Steel components within fusion reactors will be subject to high transmutation rates due to high energy neutrons. In iron based alloys such as steels, high amounts of helium accumulate through transmutation. This leads to helium embrittlement through helium accumulating on the grain boundaries of metal. Worst case scenario predictions were made for DEMO, estimating that for a grain size of 5 micro-meters, embrittlement could happen within 2 years of the blanket region of DEMO. This thesis elaborates on previous worst case scenario calculations by including inter-granular tapping mechanisms, within rate theory simulations. A rate theory code was developed for the purpose of this work, tailored towards a fusion environment. Calculations were performed using rate theory that predicted the timescales in which helium embrittlement occurred within a conceptual DEMO design in the first wall region and the blanket region. The calculations used several parameter sets, where preliminary simulations were performed using the parameter sets, that were compared with cluster density data determined using Transmission Electron Microscopy (TEM) and Positron Annihilation Spectroscopy (PAS). The simulations showed that the helium embrittlement time was heavily influenced by the chosen dislocation density, parameter set and grain size. The simulations conducted to represent the blanket region, showed an increase as high as 94% from the 2 years that has previously been predicted under certain scenarios. However results also showed that assuming a certain parameter set with a low dislocation density, showed no significant increase in embrittlement time. This was not a concern since it was concluded that advanced steel concepts would be expected to have a small average grain size, that would dramatically increase the embrittlement time. The work in this thesis also focused on defect interaction with dislocations. A model was constructed that made use of elasticity theory and VASP calculations that produced the interaction energy map for various defects with an edge dislocation. The interaction energy map for helium interstitials with an edge dislocation was compared with molecular dynamics (MD) simulations produced for this work. The model and simulations showed good agreement. Temperature effects were then included in the model that allowed the concentration around a dislocation to be temperature dependent. These temperature dependent interaction energy maps were then implemented into the advection-diffusion equation, that were solved numerically to explore the capture efficiencies and bias towards certain defects within iron. These values were then used within the rate theory simulations to produce temperature effects on the dislocation sink strengths for vacancies, SIA and helium interstitials.

In the first part of this dissertation we explore the consequences of high frequency operation of Josephson junction arrays. At high frequencies these systems are no longer well modeled by Kirchhoffs laws, and new dynamical equations are derived directly from Maxwells equations. From these equations we derive a reduced set of averaged equations which greatly simplify the analysis of high frequency arrays. The averaged equations allow us to examine experimental strategies for obtaining higher power outputs from arrays. These strategies rely on resonant architectures that place the junctions near antinodes of a desired standing wave mode of the fluctuating current. Simple, heuristic rules are derived for the proper placement of junctions. The second part of the dissertation is devoted to stochastic resonance. A new theory is proposed to explain both two-state and excitable stochastic resonance. Previous theories explaining the two types of stochastic resonance yield similar results while using different analytic strategies. A constrained asymmetric rate model is derived that in one limit produces the proper result for the two-state system, while in another limit models the excitable system. The result that the constrained asymmetric rate model gives in the excitable limit is off by a factor of two, and this discrepancy is examined. Furthermore, we study the consequences of adding a colored noise source to the classic two-state model of stochastic resonance. We will find that when both white and colored noise sources are present, stochastic resonance will occur as a function of colored noise strength only if the correlation time of the colored noise source is small enough. Two theories are proposed to explain this phenomenon and both are examined in detail.

Topics in source and channel coding for audiovisual communication systems are studied. The goal of source coding is to represent a source with the lowest possible rate to achieve a particular distortion, or with the lowest possible distortion at a given rate. Channel coding adds redundancy to quantized source information to recover channel errors. This thesis consists of four topics. Firstly, based on high-rate theory, we propose Karhunen-Loéve transform (KLT)-based classified vector quantization (VQ) to efficiently utilize optimal VQ advantages over scalar quantization (SQ). Compared with code-excited linear predictive (CELP) speech coding, KLT-based classified VQ provides not only a higher SNR and perceptual quality, but also lower computational complexity. Further improvement is obtained by companding. Secondly, we compare various transmitter-based packet-loss recovery techniques from a rate-distortion viewpoint for real-time audiovisual communication systems over the Internet. We conclude that, in most circumstances, multiple description coding (MDC) is the best packet-loss recovery technique. If channel conditions are informed, channel-optimized MDC yields better performance. Compared with resolution-constrained quantization (RCQ), entropy-constrained quantization (ECQ) produces a smaller number of distortion outliers but is more sensitive to channel errors. We apply a generalized γ-th power distortion measure to design a new RCQ algorithm that has less distortion outliers and is more robust against source mismatch than conventional RCQ methods. Finally, designing quantizers to effectively remove irrelevancy as well as redundancy is considered. Taking into account the just noticeable difference (JND) of human perception, we design a new RCQ method that has improved performance in terms of mean distortion and distortion outliers. Based on high-rate theory, optimal centroid density and its corresponding mean distortion are also accurately predicted. The latter two quantization methods can be combined with practical source coding systems such as KLT-based classified VQ and with joint source-channel coding paradigms such as MDC.

