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Global climate change is altering not only average temperatures, but also the distribution and abundance of precipitation. During winter in montane habitats, changing precipitation patterns mean changing snow fall, which will have profound ecological impacts. Snow is an effective insulator and decouples below-snow temperatures from air temperatures, providing a stable environment and determining microclimate conditions in the soil. A wide range of organisms take advantage of stable below-snow winter environments by overwinter in soil. Winter soil microclimate modulates the degree of stress, performance, and ultimately fitness for organisms that overwinter in the soil. During the coldest portions of winter, the insulating effect of snow protects organisms from potentially damaging or even lethal cold stress. However, protection from cold extremes comes at a cost: in ectothermic animals, energy consumption is dependent on body temperature, and so relatively warm below-snow conditions drain energy stores more quickly. In winter resources are limited and energy stores cannot be replenished, and complete depletion of energy stores can cause mortality. Even if organisms survive, post-winter fitness may also be impacted by energy depletion by reducing reserves available for growth and reproduction. We don’t yet understand the impacts of changing winter snow will have on overwintering organisms in montane environments. I hypothesize that winter snow cover, through regulation of winter microclimate, modulates the cause of stress and mortality (cold damage or energy depletion) for montane ectotherms overwintering in soil. By better understanding the impacts of changing winter snow cover on montane ectotherms, we may be better able to identify processes and populations that are vulnerable to climate change.My dissertation aims to expand our understanding of the impact of snow cover on overwinter stress on insects that overwinter in the soil, by examining the impact of snow cover along elevation gradients, then extending the energy use model developed in Chapter 1 to test for impacts of plasticity. Finally I examine how overwinter conditions alter physiological processes upon emergence from overwintering. This work shows that winter snow cover has far reaching impacts on overwintering ectotherms, which are not equal across elevation, and have effects that can carry over into the growing season, expanding our understanding of changing winters and population impacts of climate change.Chapter 1 establishes the energetic impacts and thermal challenges of changing snow cover along elevation gradients. Along elevational gradients snow cover increases but air temperature decreases, and it is unknown how these opposing gradients impact performance and fitness of organisms overwintering in the soil. I developed experimentally validated ecophysiological models of cold and energy stress over the past decade for the montane leaf beetle Chrysomela aeneicollis, along five replicated elevational transects in the Sierra Nevada mountains in California. Cold stress peaks at mid-elevations, while high elevations are buffered by persistent snow cover, even in dry years. While protective against cold, snow increases energy stress for overwintering beetles, particularly at low elevations, potentially leading to mortality or energetic trade-offs. Declining snowpack resulting in drier winters, will predominantly impact mid-elevation populations by increasing cold exposure, while high elevation habitats may provide refugia.Chapter 2 focuses on the impacts of plasticity in metabolic-rate-temperature relationships in dormant organisms and their impacts on energy use estimates, expanding on the model developed in Chapter 1. Ecophysiological energy use models predict long-term energy use from metabolic rates, but we do not know the degree to which plasticity in metabolic intensity or thermal sensitivity impact energy use estimates. I quantified metabolic rate-temperature relationships of dormant willow beetles (Chrysomela aeneicollis) monthly from February to May under constant and variable acclimation treatments. Metabolic intensity increased through time, and acclimation altered both metabolic intensity and the thermal sensitivity. However, incorporating these two types of metabolic plasticity into energy use models did not improve energy use estimates, validated by empirical lipid measurements. Together, this indicates that while metabolic rate temperature relationships are plastic during winter, incorporating this plasticity does not improve prediction of energy use made by ecophysiological models, partly due to large individual variability in energy reserves.Chapter 3 examines the impact that overwintering environment plays on prioritization of physiological processes upon emergence from dormancy, based on changes in gene expression. During winter, dormant organisms conserve resources through metabolic suppression and minimizing cellular processes. The transition from dormancy to active season requires a quick reversal of these processes and large-scale physiological transitions, enabling organisms to begin exploiting favorable environmental conditions. The impact of overwinter microclimate on the physiological processes involved in transitioning from dormancy to active season in insects are unknown. I conducted a field snow-cover manipulation and then profiled gene expression of willow leaf beetles Chrysomela aeneicollis during the transition out of dormancy using RNA-seq. Upon emergence from dormancy, beetles first prioritize up-regulation of transcripts associated with digestion and nutrient acquisition. The prioritization of nutrient acquisition is followed by investment into reproduction, but the timing is sex-specific with females investing sooner. Winter snow cover impacted the timing of these processes, with beetles that overwintered below snow being several days ahead of beetles that overwintered without snow. This highlights the importance of winter microclimate in regulating critical life history transitions.

Volumetric muscle loss overwhelms skeletal muscle’s ordinarily capable regenerative machinery, resulting in fibrosis and severe functional deficits which have defied clinical repair strategies. My work spans the design and preclinical evaluation of implants intended to drive the cell community of injured muscle toward a regenerative state, as well as the development of an understanding of the molecular responses of this cell community to biomaterial interventions. I demonstrate a new class of biomaterial by leveraging the productive capacity of sacrificial hollow fiber membrane cell culture; I show specifically that unique threads of whole extracellular matrix can be isolated by solvent degradation of cultured hollow fiber systems and that this matrix exhibits composition and structure appropriate for wound healing applications. I additionally demonstrate the application of an emerging pore characterization technique and contribute a new open source software for evaluation of mesoporous pore diameter distribution and surface area, key properties governing the performance of sacrificial cell culture materials. Toward a better understanding of the biomolecular systems mediating implant efficacy, I demonstrate the first transcriptomic investigation of a specific promising combinatorial cell-scaffold implant in a rat model of volumetric muscle loss, showing an expedited recovery of muscle contractile force concurrent with a coordinated upregulation of peripheral neuroregenerative signaling. Together, these findings establish a new scalable approach for the production of biomimetic implant materials in vitro as well as molecular targets informing the design of promising muscle regenerative biomaterials.

