Imaging techniques provide a method for non-invasive longitudinal monitoring of cancer therapies, but common metrics such as tumour size are late markers and do not indicate heterogeneity of response. Apoptotic cell death is an earlier marker of tumour response and produces molecular and cellular-level changes (macromolecular breakdown, membrane changes and cell shrinkage) that may be detectable by magnetic resonance imaging (MRI). Previous studies using conventional MRI methods have shown little sensitivity to apoptosis. In this thesis it is hypothesized that, using an extracellular contrast agent to affect the MRI property of relaxation for extracellular water preferentially, parameters related to water in the intracellular and extracellular environments and the exchange between them can be obtained and will be sensitive to apoptosis. It is also hypothesized that membrane changes and macromolecular breakdown are detectable by the technique of magnetization transfer. Measurements of relaxation in the presence of contrast agent in vitro demonstrated a decrease in extracellular water fraction and an increase in the rate of water exchange across the plasma membrane during apoptosis. In vivo, this method was complicated by the difficulty of delivering contrast agent to the tumour, but regions with good delivery showed correlation between high water exchange rates from MRI and apoptosis in histology. Magnetization transfer studies indicated only small changes in vitro during apoptosis and these were largely related to changes in the free water, so this method was not investigated further. Further work is required to determine the tumour lines where the water exchange methods may be applied reliably. Nevertheless, the method of measuring water exchange presented in this thesis can be performed in a clinically-feasible amount of time (~20 minutes). It therefore has potential in detecting apoptosis and predicting therapy response. It also emphasizes the role of water exchange in conventional MRI relaxation experiments.

Periods of hypoxia are a recurring issue in Brunnsviken. Main factors that trigger hypoxia in Brunnsviken are eutrophication  due to anthropogenic emission of nutrients, stratification in the water column due to salinity and temperature differences  that prevents mixing and a sill inlet that prevents water exchange. As an attempt to improve the oxygen levels, bottom water is pumped from Brunnsviken causing aerated surface water to flow back into the basin.  The objective of this Master’s thesis was to study the change in dissolved oxygen levels due to pumping.  Since  the question is  complex,  two areas  were  chosen  to focus on; oxygen variability and the impact of water exchange on dissolved oxygen.  Conductivity, temperature, depth  and oxygen  measurements, which were performed  by Stockholm Vatten, were studied.  This type of data set, with high resolution, is very rare and the data set from Brunnsviken  has not been  evaluated  thoroughly  before. The result of the evaluation was that high resolution data of oxygen are  required in order to describe  the dynamics of oxygen  in Brunnsviken and other aquatic systems properly. Measurements of oxygen once a month is not sufficient. For that reason, it is not possible to use monthly measurements to evaluate  the  effect of the pumping. However, high resolution data for approximately one year were available. Episodes of hypoxia occurred during that period. This was not surprising, as the main purpose of  the pumping was to keep the oxycline as deep as possible.  The water exchange was determined from a water balance of Brunnsviken and compared with oxygen data. The water exchange did not seem to influence the oxygen level in Brunnsviken. The reason for this is most likely that the density of inflowing water was less than the density of  the  bottom water in Brunnsviken  during  most of  the period  studied.  This  result in combination with the fact that the pump flow is small compared to the water exchange suggests that the most important result of the pumping is that water with a low oxygen level is removed. / Perioder av syrebrist är ett återkommande problem i Brunnsviken. De faktorer som i huvudsak ger upphov till utbredningen av syrefria områden i viken är övergödning orsakad av antropogena utsläpp av näringsämnen, en tröskel vid inloppet som hindrar vattenutbyte samt skiktning i vattenkolumnen till följd av salinitets-  och temperaturskillnader  som hämmar vertikal omblandning. I ett försök att förbättra syrgasförhållandena pumpas bottenvatten ut ur viken i syfte att syrerikare vatten ska strömma in.  I detta examensarbete  undersöktes pumpningens effekt på  syrgashalten.  Då detta  är en komplex fråga lades fokus på att utreda syrets variabilitet samt vilken effekt vattenutbytet har på syrgashalten.  