES TO PREVENT OVARIAN DAMAGE DURING CHEMOTHERAPY." Doctoral thesis, Universite Libre de Bruxelles, 2017. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/256747.
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De nombreux agents chimiothérapeutiques sont gonadotoxiques et peuvent donc induire une insuffisance ovarienne précoce chez les jeunes patientes traitées. La protection pharmacologique de l'ovaire pendant la chimiothérapie à l'aide d'analogues de la Gonadotropin-Releasing Hormone (GnRHa) est une option intéressante de préservation de la fertilité de par son caractère non-invasif et la possibilité d’une récupération spontanée de la fonction ovarienne. Ces molécules sont des inhibiteurs bien connus de l'axe hypothalamo-hypophyso-gonadique, mais leur efficacité dans cette indication est, cependant, controversée et leurs mécanismes d'action sont mal compris. Par conséquent, nous avons investigué les mécanismes potentiels de protection ovarienne des GnRHa pendant la chimiothérapie sur modèle murin. Nous avons montré que le cyclophosphamide (Cy) induit une déplétion folliculaire aiguë et proportionnelle à la dose affectant à la fois les follicules quiescents et en croissance. Lorsqu'ils sont administrés seuls à différentes doses et sites, l'agoniste et l'antagoniste de la GnRH altèrent les cycles oestraux, mais ne bloquent ni la folliculogenèse ni la sécrétion de la Follicle-Stimulating Hormone (FSH) chez la souris. De plus, le Cy atteint les follicules primordiaux, que les souris aient été traitées avec les GnRHa ou non. Ces résultats suggèrent que les GnRHa n'inhibent pas l'axe hypophyso-gonadique aussi efficacement chez la souris que chez la femme. Par conséquent, nous avons développé de nouveaux modèles pour étudier les mécanismes potentiels de protection ovarienne des GnRHa. Afin de différencier les effets directs des GnRHa via leurs récepteurs ovariens ou indirects par inhibition de la sécrétion de gonadotrophines, l'effet de l'agent alkylant sur le développement folliculaire et la réserve ovarienne a été testé sur des follicules cultivés in vitro avec ou sans GnRHa et in vivo chez des souris déficientes en FSHb (Fshb-/-). Pour imiter la profonde inhibition de FSH observée chez la femme après traitement aux GnRHa, nous avons étudié la toxicité de la chimiothérapie chez les souris Fshb-/-. L’administration de gonadotrophines exogènes (pregnant mare serum gonadotropin, PMSG) induit une croissance folliculaire jusqu’au stade antral mais n’influence pas le nombre total de follicules au sein de l’ovaire. Le Cy induit une perte folliculaire significative dans le groupe contrôle et dans le groupe traité au PMSG. Aucune différence concernant la prolifération ni l'apoptose n'a été observée entre les groupes traités à la chimiothérapie. A ce jour, ce modèle murin représente le meilleur modèle pour étudier l'inhibition gonadotrope induite par les GnRHa observée chez la femme. Ces résultats suggèrent que la FSH n'est pas impliquée dans la protection ovarienne potentielle des GnRHa pendant la chimiothérapie. Afin d’évaluer les effets directs des GnRHa sur les follicules en croissance et quiescents, des follicules préantraux ou des ovaires de nouveau-nés (PND4) ont été cultivés avec ou sans GnRHa avant l'exposition au métabolite actif du Cy, le 4-hydroperoxycyclophosphamide (4HC). Nous avons d'abord montré que l'exposition in vitro aux GnRHa n'affectait ni la survie et le développement folliculaire, ni la maturation ovocytaire. Dans les follicules en croissance, le 4HC diminue significativement les taux de survie et de maturation; et retarde le développement folliculaire, indépendamment du traitement aux GnRHa. La chimiothérapie diminue le nombre de cellules de la granulosa par follicule tandis que la production d’adénosine monophosphate cyclique (AMPc) par million de cellules de la granulosa n'est pas modifiée, ni par le 4HC, ni par les GnRHa. La sécrétion d'oestradiol tend à être retardée dans le groupe traité à l’agoniste mais pas dans le groupe antagoniste. De même, dans les ovaires PND4, le 4HC induit une perte folliculaire importante et atteint directement les cellules de la granulosa des follicules ovariens. Aucune différence dans la distribution folliculaire, la prolifération ou l'apoptose n'a été observée entre les groupes traités avec le 4HC, peu importe la présence des GnRHa ou non. Pour conclure, en se basant sur des modèles murins robustes et originaux, notre travail remet en question l'efficacité des GnRHa pour préserver l'ovaire contre les dommages causés par la chimiothérapie que ce soit par une action directe sur l'ovaire, ou indirectement par l'absence de FSH. D'autres investigations seront nécessaires pour comprendre les mécanismes d'action potentiels des GnRHa sur l'ovaire et les voies impliquées. Des preuves expérimentales sont encore indispensables pour clore le débat sur cette option attrayante de préservation de la fertilité.Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
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Coetsee, Tjaart Nicolaas. "Investigating the potential neuroprotective effects of statins on DNA damage in mice striatum / Tjaart N. Coetse." Thesis, North-West University, 2006. http://hdl.handle.net/10394/1682.
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Sunasaka, Yoshio. "A study on damage potential of ground motions and strength demand spectra in lifetime of structure." 京都大学 (Kyoto University), 2002. http://hdl.handle.net/2433/138454.
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Takai, Ken. "A Potential Link between Alternative Splicing of the NBS1 Gene and the DNA Damage/Environmental Stress." Kyoto University, 2008. http://hdl.handle.net/2433/124221.
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Lang, Dominik H. [Verfasser], and Jochen [Akademischer Betreuer] Schwarz. "Damage potential of seismic ground motion considering local site effects / Dominik H. Lang ; Betreuer: Jochen Schwarz." Weimar : Professur Planung von Ingenieurbauten, 2004. http://d-nb.info/1115335588/34.
