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The identification of cell-cycle related genes in response to antiretroviral drug treatment (ART) in lung cancerMarima, Rahaba Makgotso January 2017 (has links)
A Thesis submitted to the Faculty of Health Sciences (Internal Medicine), University of the Witwatersrand, in fulfillment of the requirements for the degree of Doctor of Philosophy.
Johannesburg, 2017 / South Africa has the largest ARV treatment programme in the world, wherein highly active antiretroviral treatment (HAART) has improved the health related quality of life (HRQoL) in HIV/AIDS patients. On the contrary, cancers not previously associated with HIV/AIDS (non-Aids defining cancers; NADCs) have been shown to be increasing, compared to the AIDS defining cancers (ADCs). Lung cancer, as a NADC has been documented in the HIV/AIDS population as a leading malignancy. The poor understanding of the association between ARV drugs and lung cancer places a burden on public health, both globally and in South Africa (SA). Furthermore, the deregulation of the cell-cycle is one of the hallmarks of cancer, including lung cancer. The main aim of this study was to elucidate the effects of HAART components Efavirenz (EFV) and Lopinavir/ritonavir (LPV/r) on cell-cycle related genes in an in vitro lung cancer model. To achieve this, cellular based, molecular and Bio-Informatics approaches were employed. First, the cytotoxic effects of EFV (at 4, 13, 26, 50 μM) and LPV/r (at 10, 32, 50, 80 μM), for 24h, 48h and 72h on normal lung fibroblasts (MRC-5) and lung adenocarcinoma (A549) cells, were evaluated using the Alamar Blue (AB) assay. This was then followed by cell-impedance “xCELLigence” real-time cell analysis (RTCA) assay. This was done to determine the effects of EFV (at 4, 13, 50 μM) and LPV/r (at 10, 32, 80 μM) on cell viability, cell death and proliferation. Cell-cycle analysis using propidium iodide (PI) by Fluorescence-activated cell sorting (FACS) was done to quantify DNA present at each of the cell-cycle stages of the cell-cycle in response to ARV treatment. Subsequently, an apoptosis assay using Annexin V FITC and Propidium iodide (PI) dual staining by FACS was carried out to confirm and quantify the ARVs potential apoptotic effects. Then, 4′,6-diamidino-2-phenylindole (DAPI) staining was used to assess changes in nuclear morphology exerted by the ARVs’ effects. A more in depth interrogation of the cell-cycle was performed using a focussed gene array panel of some 84 human cell-cycle related genes. First, total RNA was isolated from both treated and untreated MRC-5 and A549 cells and reverse transcribed to cDNA for use as template in the PCR array reactions. From the array gene expression results, by convention a ±2 fold up-or-down-regulation was used as the basis of target selection. Following this, a real-time quantitative PCR (RT-qPCR) validation of selected genes of interest was done to quantify and confirm the PCR array results. This was followed
by in-silico Bio-informatics analysis to map the molecular pathways regulated by the identified targets. For this purpose, STRING, Database for Annotation, Visualization and Integrated Discovery (DAVID), Reactome and Ingenuity Pathway Analysis (IPA) databases were used.
