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This study applies critical race feminism theory (CRF) to understand the experiences of women of color (WoC) who are academic librarian leaders. This study explores the obstacles they overcame to achieve their leadership roles and the skills and assets they developed throughout their journeys. The research employs semi-structured, in-depth interviews to capture the experiences of 15 WoC academic librarianship leaders. The findings of this study indicate that the challenges described by the women interviewed are in the realm of gender inequalities, cultural taxation, emotional labor, and racial fatigue. The study also examines the consequences of these challenges on their physical and mental health, even at the spiritual level. Nevertheless, the women also narrate how to navigate these challenges and how they create counterspaces to support their journey in organizations informed by Whiteness. The study aims to contribute to a better understanding of the unique challenges women of color encounter in academic librarianship leadership and the assets they cultivate to surmount these obstacles. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

This dissertation studies the experience of Italian commercial banks between 1926 and 1936. To do so, it employs a mix of qualitative and quantitative methods. It presents a new database of banking distress, which includes not only outright bank failures but also those failures that were hidden and resolved behind the doors. This reconstruction is based on extensive archival research using the classified documents of Italian banking supervision (Archivio Storico della Banca d'Italia, and Archivio Centrale dello Stato). It reveals that the distress of small and medium banks was anything but negligible. Once distressed but resolved banks are considered, the magnitude of the crisis would be considered 'systemic' by today's standards. It also shows important regional patterns: in terms of bankruptcies, Southern Italy suffered relatively more than the rest of the country. This thesis advances a new narrative on the causes of this crisis of Italian commercial banks. I argue that banking distress was not the outcome of a 'bad credit boom', but it is better understood as a process of 'financial development gone wrong'. The 1920s were a crucial period of banking development for Italy, when the number of banks and branches expanded considerably. Coeval observers, however, considered this expansion as ill-fated. Regression analysis on bank balance sheets confirms their interpretation. The archival research conducted for this dissertation also sheds new light on banking supervision under the 1926 banking law - a law mostly known in the literature for having failed to prevent the failure of the big four universal banks in the 1930s. Using unexplored archival sources, this thesis documents in detail the functioning of banking supervision. I argue that, once the day-to-day functioning of the law is taken into account, the new regulation and its enforcement through supervision had a positive impact on small and medium commercial banks.

Complex biological systems, such as cells and their organelles, are composed of regions of varying viscosity, temperature and polarity. Fluorescent molecular rotors (FMRs) based on the popular dye boron-dipyrromethene (BODIPY) have been shown to be very effective sensors of these different conditions. BODIPY-based FMRs have fluorescence lifetimes and quantum yields which have large ranges and are dependent on their local environment. The probes also fluoresce in the visible region and can be adapted to target specific organelles. However, although they are known to be excellent bio-sensors, their working mechanisms are not yet fully understood. This makes adapting them, and improving their capabilities for research in the life sciences, challenging. My thesis aims to gain a deeper understanding of the working mechanism of BODIPYbased FMRs in sensing viscosity, temperature and polarity by using a range of computational techniques, assisted with results from experimental collaborations. My studies range in scale from single molecule quantum chemical investigations of BODIPY's fundamental photophysics, to large scale simulations of full organelles. This means I use a range of tools of differing theoretical levels, from multireference wavefunction methods through to large-scale, long timeframe classical molecular dynamics. After outlining