Abstract To date, most epidemiological studies have shown a weak or moderate association between dental diseases such as periodontal infections, dental caries and tooth loss, and atherosclerotic vascular diseases. However, the nature of this association is not known; it may be due to the biological effect of oral infections on initiation or progress of atherosclerosis or it may be non-causal due to determinants in common, either biological or behavioural. Methodological shortcomings, inconsistent results and a lack of definite proof from intervention studies have led to the conclusion that causality between dental diseases and atherosclerotic vascular diseases has not been established. The aim of this study was to produce evidence on the nature of the association between dental diseases and atherosclerotic vascular diseases. The study uses data from the 1966 Birth Cohort of Northern Finland (N = 11,637). The data were collected in 1997–1998, when the cohort members had reached 31 years of age. The respondents were asked through a postal questionnaire about their oral health. In addition, respondents were asked about their general health and oral and general health habits. The response rate was 75.3%. Those who lived in Northern Finland or the capital city region were invited to clinical health examination (N = 8,463). Altogether 5,696 subjects supplied the data, representing 67.3% of those who were invited to the clinical examination. While the study showed an association of self-reported gingivitis, dental caries and tooth loss with the prevalent angina pectoris, it also showed that these self-reported dental diseases were not important determinants for elevated C-reactive protein levels. This suggests that the associations that were found between dental conditions and prevalent angina pectoris are mainly caused by factors other than biological mechanisms related to infection or inflammation. The lack of a biological explanation related to infections or inflammatory processes suggests that other biological mechanisms or biases, including confounding, should be considered as an alternative explanation. However, it must be noted that the possibility that oral infections also contribute to the development of atherosclerosis should not be rejected either.

Master of Science / Department of Geology / Saugata Datta / Elevated levels of dissolved arsenic (As), iron (Fe) and manganese (Mn) are seen in the shallow, anoxic groundwaters of southeast Bangladesh on the Ganges- Brahmaputra- Meghna River delta. Over the past decade the mechanisms of As release have been widely debated. It is understood that As can sorb onto Fe-bearing minerals and can be subsequently released when reactions, such as microbially driven processes, occur. This study takes a multi disciplinary approach to understand the extent of the natural reactive barrier along the Meghna River and to evaluate the role of the natural reactive barrier in As sequestration and release in groundwater aquifers. River water and groundwater interactions occur in the hyporheic zone, which is defined as the transient subsurface region where river water and groundwater mix. The natural reactive barrier can develop within the hyporheic zone, where Fe-bearing minerals accumulate with a potential for As sorption, along with reworking and re-deposition of sediments along the riverbank. Shallow sediment cores, and groundwater and river water samples were collected from the east and west banks of the Meghna River in Jan. 2016. Groundwater and river water samples were tested for total dissolved Fe, Mn, and As concentrations; δ₂H, δ₁₈O isotopic ratios. Fluorescence spectroscopic characterization of groundwater organic matter provided insight into the hydro-geochemical reactions active in the groundwater and the hyporheic zone. Eight sediment cores of ~1.5 m depth were collected ~10 m away from the edge of the river. Vertical solid-phase concentration profiles of Fe, Mn, and As were measured by four different methods (hand-held XRF, and ICP-OES analysis of 3 digestions: aquaregia (HNO₃: HCl 1:3), 1.2 M HCl, and 1 M NaH₂PO₄ + 1 M L-ascorbic acid extractions). Enrichment of solid phase Fe, Mn, and As and the presence of possible Fe and Mn oxides in the sediments illustrate the existence of an natural reactive barrier at this reach of the Meghna. HCl extractions of sediment revealed solid-phase As accumulation along the west riverbank reaching concentrations of ~1500 mg/kg. Aqueous geochemical results showed the highest dissolved As concentrations in shallow wells (<30 m depth), where organic matter was fresh, humic-like, and aromatic. Humic-like dissolved organic matter present in the groundwater may enhance Fe oxide dissolution. Microbial reduction of organic matter prompts the reduction of Fe³⁺ to Fe²⁺, causing As to mobilize into groundwater. This study quantified the extent of As accumulation in the sediments along a 1 km stretch of the Meghna River. These findings contribute to the understanding of geochemical processes involved in As release into groundwaters from sediments within a fluvial deltaic environment.