Interestingly, double-edged oncogenic properties of both EFV and LPV/r at different concentrations were identified. The proliferative effects of EFV at 4, 13μM and LPV/r at10 μM, were elucidated, while 26, 50μM of EFV, and 32μM of LPV/r had slight inhibitory effects on cell proliferation. LPV/r at concentrations of 50 and 80μM exerted cytotoxic effects on the cells, as demonstrated by the AB and xCELLigence RTCA assays. Cell-cycle analysis using PI staining, particularly showed cell-cycle arrest at 32μM LPV/r, and a shift to G2/M by 13μM EFV, plasma relevant doses, compared to the untreated cells. An increasing apoptosis percentage was observed with increasing LPV/r concentrations, that is, 80μM LPV/r raised the apoptosis percentage almost two-fold compared to 32μM. This was coupled by necrosis, observed in a time-dependant manner. DAPI staining confirmed loss of nuclear integrity post ARV exposure, suggesting that both EFV and LPV/r impose damage to the genomic DNA. To further assess the observed changes in nuclear morphology, the effects of EFV and LPV/r on the expression of an arrayed panel of human cell-cycle genes in cancer and normal lung cells was determined. Significantly differentially expressed targets were identified and further quantified and confirmed by RT-qPCR. Such targets included ATM, p53, cyclin-dependant kinase inhibitors (CDKIs), such as, p21, aurora kinase B (AURKB), Mitotic Arrest Deficient-Like 2 (MAD2L2) and the apoptosis related gene, caspase 3 (CASP3). Bio-Informatics analyses revealed close and direct protein-protein interactions (PPIs) between these targets, notably, with change in interaction between the gene products involved in DNA repair mechanisms, observed between ARV treated and untreated groups, as illustrated by STRING interactions. DAVID, Reactome and IPA analysis showed changes in expression of genes related to stress and toxicity and DNA damage response genes. In particular, ATM, p53 and its downstream targets such as GADD45A (growth arrest and DNA damage inducible alpha) gene were up-regulated by ARV treatment, while cyclin/CDK activity was down-regulated, resulting in reduced cell proliferation. Thus in summary, both EFV and LPV/r altered the expression levels of cell-cycle related genes, influencing overall cellular health, acting to either inhibit or stimulate cell proliferation. This suggests EFV’s and LPV/r’s proliferative and
inhibitory roles in the proliferation of lung cells. Moreover, future directions can include the transfection of lung cells with HIV provirus followed by treatment of the cells with the same ARVs under study. This could be substantiated by including HIV positive patient samples on and off ARV drug treatment with lung cancer, including HIV negative patients with cancer as one of the controls. / MT2018
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Kvicksilver i avrinningsområdet med sjön Two-Boat Lake, Grönland : Analys av kvicksilver i markprover och sedimentproverNordström, Viktoria January 2019 (has links)
Mercury is regarded as a pollution element and is transported via the atmosphere. Mercury binds to organic matter and my results show that this is the case also in the drainage area of Two- Boat Lake. Silty peat samples show the same trend in mercury concentrations with depth as those of organic matter concnetratrions. A long sediment core (30 cm) show the similar trend in mercury with depth as silty peat cores, with higher levels close to the top of the profiles as can be explaned by the industrialization that started around year 1850. Soil samples with vegetation by grass and birch show higher mercury than in the soil without vegetation (mineral soil), but wetlands with silty peat contains both higher mercury concnetrations and higher mercury inventories (mg Hg m-2). Lake sediment samples show higher carbon level in sediment taken from shallow areas with aquatic plants, but the mercury concentrations still increase with increased water depth. This is because light mineral particles and degraded organic material rich in Hg preferentially accumulate in the deep basin of the lake. Throughout the area, the terrestrial pool contains more mercury than the aquatic pool. In the terrestrial system, peat contains most mercury even though it has the smallest area and mercury per square meter is highest in peat.
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Stora Karlsö Tourism Sustainability Studies - A case study to understand & investigate impacts of water shortage and power outage on tourism.Nair, Sumit January 2019 (has links)
No description available.
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Effects of Wildfire Burn on Permafrost Landcover and Catchment Hydrology in Manitoba, CanadaAndersson, Andreas January 2019 (has links)
Permafrost is a strongly controlling factor on Arctic hydrology due to its effect on ground permeability, and thus surface and ground water flow paths. As wildfires are increasing in occurrence and magnitude in permafrost regions, they may alter the hydrological regime via permafrost thaw and degradation that increases ground permeability. Thus, it is hypothesized that in permafrost regions catchments exposed to severe wildfire burn may display a river discharge behavior different to that of unburned catchments, with reduced maximum and increased minimum flows corresponding to higher infiltration of precipitation and extended sub-surface flow paths. This study compares the seasonality and magnitude of runoff in severely burned (Odei River) and unburned (Taylor River) catchments in the sporadic permafrost region in the Canadian Shield Taiga. The investigated time span consists of 25 full calendar years with complete daily and monthly river discharge data between 1980 and 2016. They are used in conjunction with burned area data, climate data and landcover data to investigate patterns in hydrology behavior. An emerging trend is a sharply declining maximum flow and increasing minimum flow relative to precipitation in the burned catchment, indicating an accelerated increase in infiltration and buffer capacity of the soil relative to the unburned catchment. Over the entire period the apparent annual catchment storage change is decreasing in both catchments, but at a 115% faster rate in the burned catchment despite being exposed to ~1.5 C lower mean annual temperature, a factor that likely increases the rate of climate-driven aggradation of permafrost in the contrasting unburned catchment. The discrepancy found in catchment streamflow regime between the burned and unburned catchment and its alignment with the suggested permafrost disturbance effects from previous studies suggest that streamflow may serve as a useful and resource efficient indicator of wildfire-driven permafrost degradation.