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Yu, Jessica Bang Yan. "Assessing ground interaction effects and potential damage on existing tunnels before and after new excavation works." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/46078.
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The need for the research project is driven by the Crossrail project in London for which new 7 m diameter tunnels are to be constructed close to numerous existing operational tunnels of the London Underground (LU) network. The main aim of this research is to investigate the impact of new tunnel excavations on existing tunnels. This research component is based on field instrumentation and experimental work conducted on half-scale grey cast iron (GCI) tunnel lining segments with chemical composition similar to the Victorian age GCI segments in the LU network. Currently, there is great uncertainty about the behaviour of segmental linings. General belief is that the behaviour of the lining is influenced by the behaviour of the joints, but there has been little experimental work to investigate this relationship. The laboratory experiments aim to find out the deformation behaviour of the bolted segmental lining and the influence of parameters such as overburden pressure, bolt preload and presence of grommets at small distortions. The measured behaviour of the segmental lining is compared against the theoretical behaviour of a continuous lining based on the assumption of linear elasticity. The laboratory results are used to assess the validity of the tunnel assessment methods used by the industry. The results from the parametric tests will form the basis for future experimental investigations taking the half-scale test ring to large deformations and ultimately to failure. The field component involved taking measurements of existing bolted segmental grey cast iron tunnels. Small sections of tunnels constructed at the LU Acton Depot, at Tottenham Court Road Station and in the Central Line running tunnel were monitored to gain an understanding of the deformation of tunnels from construction and self-weight, from ground loading and finally from the influence of adjacent tunnelling works. The thesis proposes recommendations for future in-tunnel monitoring based on the findings obtained in this research.
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Matkar, Smita S. "Mechanism of action of potential anticancer drugs." Scholarly Commons, 2008. https://scholarlycommons.pacific.edu/uop_etds/2368.
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Traditionally, inoperable or metastatic cancers have been treated by causing massive DNA damage in order to induce self-destruction (apoptosis) of the rapidly multiplying cancer cells. Initially, this strategy works for many cancers, in particular those which express normal p53 tumor suppressor protein. However, most cancers eventually aquire mutations in either p53 or other signaling molecules and fail to initiate apoptosis in response to severe DNA damage. During this study three types of compounds were investigated for their DNA damaging and anticancer effects: a pair of novel metal containing compounds, a pair of natural products, and a known synthetic drug which had been used many years ago for completely different indication. It was shown that all stop the growth of cancer cells and that the latter two classes do not require functional p53 because they work equally well in cells with normal (wildtype), mutant or no p53. The two nickel complexes investigated in this dissertation, differ in their ability to cause DNA damage and cell death. The oxidized form of the nickel complex, [Ni(CR-2H)] 2+ causes DNA damage and cell death at a much lower concentration than its reduced counterpart [Ni(CR)] 2+ . The phenanthridine alkaloids, Sanguinarine and Chelerythine cause high levels of DNA strand breaks and extremely rapid apoptosis which is not due to DNA damage because the quick onset precludes extensive signaling. The effects of the phenanthridines were linked to production of large amounts of reactive oxygen species (ROS), in particular hydrogen peroxide (H 2 O 2 ). The importance of ROS for the action of anticancer drugs as well as antibiotics is increasingly being recognized. In addition we also investigated the thioxanthone Lucanthone or Miracil D (which was used for the treatment of parasitic worms more than 50 years ago). It causes DNA strand breaks and apoptosis. Apoptosis occurs on a timescale consistent with signaling. However, p53 does not seem to be involved and alternative mechanisms are being investigated. This work provides new directions for designing novel anticancer drugs that are not subject to the limitations of DNA damaging agents.
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Rahman, Rosanna, and n/a. "Potential causes of the delayed neural damage observed post-stroke & the effects of epigallocatechin gallate administration." University of Otago. Department of Pharmacology & Toxicology, 2006. http://adt.otago.ac.nz./public/adt-NZDU20070508.122246.
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Stroke is the 3rd leading cause of death and the leading cause of major disability worldwide. Currently, there are no neuroprotective drugs approved for the acute treatment of ischaemic stroke. The vast majority of stroke therapeutics failed in clinical trials due to toxic side effects and/or a clinically irrelevant therapeutic window. This thesis is focused on exploiting the delayed neurodegeneration that occurs in the compromised penumbra, as these cells may be capable of being saved by therapeutic intervention in a clinically obtainable window. In order to investigate the ischaemic cascade and be able to draw conclusions that are applicable to humans, the international gold standard animal model for cerebral ischaemia, the filament insertion middle cerebral artery occlusion (MCAO) model, was established at the University of Otago. This model was validated under new laboratory conditions and employed adult male Sprague Dawley rats. After testing multiple occlusion lengths, it was concluded that a 2hr ischaemic period was sufficient to produce a consistent infarct of optimal size. It has been well documented that neuroinflammation contributes to much of the delayed progression of neural injury post-stroke. Therefore, the catechin (-)-epigallocatechin gallate (EGCG), which is an anti-inflammatory, anti-oxidant and free-radical scavenging agent was investigated in the MCAO model of stroke. 50mg/kg i.p. of EGCG or saline was administered immediately post-MCAO and animals were sacrificed at 72hr post-filament insertion. The results confirmed that treatment with EGCG was neuroprotective and non-toxic. However, EGCG also induced an over 50% increase in the risk of haemorrhagic conversions. The anti-platelet effects of EGCG and lack of toxicity suggests that the catechin may prove to be an efficacious prophylactic for stroke. The contrary findings for EGCG treatment led to the re-evaluation of the neuroinflammatory pathway for alternate mechanisms to target therapeutic interventions.