As the demand for high performance small electronic devices has increased, heat removal from these devices for space use is approaching critical limits. A heat pipe is a promising device to enhance the heat removal performance due to the phase change phenomena for space thermal management system. Even though a heat pipe has a big potential to remove the thermal energy from a high heat flux source, the heat removal performance of heat pipes cannot be predicted well since the first principle of evaporation has not been established. The purpose of this study is to establish a method to apply the evaporation model based on the statistical rate theory for engineering application including vapor-liquid-structure intermolecular effect. The evaporation model is applied to the heat pipe performance analysis through a pressure balance and an energy balance in the loop heat pipe.

<p>Topics in source and channel coding for audiovisual communication systems are studied. The goal of source coding is to represent a source with the lowest possible rate to achieve a particular distortion, or with the lowest possible distortion at a given rate. Channel coding adds redundancy to quantized source information to recover channel errors. This thesis consists of four topics.</p><p>Firstly, based on high-rate theory, we propose Karhunen-Loéve transform (KLT)-based classified vector quantization (VQ) to efficiently utilize optimal VQ advantages over scalar quantization (SQ). Compared with code-excited linear predictive (CELP) speech coding, KLT-based classified VQ provides not only a higher SNR and perceptual quality, but also lower computational complexity. Further improvement is obtained by companding.</p><p>Secondly, we compare various transmitter-based packet-loss recovery techniques from a rate-distortion viewpoint for real-time audiovisual communication systems over the Internet. We conclude that, in most circumstances, multiple description coding (MDC) is the best packet-loss recovery technique. If channel conditions are informed, channel-optimized MDC yields better performance.</p><p>Compared with resolution-constrained quantization (RCQ), entropy-constrained quantization (ECQ) produces a smaller number of distortion outliers but is more sensitive to channel errors. We apply a generalized γ-th power distortion measure to design a new RCQ algorithm that has less distortion outliers and is more robust against source mismatch than conventional RCQ methods.</p><p>Finally, designing quantizers to effectively remove irrelevancy as well as redundancy is considered. Taking into account the just noticeable difference (JND) of human perception, we design a new RCQ method that has improved performance in terms of mean distortion and distortion outliers. Based on high-rate theory, optimal centroid density and its corresponding mean distortion are also accurately predicted.</p><p>The latter two quantization methods can be combined with practical source coding systems such as KLT-based classified VQ and with joint source-channel coding paradigms such as MDC.</p>

Cyclophilin A (CypA) is the well-studied member of a group of ubiquitous and evolutionarily conserved families of enzymes called peptidyl–prolyl isomerases (PPIases). These enzymes catalyze the cis-trans isomerization of peptidyl-prolyl bond in many proteins. The distinctive functional path triggered by each isomeric state of peptidyl-prolyl bond renders PPIase-catalyzed isomerization a molecular switching mechanism to be used on physiological demand. PPIase activity has been implicated in protein folding, signal transduction, and ion channel gating as well as pathological condition such as cancer, Alzheimer’s, and microbial infections. The more than five order of magnitude speed-up in the rate of peptidyl–prolyl cis–trans isomerization by CypA has been the target of intense research. Normal and accelerated molecular dynamic simulations were carried out to understand the catalytic mechanism of CypA in atomistic details. The results reaffirm transition state stabilization as the main factor in the astonishing enhancement in isomerization rate by enzyme. The ensuing intramolecular polarization, as a result of the loss of pseudo double bond character of the peptide bond at the transition state, was shown to contribute only about −1.0 kcal/mol to stabilizing the transition state. This relatively small contribution demonstrates that routinely used fixed charge classical force fields can reasonably describe these types of biological systems. The computational studies also revealed that the undemanding exchange of the free substrate between β- and α-helical regions is lost in the active site of the enzyme, where it is mainly in the β-region. The resultant relative change in conformational entropy favorably contributes to the free energy of stabilizing the transition state by CypA. The isomerization kinetics is strongly coupled to the enzyme motions while the chemical step and enzyme–substrate dynamics are in turn buckled to solvent fluctuations. The chemical step in the active site of the enzyme is therefore not separated from the fluctuations in the solvent. Of special interest is the nature of catalysis in a more realistic crowded environment, for example, the cell. Enzyme motions in such complicated medium are subjected to different viscosities and hydrodynamic properties, which could have implications for allosteric regulation and function.

No description available.