Asphaltenes are the heavy fraction of crude oil, defined operationally as being soluble in aromatic solvents (e.g. toluene), but insoluble in n-alkanes (e.g. heptane/pentane). This definition comes from the SARA analysis method, which separates the components of crude oil into saturates, aromatics, resins and asphaltenes based on their solubility and polarity. As a component of crude oil, asphaltenes have historically been viewed as problematic, causing fouling in reservoirs and process equipment such as heat exchangers and marine engines. To better understand their chemistry and structure, many researchers have fractionated asphaltenes based on their solubility in solvents of decreasing aromaticity, yet those studies have provided little clarity on the chemistry-structure relationship. In the current study, a new method of separating asphaltenes based on their interfacial activity at an oil-water interface has been considered. Through this method two subfractions are isolated (a strongly interfacially active and weakly interfacially active) and characterised to highlight differences in their chemistry and how those differences influence their structure in solvents. The main findings of this research are i) differences in aggregate structures between strongly and weakly interfacially active asphaltenes, ii) demonstrating the importance of the fractions molecular architecture, as well as heteroatom content and functional group differences, and iii) developing an understanding of how these fractions behave and interact at interfaces. The research presents new insights to the molecular-level understanding of problematic asphaltene fractions and how those molecular properties govern their aggregation behaviour. The new understandings provide opportunity to design better chemical additives that can be used to stabilise and inhibit asphaltene deposit problems.

Unwanted nucleation poses a technological problem in a number of particle processing industries, encompassing fuels, agrochemicals, pharmaceuticals, foods, etc. In this, formulated products can undergo unwanted nucleation events over a vast range of time scales, from seconds to years, however, there is currently an inability to predict when these events might occur and a lack of fundamental understanding of how to prevent these events from taking place, either entirely or by suppressing nucleation outside of storage/operational conditions. Therefore, it is necessary to develop a route to predicting when these events might take place over long time scales and also develop better understanding of how formulation conditions and nucleation inhibition additives can affect the complex processes involved in crystal nucleation from solution environments. These developments are the focus of the research presented within this thesis, which utilises both aqueous and non-aqueous crystallising systems to advance the understanding of how to accelerate, control and characterise nucleation process within solutions with a view to predicting and inhibiting unwanted nucleation events. An accelerated nucleation method, termed Isothermal by Design (IbD), is developed, which enables the rate of nucleation within solutions to be accelerated by rapidly generating high levels of solution supersaturation. Through this, induction times to nucleation are reduced by 5 orders of magnitude for p-aminobenzoic acid crystallising from mixed ethanol/water solutions and key nucleation kinetic parameters are derived over a wide range of supersaturations. A comparison of IbD with a conventional nucleation kinetic analysis route demonstrates the effectiveness of IbD for generating nucleation kinetic data both at low and high supersaturations and provides insight into the behaviour of nucleation in mixed-solvent systems. An investigation focussing on the influence of solution chemistry on the nucleation process in mixed-solvent systems builds upon these insights and is presented for the system of eicosane crystallising from mixed toluene/acetone solutions. In this, mixed-solvent solution composition is found to be responsible for concurrent trends in the crystallisability, solution thermodynamics and nucleation mechanism over the full range of compositions studied. Grid-based molecular modelling provides molecular-scale insight into the solution structure, suggestive that the high solubility solvent, toluene, dominates the local solvation environment but, as the proportion of acetone increases, a 'cage' structure constituting a secondary solvation shell forms, drawing away solvation power towards eicosane, until a critical acetone composition is reached that overcomes this behaviour. Two types of nucleation inhibition additives are investigated to provide insight into the ability of tailor-made additives and polymeric based additives to disrupt nucleation within solution environments. A workflow is developed to aid in both the understanding and designing of tailor-made additives for nucleation inhibition through a combination of grid-based molecular modelling and experimental techniques. Knowledge of the key intermolecular interactions (synthons) of the crystallising compound is key and is utilised as a foundation in the determination of three effective tailor-made additives from a screen of seven potentially effective ones, corroborated by experimental results. The impact of a commercially available polymeric based cold-flow improver additive on the nucleation of eicosane from toluene solutions is presented, introducing a developed characterisation procedure for assessing nucleation kinetics from additive systems undergoing phase separations. Insight is gained into the nucleation mechanism and kinetic effects of different additive concentrations (treat rates) as well as fundamental understanding of the inhibition effect. Conclusions are drawn from these studies and an assessment as to the success of meeting aims and objectives set out as part of this doctoral research is made, with suggested future work that could continue from the foundations built by this research study described.