The temporal profile of the primary inducible enzymes nitric oxide synthase (NOS), cyclooxygenase (COX) and arginase (and their isoforms) were quantified 0, 3 and 7 days post-stroke. In both hemispheres, total NOS activity exhibited a significant and sustained up-regulation to 7 days post-occlusion. In the ipsilateral hemisphere at least half of the total increase was accounted for by inducible NOS (iNOS) expression. Arginase, which competes with NOS for L-arginine, demonstrated a delayed but significant increase in activity by day 7 in the infarcted hemisphere, thereby correlating well with the downward slope of NOS activity (illustrating the switch in the conversion pathway). COX activity was observably increased in the ipsilateral hemisphere, but the up-regulation did not reach significance by day 7. Alternately, the contralateral hemisphere displayed a significant decrease in activity by day 3. These results give conclusive evidence that the contralateral hemisphere is NOT an appropriate internal control and imply that NOS and COX inhibitors may prove to be efficacious for a much longer therapeutic window than current treatments. However, the delayed induction of COX activity may also indicate that this enzyme has a finite therapeutic window, as it may also stimulate remodelling of surviving neural networks. The prolonged up-regulation of inflammatory mediators implies that there may be an induction of an autoimmune component to the response. Therefore, the thymus (T) lymphocyte activation was quantified up to 14 days post-stroke. Cluster of differentiation (CD) 3⁺ T lymphocytes (equally contributed to by CD4⁺ and CD8⁺ T cells) exhibited a significant and sustained up-regulation in the infarcted region from day 3 up to at least day 14 post-ischaemia. Quantitative analysis of all cells present post-stroke determined that immune cells make up an average of 73% of all cells present in the 'peak' ischaemic areas. The CD4⁺ T helper cell response was delineated by double immunohistochemical labelling. Interferon-γ positively labelled with CD4⁺ T cells at days 3, 7 and 14 post-insult detailing a Th1-driven pro-inflammatory response. This evidence indicates that the autoimmune response is critical post-ischaemia and that it may be highly susceptible to modification by anti-inflammatory therapeutic intervention.
The primary downstream effect of the pro-inflammatory/immune cascade is apoptosis. The main organelle responsible for the 'go, no go' response to apoptotic factors is the mitochondria. In order to distinguish whether mitochondrial dysfunction was initiated shortly after ischaemia induction or if it was delayed, like the inflammatory/immune response, to a clinically relevant window, the temporal profile of mitochondrial complex inactivation was studied. It was found that mitochondrial membrane viability was impaired by day 3, followed by a significant decrease in respiratory complex activation and an increase in tissue injury by oxidative stress by 7 days post-ischaemia. These results indicate that targeting the early decrease in membrane viability or mitochondrial permeability transition pore opening combined with anti-apoptotic therapeutics, may attenuate the proceeding mitochondrial impairment in oxidative phosphorylation, reactive oxygen species generation and subsequent cell death cascades. The current investigations into the temporal profile and quantitative contributions of the inflammatory, immune and apoptotic mechanisms post-stroke highlight potential strategies for modulation by acute stroke therapeutics. Furthermore, the general knowledge amassed from these studies dictates the necessity of a new approach to therapeutic intervention. The acknowledgement of so many contributing systems suggests that in addition to a thrombolytic, a combination therapy involving multiple neuroprotectants should be employed to account for the multifaceted nature of the sequelae of ischaemic stroke.
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Holtzapple, Emilee R. "RelA as a Potential Regulator of Inflammation and Tissue Damage in Streptozotocin-Induced Diabetic STAT5 Knockout Mice." Ohio University Honors Tutorial College / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1461342848.
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Pereira, Vitória Sofia Almeida Santos. "Protective effects of seaweed feed supplementation towards genetic integrity in gilthead seabream (Sparus aurata)." Master's thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/22364.
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Mestrado em Biologia MarinhaThe DNA integrity and stability are essential to organisms’ health, fitness and, ultimately, to survival. This matter has been neglected in what concerns to fish in aquaculture systems, disregarding the potential impacts of both endogenous and exogenous factors. The manipulation of rearing conditions to achieve a fast-growing performance, as well as the occurrence (intentional or accidental) of agents/conditions, such as disinfectants, anesthetics, antibiotics and waterborne contaminants, may create stressful conditions passible to affect DNA integrity. Furthermore, in the long-term, this situation may compromise growth performance, animal welfare and a reduction in revenues. Seaweeds are a potential source of natural and high value compounds, with a large spectrum of biological activities and health benefits. It has been suggested that algae-enriched diet improves the growth, lipid metabolism, physiological activity, and disease resistance of various fish species; however, its anti-genotoxic potential was scarcely evaluated. Hence, this study aimed to evaluate the anti-genotoxic properties of a macroalgae-enriched diet to provide protection in gilthead seabream (Sparus aurata) against a genotoxic challenge (i.p. injection of 40 mg.kg-1 cyclophosphamide - CP), as well as to clarify if the potentially favorable effects of algae persist beyond the end of supplementation. The enriched diet was supplemented with 5% of equal parts of three species: Ulva spp. (Chlorophyta), Fucus spp. (Phaeophyta) and Gracilaria spp. (Rhodophyta). Thus, two groups of fish were differently fed during the first 30 days, until the CP injection, where they were separated depending on the diet/stimulus. Subsequently, in order to clarify the protective effect of the supplemented diet, 3 days after injection, half of each group previously fed with this diet has changed to the standard feed, keeping all the other groups the same way, for another 7 days. Genetic damage was evaluated through the erythrocytic nuclear abnormalities (ENA) and comet assays and the involvement of the antioxidant system as indication of a pro-oxidant status was assessed by superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, as well as by total glutathione (GSHt) content. The elucidation of the oxidative DNA damage-protecting activity was made by adopting as diagnostic tool the comet assay improved with DNA lesion-specific enzymes, FPG and Endo III, which convert oxidized purines and pyrimidines into extra DNA single strand breaks, respectively. The results pointed that algae-enriched feed exhibits anti-genotoxic properties in gilthead seabream blood cells, evident in relation to DNA strand breaks and to chromosomal lesions, though it appeared more pronounced in the latter type of genotoxicity expression. This effect was depicted by fish sampled at the last sampling moment, since a significant recovery of chromosomal damage was evident in fish previously injected with CP. A clear oxidative DNA damage–protecting activity was displayed, particularly in the presence of a strong genotoxic insult occurring three days after CP injection, when purine oxidation was prevented by algae supplementation. Nonetheless, blood antioxidants were not altered by the supplemented diet, with the exception of GST activity that was induced as response to CP treatment. Considering the persistence of favorable effects, 7 days without algae uptake was enough to partially reduce the protection efficacy, mainly in what concerns to the oxidative DNA damage-protecting capacity. Overall, these results seem to be promising towards the benefits of seaweed inclusion in fish diet, offering a potential strategy to strengthen fish fitness, and thus, to invigorate aquaculture activity, also providing new insights on the mechanisms of DNA protection in fish.
