Driven by the ambition for ubiquitous networking, wireless networks had gained substantial technical advances in recent years. Using radio signals in air as data links, wireless networks can get rid of the tangling of wired cables. However, due to the inherent limitations of wireless channels and legacy protocol design, users of wireless networks today still suffer from the problems on low bandwidth and high error rates. The seven-layer Open System Interconnection (OSI) model was originally designed with wired network environments in mind. Following the seven-layer OSI model, each layer is responsible for handling specific tasks without communicating with each other. Due to the relative stability of wired channels, the strictly-layered approach works well in wired network environments. However, its adequacy is a controversy in wireless environments, since wireless networks have completely different characteristics from its wired counterparts. In wireless environments, channel conditions are highly time-varying and are affected by many factors. External interference or signal degradation may lead to severe packet loss. Even signal-to-noise ratios are fine, transmissions may still fail due to collisions when contention-based MAC protocols are adopted. Conventional protocols developed with wired network environments in mind cannot appropriately response to the characteristics of wireless channels and may make wrong reactions. For these reasons, a flexible framework to capture the rapid change conditions of wireless channels and respond to them immediately is necessary. In this dissertation, we design a cross-layer framework with the consideration of wireless network characteristics. By the coordination between the involved layers, the cross-layer framework can adapt to wireless channel conditions and significantly improve QoS in wireless networks. In order to reduce collision probabilities in wireless networks, we propose a novel protocol named Wait-and-Transmit, which effectively alleviates contentions in wireless networks. By reducing collision probabilities of wireless networks, transmission delays can be shortened and throughputs can be significantly improved. Aiming at the transmission paths containing at least one wireless link, a flexible and efficient cross-layer transmission scheme is also present in this dissertation, which separates the rapid change conditions such as collision probabilities from the relatively stable conditions and well responds to these changes. The proposed approaches significantly improve the performance of wireless networks. We believe that these approaches can contribute to the development of wireless networking.