the theory of the investigatory tools I use, I begin my thesis with an examination of the fundamental photophysics of a prototypical BODIPY FMR, phenyl-BODIPY. Not only does this serve as an opportunity to explore its basic properties, such as the effect of the rotation of its phenyl ring on fluorescence, but it also allows me to benchmark many of the computational methods involved in future chapters. Following this, I study the transition dipole moment (TDM) vector of its first excited singlet state, whose direction was unclear. I show that the TDM is aligned along the BODIPY core but that the core can become misaligned with the molecular principal axes of inertia, causing a tilted TDM. My calculations of the molecular structure also aid the interpretation of results from the Toptygin method, an experimental technique for calculating the TDM orientation in fluorophores. My second results chapter examines the viscosity-sensing mechanism of phenyl-BODIPY. I begin with ab initio molecular dynamics simulations of the probe in vacuo, to act as a control, before comparing these results to ab initio quantum mechanical/molecular mechanical (QM/MM) dynamics simulations in two solvents of different viscosities: methanol and glycerol. I consider the dynamics of the first excited singlet state in these solvents; in particular, I show that two aspects of the molecular motion, rotation of the phenyl ring and bending of the core dye with respect to the ring, are sensitive to viscosity, and, therefore, likely to underpin the mechanism for sensing local viscosity based on free-volume. In the second half of the chapter, I present the results of a joint theoretical-experimental collaboration examining the viscosity-sensing capabilities of BODIPY-C10 in lipid droplets. We show that when the probe's time-resolved fluorescence anisotropy and its fluorescence lifetime are simultaneously measured in these environments, they are able to sense four different micro-viscosity components. By comparing the experimental measurements to classical molecular dynamics simulations, we match these components to different configurations of the dye within the organelle. In my third results chapter, I explore the temperature-sensing mechanism of red BODIPYCyclopropyl FMRs. Experimental colleagues synthesised two red BODIPY-FMRs which were small enough to internalise into cells. One probe sensed both viscosity and environmental temperature, while the second was only sensitive to temperature, and the reason behind these differences were not understood. I use time-dependent density functional theory (TDDFT), compared to experimental results and a control FMR, BODIPY-C10, to show that the closer proximity of the cyclopropyl substituents in one probe causes an energy barrier between its radiative and non-radiative decay states which is unlikely to be surmountable, even in high temperatures. In the other probe, however, the barrier is smaller and more likely to be overcome at lower temperatures. In the second half of the chapter, I examine the FMR's structural properties in greater depth, including locating their ground-first excited state minimum energy conical intersections. Finally, I perform some initial tests in order to assess the best computational tools for dynamically exploring the temperature-sensing mechanism in future works. In my final results chapter, I bring together what I have learnt, thus far, in my thesis to explain the polarity-sensing mechanism in OCH3-based phenyl-BODIPY FMRs. These probes have long been known to be sensitive to polarity. In low viscosities, the non-radiative decay rates have consistently been shown to be higher in higher polarity solvents. On the other hand, the red BODIPY-Cyclopropyl FMRs examined in the previous chapter show increased temperature sensitivities in low polarities. Despite computational investigations into the polaritysensing mechanism, however, it had not yet been explained. In this chapter, I demonstrate that, rather than being a result of the energy barriers between the non-radiative and radiative decay structural regions, the mechanism is governed by coupling between the ground and excited states at the barrier between the different decay types. I use TDDFT to show that in lower polarity solvents, greater deformation of the molecular structure is possible, which changes the excited state electronic density distribution and lowers the strength of the transition dipole moment. This, in turn, reduces the non-radiative decay rate.