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Analys av vegetationen i brandområdena 2018Lundgren, Lisa, Lindqvist, Karin, Ene, Simon, Ahlstedt, Oskar, Norberg, Sandra, Lood, Olof, Haglund, Maria January 2019 (has links)
Syftet med projektet var att analysera och kartlägga vilken typ av vegetation som brann under skogsbränderna sommaren 2018. Geografiskt informationssystem, GIS, nyttjades för att analysera den geografiska data som användes för att få fram vegetationsfördelningar i brandområdena. I analysen och kartläggningen användes Naturvårdsverkets öppna Nationella Marktäckedata tillsammans med Skogsstyrelsens dataset Ungefärligt brandområde. Marktäckedata är uppbyggd av olika klasser och representerar olika typer av information, exempelvis dominerande vegetationstyp. Genom arbetet i GIS togs det fram kartor över brandområdenas marktäckedata samt cirkeldiagram och tabeller med vegetationsfördelningar. Dessa analyserades för att hitta trender i vegetationens fördelning som förklarar skogsbrändernas spridning. Efter analysen kunde slutsatsen dras att det framförallt var barrskog som brann, där vegetationstypen tallskog utgjorde den största andelen. Samtidigt stod lövskog för en mycket liten del av vegetationsfördelningen i de sex största bränderna. Eftersom det generellt var lite lövskog i områdena kring skogsbränderna var det svårt att dra slutsatser kring huruvida lövskog är brandhämmande. Våtmarker verkar i vissa fall hindrat brandspridning men brann även de när det var torrt och varmt. I det initiala skedet i brandförloppet dominerade tallskog och temporärt ej skog såsom kalhyggen eller stormfällda områden, medan andra vegetationstyper involverades allt eftersom bränderna tog fart och spred sig.
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Understanding Dog Owners’ Decision Making on Dog-related Consumption In ChinaXu, Huijia, Jiaqi, Yang January 2019 (has links)
The beneficial of keeping a dog and the booming Chinese pet dog market allowed many Chinese people considering owning a dog. However, how owners treat their dogs are extremely different. Some of them consider dogs as their child while others think dogs are just objects with special function. These different attitude leads to dog owners’ different consumption intention towards dog-related products and services. Therefore, this study aimed to identify the dog owner’s intention of buying or keeping a dog in China. The theory of planned behavior was used to analyzed in this thesis. The goal was to figure out the factors that influence owners’ intention of buying or keeping a dog. To investigate our purpose, the qualitative method with eleven semi-interviews were conducted in this thesis, and we analyzed the data using the method of qualitative content analysis. The results were shown from attitude, subject norm and perceived behavior, which comes from the theory of planned behavior.
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Efficacy of Latin dance as a health-enhancing leisure activity for adultsDomene, Pablo A. January 2015 (has links)
Despite acceptance that physical activity serves as a protective agent against the burden of non-communicable disease, half of all adults in the developed world remain insufficiently physically active. The promotion of physical activity is therefore of paramount importance to public health researchers and practitioners. Dance, as a leisure or social activity, can play a role in the engagement of adults in physically active pursuits that are not necessarily thought of as traditional exercise per se. This is especially important for those individuals not currently meeting physical activity guidelines and is fully congruent with the current public health message that "some activity is better than none". A holistic exploration of Latin dance was undertaken in this thesis in the context of physical activity and psychosocial health promotion in non-clinical adults. The research encompassed a quantitative assessment of physiological and psychological measures related to dance. Over a 3 yr period, eighty-four women and men were enrolled in a series of four interrelated Latin dance (salsa) and Latin-themed aerobic dance (Zumba fitness) studies. Research grade motion sensing and heart rate monitors were used to evaluate the physiological responses to dance, and a novel activity-specific value calibration method was developed to process the data. The monitors, which are small and unobtrusive to wear, were then utilised for collection of data during performance of dance in naturalistic settings. Psychological measures associated with dance participation were captured using previously validated questionnaires. Results indicate that Latin dance elicits physiological responses representative of moderate to vigorous physical activity when performed primarily for leisure purposes. Modest improvements were observed post-dance in measures of cardiorespiratory fitness, body composition, and inflammatory biomarkers in relation to cardiovascular health. Moreover, participation fostered interest, enjoyment, and a positive psychological outlook, and enhanced well-being, mood, and health-related quality of life with large magnitude effects. The findings of this thesis may be relevant for researchers and practitioners interested in the efficacy of dance as an expressive and creative medium for the promotion of physical and mental health.