Abstract Fluorescent molecules used as detection probes and sensors provide vital information about the chemical events in living cells. Despite the large variety of available fluorescent dyes, new improved fluorogenic systems are of continued interest. The Diaryl-substituted Maleimides (DMs) exhibit excellent photophysical properties but have remained unexplored in bioscience applications. Herein we present the identification and full spectroscopic characterization of 3,4-bis(2,4-difluorophenyl)-maleimide and its first reported use as a donor component in Forster resonance energy transfer (FRET) systems. The FRET technique is often used to visualize proteins and to investigate protein-protein interactions in vitro as well as in vivo. The analysis of the photophysical properties of 3,4-bis(2,4-difluorophenyl)-maleimide revealed a large Stokes shift of 140 nm in MeOH, a very good fluorescence quantum yield in DCM (Ffl 0.61), and a high extinction coefficient ε(340) 48,400 M-1cm-1, thus ranking this molecule as superior over other reported moieties from this class. In addition, 3,4-bis(2,4-difluorophenyl)-maleimide was utilized as a donor component in two FRET systems wherein different molecules were chosen as suitable acceptor components - a fluorescent quencher (DABCYL) and another compatible fluorophore, tetraphenylporphyrin (TPP). It has been demonstrated that by designing a FRET peptide which contains the DM donor moiety and the acceptor (quencher) motif, a depopulation of the donor excited state occurred via intermolecular FRET mechanism, provided that the pairs were in close proximity. The Forster-Radius (R0) calculated for this FRET system was 36 % and a Forster-Radius (R0) of 26 % was determined for the second FRET system which contained TPP as an acceptor. The excellent photophysical properties of this fluorophore reveal a great potential for further bioscience applications. The 3,4-bis(2,4-difluorophenyl)-maleimide fluorescent moiety was also implemented in an alternative application targeting the enzyme carbonic anhydrase (CAs) are metalloenzymes that regulate essential physiologic and physio-pathological processes in different tissues and cells, and modulation of their activities is an efficient path to treating a wide range of human diseases. Developing more selective CA fluorescent probes as imaging tools is of significant importance for the diagnosis and treatment of cancer related disorders. The kinetic TGS approach is an efficient and reliable lead discovery strategy in which the biological target of interest is directly involved in the selection and assembly of the fragments together to generate its own inhibitors. Herein, we investigated whether the in situ click chemistry approach can be implemented in the design of novel CA inhibitors from a library of non-sulfonamide containing scaffolds, which has not been reported in the literature. In addition, we exploit the incorporation of the (recently reported by us) fluorescent moiety 3,4-bis(2,4-difluorophenyl)-maleimide) as a potential biomarker with affinity to CA, as well as two coumaine derivatives representing a newly discovered class of inhibitors. The screening of a set of library with eight structurally diverse azides AZ1-AZ8 and fifteen functionalized alkynes AK1-AK12 led to the identification of 8 hit combinations among which the most prominent ones were those containing the coumarine and fluorescent maleimide scaffolds. The syn- and anti-tirazole hit combinations, AK1AZ2, AK1AZ3, AK4AZ2, and AK4AZ3 were synthesized, and in a regioisomer-assignment co-injection test it was determined that the enzyme favored the formation of the anti-triazoles for all identified combinations. The mechanism of inhibition of these triazoles was validated by incubating the alkyne/azide scaffolds in the presence of Apo-CA (non-Zn containing) enzyme. It was demonstrated that the Zn-bound water/hydroxide was needed in order to hydrolyze the coumarins which generated the actual inhibitor, the corresponding hydroxycinnamic acid. The time dependent nature of the inhibition activity typical for all coumarine-based inhibitors was also observed for the triazole compounds whose inhibition constants (Ki) were determined in two independent experiments with pre-incubation times of 3 and 25 minutes, respectively. It was observed that the lower Ki values were determined, the longer the pre-incubations lasted. Thus, a novel type of coumarin-containing triazoles were presented as in situ generated hits which have the potential to be used as fluorescent bio-markers or other drug discovery applications. The proteins from the Bcl-2 family proteins play a central role in the regualtion of normal cellular homeostasis and have been validated as a target for the development of anticancer agents. Herein, in a proof-of-concept study based on a previous kinetic TGS study targeting Bcl-XL, it was demonstrated that a multi-fragment kinetic TGS approach coupled with TQMS technology was successfully implemented in the identification of known protein-protein modulators. Optimized screening conditions utilizing a triple quadruple mass spectrometer in the Multiple Reaction Monitoring (MRM) mode was demonstrated to be very efficient in kinetic TGS hit identification increasing both the throughput and sensitivity of this approach. The multi-fragment incubation approach was studied in detail and it was concluded that 200 fragment combinations in one well is an optimal and practical number permitting good acylsulfonamide detectability. Subsequently, a structurally diverse liberty of forty five thio acids and thirty eight sulfonyl azides was screened in parallel against Mcl-1 and Bcl-XL, and several potential hit combinations were identified. A control testing was carried out by substituting Bcl-XL with a mutant R139ABcl-XL, used to confirm that the potential kinetic TGS hit combinations were actually forming at the protein's hot spot and not elsewhere on the protein surface. Although, the synthesis of all these kinetic TGS hit compounds is currently ongoing, preliminary testing of several acylsulfonamides indicate that they disrupt the Bcl-XL/Bim or Mcl-1/Bim interaction.

The study of tropical forest fragmentation addresses the difficult issues of diminishing forest area and concurrent biodiversity losses. In recent years much of the deforestation of the tropics has been challenged with policy changes and conservation efforts. The Firestone Center for Restoration Ecology, located in Costa Rica, is an area of relatively conserved and restored forest fragments that has proven resilient. This study focuses on a Geographic Information Systems (GIS) analysis, used to assess the level of forest fragmentation in the area. Fragmentation is the process by which continuous forest is diminished into smaller, geographically isolated portions of forest. It was determined that the area is relatively unfragmented, as compared to it’s status in 1972. Though anthropogenic stresses continue, fragmentation of primary forest is limited and the majority of forested area is in large, semi-continuous blocks made up of a mixture of primary and secondary forest, which likely allows for a preservation of biodiversity in the region. Further on-site studies are necessary to fully evaluate the level of anthropogenic stress on the region. However, compared to many tropical areas, Costa Rica is conserving forest and ecological diversity.

This thesis investigates logical formalizations of Castelfranchi and Falcone's (C&F) theory of trust [9, 10, 11, 12]. The C&F theory of trust defines trust as an essentially mental notion, making the theory particularly well suited for formalizations in multi-modal logics of beliefs, goals, intentions, actions, and time. Three different multi-modal logical formalisms intended for multi-agent systems are compared and evaluated along two lines of inquiry. First, I propose formal definitions of key concepts of the C&F theory of trust and prove some important properties of these definitions. The proven properties are then compared to the informal characterisation of the C&F theory. Second, the logics are used to formalize a case study involving an Internet forum, and their performances in the case study constitute grounds for a comparison. The comparison indicates that an accurate modelling of time, and the interaction of time and goals in particular, is integral for formal reasoning about trust. Finally, I propose a Horn fragment of the logic of Herzig, Lorini, Hubner, and Vercouter [25]. The Horn fragment is shown to be too restrictive to accurately express the considered case study.