Cheminformatics methods such as Matched Molecular Pair Analysis (MMPA) and Quantitative Structure-Property Relationship (QSPR) models based on molecular structure have been widely used to address challenges faced during the Discovery stage of pharmaceutical product development. This thesis builds upon these concepts by including the solid state consideration to address challenges associated with the Development stage. Polymorph propensity of molecules and solid state specific melting point (as a surrogate for solubility) were focused upon in the thesis. Matched Molecular Pair Analysis (MMPA) was used for the propensity study. However, no statistically significant molecular transformations were identified due to the small number of MMPs identified and the limited size and quality of polymorphism data. The issue of the small number of MMPs was further analysed by constructing a Matched Molecular Graph. The graph approach allowed the comparison of the properties of datasets from different stages of the pharmaceutical development process. Datasets taken from Development stage contain fewer molecules with at least one MMP (25.1 %) and the lower total number of MMPs (2,776) compared to Discovery datasets of the same size (58.2 % and 10,321), making the analysis method less suitable. A benchmarking dataset for crystal structure classification (into polymorphs and redeterminations) was curated, and the developed machine-learning based method (F1=0.910) along with existing methods (F1=0.780) of classification were compared. A Message Passing Neural Network was used to develop a QSPR model using molecular and crystal information. The best model that only used molecular information achieved R2 of 0.628 on the validation set, while the model trained with the crystal information obtained 0.649. The improvements were limited when compared to the QSPR model that only utilised molecular information; likely due to the limited polymorphic data and the typically small effect the crystal packing differences causes. The best model achieved test set R2 value of 0.550. This thesis provides partial solutions to the challenges of solid form informatics and forms a starting point for further research in the area.

The thesis studies mixtures of alkanes, alkanols, and triglycerides that are used to provide structure to cosmetic products. These materials are blended together in such a way to create a product that is stable and rigid in the packaging, but deposits a thin film of material when rubbed on the skin. This research is driven by the industrial need to understand further the fundamental mechanisms occurring when the product is processed for the purpose of predicting scale-up behaviour. The aim of the project is to discover links between process conditions, crystallisation, polymorphism, physical properties and product performance. The morphology, crystal structure, composition, thermal and physical properties of individual components, HCO, Petrolatum and 1-Octadecanol, was characterised using an array of analytical techniques including DSC, TGA, XRD, GC, SEM, AFM and Hot-Stage Microscopy. The properties of the three structuring materials were compared and contrasted to discover their role in the formulation. Before studying the binary mixtures of 1-Octadecanol; HCO, solubility, thermodynamics and crystallisation kinetics of these materials were studied in a range of relevant non-polar and polar solvents including Dodecane, Undecane, Ethanol, Acetone and D5 using polythermal turbidity data. The data was analysed using van ‘t Hoff, and KBHR analysis and both materials were found to be most soluble in protic polar solvents and least soluble in non-polar solvents. Binary mixtures have been studied through creating a series of phase diagrams using DSC and morphology, and mechanical property information has been superimposed with respect to composition using AFM. Binary mixtures of HCO and 1-Octadecanol have found to exhibit 4 distinct morphologies. The final part of the project focused on the impact of shear and solvent on the crystal structure, polymorphism and rheology of the main structuring ingredient. Experiments using an online custom-made shear cell at a synchrotron allowed structural, rheological, and temperature data to be captured simultaneously, giving insight into mechanisms occurring during processing of the cosmetic products. The presence of shear and solvent has been found to induce phase separation of the rotator and gamma phases of 1-Octadecanol.

Using two Atlantic World events— the Haitian Revolution and Nat Turner’s Rebellion— as temporal bookends, this study examines the ways in which enslaved peoples of African descent were not only affected by, but influenced, the major societal and economic changes in Louisiana’s evolution into a slave society. In addition to analyzing Louisiana as a geographical and imperial borderland, I situate my study at the convergence of several sub-fields of Atlantic World slavery: studies of the impact of specific West African cultures on the New World, the scholarship on the Age of Revolution, and the literature on slave resistance. Relying on an array of Spanish, French, and English sources— from civil documents to church registers, and from judicial cases to plantation records— I re-construct the various identities that enslaved people developed as participants in the contested construction of a slave regime. Slaves were faced with two demographic upheavals that dramatically altered their culture, communities, and social relations during this period. First, in the 1790s, the slave population of Louisiana became “re-Africanized” as thousands of African-born slaves were shipped to the colony for the first time in several decades. Using the Catholic Church to incorporate these new arrivals, many of whom were Congolese, into their communities, enslaved people in Louisiana navigated this internal challenge at the same time they continued to tweak the slave control regime that American governance sparked. Second, with the close of the trans-atlantic slave trade in 1808, Louisiana’s slave population entered its second period of creolization. Given the immense numbers of forced migrants from the Upper South during the 1810s and 1820s, I argue that the domestic slave trade presented similar cultural challenges to the state’s re -Africanized slave population. In the end, slaves in Louisiana minimized African ethnic differences so much that the long-held goal of whites— establishing a biracial hierarchy that equated race with slavery— was fulfilled. While the Haitian Revolution had created near hysteria among frightened white Louisianans during the 1790s, their later counterparts perceived Nat Turner’s Rebellion to be evidence of their society’s stability.

Scholarship on slave families has focused on the nuclear family unit as the primary socializing institution among slaves. Such a paradigm ignores the extended family, which was the primary form of family organization among peoples in western and central Africa. By exploring slave trade data, I argue that 85% of slave imports to Virginia in the 18th century were from only four regions. Peoples from each region-the Igbo, the Akan, Bantu speakers from Angola and Congo, and the Mande from Senegambia-were marked by the prevalence of the extended family, the centrality of women, and flexible descent systems. I contend that these three cultural characteristics were transferred by slaves to Virginia. Runaway slave advertisements from the Virginia Gazette show the cultural makeup of slaves in eighteenth-century Virginia. I use these advertisements to illustrate the prevalence of vast inter-plantation webs of kin that pervaded plantation, county, and even state boundaries. Plantation records, on the other hand, are useful for tracking the development of extended families on a single plantation. William Massie's plantation Pharsalia, located in Nelson County, Virginia, is the focus of my study of intra-plantation webs of kin. Finally, I examine the years after the Civil War to illustrate that even under freedom, former slaves resorted to their extended families for support and survival.