I Brunnsviken pågår sedan omkring ett år tillbaka konduktivitet-, temperatur-, djup-  och syremätningar med hög tidsupplösning. Dataserien är en av mycket få serier  i sitt slag  och någon grundlig utvärdering av dessa mätningar har inte gjorts tidigare.  Resultatet av utvärderingen  visade  att  syremätningar måste göras mycket ofta för att beskriva syredynamiken i Brunnsviken och andra akvatiska system på ett korrekt sätt, eftersom syrgashalten varierar mycket på kort tidsskala.  Det är därför inte möjligt att använda månadsmätningar för att utvärdera vilken effekt pumpningen har haft på  syrgashalten i Brunnsviken. Högupplösta data visade att syrebrist inte varit möjligt att undvika  i Brunnsviken. Detta var heller inte att vänta då målet med pumpningen främst varit att hålla ner oxyklinen.     Vattenutbytet beräknades utifrån  Brunnsvikens vattenbalans och jämfördes med syredata. Någon effekt på  syrgashalten orsakad  av vattenutbytet har inte gått att påvisa. Det beror troligen på att densiteten på det inströmmande vattnet varit lägre än densiteten på bottenvattnet i Brunnsviken under nästan hela den studerade perioden. Detta i kombination med att pumpflödet är mycket litet i förhållande till det naturliga vattenutbytet gör att det viktigaste med pumpningen är att syrefattigt vatten förs bort från viken.

This study investigated the concentrations of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in the particulate and dissolved phase, as well as concentrations of PAHs in the sediment in Kaohsiung Harbor lagoon. Sources of PAHs in the water column were determined by isomer ratios, hierarchical cluster analysis (HCA) and principal components analysis (PCA). The net and annual fluxes of PAHs were calculated after a lagoon-wide water sampling campaign and compared with those found in a previous study (Fang, 2007) in which data from only one water sampling station was used. ¡@¡@In rain season, total PAH concentrations ranged from 21.6 to 36.2 ng/L for water samples, with dissolved and particulate phase concentrations ranged from 15.5 to 27.2 ng/L and from 3.4 to 8.6 ng/L, respectively. In dry season, total PAH concentrations ranged from 13.2 to 31.5 ng/L for water samples, with dissolved and particulate phase concentrations ranged from 8.0 to 21.1 ng/L and from 5.3 to 10.5 ng/L, respectively. Total PAH concentrations were found higher in rain season than in dry season. The highest total PAH concentration in dry season was observed in Chianjen River estuary. Relatively high PAH concentrations were also observed in these southern stations of Kaohsiung Harbor because of their location near Dalin industrial park. Total PAH concentrations ranged from 81.7 to 2279 ng/g for sediment samples, with average of 895 ng/g. The correlations between PAH concentrations and organic carbons, water temperature, salinity and suspended particles were also examined in this study. PAH concentration in dissolved phase was negatively correlated with water temperature (p<0.05). PAH concentration in sediment was positively correlated with organic carbons (p<0.05), and negatively correlated with median diameter (p<0.01). The logKoc¡ÐlogKow relationship in rain and dry season was compared with literature. It was found that the logKoc values were higher than those reported in literature, suggesting that soot particles might play an important role in the transport and distribution of PAHs in the study area. In rain season, PAHs in dissolved phase were mainly from pyrogenic origins; while mainly from petrogenic origins in particulate phase. In contrast, in dry season, PAHs in dissolved phase were mainly from petrogenic origins; while mainly from pyrogenic origins in particulate phase. In addition, it was found, relatively, that petrogenic pollution was introduced maily from the northern area of the lagoon. In rain season, total PCB concentrations ranged from 1.1 to 2.7 ng/L for water samples, with dissolved and particulate phase concentrations ranged from 0.42 to 2.1 ng/L and from 0.24 to 1.4 ng/L, respectively. In dry season, total PCB concentrations ranged from 0.54 to 1.3 ng/L for water samples, with dissolved and particulate phase concentrations ranged from 0.20 to 0.74 ng/L and from 0.32 to 0.76 ng/L, respectively. The direction of net fluxes of PAHs in this study are from water to air (net volatilization) in summer. In winter, however, the absorptive PAH fluxes obtained for four to six-ring PAH, such as fluoranthrene, chrysene + triphenylene and benzo[a]anthracene, indicating that PAHs were absorbed into surface waters. According to our results, it was suggested that the results from previous study (Fang, 2007) might underestimate the net fluxes of Pyrene and total fluxes in dry season. The annual fluxes of PAHs estimated in this study were 212 mg/m2 /year and 5.7 kg of PAHs were emitted annually from the harbor lagoon surface waters to the ambient atmosphere.