The present study investigated age differences in implicit memory for positive, negative and neutral words. We also explored how cognitive control and time of testing influence emotional memory. Participants completed a one-back picture comparison task with superimposed distracting emotional and neutral words. Memory for distracting words was tested using an implicit memory test and cognitive control by a flanker task. Priming was significant for negative but not for positive and neutral words. Memory for distracting negative words was greater at non-optimal times of day for young adults but similar across the day for older adults. A high level of cognitive control was related to greater priming for negative words in young adults and lower priming in older adults. Priming for neutral words was enhanced in high cognitive control participants when stimuli contained emotional words that were relevant to one’s goals, implicating the use of emotion regulation at an unconscious level.

The present study investigated age differences in implicit memory for positive, negative and neutral words. We also explored how cognitive control and time of testing influence emotional memory. Participants completed a one-back picture comparison task with superimposed distracting emotional and neutral words. Memory for distracting words was tested using an implicit memory test and cognitive control by a flanker task. Priming was significant for negative but not for positive and neutral words. Memory for distracting negative words was greater at non-optimal times of day for young adults but similar across the day for older adults. A high level of cognitive control was related to greater priming for negative words in young adults and lower priming in older adults. Priming for neutral words was enhanced in high cognitive control participants when stimuli contained emotional words that were relevant to one’s goals, implicating the use of emotion regulation at an unconscious level.

With the ever-increasing demands of the nuclear power community to extend fuel cycles and overall core-lifetimes in a safe and economic manner, it is becoming more necessary to extend the working knowledge of nuclear fuel performance. From the atomistic to the macroscopic level, great morphological changes occur within the fuel over its lifetime. The main initial damaging events produced by fuel recoils from fast neutrons and fission fragment spiking leads to the onset of grain growths and fuel restructuring. Therefore, it is desirable to have a more detailed understanding of the initial events leading to fuel morphology changes at the atomistic level. However, this is difficult to achieve with the fission fragments due to the wide variability of their species (charge, mass, and energy) and the large averaging of their relative yields in the nuclear data files. This work is our first iteration at developing a general methodology to characterize a procedure, based on Monte Carlo principles, for generating individual fission event result channels and analyzing their specific response in the fuel. We utilized the nuclear reaction simulation tool, TALYS, to generate energy-dependent fission fragment yield distributions for different fissile/fissionable isotopes. These distributions can then be used in conjunction with fuel isotopics and a neutron energy spectrum to generate a fission-reaction-rate-averaged distribution of the fission fragment yields. We then used Monte Carlo sampling to generate the result channels from individual fission events, using the Q-value of the prompt fission system to either accept or reject. The simulation tool: Transport of Ions in Matter (TRIM) was used to characterize the general response of the fission fragment species within Uranium Dioxide (UO2), including the range, energy loss, displacements, recoils, etc. These responses were then correlated which allowed for the quick calculation of the response of the individual fission fragment species generated from the Monte Carlo sampling. As an example of this strategy, we calculated the response on a PWR fuel pin where MCNP was used to generate a high-fidelity neutron energy spectrum.