Pentameric ligand-gated ion channels (pLGICs) are important proteins, embedded in the lipid membranes of nerve cells, which are of great pharmacological relevance. They mediate fast synaptic transmission and are involved in many diseases. For this reason, their fundamental understanding at an atomistic level is paramount for the design of new, targeted pharmaceuticals. Phenomena of interest include ligand binding/unbinding, opening and closing of the inner ion channel, mechanical signal propagation, allosteric modulation by lipids of the cell membrane and/or by other ligands, and more. Depending on the time scales of the specific phenomenon of interest, a variety of computational (or in-silico) techniques can be employed for their study. One of the most common is molecular dynamics, which involves the solution of Newton's equations of motion for every particle that belongs to the system under investigation. This technique allows for the study of equilibrium and out-of-equilibrium phenomena, typically in the range of nanoseconds-to-microseconds, depending on the size of the system (between orders of 103 atoms to orders of 106 atoms in the case of bio-systems). However, rare events are hardly sampled by the usage of molecular dynamics, thus requiring the introduction of the so called enhanced sampling techniques. Among these are metadynamics, umbrella sampling, steered molecular dynamics, and many others. The goal of this PhD project is the investigation of several phenomena revolving around one pLGIC, namely the serotonin-activated type 3 A ion channel, or 5-HT3A receptor. The importance of this receptor is proven by its involvement in diseases such as schizophrenia, drug abuse, and many others. In this system, the binding of serotonin triggers a cascade of conformational changes that ultimately culminates with the opening of a hydrophobic gate, leading to a flow of ions through the inner ionic channel. This cascade of events typically occurs over a time window of milliseconds: in this context, molecular dynamics is an ideal tool to study single phenomena that make up the overall cascade. Its complete mechanism is, however, far from being fully understood. We focus here on studying phenomena that occur in different parts of this protein, and that, globally, contribute the overall mechanism of this molecular machine. The first chapter of this thesis aims at providing all relevant information about pLGICs and relative ligands, with a particular focus on the 5-HT3A receptor, while the second chapter provides theoretical details on all-atom molecular dynamics and on the enhanced sampling methods used. The subsequent chapters describe the results obtained in each of the projects carried out during the PhD years, providing an introduction to the specific phenomena studied, their relevance, and a relative literature review. Specifically, in the third chapter, we investigate the possibility that the propagation of mechanical signal across the extracellular and the transmembrane domains of the receptor is mediated by the isomerisation of a proline located at their interface. This consists in the rotation of a torsional angle linking this amino-acid and the subsequent residue. This study is carried out both with molecular dynamics and with metadynamics, with the aim of capturing structural differences that the different proline isomers induce in the surroundings, and of reconstructing the free energy associated with the isomerisation process. In this way, we are able to assess how the protein environment and the proline isomerisation influence each other. In the fourth chapter, we focus our attention to what happens at the interface between the protein transmembrane domain and the lipid membrane. In recent years, the modulation by the lipids (phospholipids and cholesterol in particular) onto the working mechanism of several pLGICs has been proved both in-silico and experimentally. In this context, our goal is to characterise, via molecular dynamics simulations, lipid-protein interactions, i.e. the binding of specific lipids to the surface of the protein, to assess the effects that lipids have on structural and dynamical properties of the protein, and to show how these are influenced by the exact concentrations of the lipid species. In the fifth chapter, we investigate the role of the outermost M4 α helices of the transmembrane domain on the protein function. According to experimental results, disrupting crucial interactions in this section of the protein may alter the overall protein function. Here, we perform molecular dynamics simulations to assess how a specific mutation on the M4 helix, i.e. Y441A, is able to alter structural and dynamical properties of the M4 itself and of its surroundings, with the aim of shedding light on how the M4 is relevant for the mechanism of the serotonin-activated receptor. In the sixth chapter, we present a preliminary study of the unbinding of serotonin from the orthosteric pocket, located in the extracellular domain of the receptor. We perform this study by means of both molecular dynamics and metadynamics simulations, with the aim of understanding the fundamental interactions involved in the process. Overall, the original work carried out and explained in this thesis contributes to the fundamental understanding of the 5-HT3A receptor, and by extension of pLGICs in general.