Plankton communities are influenced, in part, by water exchange with adjacent estuarine and oceanic ecosystems. Reduced advective transport through tidal passes or with adjacent bay systems can affect chemical processes and biological interactions, such as nutrient cycling, phytoplankton abundance and productivity, community respiration, and zooplankton biovolume. The most threatened estuarine ecosystems are shallow, bar-built, microtidal estuaries with small water volumes and restricted connections through tidal passes and other water exchange points. This research explored spatio-temporal trends in plankton communities and the physicochemical environment in Mesquite Bay, Texas a microtidal, bar-built, subtropical estuary in the Gulf of Mexico. This research couples sampling at fixedstations for multiple physical and biological parameters with high-resolution spatial mapping of physicochemical parameters. Spatial trends were less in magnitude and affected fewer parameters in fixed station and spatial data. Two dimensional ordination plots indicated spatial heterogeneity with a more pronounced temporal trend affecting parameters including temperature, salinity as a function of inflow timing, and seasonal wind direction affecting primary production and zooplankton biovolume. Temperature was positively correlated with gross production and respiration rates during spring and late summer with sporadic positive and negative correlations with phytoplankton biomass. The timing and magnitude of freshwater inflow affected various physicochemical and biological parameters. Higher than 71-year inflow rates resulted in low salinity system wide, with spatial heterogeneity increasing over the course of the study, which was confirmed by spatial maps. Additionally, high inflow rates led to two periods of increased inorganic nutrients and dissolved organic matter. Low salinity periods coincided with persistence of higher turbidity, likely because of decreased sediment flocculation. Gross production was low at this time, and likely from light limitation. Additionally, wind magnitude and direction created spatial heterogeneity in turbidity levels and phytoplankton biomass. Zooplankton biovolume was highest during spring and late summer with high species diversity in total rotifers. Copepod biovolume and phytoplankton biomass were positively correlated. Other zooplankton taxonomic groups exhibited variable correlations with phytoplankton biomass and other taxonomic groups. Further long-term studies are needed to determine interactions of various components of trophic food-webs and account for interannual variability in all system parameters.

White shrimp (Litopenaeus vannamei) were cultured in isolated environment using zero-water exchange to investigate optimum cultivation method. Except density experiment, culture density was 100 shrimps/m2 in all other experiments. The results indicated that simple quarantine facility could prevent virus infection of pond shrimps. After 83 days of cultivation, survival rate, final weight, yield and growth rate (90.7%, 16.8 g, 1.52 kg/m2, 1.36 g/week) of zero-water exchange group was not significantly different from those of water exchange group, but FCR was lower (p<0.05) instead. Addition of brown sugar increased final weight and growth rate of shrimp and lowered FCR (18.6 g, 1.60 kg/m2, 1.64 ¡Ó 0.04) (p<0.05), but nitrification was inhibited. Application of two mats per tank gave highest increases in final weight and yield and lowest FCR (p<0.05). Bottom sand increased final weight and yield and lowered FCR (p<0.05), stabilized pH and increased de-nitrification efficiency. Salinity of 25 ppt had highest final weight and yield and lowest FCR (p<0.05). Density of 200 shrimps/m2 had highest final weight and lowest FCR (p<0.05) and yield twice as that of density of 100 shrimps/m2. At the end of cultivation, water quality condition between 37% and 32% protein feed were not significantly different. But, the shrimps of 37% protein feed had higher final weight, lower FCR (p<0.05) and 26% more yield. The above results indicated that the risk of shrimps infected by virus could be prevented using zero-water exchange culture method. As long as solid was held suspending by sufficient agitating, good water quality could be maintained. Hence, zero-water exchange culture could not only decrease electricity of water pump and quantity of water use, but also increase the value of product and incorporation efficiency of feeds.