A integridade e estabilidade do ADN são essenciais para a saúde e condição fisiológica geral dos organismos e, em última instância, para a sua sobrevivência. Este tema tem sido negligenciado no que diz respeito a peixes em sistemas de aquacultura, descurando os potenciais impactos de fatores endógenos e exógenos. A manipulação das condições de cultivo para alcançar um crescimento rápido, assim como a ocorrência (intencional ou acidental) de agentes/condições tais como desinfetantes, anestésicos, antibióticos e contaminação aquática podem criar estados de stresse passíveis de afetar a integridade do ADN. Além disso, a longo prazo, esta situação pode comprometer o desempenho do crescimento, o bem-estar animal e reduzir as receitas. As macroalgas marinhas são uma fonte potencial de compostos naturais de elevado valor, com um amplo espectro de atividades biológicas e benefícios para a saúde. Tem sido sugerido que uma dieta enriquecida com algas melhora o crescimento, metabolismo dos lípidos, atividade fisiológica e a resistência a doenças de várias espécies de peixes. No entanto, o seu potencial anti-genotóxico permanece por explorar. Assim, este estudo teve como objetivo central avaliar as propriedades anti-genotóxicas de uma ração enriquecida com macroalgas, em dourada (Sparus aurata), após um desafio genotóxico (injeção intraperitoneal de 40 mg.kg-1 de ciclofosfamida - CP). A ração enriquecida foi suplementada com um total de 5% de algas, incorporando três espécies em partes iguais: Ulva spp. (Chlorophyta), Fucus spp. (Phaeophyta) e Gracilaria spp. (Rhodophyta). Deste modo, dois grupos de peixes foram alimentados de forma diferenciada nos primeiros 30 dias, até ao momento da injeção, onde foram separados consoante a dieta/estímulo. Posteriormente, de modo a esclarecer o efeito protetor da ração enriquecida, 3 dias após a injeção, metade de cada grupo previamente alimentado com esta dieta viu a sua alimentação alterada para a ração padrão, mantendo-se todos os outros grupos iguais, durante mais 7 dias. Foi avaliado o dano genético através dos ensaios do cometa e de anomalias nucleares eritrocíticas (ANE), em paralelo com o estudo do envolvimento do sistema antioxidante, como indicação de um estado pró-oxidante, determinando as atividades da superóxido dismutase (SOD), catalase (CAT), glutationa-S-transferase (GST), glutationa peroxidase (GPx) e glutationa redutase (GR), bem como o teor total de glutationa (GSHt). A elucidação do dano oxidativo de ADN foi feita através do ensaio do cometa melhorado pela incubação com enzimas específicas de reparação de ADN, FPG e Endo III, que convertem purinas e pirimidinas oxidadas em ruturas extra de cadeia única, respetivamente. Os resultados demonstraram que a alimentação enriquecida com algas apresenta propriedades anti-genotóxicas em células sanguíneas de dourada, evidentes em relação às quebras de cadeias de ADN e a lesões cromossómicas, embora pareça mais pronunciada no último tipo de expressão genotóxica. Esse efeito foi particularmente notório no último momento de amostragem, uma vez que foi conseguida uma completa recuperação do dano cromossómico em peixes previamente injetados com CP. Foi ainda evidenciada uma clara atividade de proteção contra o dano oxidativo do ADN, particularmente na presença de um forte insulto genotóxico ocorrido três dias após a injeção de CP, o que foi expresso no impedimento da oxidação de bases purínica pela suplementação de algas. No entanto, os antioxidantes não foram alterados pela dieta suplementada, com exceção da atividade da GST que foi induzida como resposta ao tratamento de CP. Considerando a persistência de efeitos favoráveis, 7 dias após a remoção de algas da dieta foram suficientes para reduzir parcialmente a eficácia da proteção, principalmente no que diz respeito à capacidade de contrariar o dano oxidativo de ADN. Globalmente, estes resultados são promissores quanto à identificação dos benefícios da inclusão de algas na dieta de peixe, oferecendo uma estratégia potencial para fortalecer a condição dos peixes e, assim, revigorar a atividade aquícola, fornecendo também novos conhecimentos sobre os mecanismos de proteção do ADN em peixes.
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Pendry, Barbara. "Analysis of selected medicinal plants as antioxidants with therapeutic potential for treating diseases related to free radical damage." Thesis, Middlesex University, 2005. http://eprints.mdx.ac.uk/7898/.