>Magister Scientiae - MSc / Nitric oxide (NO) has been shown to orchestrate multiple defense responses to both abiotic and biotic stress. Importantly, elevation of nitric oxide content in plants by using nitric oxide generating compounds has been shown to enhance plant tolerance to abiotic stresses such as salt and drought via up-regulation of genes involved in the regulation of plant responses to abiotic stress. In this study, the effect(s) of nitric oxide (generated from 10 μM of the nitric oxide donor DET/NO) on the expression of a novel soybean cystatin gene (Glyma20g08800), lipid peroxidation, caspase-like activity and cell death in salt (150 mM)-stressed soybean leaves, roots and nodules were investigated. Salt treatment resulted in elevated lipid peroxidation, caspase-like activity and increased cell death in organs studied while the observed detrimental effects of salt stress were reversed by NO treatment. Salt stress suppressed the expression of Glyma20g08800 while the levels of expression of Glyma20g08800 returned towards those of unstressed plants when the salt-stressed plants were supplemented with nitric oxide (DETA/NO). Furthermore, promoter sequences of GmCYS1p626 and three of its homologues (Glyma20g08800, Glyma14g04250 and Glyma18g12240) were analyzed for putative abiotic stress and/NO cisregulatory elements based on co-expression analyses using bioinformatics. Several abiotic stress induced transcription factors (TFs) were identified and were hypothesized to be co-acting either directly or indirectly through additional factors in the regulation of soybean cystatin expression in response to NO and abiotic stress. Taken together, these results highlight the possibility of using NO to drive high levels of expression of cystatins during salt stress and lead to accumulation of the cystatin to levels that are sufficient to inhibit salt stress-induced caspase-like activity, which will inhibit salt stress-induced cell death and thus enhance the tolerance of the plant to salt stress and possibly tolerance to drought stress as well.

>Magister Scientiae - MSc / Nitric oxide (NO) is a signaling molecule involved in mediating plant responses to various biotic and abiotic stresses. Major abiotic stresses (drought, salinity, cold) induce common cellular responses, causing osmotic stress in plants. This results in oxidative stress due to increased production of reactive oxygen species (ROS). The increased ROS levels simultaneously induce the antioxidative system (including antioxidant enzymes such as superoxide dismutase) that regulates ROS toxicity and enhance stress tolerance in plants. It is suggested that the scavenging of ROS by antioxidant enzymes can be controlled by NO. The aim of this study was to evaluate the role of exogenously applied NO on soybean (Glycine max L. Merr.) during osmotic stress, with the purpose of determining the effects of NO on the superoxide dismutase (SOD) activity in response to osmotic stress. This study also aimed at identifying and characterising SOD isoforms induced in soybean in response to osmotic stress and exogenous NO. To achieve these aims, soybean plants were treated with sorbitol (to induce osmotic stress), an NO donor [2,2'-(hydroxynitrosohydrazono)bis-ethanimine, DETA/NO] and its respective control (Diethylenetriamine, DETA). The results showed that exogenous NO alleviated osmotic stress-induced damage by reducing the superoxide radical content, lipid peroxidation levels and also maintaining cell viability in soybean leaves, nodules and roots. Only two SOD isoforms i.e. manganese SOD (MnSOD) and copper/zinc SOD (CuZnSOD) were identified and characterised in soybean leaves and roots, iron SOD (FeSOD) was not induced. The isoforms identified exhibited low SOD activity in response to osmotic stress, with the exception of a few isoforms that had increased activity. The SOD activity was regulated by exogenously applied NO. The enzymatic activity of SOD isoforms was up-regulated by exogenous NO, except for a few SOD isoforms that were not responsive to NO. The results also showed that the increased SOD activity was associated with reduced lipid peroxidation levels. The results obtained from this study suggest that exogenous NO improves osmotic stress tolerance in soybean by regulating and increasing the SOD activity of only specific isoforms. The increased SOD activity maintains the redox homeostasis balance by detoxifying and controlling the superoxide radical levels, subsequently reducing lipid peroxidation and maintaining cell viability.

