Characterizing the Physiological Role of Inward Rectifier Potassium (Kir) Channels in Tick Salivary Gland Function

The tick salivary gland is a critical tissue that enables blood feeding, maintenance of the ionic gradients, and facilitates pathogen transmission. Therefore, the broad objective of this investigation was to leverage pharmacological approaches to investigate the role of potassium ion channels to salivary gland function of Amblyomma americanum in an effort to identify a tractable target site for therapeutic development. Data collected in Chapter 2 clearly illustrated that the A. americanum salivary gland is reliant upon inward rectifier potassium (Kir) channels for fluid secretion, which was similar to previous work performed by our laboratory on Drosophila salivary gland. Therefore, the physiological role of Kir channels was further characterized in fluid secretion, osmoregulation, and feeding capability in live ticks. Further characterization showed that a subtype of Kir channels, termed ATP-gated Kir channels (KATP channels), are critical for proper salivation because the agonists VU0071063 and pinacidil inhibited salivation with an IC50 of 2 µM and 200 µM, respectively. Importantly, the inhibitory effect was negated by pre-treatment with ATP, which is known to inhibit KATP channels and provides support that VU0071063 is indeed reducing salivation through modulation of KATP channels. In Chapter 3, we tested the hypothesis that KATP channels are critical for ion secretion and absorption, thus osmoregulation. KATP channel agonists were found to increase the concentration of Na+, K+, and Cl- ions in the secreted saliva by 10-15 fold when compared to control. These data suggest that KATP channels are likely maintaining, at least in part, the intracellular loop currents that drive ion secretion and/or reabsorption during salivary gland activity. In Chapter 4, we aimed to translate the in vitro data collected in chapters 2 and 3 into a functional study that tested the utility of KATP modulators to alter feeding and survivability to a live tick. Data show that both KATP agonists, pinacidil and VU0071063, increased the rate of detachments during blood feeding, reduced the volume of ingested blood, and lead to mortality. The data collected in this thesis provide significant support for targeting Kir/KATP channels in future therapeutic development campaigns to reduce the burden of tick vectored pathogens

Sampling Strategy and Accuracy Assessment for Digital Terrain Modelling

In this thesis, investigations into some of the problems related to three of the main concerns (i. e. accuracy, cost and efficiency) of digital terrain modelling have been carried out. Special attention has been given to two main issues - the establishment of a family of mathematical models which is comprehensive in theory and reliable in practice, and the development of a procedure for the determination of an optimum sampling interval for a DTM project with a specified accuracy requirement. Concretely, the following discussions or investigations have been carried out:- i). First of all, a discussion of the theoretical background to digital terrain modelling has been conducted and an insight into the complex matter of digital terrain surface modelling has been obtained. ii). Some investigations into the improvement of the quality of DTM source data have been carried out. In this respect, algorithms for gross error detection have been developed and a procedure for random noise filtering implemented. iii). Experimental tests of the accuracy of DTMs derived from various data sources (i. e. aerial photography, space photography and existing contour maps) have been carried out. In the case of the DTMs derived from photogrammetrically measured data, the tests were designed deliberately to investigate the relationship between DTM accuracy and sampling interval, terrain slope and data pattern. In the case of DTMs derived from digital contour data, the tests were designed to investigate the relationship between DTM accuracy and contour interval, terrain slope and the characteristics of the data set. iv). The problems related to the reliability of the DTM accuracy figures obtained from the results of the experimental tests have also been investigated. Some criteria have also been set for the accuracy, number and distribution of check points. v). A family of mathematical models has been developed for the prediction of DTM accuracy. These models have been validated by experimental test data and evaluated from a theoretical standpoint. Some of the existing accuracy models have also been evaluated for comparison purposes. vi). A procedure for the determination of the optimum sampling interval for a DTM project with a specified accuracy requirement has also been proposed. Based on this procedure, a potential sampling strategy has also been investigated

LEGISLATIVE BACKGROUND AND PROCEDURAL ARRANGEMENT OF STRATEGIC ENVIRONMENTAL ASSESSMENT IN CHINA AND GERMANY: TAKING SPATIAL PLANNING AS EXAMPLE

Having witnessed significant advancement from an academic aspect and practical experiences, strategic environmental assessment (SEA) in China is still undergoing a series of challenges. These challenges result from the legislative background or procedural arrangement. Moreover, with the increasing significance of spatial planning in China, the integration of SEA into the Chinese spatial planning system is becoming a hot topic; whereas, the practice of SEA in the Chinese spatial planning system is currently rather weak. Against these backgrounds - urgency of the integration of SEA into the spatial planning system, lack of related experiences and a SEA system with challenges in China, and SEA for the spatial planning with abundant experiences and lessons in Germany-, this research takes the form of a comparative study on SEA in China and Germany, using the example of spatial planning. Its primary concern is to identify legislative and institutional differences and similarities between SEA in the two countries and analyse the reasons causing these differences. Based upon these, feasible recommendations are proposed to address these challenges which the Chinese SEA is facing. A total of four SEA cases from China and Germany were described and analysed, and 22 experts were interviewed in the form of semi-structured interviews. The specific objectives of the research are to: • to obtain an overview of the SEA application in Chinese and German spatial planning systems; • to compare legal requirements, institutional and procedural arrangements for SEA between China and Germany, taking the examples of spatial planning; • to identify similarities and distinctions lying in both systems, and explore the reasons and motivations causing them; and • to propose recommendations and suggestions for the optimization of Chinese and German SEA, in particular in the aspects of legal requirements, institutional arrangements and operational procedures. Comparative outcomes indicate both SEA systems possess some similar general requirements while delivering differences as well. Main similarities are embodied in SEA understandings, the establishment of related national legislation and adoption of some common steps, reflecting the two SEA systems are influenced by international SEA development. However, significant differences exist in many aspects, especially regarding SEA modes, application of some stages owned by the individual country as well as the concrete requirements for the same stages which both nations have. Outcomes of this research show different SEA characteristics in the two countries. From the aspect of legislative background, German SEA legislation holds a dynamic nature and highlights communication and cooperation. This communication and cooperation can take place between the EU and Germany, the German federal government and the Federal States or even between Federal States. Comparably, Chinese SEA legislation has less interaction with other planning laws and is mainly dependent on the frequent formulation of related technical guidelines and rules. From procedural arrangements, Germany aims to develop an integrated, highly transparent, efficient and wide participation SEA process while China values the independence of the SEA approach, cherishes experts’ opinions and advantages of the intervention of environmental authorities. Based upon the comparative outcomes, several recommendations to improve the application of SEA in Chinese spatial planning are provided

Accurate gradient computations at interfaces using finite element methods

New finite element methods are proposed for elliptic interface problems in one and two dimensions. The main motivation is not only to get an accurate solution but also an accurate first order derivative at the interface (from each side). The key in 1D is to use the idea from \cite{wheeler1974galerkin}. For 2D interface problems, the idea is to introduce a small tube near the interface and introduce the gradient as part of unknowns, which is similar to a mixed finite element method, except only at the interface. Thus the computational cost is just slightly higher than the standard finite element method. We present rigorous one dimensional analysis, which show second order convergence order for both of the solution and the gradient in 1D. For two dimensional problems, we present numerical results and observe second order convergence for the solution, and super-convergence for the gradient at the interface