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Oxidative damage is implicated in the pathogenesis of a number of diseases. Scientific research shows positive links between accumulated free radical damage and age-related diseases such as atherosclerosis and osteoarthritis. There is great interest in the possibility that the antioxidant potential of plant-derived compounds such as flavonoids may reduce the risk of developing these conditions. The aim of this study was to evaluate the antioxidant activity of selected non-food plants, traditionally used by herbalists in their treatment of osteoarthritis, using crude plant extracts and herbal tinctures, the most commonly used form of plant extract. As herbalists traditionally argue that herbs used in combinations or formulae will increase in efficacy when used together, an exploratory study was further carried out to investigate whether the antioxidant activity of two herbs tested in combination was greater than the sum of both herbs tested singly. Eight plants were selected for phytochemical analysis and investigation for antioxidant activity, based on discussions with clinic supervisors from four herbal medicine training clinics and a review of patient's case notes. The prescriptions from a pilot study investigating outcomes for the herbal treatment of osteoarthritis were used as selection criteria. Chromatographic analysis of each plant by TLC, HPLC and GCMS confirmed the presence of a number of flavonoids reported in the literature and of other compounds which were not possible to identify. Previous studies have established that certain flavonoids in vitro can exert pro-oxidant or antioxidant effects according to the concentration and presence of transition metal ions such as copper and iron. In view of the pro-oxidant effects observed for some extracts during biochemical analysis, metal analysis by ICP was carried out on the selected plant material to test for the presence of selected metal ions known to catalyse free radical reactions. ICP analysis showed the presence of most of the selected metals in all the plant samples. Several pathways, by which flavonoids and other plant phenolics may exert their effects on chemical oxidation have been identified, one of which is their free radical scavenging capacity to halt the propagation stage of lipid peroxidation. Since lipid peroxidation is implicated in the pathogenesis of osteoarthritis, assays to measure this in vitro were investigated and the following two assays selected: - lipid peroxide assay using the ferric thiocyanate method for the detection of peroxides and an assay using the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) an established method for investigating the potential free radical scavenging activity of plant extracts. The lipid peroxide assay and method of analysis was re-evaluated and a standardised procedure established. All eight crude plant extracts showed marked antioxidant activity in both assays. Results for the crude plant extract in the lipid peroxide assay varied according to concentration, with 0.1% w/v giving the best results. The crude plant extracts in almost all cases seemed to be more active as antioxidants than tinctures (fluid extracts). When combinations of crude plant extracts were tested in pairs for antioxidant activity, results demonstrated synergy from five of the pairs and antagonism from three, approximately one third of the possible 28 two-herb combinations tested. The synergistic interactions observed could form the foundation for the future development of an antioxidant formula to offset the effects of free radical damage.
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Amin, Alla Mohammed Hussain. "Cold ischaemia and reperfusion injury in liver : the potential for damage to cellular DNA in the rat model." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248455.
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Hesse, Linda Li [Verfasser]. "Auditory nerve damage and adaption in the central auditory system : a potential cause for Tinnitus / Linda Li Hesse." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2018. http://d-nb.info/1168781809/34.
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Pfister, Sophia Xiao. "The three methyls : the function and therapeutic potential of histone H3K36 trimethylation." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:83cfd649-b75c-49f6-b881-1c1e96cafb08.
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DNA is wrapped around proteins called histones, whose modification regulates numerous cellular processes. Therefore it is not surprising that mutations in the genes that modify the histones are frequently associated with human cancer. For example, mutations in SETD2, encoding the sole enzyme that catalyses histone H3 lysine 36 trimethylation (H3K36me3), occur frequently in multiple cancer types. This identifies H3K36me3 loss as an important event in cancer development, and also as a potential therapeutic target. This thesis investigates the following questions: (1) how does the loss of H3K36me3 contribute to cancer development; and (2) what therapy can be used to kill cancers that have already lost H3K36me3. To answer the first question, this thesis shows that H3K36me3 facilitates the accurate repair of DNA double-stranded breaks (DSBs) by homologous recombination (HR). H3K36me3 promotes HR by recruiting CtIP to the site of DSBs to carry out resection, allowing the binding of HR proteins (such as RPA and RAD51) to the damage sites. Thus it is proposed that error-free HR repair within H3K36me3-decorated transcriptionally active genomic regions suppresses genetic mutations which could promote tumourigenesis. To answer the second question, this thesis reveals a clinically relevant synthetic lethal interaction between H3K36me3 loss and WEE1 inhibition. WEE1 inhibition selectively kills H3K36me3-deficient cells by inhibiting DNA replication, and subsequent fork stalling results in MUS81 endonuclease-dependent DNA damage and cell death. The mechanism is found to be synergistic depletion of RRM2 (ribonucleotide reductase small subunit), the enzyme that generates deoxyribonucleotides (dNTPs). This work reveals two pathways that regulate RRM2: one involves transcriptional activation of RRM2 by H3K36me3, and the other involves RRM2 degradation regulated by Cyclin-Dependent Kinase, CDK1 (which is controlled by WEE1, CHK1 and ATR). Based on this mechanism, the synthetic lethal interaction is expanded, from between two genes, to between two pathways. Supported by in vivo experiments, the study suggests that patients with cancers that have lost H3K36me3 could benefit from treatment with the inhibitors of WEE1, CHK1 or ATR.
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Zauri, Melania. "Tet2 and relevant potential intervention in cancer." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:09208267-5766-47b6-b9f4-5c97a6e6b5a2.
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Hindle, Paul. "The chondrogenic potential of perivascular stem cells from the infra-patellar fat pad." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/22903.
