We present an investigation into the design of an evolutionary mechanism for multiagent protocol constraint optimisation. Starting with a review of common population based mechanisms we discuss the properties of the mechanisms used by these search methods. We derive a novel algorithm for optimisation of vectors of real numbers and empirically validate the efficacy of the design by comparing against well known results from the literature. We discuss the application of an optimiser to a novel problem and remark upon the relevance of the no free lunch theorem. We show the relative performance of the optimiser is strong and publish details of a new best result for the Keane optimisation problem. We apply the final algorithm to the multi-agent protocol optimisation problem and show the design process was successful.

Recently, Gualtiero Piccinini and Carl Craver (2011) have argued that functional analyses in psychology lack explanatory autonomy from explanations in neuroscience. In this thesis I argue against this claim by motivating and defending a pragmatic-epistemic conception of autonomous psychological explanation. I argue that this conception of autonomy need not require that functional analyses be distinct in kind from neural-mechanistic explanations. I use the framework of Bas van Fraassen’s Pragmatic Theory of Explanation (van Fraassen 1980) to show that explanations in psychology and neuroscience can be seen as seeking understanding of autonomous levels of mechanistic phenomena.

This study was concerned with the relationships between the concepts of dogmatism, anxiety, and self-ideal discrepancy. In order to measure these relationships, Rokeach's Dogmatism Scale, Cattell's IPAT Self Analysis Form, and Bill's Index of Adjustment and Values were utilized, Sex differences, as measured on the Dogmatism Scale, were also investigated.

N-linked glycosylation is the most common form of post-translational modification in nature and is essential to almost all enveloped viruses, including members of the Flaviviridae family. The host cell N-linked glycoprotein processing pathway is utilised by these viruses and as such has long been identified as a potential target for the development of antiviral drugs. Here, the antiviral mechanisms of three classes of small molecules targeting the secretory pathway and altering viral envelope glycosylation are investigated, using the HCV surrogate model, BVDV. The antiviral activity of imino sugars, principally through α-glucosidase inhibition, is well-characterised and here, a group of novel adamantyl coupled imino sugars are investigated and demonstrated to inhibit ER α glucosidases, which correlates with their antiviral activity against BVDV. Additionally, BVDV is used to study the antiviral mechanism of action of nitazoxanide. Nitazoxanide, the parent compound of the thiazolide class of structures, is a broadly antimicrobial compound with antiviral activity against HBV, HCV, influenza, JEV and others. Here, nitazoxanide is shown to be antiviral against BVDV by inducing Ca²⁺ release from ATP-sensitive intracellular calcium stores, disrupting ER-Golgi trafficking and inhibiting complex glycan formation. Finally, the potential of Golgi endo-α-mannosidase as an antiviral target is explored, using the endomannosidase inhibitor glucose-isofagomine in conjunction with the imino sugar α-glucosidase inhibitor NAP-DNJ. Endomannosidase is shown to be a valid antiviral target for BVDV, both alone and in combination with α-glucosidase inhibition, and is utilised by viral glycoproteins to acquire complex glycan structure, even in the absence of α-glucosidase inhibition. Altogether, this work furthers our understanding of the varied antiviral mechanisms of small molecules targeting the secretory pathway, enhancing the search for novel antiviral drugs directed against host cell machinery.

No description available.