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The effect of acupuncture with electrical stimulation on the plasma acth and corticosterone levels of morphine addicted rats and mice.January 1978 (has links)
Yu-fui Tsang. / Title also in Chinese. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1978. / Bibliography: leaves 73-80.
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The physiologic correlates of learning in the classroom environmentFrustace, Bruno Salvatore 22 January 2016 (has links)
This study served to further investigate learning and memory, and to offer a potential tool to support educational interventions. More specifically, this was accomplished by an investigation of the physiologic changes in the brain that occurred while students learned medical anatomy. A group of 29 students taking the Gross Anatomy course at Boston University School of Medicine participated in the study. Testing occurred in two sessions: prior to the course and at the completion of the course. For each session, scalp EEG was recorded while participants were shown 176 anatomical terms (132 relevant to the course and 44 obscure) and asked to respond with "Can Define", "Familiar", or "Don't Know". Behavioral results indicated a positive correlation between participants' course grades and performance on the experimental tasks. EEG results were analyzed for event-related potential (ERP) components related to two memory components: familiarity and recollection. Results had a number of indications. For Don't Know responses, a stronger early frontal, late parietal, and late frontal effect occurred more so for terms of Session 1 compared to Session 2. For an analysis of just Session 2 data, results indicated increased activity of the early frontal, late parietal, and late frontal effects for Can Define responses only. Session 2 Can Define responses elicited a stronger early frontal ERP, occurring between 300 and 500 milliseconds yet, the most post-retrieval processing and monitoring appeared for Can Define terms of Session 2. Ultimately, we focused on investigating two points: 1) the effect of classroom learning on memory, and 2) the examination of ERPs as a tool to guide education interventions. Specifically, ERPs would potentially indicate markers to predict whether students would retain materials long before behavioral measures indicate these results. This has potential to determine whether long-lasting or transient learning will occur; as well as the potential to support early intervention strategies for not just students, but also individuals with learning disabilities or memory impairments.
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The influence of pain-related fear levels on structural brain changes in pediatric complex regional pain syndromeZhang, Kunyu 08 April 2016 (has links)
Complex Regional Pain Syndrome (CRPS) is a chronic neuropathic pain condition associated with significant alterations in the somatosensory and motor cortex brain regions. Cognitive-affective alterations have recently been recognized in patients suffering with CRPS, however, relatively little neuroimaging research has been done to examine these dimensions. Moreover, many children and adolescents suffer from CRPS, but very little is known about the impact of this condition on brain states in the pediatric population. The aim of this paper is to assess the structural brain differences between children with CRPS and healthy controls and to examine to what degree fear level influences such differences. This study is part of a larger investigation that integrates functional and structural brain differences to evaluate fear-related brain circuitry in patients with CRPS. Thirty-seven patients with CRPS were age and gender matched with 35 healthy controls. The two groups underwent structural magnetic resonance imaging (MRI) scans as well as completed the Fear of Pain Questionnaire, child report (FOPQ). To examine gray matter differences, voxel-based morphometry (VBM) and cortical thickness (CT) analysis was completed. Patients with CRPS in this study had an average age of 13.2 (SD=2.7) and were predominantly female (73%). Of the 35 patients who completed FOPQ, 49% reported clinically significant pain-related fear. Compared with healthy controls, CRPS patients had significantly less in gray matter (GM) volume in pain- and fear-related brain regions, including the dorsolateral prefrontal gyrus, motor and somatosensory cortex, anterior and posterior cingulate cortex, nucleus accumbens, putamen, amygdala, and hippocampus. Furthermore, gray matter decreases in regions such as anterior midcingulate cortex, nucleus accumbens, and putamen were associated with elevated pain-related fear in patients. Differences in gray matter volume in fear-circuitry areas could potentially be one mechanism by which abnormal fear learning and extinction develops in youth suffering with CRPS. Further research examining brain changes post-treatment is needed to determine if treatments that target improving pain and fear levels are associated with concomitant normalization of brain structures.
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