>Magister Scientiae - MSc / This study investigated the effects that drought stress imposed on the growth and development of soybean plants. Soybeans were initially observed at the whole-plant level in order to identify the physical changes that had taken place in response to drought. Further investigation of the effects of drought stress on Soybean plants were quantified at the molecular level. Physical changes of soybeans in response to drought stress were typified by the change in leaf morphology and pigmentation. At the molecular level, it was observed that drought stress resulted in the accumulation of hydrogen peroxide in soybean leaves, which was met by elevated levels of lipid peroxidation. The effects of drought on the modulation of (and interplay between cystatins) cysteine protease (caspase-like) activity and programmed cell death (PCD) were also investigated. Total caspase-like activity and cell death were enhanced in response to water deficit despite the up-regulation in gene expression of the cystatin Glyma14g04250. The cystatin Glyma18g12240 was not expressed in soybean leaves, whilst the gene expression of the cystatin Glyma20g08800 remained unchanged in response to drought. This study was aimed at the characterization of two single domain soybean cystatins, namely, Glyma14g04250 and Glyma20g08800 which could potentially be overexpressed in transgenic soybean plants in an attempt to alleviate the effects of drought stress. / National Research Foundation (NRF)

Reactive attitudes are distinctively moral emotions that occur when a moral harm has occurred. Recent studies in moral psychology suggest that our reactive attitudes may be influenced by factors extraneous to moral evaluation, such as hunger, sleep deprivation, and negative moods. I argue that these influences lead us to sanction unfairly. Even though reactive attitudes may be a natural response to perceived moral wrongdoing, we cannot justifiably inflict undeserved harm. However, if we can learn to recognize and eliminate the effects of these irrelevant influences, then we can use our reactive attitudes productively in holding others morally accountable.

Breast cancer is the most prevalent type of cancer and second leading cause of death in women. Among others, the triple negative breast cancer (TNBC) is the most invasive as it has the highest recurrence and death rates with no targeted therapeutic available thus far. Epidermal Growth Factor Receptor (EGFR) is one of the important targets as more than fifty percent of the TNBC overexpress it but all the therapies designed against it have failed to show significant results. The juxtamembrane domain of EGFR has been explored comparatively recently and has been used to design a decoy peptide with the anticipation to affect the EGFR downstream functions. Previous research has shown it to cause cell death in cancer cells. This study is aimed towards deciphering the mechanism of action of the stapled form of this decoy peptide-SAH5. It presents evidence that the peptide leads to an immediate intracellular calcium release from the Inositol 1,4,5 triphosphate on the endoplasmic reticulum, an inhibition of which can rescue SAH5 induced cell death. The study also demonstrate that the peptide is able to increase the production of Reactive Oxygen Species (ROS) in mitochondria, part of which is triggered by the peptide-induced calcium release.

Ischemic stroke is characterized by a disruption of blood supply to a part of the brain tissue, which leads to a focal ischemic infarct. The expression and activity of MMP-9 is increased in ischemic stroke and is considered to be one of the main factors responsible for damages to the cerebral vasculature, resulting in compromised blood-brain barrier (BBB) integrity. However, the regulatory mechanisms of MMP-9 expression and activity are not well established in ischemic stroke. Since hypoxia/ischemia and reperfusion generates reactive oxygen species (ROS), I hypothesize that ROS is one of factors involved in up-regulation of MMP-9 expression in brain cells and ROS-mediated effect may occur via MAPK signaling pathway. My study has provided the evidence that ROS is responsible for an increase in MMP-9 expression in astrocytes mediated via MAPK-AP1 signaling pathway. Preliminary studies with an in vitro model of the BBB suggest that inhibition of MMP-9 is a critical component of reducing ROS-induced BBB permeability.