In this thesis study wind-induced circulation and sediment transport in semi-enclosed basins are carried out for Fethiye Bay. Hydrodynamics of bays are very complex, mainly affected by wind and wave climate, sea bed slope and sediment characteristics. The sea bed profile at the bay changes under winter and summer storms of different speeds and directions. A case study is carried out with the developed methodology. For this reason, Fethiye Bay is selected for the study area. Present structure of Fethiye Bay is determined, sea bed changes since the year 1956 are analyzed. A circulation modeling is applied to the study area. For this purpose, Finite Volume Coastal Ocean Model (FVCOM) numerical model is used. Water exchange and current pattern in the study area for different wind conditions is analyzed. Sediment distribution in the bay is analyzed for different wind directions, river discharges and sediment loads.

Oxygenic photosynthesis in plants, algae and cyanobacteria converts sunlight into chemical energy. In this process electrons are transferred from water molecules to CO2 leading to the assembly of carbohydrates, the building blocks of life. A cluster of four manganese ions and one calcium ion, linked together by five oxygen bridges, constitutes the catalyst for water oxidation in photosystem II (Mn4CaO5 cluster). This cluster stores up to four oxidizing equivalents (S0,..,S4 states), which are then used in a concerted reaction to convert two substrate water molecules into molecular oxygen. The reaction mechanism of this four-electron four-proton reaction is not settled yet and several hypotheses have been put forward. The work presented in this thesis aims at clarifying several aspects of the water oxidation reaction by analyzing the mode of substrate water binding to the Mn4CaO5 cluster. Time-resolved membrane-inlet mass spectrometric detection of flash-induced O2 production after fast H218O labelling was employed to study the exchange rates between substrate waters bound to the Mn4CaO5 cluster and the surrounding bulk water. By employing this approach to dimeric photosystem II core complexes of the red alga Cyanidoschyzon merolae it was demonstrated that both substrate water molecules are already bound in the S2 state of the Mn4CaO5 cluster. This was confirmed with samples from the thermophilic cyanobacterium Thermosynechococcus elongatus. Addition of the water analogue ammonia, that is shown to bind to the Mn4CaO5 cluster by replacing the crystallographic water W1, did not significantly affect the exchange rates of the two substrate waters. Thus, these experiments exclude that W1 is a substrate water molecule. The mechanism of O-O bond formation was studied by characterizing the substrate exchange in the S3YZ● state. For this the half-life time of this transient state into S0 was extended from 1.1 ms to 45 ms by replacing the native cofactors Ca2+ and Cl- by Sr2+ and I-. The data show that both substrate waters exchange significantly slower in the S3YZ● state than in the S3 state. A detailed discussion of this finding lead to the conclusions that (i) the calcium ion in the Mn4CaO5 cluster is not a substrate binding site and (ii) O-O bond formation occurs via the direct coupling between two Mn-bound water-derived oxygens, which were assigned to be the terminal water/hydroxy ligand W2 and the central oxo-bridging O5. The driving force for the O2 producing S4→S0 transition was studied by comparing the effects of N2 and O2 pressures of about 20 bar on the flash-induced O2 production of photosystem II samples containing either the native cofactors Ca2+ and Cl- or the surrogates Sr2+ and Br-. While for the Ca/Cl-PSII samples no product inhibition was observed, a kinetic limitation of O2 production was found for the Sr/Br-PSII samples under O2 pressure. This was tentatively assigned to a significant slowdown of the O2 release in the Sr/Br-PSII samples. In addition, the equilibrium between the S0 state and the early intermediates of the S4 state family was studied under 18O2 atmosphere in photosystem II centers devoid of tyrosine YD. Water-exchange in the transiently formed early S4 states would have led to 16,18O2 release, but none was observed during a three day incubation time. Both experiments thus indicate that the S4→S0 transition has a large driving force. Thus, photosynthesis is not limited by the O2 partial pressure in the atmosphere.