Nanoparticles are characterized by their small and finite-size. Indeed they are made of tens to thousands of atoms, corresponding to a size of 1 to tens nanometers. Nanoparticles' finite-size entails three significant implications: internal transitional symmetry breaking occurs, electronic confinement effects are relevant, and nanoparticle's surface to volume ratio is not neglegible. In turn, at the nanoscale, we witness: the occurrence of many peculiar structures, the arising of unique optical, magnetic, and catalytic properties (different from the one of the single atom and of its bulk counterpart) and characterized by peculiar structureproperty relationships, the failure of bulk thermodynamics modeling in the prediction of the nanoparticle structural stability, also for the case of relatively large systems. Indeed size- and shape-effects are known to non-trivially affect the (meta)stability of a nanoparticle against melting and pre-melting. Borrowing the words spelt by Richard Feynman during his famous talk 'There is plenty of Room at the bottom': "When we get to the very, very small world ... we have a lot of new things that would happen that represent completely new opportunities for design". Tailoring the nanoparticles architecture - i.e. size, shape, chemical composition and ordering - at will, one could harness their full potential in technological devices which will trigger a revolution in many fields, ranging from biomedicine to catalysis and optics. The identification of optimal nanoparticle architectures for target purposes is, from here on, mentioned under the name of rational design. The complexity inherent to this practice represents a longstanding high-reward challenge as it hinges on the understanding of how each structural feature contributes towards the nanoparticle global chemophysical property. Moreover, the rational design of nanoparticles for target application should encompass the in depth study of the (meta)stability of the chosen bespoke nanoarchitecture. Indeed, coming back again to Feynman's notorious contribution to nanoscience, he mentioned that "... [he was] not afraid to consider the final question as to whether, ultimately - in the great future - we can arrange the atoms the way we want; the very atoms, all the way down! ... (within reason, of course; you can't put them so that they are chemically unstable, for example)". A degree of atomistic control of the nanoparticle components is currently at reach during both colloidal and physical growth methods. Thus, it is of fundamental importance to assess whether the so synthesized nanoparticles present a satisfactory structural stability, or if their inherent (meta)stability manifests and determines too dramatic changes in the nanoparticles chemophysical properties, and thus in the performance of the device which exploits them. This thesis will contain a discussion of the application of state-of-the-art sampling techniques to probe the complexity of the conformational and energetic landscape of noble and quasi-noble metal nanoparticles of 100-1000 atoms. Conversely, a thorough characterization of the mechanisms driving melting and pre-melting will be sought and rationalized in terms of size, shape, and composition effects. As a final case study, the structural properties of Pt nanoparticles will be carefully assessed to predict their performance for Oxygen reduction reaction, identifying design criteria towards the synthesis of nanoarchitectures with enhanced catalytic properties. Chapter I will introduce the state-of-the-art of metallic nanoparticles characterization, synthesis, theoretical modelling, and application as nanocatalyst. Chapter II will present the numerical techniques employed to study the melting and pre-melting of metallic (group X and XI) nanoparticles and the prediction of their catalytic properties. Chapter III and IV will follow with a thorough investigation of solid-solid transitions in mono- and bimetallic nanoparticles. Structural rearrangements will be discussed with a focus on size and composition effects determining whether they are concerted or diffusion driven. Chapter V will tackle a discussion on how to disentangle univocally kinetic and thermodynamic contributions determining phase changes in metallic nanoparticles as well as to discriminate faithfully solid and liquid structures. Finally, Chapter VI will detail the application of a method based upon a geometrical descriptor to determine design criteria towards the synthesis of Pt nanoparticles highly active towards oxygen reduction reaction.