<p>Catalysis has a responsibility to provide solutions to the growing grand challenge of sustainability in the fuels and chemical industry to help combat climate change. These changes; however, cannot be realized without a more fundamental understanding of the active sites that catalyze chemical reactions, and how they can be tuned to control rates and selectivities. Four specific examples of active site modification will be considered in this work: the speciation of isolated metals in zeolite frameworks, solvent thermodynamics and structure at defects in zeolite frameworks, the electronic modification of platinum through alloying in well-defined intermetallic nanoparticles, and the mobility and shape of gold nanoparticles in zeolite channels. Each will highlight how quantum chemistry calculations can provide a fundamental understanding of how these active site modifications influence the kinetics of chemical reactions, and how they can be controlled to pursue solutions to the reduction of carbon through sustainable utilization of shale gas as well as renewable chemicals production through biomass upgrading.</p> <p>Zeolites exchanged with metal heteroatoms can behave as solid Lewis or Br<a>ø</a>nsted acids depending on heteroatom identity. Lewis acid heteroatoms can adsorb water and hydrolyze to speciate into “open sites” which have been shown to differ in their ability to catalyze reactions such as glucose isomerization as compared to “closed sites” which are fully coordinated to the zeolite framework. The structure and catalytic properties of these sites are interrogated by a gas phase reaction, ethanol dehydration, in Sn-Beta by a combined Density Functional Theory (DFT) and experimental study. DFT is used to map the possible reaction mechanisms for ethanol dehydration, including the speciation of Sn sites into hydrolyzed configurations from water or ethanol. A microkinetic model for ethanol dehydration including unselective and inhibitory intermediates is constructed. This microkinetic model predicts the population of reactants and products on the catalyst surface as well as the sensitivity of individual elementary steps to the total rates. Powerful anharmonic entropy methods using <i>ab-initio </i>molecular dynamics (AIMD) is used to capture the entropy of confined reactive intermediates, which is shown to be necessary to compare with experiment. Results on closed and hydrolyzed open zeolite sites can then be compared with ethanol dehydration on “defect open” sites which were shown experimentally to occur at material stacking faults. A grain boundary model is constructed of zeolite Beta, where unique sites have similar ligand identity as hydrolyzed open sites. These defect open sites are found to not contribute to the observed reaction rate as they cannot stabilize the same transition state structures that were observed in internal Beta sites. </p> <p>Intuition about the ethanol dehydration reaction in Sn-Beta was then used to map a more expansive and diverse chemical network, the synthesis of butadiene from acetaldehyde and ethanol. For elementary reactions in this mechanism, which included aldol condensation, MPV reduction, and crotyl alcohol dehydration in addition to ethanol dehydration, the hydrolyzed open sites were found to be crucial reactive intermediates. Hydrolyzed sites were necessary to stabilize favorable transition states, which requires reconstruction of the local framework environment. Methods to preferentially stabilize hydrolyzed sites were then explored, using a screening algorithm developed to consider all possible sites in each zeolite framework. It was found that the stability of these hydrolyzed sites could be correlated to the local strain exerted by the surrounding silica matrix. This provides a new descriptor that stabilizes intermediates relevant to the synthesis of butadiene and ethanol dehydration.</p> <p>Next, the structure and thermodynamic stability of water networks around Sn-Beta defects and heteroatom active sites was considered using AIMD. As many biomass reactions occur in the presence of water, the interactions of water with hydrophobic and hydrophilic functionalized defects dictate how the stability of reactive intermediates and transition states is affected by a solvating environment. Locally stable and strongly nucleated clusters of water were observed to form at Sn defects, with less densely packed water structures stable at hydrophilic defects. This is in comparison to defect-free siliceous Beta, where significantly less water uptake is observed. These local clusters are in equilibrium with the less dense liquid-like phase that extends between defects. These results motivate localized cluster models around active sites in Lewis acids, as well as advance the fundamental understanding of hydrophobic/hydrophilic interactions in microporous materials. The local cluster models are then applied to the ethanol dehydration reaction in protonated aluminum Beta zeolites where experimentally observed non-unity coefficient ratios are rationalized by quantifying a different degree of solvation for the ethanol reactant state as opposed to the transition state, validated by a thermodynamic phase diagram.</p> <p>Changes in the electronic energy levels of <i>d</i> electrons upon alloying was studied in conjunction with a new spectroscopic technique being performed at Argonne National Laboratory to develop new descriptors to predict the degree of coking for different alloys. Resonant Inelastic X-ray Scattering (RIXS) simultaneously probes the occupied and unoccupied valence states of platinum in nanoparticles at ambient conditions. The specific excitation process of this spectroscopy is particularly amendable to DFT modeling, which was used to provide richer chemical insight into how changes in observed RIXS signature related to the electronic structure changes of platinum upon alloying. From a suite of multiple 3d alloy promoter catalysts synthesized, a quantitative comparison with DFT modeled spectroscopy was developed. The stability of DFT calculated coke precursors, relevant to dehydrogenation catalysts to convert light alkanes into olefins, was then correlated to DFT modeled RIXS spectra, which is a better descriptor for adsorption of unsaturated chemical intermediates that used previously, as well as being a descriptor accessible to direct experimental usage.</p> <p>Finally, the diffusion of gold nanoparticles in the TS-1 catalyst was studied using AIMD to help understand what structural motifs of gold are present under reaction conditions and how the shape and binding sites of gold is strongly influenced by deformation by the zeolite framework. This is used to help predict new zeolites for use in direct propylene epoxidation using molecular oxygen and hydrogen. The optimization of this catalyst is environmentally relevant to reduce the usage of inorganics and reduce the cost associated with production of hydrogen peroxide. Following these discussions, the role of computation in the prediction of active site structures and kinetics in conjunction with experiment was included. The broader impact of these findings will also be considered, which span beyond these specific reactions and materials.</p>

The reactions of cobalt halides with lithium dialkylamides have been investigated. The reaction with lithium diethylamide proved to be very unusual. This reaction was fully studied and the main products were shown to be lithium chloride, cobalt metal and bis(4-ethylimino-2-butene-2-ethylamino)Cob~lt(II). The latter product which was a volatile brown liquid was identified by its physical and . . chemical properties and the physical properties of derivatives prepared from the ligand after removal of the cobalt. Bis-(4-ethylimino-2-butene-2-ethylamino)cobalt(II) is a nitrogen analogue of the metal acetylacetonates and shows many similar properties. The ligand 4-ethylimino-2-ethylamino-2-butene • was shown, by the magnetic moment and electronic spectra of the tetrahedral cobalt compound, to produce a very high ligand field. A reaction mechanism has been proposed to explain the products 'of the reaction of cobalt chloride with lithium diethylamide. The reactions of other lithium dialkylamides with cobalt halides haye shown that dialkylamino compounds of cobalt(II) exist but are generally unstable thermally and very oxygen sensitive. The only stable (thermally) dialkylamino cobalt(II) compound prepared was bis-hexamethyldisilylamino cobalt(II). In solution this compound was shown· to be a linear two coordinate compound of cobalt(II). This unusual stereochemistry for cobalt(II) presents many theoretical problems before the magnetic and spectral properties ,are fully understood. It was found that the other dialkylamino cobalt(II) compounds produced were u!lstable.thermally decomposing above room temperature. The most stable compounds were formed when the dialkyl- group produced large steric hindrance. Two new alkolides were prepared from the dialkyamino cobalt(II) compounds. The magnetic and spectral properties of these compounds indicate that they are polymeric. possibly three coordinate compounds of cobalt.