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Articular cartilage damage and degeneration is a siginficant clinical problem which no technique has been able to adequately and reliably repair or regenerate. Recent research has investigated the use of cell-based therapies to treat focal cartilage lesions. In clinical practice proliferated autologous chondrocytes are used and clinical trials are investigating the use of mesenchymal stem cells. The aim of this thesis was to assess aspects of current cell-based therapy and to investigate the potential of perivascular stem cells for articular cartilage repair. The phenotype of expanded matrix-applied autologous chondrocytes utilised in current cell therapies was confirmed using immunocytochemistry and polymerase chain reaction (PCR) expression of hyaluronan and proteoglycan link protein 1 (HAPLN1), transcription factor sox-9 (SOX9) and aggrecan (ACAN). Quantitative real-time PCR demonstrated that they were down-regulated for expression of COL2A1, SOX9 and ACAN but up-regulated for COL1A1 compared to unproliferated chondrocytes. Confocal laser-scanning microscopy (CLSM) demonstrated a significant decrease in cell viability and density when the membranes were subjected to levels of trauma similar to those that could be experienced during surgery. Hyperosmolar solutions did not confer a chondroprotective effect. Pericytes and adventitial cells, collectively termed perivascular stem cells (PSCs), from the infra-patellar fat pad were identified using immunohistochemistry and isolated using enzymatic digestion and fluorescence-activated cell sorting (FACS). Cell identity was ascertained using PCR, FACS and mesenchymal differentiation (osteogenesis, adipogenesis and chondrogenesis). Quantitative real-time PCR analysis of micromass cultures indicated that PSCs displayed increased chondrogenic potential compared to mesenchymal stem cells. An ovine model of perivascular stem cells was developed and a pilot study using three sheep was undertaken to confirm the viability of the model. Autologous ovine PSCs were isolated and re-implanted into articular cartilage defects. Green fluorescent protein transfected cells were identified in the cartilage defect four weeks following re-implantation using CLSM. This thesis has examined aspects of matrix-applied autologous chondrocyte implantation for cell based cartilage repair and has identified a new source of prospectively identified and purified stem cells that have demonstrated increased chondrogenic potential compared to mesenchymal stem cells, which are commonly used in clinical research. The methods to identify and purify ovine perivascular stem cells were developed to investigate the use of autologous PSCs and to track the cells following implantation.
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Reich, Doreen Melanie. "Investigation of the Therapeutic Potential of (Stem) Cell Containing Human Umbilical Cord Blood Fractions for Repair of Ischemic Neuronal Damage." Doctoral thesis, Universitätsbibliothek Leipzig, 2010. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-63584.
Full textAbstract:
In Form einer Zusammenfassung aus zwei Publikationen und bisher unveröffentlichtem Material stellt die vorliegende Arbeit die Frage, welche der Zellfraktionen (HUCB-MNC, CD45+/CD34+ und CD45+/CD133+) innerhalb des heterogenen HUCB die am effektivsten wirksame in Hinblick auf die Neuroprotektion nach einem experimentellen Schlaganfall ist und welche Mechanismen dabei zum Tragen kommen.
Für die Untersuchung der molekularen Mechanismen des Zusammenwirkens zwischen den genannten HUCB Fraktionen und neuronalen Zellen bzw. Gewebe, kamen ein selbst etabliertes Zellkulturmodel neuronaler Hypoxie bzw. OGD geschädigte hippocampale Schnittkulturen zur Anwendung. Die zu untersuchenden HUCB Zellfraktionen wurden direkt oder indirekt appliziert und ihr Effekt wurde über drei aufeinanderfolgende Tage hinweg untersucht.
Das molekulare Mikromilieu, welches durch die hypoxisch geschädigten neuronalen Zellen produziert wurde, stimulierte alle untersuchten HUCB Fraktionen zur Sekretion neurotrophischer Faktoren und/oder immunologisch aktiver Mediatoren, die die neuronale Apoptose günstig beeinflussten. HUCB-MNC zeigten, sowohl in der direkten als auch in der indirekten Kokultur mit geschädigten neuronalen Zellen eine sehr überzeugende Fähigkeit zur Neuroproduktion. In den direkten Kokulturen reduzierten sie die Apoptose der neuronalen Zellen sogar bis auf das Niveau der Kontrollen. Dies kann auf den deutlichen Anstieg der von den HUCB-MNC produzierten Chemokine CCL5; CCL3 und CXCL10 zurückgeführt werden. Weiterhin war zu beobachten, dass HUCB-MNC aktiv zu geschädigten neuronalen Zellen migrierten und sich, vorzugsweise unter Ausbildung von direkten Zell-Zellkontakten, an Axonen und Somata anlagerten. Überraschenderweise zeigte die CD45+/CD133- Zellfraktion ein ähnliches Potential wie HUCB-MNC. Für diese nahezu stammzellfreie Fraktion konnten in den indirekten Kokulturen hohe Konzentrationen an CCL3 und neuroprotektiven G-CSF nachgewiesen werden, wobei letzteres für die Aufrechterhaltung des neuronalen Phänotyps verantwortlich gemacht werden kann. CD45+/CD133+ Stammzellen, die aus der HUCB-MNC Fraktion isoliert wurden, konnten die neuronale Apoptose in direkten Kokulturen signifikant reduzieren. Die Konzentration an löslichen Faktoren, die von den Stammzellen produziert wurde, lag dabei unterhalb der Nachweisbarkeitsgrenze.
Die Ergebnisse aus den Untersuchungen der hippocampalen Schnittkulturen zeigen, dass HUCB-MNC direkt neuroprotektiv wirken. Dies gilt insbesondere, wenn sie direkt und in ausreichender Konzentration (12.5x104 Zellen pro Schnitt) appliziert werden. In Kokulturen mit der CD45+/CD34+ Stammzellfraktion fand sich eine verringerte Sekretion an Nervenwachstumsfaktor und damit verbunden eine geringere Anzahl degenerierter Pyramidenzellen. In Kokulturen in welchen die stammzellfreie CD45+/CD34- Fraktion verwendet wurde, trat dieser Effekt nicht auf.