Recent regulation mandates that ships conduct mid ocean ballast water exchange (BWE) prior to discharging foreign ballast in territorial waters of Australia, the U.S. and elsewhere. The enforcement of ballast water exchange legislation is undermined, however, by a lack of sensitive and reliable methods for verifying compliance. One way to assess compliance is to compare the concentrations of chemical tracers in ballast tanks with their known distributions in the open ocean. In this work, dissolved organic matter and trace elements are investigated as potential tracers of mid-ocean ballast water exchange on commercial voyages in the North Pacific and Atlantic Oceans. The optical properties of chromophoric dissolved organic matter (CDOM) are frequently used as tracers of water masses in bays and estuaries. Characterization of the underlying fluorescence spectra in seawater dissolved organic matter was performed using parallel factor analysis, allowing the identification of at least nine independently varying fluorescent components present in varying concentrations in the ocean and in ballast water. Two of the humic components were terrestrial in origin and their signals could be traced in the open ocean (Pacific and Atlantic) at levels of approximately 1.5% of riverine concentrations. One humic terrestrial component was sufficient for predicting the coastal vs. oceanic source of most ballast water samples, suggesting that single and dual channel fluorometers could be optimized for verifying ballast water exchange. Barium, manganese and phosphorus were also investigated as potential tracers. Measurements of Ba and P obtained via engine-cooling pipes on commercial vessels were consistent with previous oceanographic measurements. While Ba behaved conservatively in ballast water, concentrations of phosphorus fluctuated and Mn was removed in ballast tanks over time. Ba and P demonstrated considerable promise as ballast water tracers, exhibiting predictable concentrations in exchanged ballast tanks, given a priori knowledge of the ocean (Atlantic versus Pacific) in which BWE was performed.

Measuring transmembrane water exchange can provide potential biomarkers for tumors and brain disorders. Diffusion Magnetic Resonance Imaging (dMRI) is a well-established tool that can non-invasively measure water exchange across cell membranes. Diffusion Exchange Spectroscopy (DEXSY) is one of the dMRI-based frameworks used to estimate exchange. DEXSY provides a detailed picture of multi-site exchange processes but requires a large quantity of data. Several models based on the DEXSY framework have been proposed to reduce the acquisition time. Filter Exchange Imaging (FEXI) and curvature models are two of them that only require certain samples of the DEXSY dataset. Diffusion-Exchange Weighted (DEW) Imaging model is another data reduction method accounting for restricted diffusion within cells and can use a specific subset of the DEXSY dataset to measure exchange. Furthermore, a more general expression of the DEXSY signal, referred to as the general model, can theoretically analyze the full space or reduced DEXSY datasets and estimate exchange. However, the results of the subsampling schemes and the data reduction models have not been compared to the full space estimation.  Therefore, this thesis aims to experimentally explore the feasibility of estimating exchange using these four models (the general, FEXI, curvature and DEW models) with the data acquired using a low-field benchtop MR scanner, and compare the estimates from the general model with different subsampling schemes and the data reduction models to the full space estimation. For this purpose, a double diffusion encoding (DDE) sequence was modified from an existing sequence on the benchtop MR scanner and a DEXSY experiment was conducted on this MR scanner and a yeast phantom to acquire a full space dataset. The exchange parameters estimated from the full space dataset using the general model were used as "ground truths" to evaluate the estimates from the reduced datasets analyzed using the general, FEXI and curvature models. Moreover, two alternative subsampling schemes named the shifted DEW and new trajectory schemes were proposed and employed to measure exchange. The results indicate that all the methods except the curvature sampling scheme employed with both the general and curvature models provided comparable estimates to the "ground truths". The shifted DEW and new trajectory sampling schemes performed better over others in terms of consistency with the "ground truths" and low variations between voxels, suggesting the theoretical and experimental optimization of these two subsampling schemes can be further studied and developed.