Tens of thousands of metric tons of highly radioactive, nuclear waste have been generated in the United States. Currently, there is no treatment or disposal facility for these wastes. Of the radioactive elements in high-level nuclear waste, neptunium (Np) is of particular concern because it has a long half-life and may potentially be very mobile in groundwaters associated with a proposed underground disposal site at Yucca Mountain, Nevada. Aqueous Np concentrations observed in previous, short-term solubility experiments led to calculated potential doses exceeding proposed long-term regulatory limits. However, thermodynamic data for Np at 25°C showed that these observed aqueous Np concentrations were supersaturated with respect to crystalline NpO 2 . It was hypothesized that NpO 2 is the thermodynamically stable solid phase in aqueous solution, but it is slow to form in an aqueous solution of NpO 2 + on the time scale of previous experiments. The precipitation of NpO 2 would provide significantly lower aqueous Np concentrations leading to calculated doses below proposed regulatory limits. To test this hypothesis, solubility experiments were performed at elevated temperature to accelerate any slow precipitation kinetics. Ionic NpO 2 + (aq) was introduced into very dilute aqueous solutions of NaCl with initial pH values ranging from 6 to 10. The reaction vessels were placed in an oven and allowed to react at 200°C until steady-state aqueous Np concentrations were observed. In all cases, aqueous Np concentrations decreased significantly from the initial value of 10 −4 M. The solids that formed were analyzed by x-ray powder diffraction, x-ray absorption spectroscopy, and scanning electron microscopy. The solids were determined to be high-purity crystals of NpO 2 . This is the first time that crystalline NPO 2 has been observed to precipitate from NpO 2 + (aq) in near-neutral aqueous solutions. The results obtained demonstrate that Np will precipitate as NpO 2 in aqueous solutions thereby leading to significantly lower aqueous Np concentrations.

There is an ever-increasing use of sustainable, bio-derived feedstocks in fuel oils including hydrogenated vegetable oil (HVO) from agricultural or recycled sources. HVO fuels consist of a narrow alkane distribution mainly octadecane (C18) and hexadecane (C16). Such fuels crystallise easily, which can lead to vehicle failures in cold weather conditions. This thesis examines the interplay between crystallisation kinetics, crystal structure and phase behaviour using model C18/C16 alkane mixtures. Computational systematic search modelling in combination with high resolution synchrotron X-ray powder data yields its crystallographic structure for C18 and C16 together with their volume thermal expansion coefficients: 4.39±(1.94)× 〖10〗^(-4) ˚C-1 and4.17±(2.48)× 〖10〗^(-4) ˚C-1. Morphological analysis of C18 crystals reveals a plate-like morphology dominated by the {001} habit plane with smaller side faces (depending upon supersaturation). Analysis of C18/C16 binary phase diagram reveals five single phases (liquid, R1, Mdcp, Op and T18) and five three-phase-equilibrium invariants (eutectic and peritectic at high temperature, eutectoid and peritectoid at low temperature). Kinetic studies reveal the crossover behaviour of the R1 existed in a transient to metastable to stable phase, which the stability is affected by both composition and alkane chain length. Studies of the ternary C18/C16/kerosene system reveal a variety of different structures with compositions close to that of its pure components forming solid-solution in triclinic structures, whilst high relative fractions result in its formation of multiple phases (triclinic and two higher symmetry structures). Rotator induced crystallisation observed in melt phase crystallisation is also formed in solution crystallisation but only for C18/C16 mixtures with its metastability depending on the composition. Solubility studies reveal the closest to the ideal condition with highest solubility in n-dodecane followed by kerosene and toluene respectively. Calculated activity coefficients reflect the non-identical phase formation in the solution phase with higher deviations for C18 molar compositions of x=0.1, 0.5-0.7. Solvents type is not found to have any significant effect on its solid for structure behaviour for C18/C16 mixtures. Crystallisation of C18/C16 mixtures for most compositions in the three solvents are found to be mediated by progressive nucleation mechanism. Cases of instantaneous nucleation are also seen in particularly compositions with higher C18 concentration. Progressive nucleation reveals well correlated with wider metastable zone width and concomitant larger interfacial tension (1.33-1.64 mJ/m^2 ). Higher solubility is found to accelerate the instantaneous nucleation by increasing effective solute concentration, whilst inhibit the progressive nucleation by causing larger interfacial tension.