Die Resultate, die in den beiden hier verwendeten in vitro Modellen gefunden wurden, legen nahe, dass der Einsatz von HUCB-MNC eine stabile Neuroprotektion hervorruft. Im Vergleich der verwendeten Modelle lieferten die Applikationen von verschiedenen Stammzellfraktion keine einheitlichen Ergebnisse. Damit wird eine starke Systemabhängigkeit induziert.
Speziell im Hinblick auf den klinischen Einsatz scheint es keinen deutlich überlegenen Vorteil durch die Verwendung reiner, aus der HUCB-MNC Fraktion gewonnener Stammzellfraktionen zu geben, der den Aufwand rechtfertigt eine zahlenmäßig so geringe Zellfraktion aus der HUCB-MNC Fraktion zu separieren.
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Olmer, Kurt J. "The effect of weed density, root senescence, and egg density on western corn rootworm larval establishment, survivorship, and damage potential." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/5009.
Full textAbstract:
Thesis (M.S.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on October 31, 2007). Includes bibliographical references.
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Mohd, Nasir Mohd Hamzah. "Activation of endothelial cells and its potential involvement in blood-brain barrier damage in cerebral malaria : an in vitro study." Thesis, Keele University, 2015. http://eprints.keele.ac.uk/3252/.
Full textAbstract:
One of the severe complications of a Plasmodium falciparum infection is cerebral malaria (CM). CM is characterised by the accumulation of mature infected red blood cells (RBC) in the brain microvasculature. One of the consistent detrimental effects of sequestration is the breakdown of the blood-brain barrier (BBB), often with a fatal outcome in children in endemic areas. This study investigates the mechanisms underlying BBB breakdown secondary to sequestration, using immortalised human brain microvascular endothelial cells (tHBEC) as an in-vitro model of BBB and ITG-strain Plasmodium falciparum. First, the tHBEC monolayer was co-cultured with Plasmodium falciparum infected red blood cell (PRBC) or uninfected red blood cells (uRBC) control for 20 hours and the supernatant was recovered for subsequent analysis. The co-culture supernatants showed upregulation of inflammatory mediators (MCP-1 and IL-8) and a member of metalloproteases (ADAMTS-1, ADAMTS-4, MMP-2 and MMP-9) in the PRBC-tHBEC co-culture supernatants. The PRBC-tHBEC co-culture supernatants induced loss of endothelial cell monolayer integrity, represented by real time reduction in the transendothelial electrical resistance, measured using Electrical Cell-Substrate Impedance Sensing (ECIS™). The same supernatants also increased the permeability of tHBEC monolayer to the fluorescently labelled 40 kDa dextran showing leakage across the tHBEC monolayer. Interestingly, the loss of barrier function of tHBEC monolayer is partially inhibited by the addition of protease inhibitors GM6001 and rhTIMP-3. Prolonged exposure to PRBC-tHBEC co-culture supernatants reduced the level of vinculin. This study demonstrates that the interactions between PRBC and tHBEC induces activation of tHBEC and the release of proteases that contribute to BBB breakdown in CM, and could be a potential drug target for adjunct therapy in CM.
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GRECCHI, ISABELLA. "EFFECTS OF HYBRID, HARVEST TIME AND HAIL DAMAGE ON CHEMICAL, NUTRITIONAL AND BIO-METHANE POTENTIAL PROPERTIES OF WHOLE PLANT CORN." Doctoral thesis, Università Cattolica del Sacro Cuore, 2016. http://hdl.handle.net/10280/11843.
Full textAbstract:
Il mais rappresenta una delle colture più diffuse nel Nord Italia. Negli ultimi anni si è assistito ad un notevole incremento della superficie a mais legato soprattutto all'uso dell'insilato di mais come substrato per la produzione di biogas.
Per questo motivo è necessario avere il maggior numero di informazioni possibili per migliorare le performance della coltura.
In letteratura ci sono molti studi che valutano l’impatto dell’ambiente e del management sulle caratteristiche chimico nutrizionali e sul potenziale metanigeno del foraggio di mais ma non ci sono lavori che considerano entrambi i parametri.
L’obiettivo della tesi è stato quello di investigare come il danno da grandine , la genetica e il momento di raccolta possano influenzare la composizione della pianta intera tradotta come potenziale metanigeno e valore nutrizionale del foraggio.In the Po Valley the maize crop represent one of the most cultivated plant used for cattle feeding but in the last 10 years it is also used as biogas substrate. Considering the importance of this cultivation, there is the continuous need to obtain information about this plant with the aim to improve the crop performance. There are numerous studies investigating the impact of environmental aspects and management practices on chemical and nutritional composition, and methane production in the literature but very few that evaluate those parameters together. The general objective of this thesis is to investigate how hail damage, type of hybrid and the harvesting date affect the whole plant composition. To accomplish this, two specific objectives are posed: i) verify the effects of hail damage levels on yield, chemical and nutritional feature as well as on BMP of maize grown in the Po Valley; and ii) to evaluate the value of different hybrids for animal nutrition and methane production in anaerobic fermenters and as delaying harvesting after the usual stage of maturity affects these features. It was also aimed to verify if chemical composition and in vitro digestibility tests could allow to estimate methane yield potential in maize whole plant.
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GRECCHI, ISABELLA. "EFFECTS OF HYBRID, HARVEST TIME AND HAIL DAMAGE ON CHEMICAL, NUTRITIONAL AND BIO-METHANE POTENTIAL PROPERTIES OF WHOLE PLANT CORN." Doctoral thesis, Università Cattolica del Sacro Cuore, 2016. http://hdl.handle.net/10280/11843.