<p>Knowledge of the relationship between <i>in vivo</i> contrast agent concentration and magnetic resonance (MR) signal response is an important requirement in contrast enhanced MR imaging in general and in MR based perfusion imaging in particular. This relationship is a complex function of the properties of the contrast agent as well as the structure of the target tissue. The aim of the present work was to quantify the effects of the iron oxide nanoparticle based intravascular contrast agent, NC100150 Injection, on proton relaxation rates in different tissue systems <i>in vivo</i> in a pig model and <i>ex vivo</i> in phantoms containing whole blood. Methods that enabled accurate relaxation rate measurements in these organs were developed, and validated. From these measurements, trans-compartmental water exchange rates and blood volume could be estimated and the MR signal response could be predicted as a function of contrast agent concentration under relevant imaging conditions. </p><p>Using a 1.5 Tesla clinical MR system, the longitudinal (R₁=1/T₁) proton relaxation rates in blood, renal cortex, paraspinal muscle and myocardium were measured <i>in vivo</i> as a function of plasma concentration (C_p) of NC100150 Injection. The transverse (R₂^* = 1/T₂^*) relaxation rates were measured <i>in vivo</i> in blood, renal cortex and muscle as a function of C_p and <i>ex vivo</i> in blood as a function of C_p and blood oxygenation tension. The proton nuclear MR (NMR) linewidth and lineshape were analysed as a function of C_p and blood oxygen tension <i>ex vivo</i> at 7.05 T. </p><p>In muscle and renal cortex, there was a linear correlation between R₂^* and C_p whereas R₂^* increased as a quadratic function of C_pin blood. The NMR linewidth increased linearly with C_p in fully oxygenated blood whereas in deoxygenated blood the linewidth initially decreased with increasing Cp, reaching a minimum and then increasing again with further increase in C_p. R₁ increased linearly with C_p in blood and from the slope of R₁ vs. C_p the T₁-relaxivity (r₁) of NC100150 Injection in blood at 1.5 T was estimated to be (mean ± SD) 13.9 ± 0.9 s^-1mM^-1. In tissue, the maximum increase in R₁ was limited by the rate of water exchange between the intravascular and interstitial tissue compartments. Using a two-compartment exchange-limited relaxation model, the permeability surface area (PS) product was estimated to be 61.9 ± 2.9 mL/min/g in renal cortex and 10.1 ± 1.5 mL/min/g in muscle and the total myocardial water exchange rate, <i>k</i><i>t</i>, was 13.5 ± 6.4 s^-1. The estimated blood volumes obtained from the same model were 19.1 ± 1.4 mL/100 g, 2.4 ± 1.4 mL/100 g and 11.2 ± 2.1 mL/100 g, respectively in renal cortex, muscle and myocardium.</p><p>Current T₂^* based first-pass MR perfusion methods assume a linear correlation between R₂^* and C_p both in blood and tissue and our results therefore suggest that quantitative perfusion values can not easily be obtained with existing tracer kinetic models. The correlation between MR signal response and C_p is further complicated in the kidney by a significant first-pass increase in R₁ which may lead to an underestimation of C_p. In T₁-based perfusion methods, low concentrations of NC100150 Injection must be used in order to maintain a linear dose-response relationship between R₁ and C_p. The effect of blood oxygenation on the NMR linewidth in the presence of NC100150 Injection enabled accurate estimation of magnetic susceptibility of deoxyhemoglobin and the effect can potentially be used to determine blood oxygenation status.</p><p>In conclusion, NC100150 Injection is well suited as a T₂^* perfusion agent due to the large magnetisation and intravascular biodistribution of this agent. T₁-based perfusion imaging with this agent is limited by water exchange effects and large T₂^* effects at higher contrast agent concentrations. Quantitative perfusion assessment is unlikely to be feasible with any of these approaches due to the non-linear dose response.</p>