The APIs mechanical properties particularly, tabletability and flowability are of significant interest in the drug dosage tabletting. Insights into the APIs mechanical behaviour not only assist in the selection of optimum tabletting process but the choice of suitable excipients for dosage blend. Prediction of the mechanical properties of seven solid forms was described in this study two of which were used at the initial stage to develop the model. The objective of the model is to test the reliability of applying molecular and crystallographic modelling to predict the slip behaviour of APIs which will provide a quick tool for observing the mechanical properties. Plane rugosity and interlock properties were calculated for the first time by taking the crystallographic properties of each compound. The prediction model comprises of three main components. Firstly, the identification of likely dislocation Burgers vectors based on lattice geometry and dependency to line dislocation; secondly, selection of slip planes for plastic deformation using the calculation of interplanar interactions, rugosity and surface energy and thirdly, characterisations of slip systems or propensity for cleavage and fracture. The pentaerythritol and its derivative, pentaerythritol tetranitrate were selected as the basis structure during development of model because of known cleave and plastic behaviour. From the calculation, the primary Burgers vector for pentaerythritol was identified as ½ [111], and the prominent slip plane for pentaerythritol is a non-habit plane of (001). The (001) was 94% behaving as an ideal slip plane. However, the primary slip system of pentaerythritol was inactive because the Burgers vector was not in the (001) plane. Pentaerythritol was predicted to cleave at (001) because of strong intraplanar intermolecular interactions. In contrast, pentaerythritol tetranitrate was predicted to undergo deformation by slipped on the plane (110) and in the direction of [001]. The (110) was behaving with 82% of ideal slip plane. The predicted slip behaviour was agreeing with the micro-indentation measurements in the literature. Five solid forms of paracetamol, namely polymorph I and II, paracetamol theophylline, paracetamol trihydrates and paracetamol hydrochloride monohydrate were tested using the developed model to verify the prediction robustness. The influence of each component towards the mechanical behaviour of paracetamol varies depending on intermolecular interactions present in the crystal system.

Intermolecular pairwise interactions (synthons) have previously been used to predict physical properties of molecular crystals, such as polymorphism, morphology and mechanical properties. The overall goal of this research was to correlate the synthon strength and nature found in the crystal structures of the α- and β-forms of 4-aminobenzoic acid to experimentally observed data, assessing their applicability for predicting crystallisation conditions that would produce crystals of desirable physical properties. The strength and nature of the synthons found in the α-structure were found to significantly vary, while the strength and nature of the synthons in the β-structure were found to be much more similar. These synthons were also found to influence the conformation of the COOH and NH2 groups in both structures. Water was calculated to favourably bind to the COOH group than ethanol, along with the OH...O H-bonding dimers being calculated to be less stable in aqueous than ethanolic solutions. This suggests that water may hinder the formation of the α form more so than other solvents. The attachment energy morphological prediction of α-pABA was less needle-like than often observed, probably due to the growth rate of the capping faces growing by a rough interfacial growth mechanism along the long axis of the needle dominated by π-π stacking interactions, being underestimated. Nitromethane (NMe) was calculated to interact more strongly with the phenyl ring than other solvents and hence addition of NMe to ethanolic solutions shortens the long axis of the needle. The experimentally measured local surface molecular chemisty was found to vary between measurements of the bulk and surface at the (1 0 -1) surface, which is predicted to have unsaturated H-bonds at the surface. Complementing this, spatially resolved measurements across the (1 0 1) surface also showed changes in structure of a supposedly periodic surface. This study revealed how predicting the strength and nature of the synthons in the bulk structure and at the surface, along with their interaction with solvent molecules and stability in solution, can influence the morphology and polymorphism of the crystals produced from solution.

Wax formation in diesel and biodiesel fuels at low temperatures is one of the major problems faced by the fuels industry as crystallisation of the saturated compounds present in these solutions can plug up filters and obstruct pipelines. Preventing wax formation in these multicomponent mixtures requires a good understanding of the crystallisation behaviour of both n-alkanes and Fatty Acid Methyl Esters (FAMEs). This work studies solutions of methyl palmitate and stearate in representative mixtures of diesel fuels and unsaturated esters solvents, providing an overall assessment of their solubility and nucleation kinetics. An in-depth analysis of the growth kinetics and crystal morphology for methyl stearate crystallising from n-dodecane, kerosene and toluene solvents is also presented. To perform this study methodologies are developed for the assessment of nucleation kinetics and morphological indexation of crystal specific faces. Models for the analysis of crystal growth kinetics are also derived. These describe the effect in series of the diffusion of growth units within the bulk of the solution and a rate of incorporation of these units which is associated to the molecular structure of the crystal faces´ surface. It was found that the solubility and crystallisation kinetics of methyl palmitate and stearate is very dependent on the solution environment in particular solvent type. Solubilities are higher in solvents whose molecules have more compact structures, such as in the case of toluene and methyl-cyclohexane and are lower in unsaturated methyl ester type solvents. The nucleation process in these systems is found to be much more thermodynamically controlled in the case of diesel type solvents and show a greater kinetic influence in the case of unsaturated methyl esters solvents. The growth kinetics of methyl stearate crystals is found to be strongly associated to the level of solvation of these solutes molecules as well as to the chemical structure of the crystal-solution interface. Accordingly, the rate limiting step is suggested to be the integration of growth units to the surface of the crystal in the case of methyl stearate growing from n-dodecane solvent, and more diffusional controlled in the case of methyl stearate growing from kerosene and toluene solvents. The morphology of methyl stearate crystals however is not found to be strongly influenced by solvent type, only showing changes as a function of supersaturation in the case of kerosene solvent.