Hexagonal Ice (Ih) plays a number of essential roles in controlling and maintaining the natural environment on Earth. It is the predominant crystalline form of ice and permanently covers at least 10% of all land. Within the atmosphere ice forms cirrus clouds which are involved in the greenhouse e↵ect. The altitude and thickness of the clouds controls the balance of solar heating and infrared cooling from Earth to space, and is governed by the sizes and shapes of the constituent ice crystals. The shape of vapour grown ice crystals depends strongly on temperature and vapour pressure. At low vapour pressures, simple hexagonal prisms form with an aspect ratio that depends on the relative rate of growth of its two crystallographic surfaces - the basal and prism surface. The competing action of the two rates results in thin hexagonal plates at very low temperatures and elongated prisms at higher temperatures. Curiously, as temperature is increased further, thin plates form once again. The reasons why growth occurs preferentially along the basal and prism surfaces at different temperatures remain unknown. Progress in climate science is hindered by an incomplete grasp of the underlying mechanisms involved in ice growth in cirrus clouds. A comprehensive understanding of ice crystal growth is essential if we are to overcome the colossal climate change challenges we face. In this project we investigate the basal and secondary prism surfaces of hexagonal ice at a range of temperatures between 240 K and 270 K using molecular dynamics and metadynamics. Metadynamics is an enhanced sampling technique that enables efficient sampling of rare events and yields an estimate of the free energy as a function of selected collective variables. Our simulations show the formation of a disordered quasi-liquid layer (QLL) on the surfaces of ice. The QLL mediates crystal growth and has a thickness which varies with temperature. We investigate how the ice/QLL and QLL/vapour interfaces influence the water adsorption potential, surface diffusion properties and growth shape. Our findings reveal that the outer surface structure at the QLL/vapour interface depends weakly on the underlying crystal lattice. The desorption energy costs are equivalent for the basal and prism surfaces, however, the crystal lattice impacts the dynamics within the QLL. Our results show that there are distinct diffusion energy barriers at the basal and prismatic QLL/ice interfaces. The implication of our work is that the QLL/ice interface is key to the overall kinetics of ice growth in vapour whereas the QLL/vapour interface plays a secondary role.

Pentameric ligand-gated ion channels (pLGICs) are a family of membrane proteins that mediate the fast synaptic communication between neurons. The delicate role played by these neuroreceptors makes them major therapeutic targets for a variety of neuronal disorders, including Alzheimer's disease, which can be attributed to flaws in neuronal signalling. pLGICs are formed by five subunits arranged around an ion permeable pore and are activated by the binding of small molecules, the neurotransmitters, which triggers a wave of conformational changes culminating with the opening (gating) of the ion channel. In spite of their importance, we still have a very limited understanding of their behaviour and only in recent years the availability of structural information from experiments and progress in computational methods are opening new possibilities to tackle their complexity at the atomic level. In this project, we investigated the activation mechanisms of prototypical pLGICs with the aid of a number of state-of-the-art and novel computational techniques. In particular, molecular dynamics and metadynamics, a powerful enhanced sampling method to accelerate rare events, were employed to study the binding process of the neurotransmitter GABA to the insect RDL receptor, complementing mutagenesis electrophysiology experiments; binding free energy landscapes and anities were evaluated both for the wild-type and selected mutants and plausible binding paths were identified. The role of the trans-cis isomerisation of a highly conserved proline on the gating of the serotonin-activated 5-HT3 receptor was also explored with metadynamics. Experiments found this single process to be crucial for the correct functioning of the gate and our simulations showed a correlation between the isomerisation of this proline and conformational changes in the helices lining the pore. Understanding the conformational preference of protein building blocks may thus hold the key to fully comprehend the behaviour of whole receptors. Hence, a novel protocol, based on metadynamics and the dimensionality reduction algorithm sketchmap, was developed to map the conformational free energy of amino acids. As an example, it was applied here to aspartic acid, for which a number of stable conformers, including those experimentally observed with rotational spectroscopy, were identified. The results obtained in this thesis contribute to the fundamental understanding of pLGICs by helping unravel the complexity of the neurotransmitter binding and channel gating processes. Given the number of experimental structures recently made avalable, they are particlarly timely in paving the way for future studies on this important family of proteins.