Full textAbstract:
Il mais rappresenta una delle colture più diffuse nel Nord Italia. Negli ultimi anni si è assistito ad un notevole incremento della superficie a mais legato soprattutto all'uso dell'insilato di mais come substrato per la produzione di biogas.
Per questo motivo è necessario avere il maggior numero di informazioni possibili per migliorare le performance della coltura.
In letteratura ci sono molti studi che valutano l’impatto dell’ambiente e del management sulle caratteristiche chimico nutrizionali e sul potenziale metanigeno del foraggio di mais ma non ci sono lavori che considerano entrambi i parametri.
L’obiettivo della tesi è stato quello di investigare come il danno da grandine , la genetica e il momento di raccolta possano influenzare la composizione della pianta intera tradotta come potenziale metanigeno e valore nutrizionale del foraggio.In the Po Valley the maize crop represent one of the most cultivated plant used for cattle feeding but in the last 10 years it is also used as biogas substrate. Considering the importance of this cultivation, there is the continuous need to obtain information about this plant with the aim to improve the crop performance. There are numerous studies investigating the impact of environmental aspects and management practices on chemical and nutritional composition, and methane production in the literature but very few that evaluate those parameters together. The general objective of this thesis is to investigate how hail damage, type of hybrid and the harvesting date affect the whole plant composition. To accomplish this, two specific objectives are posed: i) verify the effects of hail damage levels on yield, chemical and nutritional feature as well as on BMP of maize grown in the Po Valley; and ii) to evaluate the value of different hybrids for animal nutrition and methane production in anaerobic fermenters and as delaying harvesting after the usual stage of maturity affects these features. It was also aimed to verify if chemical composition and in vitro digestibility tests could allow to estimate methane yield potential in maize whole plant.
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Black, Jennifer. "Discerning the Mechanism of Gamma Delta T Cell-Mediated Damage in Multiple Sclerosis: the Potential Role of Antibodies in Disease Pathogenesis." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/31925.
Full textAbstract:
Background: Both the innate and adaptive immune systems contribute to autoimmune injury in multiple sclerosis (MS). We have been particularly interested in elucidating the role of the innate γδ T-cell population in MS pathogenesis. In particular, some γδ T-cells that express Fc receptors (FcR), such as CD16, that bind antibody are more prominent with MS disease progression and have been shown to exert cytolysis via antibody-dependent cellular cytotoxicity (ADCC). We postulated that if there were also relevant and detectable antibodies in MS patients that might engage these FcR-bearing γδ T-cells then this might be a purported mechanism of neuro-axonal injury. A search for antibodies specific to axonal elements in MS revealed the presence of antibodies to neurofascin (Nfasc).
Methods: Anti-Nfasc antibody titres, and concentrations of the light and heavy chains of neurofilament (NfL and NfH, respectively), markers of neuro-axonal injury, were measured in the sera and cerebrospinal fluid (CSF) of MS patients using enzyme-linked immunosorbent assays (ELISA), including those that underwent autologous hematopoietic stem cell transplantation (aHSCT), both prior to and yearly for 3 years thereafter. HeLa cells were transfected with the axonal variant of Nfasc, Nfasc-186, and were utilized as targets in ADCC assays involving γδ T-cells as the effectors, and anti-Nfasc antibodies that were enriched from MS patient sera.
Results: Positive anti-Nfasc antibody titres were detected in of 22% and 25% of MS patient sera and CSF, respectively. The most elevated serum titres were in secondary progressive MS (SPMS), and highest CSF titres in relapsing-remitting MS (RRMS) (p<0.05 and p<0.0001, respectively, vs. other neurological disease [OND] controls). Patient serum and CSF antibody titres correlated and, in the CSF, the titres correlated positively with the concentration of NfL. Though NfL and NfH concentrations declined markedly following aHSCT in the CSF, anti-Nfasc antibody titres failed to decline. When co-cultured with CD16+ γδ T-cells in the presence of MS patient-derived anti-Nfasc antibodies, the percent specific cytolysis of the Nfasc-transfected HeLa cells was significantly greater than that of the non-transfected control HeLa cells, at 18% and 1%, respectively, indicating cytolytic kill via ADCC.
Summary: Anti-Nfasc antibodies were detectable in the sera and CSF of MS patients, and rarely in OND controls, suggesting they are relevant to MS. Higher titres in the serum support peripheral synthesis, while higher CSF titres in the relapsing phase, that correlate with serum titres, imply that antibodies access the CNS during periods of active inflammation that are associated with disruption of the blood-CSF barrier. CSF anti-Nfasc antibody titres correlated strongly with the release of NfL, suggesting that axonal injury could be related to the presence of Nfasc-specific antibodies. Following aHSCT, CSF NfL and NfH release were reduced without concomitant CSF anti-Nfasc antibody reductions, suggesting that the presence alone of anti-Nfasc antibodies is not enough to cause axonal injury. Indeed, when co-cultured with CD16+ γδ T-cells in the presence of MS patient-derived anti-Nfasc antibodies, the percent specific cytolysis of the Nfasc-transfected HeLa cells was significantly greater than that of the non-transfected control HeLa cells, proving that FcR-bearing γδ T-cells can cause axonal damage by lysing axonal membranes via ADCC, when armed with axon-specific antibodies such as anti-Nfasc. This is the first report of γδ T-cell-mediated cytolysis by ADCC using both γδ T-cells and antibodies derived from MS patients.
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Jennings, David Scott. "Assessment of the potential role of blizzard damage in the spatial distribution of southern pine beetle infestation in Unicoi County, Tennessee." [Johnson City, Tenn. : East Tennessee State University], 2001. http://etd-submit.etsu.edu/etd/theses/available/etd-0401102-152014/restricted/JenningsD.041802.pdf.
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