This thesis sets out to evaluate the effects of milling on the microstructural changes to gamma-Alumina, a well-used catalyst support. It reviews the literature as it relates to the characterisation that has been done so far on this material, different milling methods and effects of milling. The review section considers the strengths and weaknesses of previous work in the areas of structural characterisation of gamma-Alumina as well as reports on the effects of milling of the material with particular interest in size reduction and phase transformation. Working from the base of current knowledge, experiments that can fill in the gap identified from the review are designed. The material under investigation is characterised as received for particle size and morphology and this gives a base for further experimental investigations. Various experiments are designed centred around exposure of gamma-Alumina to different milling conditions. These include the use of different mills, variation of milling conditions and isolation of stress modes. Furthermore, results from Discrete Element Method simulations of one selected mill, provided by Professor Junya Kano of Tohoku University in Japan are analysed for energy quantification. Data processing of the results of the operation of a second mill, simulated by Discrete Element Method at the University of Leeds by Dr Colin Hare and Dr Ali Hassanpour is also used to quantify energies associated with the milling process. It is concluded that microstructural changes to gamma-Alumina are very much energy driven processes. The jet mill has proven a worthy candidate for size reduction in small scale processes. The size reduction analysis shows that gamma-Alumina requires the presence of a dispersive agent such as water or compressed air for efficient size reduction. The characterisation work combined with the simulation results show that the amount of energy dissipated into the microstructure of gamma-Alumina during a collision governs the extent of microstructural effects. Results also show that with the supply of different energies to milling processes, mechanical energy can achieve a phase transformation from gamma-Alumina to alpha-Alumina similar to that achieved by calcination where delta-alumna and theta-Alumina are observed as intermediate phases. Simulation also provides a tool for prediction and selection of milling processes appropriate for the required end product.

The structural pathway from a single molecule to clustering through to nucleation during a crystallisation process is not fully understood. As such the solution state structure, nucleation kinetics and phase transformation kinetics of p-Aminobenzoic (PABA) acid are probed using a combination of in-situ crystallisation characterisation techniques and nucleation kinetic analysis methods. The solubility of alpha PABA is measured in a number of solvents where van’t Hoff analysis shows that solute-solute interactions are probable in all solvents. Solution state FTIR studies reveal the presence of a distribution of solvated monomer and carboxylic acid dimer species in acetonitrile solutions. This provides a link between solution state structural synthons and the carboxylic acid dimer structural synthon of the alpha PABA solid phase. Isothermal nucleation kinetic analysis reveals that calculated interfacial tension, γeff, values are found to be low for an organic material; where γeff values are 0.85 – 1.31 mJ/m2 in ethanol and 2.36 – 2.60 mJ/m2 in water. Due to this the critical cluster sizes are in the region of 0.48 – 1.98 nm. Poly-thermal kinetic analysis reveals a nucleation mechanism change from instantaneous to progressive as a function of decreasing solubility in ethanol, acetonitrile and water. This is caused by an increase in attachment frequency due to decreasing de-solvation free energy of PABA found from molecular dynamics simulations, this in combination with increasing γeff causes the thermodynamic component of the nucleation rate to become limiting. Isothermal and poly-thermal X-ray scattering studies of PABA nucleation reveal the formation of large liquid-like clusters of PABA, >40nm, in the under-saturated state. These Nano-scale assemblies increase in size and structural ordering, indicated by an increase in fractal dimensionality from 1 – 2 as a function of driving force. The Guinier region of the high q structures is found to increase from Rg = 0.46nm to 0.53 nm which indicates a population of monomers and dimers of PABA in the supersaturated state. This was confirmed as the carboxylic acid dimer structure from form factor fitting of known structural synthons of the alpha phase. In-situ XRD studies of the polymorphic phase transformation of the beta-alpha phase, indicates that the dissolution and growth processes are consistent with zero order nucleation kinetics and first and zero order kinetics respectively with the latter seemingly temperature dependant. UV/Vis analysis in combination with the XRD data reveal the transformation is a dissolution controlled process explained by particle morphology. The transformation temperature was also estimated from the growth and dissolution rate constants as 22.8 – 23.6 °C.

This thesis takes three different perspectives, using theoretical and experimental techniques, on time-inconsistent preferences and how the existence of multiple selves can affect both consumer behaviour and policy design. Across domains such as retirement saving, health, and educational achievement, intertemporal choice presents a challenge for both individuals and policymakers. The first paper, 'Choosing When to Nudge: Designing Behavioural Policy around Decision-Making Costs,' considers how behavioural policy, which has proven increasingly popular with policymakers, affects welfare. I find that for present-biased consumers, behavioural policies help some consumers but can inefficiently discourage others from optimizing. Such policies therefore have an ambiguous effect on welfare, and similar to traditional policies, can impose equity-efficiency tradeoffs. Monopolies may increase welfare given their incentive to simplify consumer decisions instead of exploit switching costs. The second paper, 'Virtue and Vice with Endogenous Preferences,' considers behaviour when preferences are affected by consumer decisions. I introduce agents whose temptation to consume in the present is affected by how much they choose to save for the future. I find that differences between agents can trap them in divergent paths of self-improvement -- saving more, they value the future more, making saving optimal -- or binging -- consuming more makes them indifferent to future costs, making consumption optimal. At the extreme, it is frequently an optimum for a consumer to consume their entire wealth. The final paper, 'Bet You Can't Eat Just One: Consumption Complementarity and 'Self'-Control' considers an intrapersonal game between a moderate cold self and a hot self that wants to indulge. In equilibrium, sophisticated selves best respond to each other's behaviour: the cold self over-abstains and the hot self over-indulges to avoid inducing the other state. I test these ideas in the lab, and find that subjects on a diet who were induced to consume a piece of chocolate before the experiment indulge more in chocolate during the experiment, even when the initial indulgence was imposed by the experimenter. Eating a piece of chocolate, this suggests, can induce a period during which chocolate is more appealing.