Abstract The enzyme phenylethanolamine N-methyltransferase (PNMT) catalyses the biosynthesis of adrenaline. Although adrenaline is a significant central nervous system (CNS) neurotransmitter, and has been associated with various physiological processes such as the control of blood pressure and the neurodegeneration observed in Alzheimer’s disease, its exact role in the CNS is unclear. As part of an international collaborative effort, this project aimed to develop PNMT inhibitors suitable for probing the role of CNS adrenaline, and to generate novel drug leads. Towards the goal of developing potent and selective PNMT inhibitors, this thesis utilised three general approaches. The first approach involved classical structure-guided drug discovery using X-ray crystallography, and is described in Chapter 2. Characterisation of the PNMT pharmacophore provided results that led to a new understanding of how PNMT recognises inhibitors. Structures described in this thesis revealed a cryptic binding pocket that is only revealed on binding of inhibitors that were predicted to be too large to interact with PNMT. The findings therefore demonstrated an extraordinary degree of flexibility inherent to the PNMT binding pocket, and emphasise the need to include greater protein flexibility in inhibitor design strategies. Secondly, this thesis investigated the catalytic mechanism of PNMT, described in Chapters 3 and 4. This research characterised the binding of substrates to wild type and variant PNMT, including the physiological substrate noradrenaline, and model substrates as well as substrate-analogue inhibitors of the enzyme. PNMT catalyses the methylation of a range of substrates. However, differential substitutions to these substrates can dictate the ligand binding position and thereby determine whether methyl transfer will occur. Additionally, the results provided new lessons for the routine use of point mutations in the study of enzymes, because changes are not always simply an indication of the difference in the residue functionality. I found, for example, that single site mutations can induce large movements in enzyme. Therefore structural characterisation of enzyme variants is an important addition to kinetic studies to enable a comprehensive examination of catalytic function. Finally, I have implemented a fragment based screening (FBS) approach to the discovery of novel lead compounds that inhibit PNMT, described in Chapters 5 and 6. The FBS approach has many advantages over existing drug discovery methods including higher hit rates, higher efficiency hits, and the ability to sample a larger range of chemical space. This thesis describes the application of FBS by X-ray crystallography to PNMT. The approach was used to screen a library of 384 compounds yielding 12 novel PNMT fragment leads. Furthermore, chemical elaboration and kinetic evaluation of these hits was performed in Chapter 7. In summary, this thesis has made a significant contribution to our understanding of the chemistry, kinetics and structure of PNMT. This understanding will be important in ongoing efforts to develop potent, selective, and CNS-active inhibitors of the enzyme.

The thesis Mapping the Self-Portrait: Navigating Identity and Autobiography in Visual Art is a practical project. It explores the relationship between autobiography and self- portraiture, and how these notions of the self can be represented in visual art. The exhibition 360 Potential Truisms forms the major component in this thesis, and is accompanied by a written exegesis. This exegesis explores notions of the self-portrait and autobiography in relation to identity, with focus on a post-structural approach to fragmentation and movement. Artworks have been developed to reflect a shift towards an idea of the fragmented self, involving drawing, photography, and text to allow a constantly changing interpretation of self-portraiture.

PhD / The aims of this study were to test the efficacy of immunoglobulin and its Fab and Fc fragment in the treatment of experimental autoimmune neuritis (EAN) in Lewis rats, to investigate which portion of immunoglobulin is operative in the effect of IVIg, and to clarify the possible mechanisms by which immunoglobulin exerts its action in the treatment of rats EAN. EAN was induced by immunization with whole bovine peripheral nerve myelin. The immunized rats were randomized into groups, assessed clinically, electrophysiologically, and histologically, and intravenously injected with normal saline, albumin, human IVIg preparation, purified Fab or Fc fragments. The treatment efficacy was compared between normal saline and albumin groups, albumin and IVIg groups, albumin and Fab groups, albumin and Fc groups, Fab and Fc groups, Fab and IVIg groups, and Fc and IVIg groups. Methods of myelin isolation, antibody purification, and Western blot techniques were also applied. The results revealed that treatment with Fc fragment and IVIg at the onset of signs of disease effectively prevented further progression of disease, shortened disease duration, and facilitating recovery from illness as shown in clinical, electrophysiological and histological parameters. In the study which the efficacy of albumin and IVIg was compared, 5 out of 17 rats (29%) in the albumin group and 12 out of 17 (71%) in the IVIg group completely recovered from the clinical disease by day 30. The animals receiving IVIg treatment exhibited lower clinical scores, less prolongation of S wave latencies, better maintained S wave amplitudes, less reduction of distal motor NCVs, better maintained distal and proximal CMAP amplitudes, and lower histological grades. In the study which the efficacy of albumin, Fab fragment, Fc fragment, and IVIg was compared, 0 out of 8 (0%) in the albumin group, 1 out of 8 (13%) in the Fab group, 4 out of 8 (50%) in the Fc group, and 6 out of 9 (67%) rats in the IgG group completely recovered from the clinical disease by day 30. The animals receiving Fc fragment and IVIg treatment exhibited lower clinical scores, less prominent weight loss, less prolongation of S wave latencies, better maintained S wave amplitudes, less reduction of distal motor NCVs, better maintained distal and proximal CMAP amplitudes, and lower histological grades.