There has been a flurry of legislative action at the international and regional levels to address the global problem of trafficking in persons, which victimises epidemic-proportions of individuals and generates one of the largest proceeds of organised crime. The harmonisation of national legal responses based on minimum standards around prevention, prosecution, and protection as espoused by those international and regional instruments is a prerequisite for effective and wide cooperation among countries of origin, transit, and destination. However, the reluctance of states to lift to the lofty heights of international consensus the contentious policy issues surrounding trafficking, including prostitution, has resulted in the adoption of rather ambiguous anti-trafficking norms and obligations, which allow states to individually determine what constitutes 'trafficking in persons' within their own jurisdictions. The subsequent divergence in national responses reveals that legal harmonisation has not taken place. The mechanisms of enforcement, which attach directly or indirectly to those international and regional instruments, therefore, have the formidable task of assisting states in the implementation of the substantive content of anti-trafficking norms and obligations through their monitoring and reporting mandates. However, their work remains a neglected area of academic research, compared to writings on the ambiguity of the international anti-trafficking framework. The challenge to international regulation of the trafficking problem, as identified in this thesis, relates on a fundamental level to the systemic limitations of the formal processes of law based on state consent and respect for the principles of sovereignty and territorial integrity. Through a comparative legal analysis of international and European legal responses to sex trafficking in women, this thesis illuminates the main systemic challenges to combating trafficking in Belgium, the Czech Republic, Finland, the Netherlands, Romania, and Sweden, and how the work of those enforcement mechanisms remedies some of those challenges.

Thesis. 1978. B.S.--Massachusetts Institute of Technology. Dept. of Mechanical Engineering. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING. / Bibliography: leaves 61-62. / by Charles B. Fly. / B.S.

Walking is an essential behavior across the animal kingdom. To navigate complex environments, animals must have highly robust, yet flexible locomotor behaviors. One crucial aspect of this process is the selection of an appropriate walking speed. Speed shifts entail not only the scaling of behavioral parameters (such as faster steps) but also changes in coordination to produce different gaits, and the details of how this switch occurs are currently unknown. Modulatory substances, particularly small biogenic amine neurotransmitters, can alter the output and even the connectivity of motor circuits. This work addresses the hypothesis that one such neuromodulator – serotonin (5HT) – is a key regulator of walking speed at the level of motor circuitry. To explore this question, I use the model organism Drosophila melanogaster which, like vertebrates, displays complex coordinated locomotion at a wide range of speeds. In Chapter 2, I will describe our efforts to characterize the anatomy of the serotonergic cell populations that provide direct input to motor circuitry. I find that innervation of the neuropil of the ventral nerve cord - a structure roughly analagous to the mammalian spinal cord - is provided primarily by local modulatory interneurons. Using stochastic single cell labeling techniques, I will detail the specific anatomy of individual neuromodulatory cells, and also the distribution of synapses across their processes. In Chapter 3, I will show that optogenetic activation or tonic inhibition of VNC serotonergic neurons produces opposing shifts in walking speed. To analyze behavior, I will use two complementary approaches. On the one hand, I will use an arena assay to holistically assess walking velocity and frequency. On the other, I will use a behavioral assay developed in the lab - the Flywalker - to assess walking kinematics at high resolution. The combination of these technique will give us a broad and specific picture of how the VNC serotonergic system modulates walking. In Chapter 4, I will identify natural behavioral contexts under which serotonin is used to shift walking behavior. I will use a variety of paradigms that induce animals to shift their speed, from changes in orientation and nutrition state, to pulses of light, odor, and a vibration. I will assess the requirement for the VNC serotonergic system under all of these conditions, to build a clearer picture of its role in modulating behavioral adaptation. In Chapter 5, I will describe our efforts, in collaboration with Pavan Ramdya's lab at EPFL, to functionally image VNC serotonergic cells while the animal is walking, to understand how activity is endogenously regulated in this population. Finally, in Chapter 6 I will characterize the circuit elements which might be responsible for serotonin's effect on walking. I will use recently developed mutant lines to identify the particular serotonergic receptors responsible for enacting shifts in walking behavior. Using genetic labeling tools, I will identify potential targets of serotonergic signaling in the VNC, and formulate a model by which action on these targets could adjust locomotor output. Altogether, this work seeks to characterize the anatomy and behavioral role of the VNC serotonergic system in Drosophila. I hope that through this work, I will gain a deeper understanding of not only this particular modulatory system in this particular behavioral context, but also of how static circuits are conferred with essential flexibility in behaving animals.