The surface properties of single and agglomerated micro-crystals are characterised using the micro-focus X-ray beams available at a third generation synchrotron light source together with other laboratory facilities. The influence of the crystallisation environment, on the resultant product crystals is studied by both varying the cooling rates during crystallisation and through the addition of impurities and cross-correlated with the morphology and size changes. Unmodified urea crystallised in 99% ethanol produce needle-like crystals whilst addition of 4% of biuret in crystallisation of urea produce a more prismatic crystal shape. At faster cooling rates smaller sized crystals are produced and vice versa. Dispersive surface energy analysis using inverse gas chromatography (IGC) shows that unmodified urea has lower dispersive surface energy than urea modified by biuret. The dispersive surface energy also increases as the cooling rates increased. Both the morphology changes and surface energy measurements are validated using molecular modelling. The morphological prediction intermolecular force calculations of unmodified urea and urea modified by biuret are used to calculate a weighted value for the whole crystals’ dispersive surface energies. The results are in good agreement with experimental results from IGC. The sorption of urea crystals on water moisture showed that unmodified urea samples adsorbed water higher than urea modified by biuret by the observation of the percentage of mass change with respect to the relative humidity. The study of variability within powdered samples was found that no significant different in the unit cell parameters values of each single crystals. The orientation relationship between agglomerated micro-crystalline particles of aspirin showed the agglomerates tend to interact at the faces that have ability to form bonding. In urea samples, most of the agglomerates are mostly aligned due to epitaxy growth of the crystals. The XMT experiment also was carried out on agglomerated α-LGA and the 3-dimensional (3D) shape the samples were obtained.

The drying of pharmaceutical powders following their isolation via crystallization and filtration is examined using a laboratory-scale agitated filter dryer (AFD). Vacuum contact and through-circulation convective drying with and without agitation of aspirin powders with pure and mixed solvents are studied through an integrated experimental and modelling approach. Experiments were carried out under different operating conditions by using aspirin particles and water/water-ethanol as typical solid-solvent systems. Two approaches were used to study the drying behaviour of aspirin: 100 µL small-scale drying using thermal gravimetric analysis (TGA) and 5 L medium-scale drying in a laboratory AFD. While the TGA tests provided a better understanding of drying kinetics as functions of temperature, vacuum level, solvent type and particle size, the AFD study revealed the effects of industry-relevant operating parameters (such as the heating rate, vacuum level, agitation speed and regime, gas flow rate, and initial solvent content) on the drying of aspirin particles. In the TGA experiments, the constant and falling rate periods are observed for drying with pure water, while only the falling rate period is observed for pure ethanol and water-ethanol mixed solvents. In the laboratory-scale AFD experiments, drying cycle time is found to decrease with increasing agitation speed, vacuum level, heating power supplied and gas flow. The critical solvent content is determined by identifying the transition point on the temperature-time and the torque-time plots during the drying process. Particle size distribution and morphology analysis of aspirin particles before and after drying with agitation indicate that the particles tend to agglomeration at lower stirring speeds while they are prone to attrition at higher speeds. An increase of the circularity of the particles with the increase of the agitation speed is observed due to attrition effect. Drying models based on a lumped-parameter (LPM) approach are developed for the static and agitated bed vacuum contact drying and combined LMP and distributed-parameter model (DPM) for the convective drying. Within this modelling approach, only one parameter that is the critical solvent content needs to be estimated from experimental results compared to other LPMs which greatly reduced the degree of parameter estimation. These computationally expedient models can be used for the prediction of drying time in a fast and reliable way. The model equations are implemented in gPROMS software and the models are applied to simulate the experiments carried out in the 5 L AFD. The vacuum contact drying experiments were also simulated using a DPM embedded in the gPROMS software. The modelling results of LPM were compared with that obtained using the DPM. Overall, a good agreement between the calculated and measured drying curves is obtained and the measured drying times are well predicted at varied drying conditions. This research presented the following improvements over the current studies on powder bed drying with limited research on organic crystalline materials and mixed solvent: holistic studies on drying behaviour with varied external drying conditions as well as internal material properties using different scale apparatus: TGA and AFD. Over the previous LPMs on powder bed drying, the modelling approach presented the following improvements: the models developed in this work need less parameter estimation. Three consistent approaches to measure the required parameter at the laboratory scale have been described in this work. The models provide a potential for industrial application on AFD drying.

A detailed study into the crystal habit modification of the NaClO3 / Na2S2O6 (host / impurity) system is presented. Ordinary morphology of NaClO3 present faces of {001}, {110} and {111} types. The presence of impurity Na2S2O6 has led to rapid development of new faces of {111} type on the NaClO3 crystals grown from solution. Above 70ppm doping concentration, the morphology of NaClO3 crystal is dominated by {111} faces. Crystal twinning occurred under 800ppm doping concentration and above. X-ray topography was used to investigate the growth history and defect configuration of the pure and doped crystals. Lattice distortions at various lattice planes within the pure and doped crystals were determined using X-ray multiple-wave diffraction (XRMD). The local structure of S2O6 2- in NaClO3 crystal was determined using X-ray absorption fine structure (XAFS). Molecular modelling was applied to investigate the molecular similarity between the impurity and the host. Strong impurity incorporation in the {111} sectors was revealed by X-ray topography. The growth history of doped crystal was reconstructed and interpreted with respect to the inhibiting effect of S2O6 2-. Disturbance in lattice planes of doped crystals was investigated, which was attributed to the incorporation of S2O6 2- on { 111} faces. It also revealed different types of local strain on the { 111 } faces along two different directions. The three-dimensional orientation and the actual structure of S2O6 2- impurity on the {111} faces of NaClO3 crystal were obtained. A structural model for the impurity incorporation was established, showing good consistency with the experimental results. In addition, the segregation coefficient of the impurity was determined by elemental mapping, indicating strong impurity incorporation on the {111} faces rather than others. The incorporated S2O6 2- was concluded to be capable of disrupting the proper packing structure of the {111} faces, obstructing the generation and propagation of growth steps, and decreasing of driving force for crystal growth.