G-quadruplex forming human telomere sequence (HTS) DNA, has been widely studied due to the telomere's implied role in biological processes, including cellular ageing and cancer physiology. The goal of these previous efforts has been to characterize the physiologically relevant structures and their stability and dynamics in order to develop therapeutic applications. Unfortunately, understanding the biologically relevant form of the human telomere DNA is complicated by the fact that HTS-derived sequences are highly polymorphic. To further complicate the issue, recent investigations have demonstrated the ability of "cell-like" co-solvents to alter the preferred G-quadruplex fold of HTS DNA. However, the origins of G-quadruplex structure selection, the relative contributions of crowding versus dehydration, and the possible effects of co-solvents on kinetically determined folding pathways remain unresolved. Towards answering these questions, I investigated HTS DNA G-quadruplex in extreme anhydrous and high viscosity conditions utilizing a deep eutectic solvent (DES) consisting of choline chloride and urea. Herein I report that the water-free DES supports an extremely stable parallel stranded structure, consistent with observations that diminished water activity is the main cause of structural transitions to the "parallel-propeller" form. Furthermore, my research shows that the highly viscous nature of the solvent enables significant diffusion based control over HTS g-quadruplex folding rates and topology, fully consistent with Kramers rate theory. To the best of my knowledge, this is the first example of the kinetic exploration of G-quadruplex folding utilizing high friction solvent; the results of which display a decreased intramolecular folding rate of HTS DNA to a never before encountered time scale on the order of days at physiological temperature. Moreover, I have demonstrated that the folding pathway of a G-quadruplex can be altered with increased solvent friction. These discoveries are important because they highlight the need to consider the viscosity when exploring the dynamics of human telomeres specifically drug binding and folding of G-quadruplexes in vivo where cellular viscosity has been reported to be as high as 140cP. Lastly, it appears that tuning solvent viscosity could prove useful to the continued study of G-quadruplex dynamics.

No description available.