The current study evaluated whether NO synthase (NOS) contributes to cutaneous vasodilation and sweating during prolonged exercise in the heat. In addition, we determined if prolonged exercise-induced increases in reactive oxygen species (ROS) and activation of angiotensin II type 1 receptors (AT1R) impair heat loss responses. On two separate days, eleven young men completed 90-min of continuous cycling at ~600W of metabolic heat production followed by 40-min of recovery in the heat (40ºC). To evaluate the role of excess fluid loss via sweating, participants completed a second session of the same protocol while receiving fluid replacement (FR) determined during the first session (No-FR). Cutaneous vascular conductance (CVC) and local sweat rate (LSR) were measured at four intradermal microdialysis forearm sites perfused with either: (1) lactated Ringer (Control); (2) 10 mM NG-nitro-L-arginine methyl ester (L-NAME, NOS inhibition); (3) 10 mM ascorbate (non-selective anti-oxidant); or (4) 4.34 nM Losartan (AT1R inhibition). Ascorbate treatment increased CVC at 60- and 90-min of exercise versus Control during the FR (P < 0.02), but not the No-FR condition (P > 0.31). CVC was reduced at the L-NAME treated site (P < 0.02), but was not different relative to Control at the Losartan treated site (P > 0.19) irrespective of condition. LSR did not differ between sites or as a function of condition (all P > 0.10). We conclude that NO regulates cutaneous vasodilation but not sweating, irrespective of fluid replacement, and ascorbate sensitive ROS impair cutaneous vasodilation during prolonged exercise in the heat with FR.

Carbonate diagenesis encapsulates a wide range of water rock interactions that can occur within many environments and act to modify rock properties such as porosity, permeability, and mineralogical composition. These rock modification processes occur by the supply of reactant-laden fluids to areas where geochemical reactions are thermodynamically and kinetically favoured. As such, understanding the development of diagenesis requires an understanding of both palaeohydrology and geochemistry, both of which have their own complexities. However, within geological systems, both the conditions that control fluid migration and the distribution of thermodynamic conditions can change through time in response to external factors. Furthermore, they are often coupled, with rock modification exercising a control on fluid flow by altering the permeability of sediments. Numerical methods allow the coupling of multiple complex processes within a single mathematical formulation. As such, they are well suited to investigations into carbonate diagenesis, where multiple component subsystems interact. This thesis details the application of four separate types of numerical forward modelling to investigations of diagenesis within two Carboniferous carbonate platforms, the Derbyshire Platform (Northern England) and the Tengiz Platform (Western Kazakhstan). Investigations of Derbyshire Platform diagenesis are primarily concerned with explaining the presence of Pb-mineralisation and dolomitisation observed within the Dinantian carbonate succession. A coupled palaeohydrology and basin-development simulation and a series of geochemical simulations was used to investigate the potential for these products to form as a result of basin-derived fluids being driven into the platform by compaction. The results of these models suggest that this mechanism is appropriate for explaining Pb-mineralisation, but dolomitisation requires Mg concentrations within the basin-derived fluids that cannot be attained. Geothermal convection of seawater was thus proposed as an alternative hypothesis to explain the development of dolomitisation. This was tested using an advanced reactive transport model, capable of considering both platform growth and dolomitisation. The results of this suggests that significant dolomitisation may have occurred earlier on in the life of the Derbyshire Platform than has previously been recognised. An updated framework for the development of diagenesis in the Derbyshire Platform is proposed to incorporate these new insights. The Tengiz platform forms an important carbonate oil reservoir at the northeastern shore of the Caspian Sea. The effective exploitation of any reservoir lies in an understanding of its internal distributions of porosity and permeability. Within carbonate systems, this is critically controlled by the distribution of diagenetic products. A model of carbonate sedimentation and meteoric diagenesis is used to produce a framework of early diagenesis within a sequence stratigraphic context. The studies mentioned above provide a broad overview of the capabilities and applicability of forward numerical models to two data-limited systems. They reveal the potential for these methods to guide the ongoing assessment and development of our understanding of diagenetic systems and also help identify key questions for the progression of our understanding in the future.