The crystal growth of ibuprofen as a function of crystallisation environment is presented. Measurement of solubility as a function of solvent (ethanol 95%, ethyl acetate, acetonitrile and toluene) and temperature using UV/Vis spectroscopy and gravimetric analysis reveals less than ideal behaviour, consistent with strong solute-solute interactions, particularly in the case of acetonitrile. Examination of the nucleation kinetics reveals a comparatively small metastable zone width (MSZW) (ΔT = 10.0 - 13.9oC) with interfacial tensions in the range 2.56 – 5.52.10-3 (J/m2). The growth rates for the {001} and {011} faces of spontaneously nucleated single crystals are precisely measured in-situ using optical microscopy revealing that their growth rates increase with increasing supersaturation to different extents, depending on the solvent type with concomitant impact on the crystal habit. For similar supersaturations, the growth rate of {011} is lowest in ethanol and highest in acetonitrile, whilst that of {001} is lowest in toluene and highest in ethanol. The aspect ratios, as a function of supersaturation, are generally higher at the 15 mL than the 0.5 mL crystalliser scale size. The data is consistent with a 2-D Birth and Spread growth model for both surfaces and scale sizes. This is in good agreement with the calculated surface entropy α factor. The measured growth rate dispersion for these faces is much less for these spontaneously nucleated crystals in stagnant, supersaturated solutions when compared to the literature data obtained for a stirred batch crystalliser. Additional higher index re-entrant faces are found at high levels of supersaturation consistent with their alignment either parallel to the {012} or {112} face. The growth rate in the non-agitated jacketed vessel is found to be slightly higher than that for the agitated reactors with both being in quite in a good agreement with literature data suggesting that these results on single crystals will have utility in representative the growth rates of a population of crystals in an agitated crystallizer. Observations are is rationalised using molecular and crystallographic modelling revealing e.g. that polar protic solvents inhibit the growth rate of faces containing available hydrogen bonding binding sites, such as carboxylic acid groups. Molecular conformational searching reveals the molecular structure in the solid-state to be close to that of molecules minimum intra-molecular energy. Conformer population analysis as a function of solvent reveals no significant solvent effect on the low energy conformer distribution indicative a low likelihood of polymorphic behaviour for this compound in good agreement with literature.

The application of ultrasonic techniques for crystal size distribution (CSD) and solid volume concentration measurements in batch crystallization processes was investigated in situ and on-line, with emphasis on the crystallization of the copper sulphate pentahydrate crystallization system. The fundamental crystal characteristics of copper sulphate pentahydrate including the solubility, metastable zone width, and induction time were assessed. The kinetic analyses carried out were independent of the acoustic measurement of the copper sulphate pentahydrate and provided the research background for the acoustic study. The potential of ultrasonic spectroscopy was demonstrated using an experimental approach, focusing on the problem of cooling crystallization of copper sulphate pentahydrate from an aqueous solution in a 20 litre scale reactor. The set up of the physical properties matrix for the system allowed the ultrasound spectra to be converted into the particle size and particle volume infonnation. Different cooling conditions were optimized due to the limitations of the instrument. The overall growth rate as a function of the relative solution supersaturation was determined from the combination of particle size and solid concentration. A new method derived from the Modified Urick equation focusing on the on-line measurement of the crystal volume concentration without the phase separation was built up, which was modified from the prototype applied in the non-soluble oil-in-water system. The extended application on the copper sulphate pentahydrate crystal volume concentration during the dynamic process was successfully developed. The third generation prototype acoustic spectroscopy Alphasizer developed by Malvern Ltd for on-line acoustic attenuation and velocity measurement was calibrated. Particle size distribution was successfully calculated from the manually calibrated attenuation spectra. The feedback closed loop supersaturation control based on Alphasizer was designed. The control algoritluns and a corrununication system were built up.

Four essays, or chapters, model the capital structure, governance, and investment decisions as part of a sequential game. Each chapter is separate in its context, assumptions, and conclusions. The titles of the chapters are below. Abstracts of each essay or chapter can be found at the beginning of each chapter. The titles of the chapters or essays are as follows: I. Managerial Ownership with Rent-Seeking Employees, II. Financing Professional Partnerships, III. Sunk Cost Efficiency with Identical Competitors, and IV. Business Stealing and Bankruptcy. With the exception of Chapter III, which is meant to complement Chapter IV, these essays argue that the structure of financial contracts can affect the real behavior of firms. The first chapter argues that financial governance policies affect the behavior of rank-and-file employees. In Chapter II, the governance and capital structure of professional service firms affects clients’ expectations of the firm’s quality. In Chapter IV, the enforcement of financial contracts by bankruptcy courts affects the number of firms that enter and exit the industry.