This research explores the links between the structure and dissociation energetics of ionized non-covalent complexes. In chapter 3, a large series of similar non-covalent complexes were probed using electrospray tandem mass spectrometry (ESI-MS/MS) and RRKM modelling in order to identify any trends in the dissociation energetics based on charge state, overall size of the complex, or size of the substrate. Ion mobility spectrometry (IMS) in conjunction with molecular mechanics/molecular dynamics (MM/MD) was used to study the conformations of these non-covalent complexes in order to determine if the same trends identified in the energetics could be corroborated independently based on structure. The system of study consisted of varying lengths of the synthetic polymer, polymethylmethacrylate (PMMA) complexed with singly or doubly protonated diaminoalkanes (DAA) of varying length. The critical energies of dissociation (E0) increased as the length of the polymer increased and was not significantly affected by the length of the singly protonated DAA substrates. The E0 of dissociation of doubly protonated complexes was strongly influenced by the length of the DAA; longer DAA substrates had greater separation of charge which decreased coulombic repulsion within the complex resulting in higher E0 values. MM/MD low energy structures of all complexes were validated with experimental IMS measurements and showed that the arrangement between the polymer and DAA were similar for different singly protonated DAAs. When doubly protonated, the length of DAA was the most important factor in determining the overall structure of the complex. In chapter 4, a direct link is shown between the observed E0 dissociation energies and the molecular conformations for eight different peptide–saccharide complexes containing either a tri-saccharide (d-(+)-raffinose and d-panose) or tetra-saccharide (stachyose and maltotetraose) with a small peptide (FLEEL and FLEEV). The E0 values were highly related to the overall conformation adopted by the non-covalent complex in the gas phase. Complexes containing peptide FLEE(L/V) with the tri-saccharide raffinose or panose had similar E0 of dissociation (∼0.64 eV) and similar conformations based on MM/MD simulations and IMS drift times. Conversely, for complexes containing a FLEE(L/V) peptide with one of the isomeric tetra-saccharides; stachyose had a E0 ∼0.08 eV greater than maltotetraose. This difference of intermolecular interaction was also reflected by the IMS drift times; maltotetraose in complex with FLEEV or FLEEL had a 5.9% and 2.3% faster IMS drift time than stachyose respectively. This indicated that the molecular arrangement between maltotetraose and the peptides was more compact than the stachyose-peptide complexes. In chapter 5, RRKM modelling of breakdown diagrams is not possible when the reactant ion signal is overlapped by other isobaric species. Trimeric, non-covalent complexes that contained two PMMA molecules and a doubly protonated DAA, [(PMMAa)(DAA+2H)(PMMAb)]+2, have m/z signals that contain multiple different complexes having the same total number of polymer repeat units but differ in the length of the each polymer. In this situation, the applicability of using the simple kinetic method to gain insight into relative binding energies was explored. The major factors which determined the suitability of the kinetic method for this system were identified as the structural arrangement of the reactant ion complex, possible reverse activation barriers, and the evaluations of Δ(ΔS‡). MM/MD simulations coupled with IMS suggests that within the reactant ion, the DAA is almost equally shared between two PMMA oligomers and that the two PMMA oligomers interact predominately with the DAA, and not with each other. MS/MS of the trimeric reactant complexes proceeds by neutral loss of one polymer and is suggested to proceed with little or no reverse activation barrier based on the low coulombic repulsion factors. The IMS drift times of [(PMMAa)(DAA+2H)]+2 complexes that were generated directly by ESI-MS or by dissociation of a trimeric, [(PMMAa)(DAA+2H)(PMMAb)]+2 complex were found to be identical. This provides some evidence that Δ(ΔS‡) ≈ Δ(ΔS) and using a statistical mechanics approach, Δ(ΔS) ≈ 0. The effective temperature (Teff) variable in the kinetic method expression was found to decrease as a function of the size of the trimeric complex, suggesting that the population distribution of the dissociating ensemble of complexes narrows as size increases. Overall, when RRKM fitting is not possible, the simple kinetic method could provide relative energetic ranking of competing dissociations reactions however the Teff term contributed to the greatest uncertainty in obtaining absolute quantities. Fitting MS/MS breakdown diagrams of non-covalent complexes with multiple dissociation channels is difficult due to the number of total fitting variables. Building from the simple kinetic method, chapter 6 shows that the relationship between the natural logarithm of competing fragment ions and reciprocal collision energy yields a branching relationship that allows for the sign of Δ(ΔS‡) and Δ(E0) between the channels to be obtained. Furthermore, the relationships between the fitting variables of RRKM modelling are empirically related to the theoretical branching relationship characteristics. This allowed for the fitting variables of all dissociation channels to be expressed as a function of a single channel so that the theoretical branching relationship matches the experimental branching relationship. Using this method, RRKM fitting of a MS/MS breakdown diagram for APCI ionized anthracene determined the E0 and ∆S‡ was 4.69 ± 0.29 eV and -3 ± 17 J K-1; 4.21 ±0.29 eV and -19 ±15 J K-1; and 4.81 ± 0.29 eV and 36 ±22 J K-1 for hydrogen loss, acetylene loss and diacetylene loss respectively. With one exception, these values are within experimental error of the iPEPICO derived energetic values. In chapter 7, MS/MS of ammoniated triacylglycerides at multiple collision energies and computational analysis are used to explain the cause of uneven dissociation rates of the FAs from different positions on the glycerol backbone. The loss of sn-1 and sn-3 FAs are found to have lower activation energies than the loss of the sn-2 position FA, however the loss of the FA from the sn-2 position is more entropically favourable. Theoretical MS/MS breakdown curves were fit to experimental values using RRKM theory to estimate the E0 of dissociation of FAs from the three glycerol positions. The E0 values for cleavage from the sn-1 and sn-3 positions were found to be approximately 1.52 eV, while that for the sn-2 position was highly dependent on the identity of the FA at that position. Computational structures and energy analysis suggest that an important step in the dissociation of [TAG+NH4]+ is the loss of ammonia. In a model system, glyceryl tributyrate, the loss of NH3 produced two distinct [TAG+H]+ product structures sitting 148 kJ and 160 kJ in energy above the ammoniated structure. The [TAG+H]+ structure that leads to the loss of the sn-1(3) is 12 kJ lower than the [TAG+H]+ structure that leads to the loss of the sn-2 FA. From this, the loss of a neutral FA that follows sits only an additional 35–48 kJ above the [TAG+H]+ structures. In Chapter 8, singly deprotonated β-cyclodextrin monomers, [(β-CD-H+]-1, and doubly deprotonated dimers, [(β-CD)2-2H+]-2, are both present following ESI-MS and have the same monoisotopic m/z. Similar to chapter 5, this makes it difficult to generate an MS/MS breakdown diagrams that can be modelled with RRKM theory. IMS was used to mobility separate [(β-CD-H+]-1 and [(β-CD)2-2H+]-2 and was followed by MS/MS of the [(β-CycD)2-2H+]-2 ion. A second problem when generating a MS/MS breakdown diagram of non-covalent complexes that contain identical components is that the fragment ions could have an identical monoisotopic m/z as the reactant ion. MS/MS of [(β-CycD)2-2H+]-2 results in two [(β-CD-H+]-1 fragments. To overcome this, breakdown diagrams were then generated by monitoring the changes in the isotopic profile. The RRKM derived E0 for dissociation of [(β-CycD)2-H+]-1 and [(β-CycD)2-2H+]-2 were 1.85 ± 0.11eV and 1.79 ± 0.09eV, respectively, corresponding to a slight decrease in complex stability due to increased charge-charge repulsion in the dianion.