Surfactant aggregate structures in bulk solutions have maintained their crucial importance in science and technology as they have a wide range of applications in a plethora of different industries. Surfactant molecules consist of polar head groups and nonpolar tails. Because of this chemical composition, surfactant molecules spontaneously self-assemble into aggregate structures when their concentration in water exceeds their critical micelle concentration. This thesis focusses specifically on the interaction of drug molecules within surfactant monolayers and micelles. The hydrophobic microenvironment arising from the resulting aggregate structures can be used to enhance the solubility of other, partially soluble substances by a process referred to in the literature as “solubilisation”. The encapsulation of these poorly water soluble drug compounds, within surfactant micelles, enables their oral delivery to patients. Sodium dodecyl sulphate micelles show great promise as drug delivery vehicles for hydrophobic compounds in general and the purpose of this thesis is to develop an understanding of how the molecular components of a micellar drug delivery system affect the observed encapsulation ability. Using a combination of atomistic molecular dynamics and well-tempered metadynamics simulations, the interaction of testosterone-based compounds within dodecyl sulphate monolayers and micelles with different counterions has been investigated in detail. In addition, the resulting effects on the structural and interfacial properties of these aggregate structures is investigated thoroughly. The results presented within this thesis show that ammonium ions compete with water molecules to form hydrogen bonds with the dodecyl sulphate headgroups. In doing so, they result in distinctly different interfacial properties of dodecyl sulphate monolayers compared to those with sodium ions, including the dehydration of the surfactant headgroups. This provides a possible explanation for the recently discovered experimental observation that SDS micelles encapsulate significantly more testosterone-based compounds than ADS micelles, despite the micelles being similar in size. Furthermore, the simulation results reported within this thesis reveal that the orientational behaviour of testosterone-based compounds varies depending on the number of polar interaction sites contained within each molecule. This is an effect which could have profound implications of the encapsulation behaviour of the drug compounds studied. The testosterone-based compounds are used as model drug molecules within the framework of this thesis, however the results obtained will aid the rationale design of new oral medications in the future. Moreover, the novel methods which have ben developed to construct an intrinsic surface of planar and (approximately) spherical interfaces of soft matter have significant scope for application in understanding the interfacial properties of these systems as studied within simulations and also as a collective variable when carrying out enhanced sampling simulations using techniques such as metadynamics.

Green tea catechins have been in use for some time as a curative for a number of disorders and illnesses, however their direct benefits are still disputed. In this thesis several computational techniques have been applied to systems involving green tea catechins in order to study their properties and better ascertain their supposed health benefits. Based on first principles data, classical force fields of four selected green tea catechins (-)-Epigallocatechin 3-Gallate (EGCg), (-)-Epicatechin 3- Gallate (ECg), (-)-Epigallocatechin-3-O-(3-O-Methyl)-Gallate (EGCmg) and (-)-Epigallocatechin (EGC) have been parametrised in order to examine their behaviour under different conditions. Classical Molecular Dynamics coupled with Metadynamics has been used to explore the potential energy surface of these molecules as a function of selected torsions deemed crucial to the conformation of the system. In depth analysis of their interactions under classical conditions has been carried out in gas phase, water and chloroform. The catechins EGCg and EGC were further examined using Density Functional Theory (DFT) to determine their radical properties which are closely linked to their antioxidant activity. By calculating their ionisation potentials, bond dissociation enthalpies and acidity in gas phase, water and benzene solution we find little difference in their energies, despite large structural differences, and we investigate the limit of DFT in accurately describing these systems. Classical simulations of the cardiac protein Troponin C (a protein known to be crucial to the process of heart contraction), in complex with EGCg, were carried out from the basis of previous experimental work and it was found that EGCg exerts a stabilising effect on the calcium ion mobility present in the system and may help regulate calcium signalling in the cardiac sarcomere. Using sparse experimental data as a guide, alternative proteinligand binding possibilities were uncovered and used to help validate and expand the current experimental knowledge on the troponin C - troponin I system, giving rise to two low affinity, non-specific binding sites for EGCg which also affect calcium mobility.

Material simulation using molecular dynamics (MD) at the quantum mechanical (QM) accuracy level has gained great interest in the community. However, the bottleneck arising from the O(N3) scaling of QM calculation has enormously limited its investigation scope. As an approach to address this issue, in this thesis, I proposed a machine-learning (ML) MD scheme based on Bayesian inference from CPU-intensive QM force database. In this scheme, QM calculations are only performed when necessary and used to augment the ML database for more challenging prediction case. The scheme is generally transferable to new chemical situations and database completeness is never required. To achieve the maximal ML eciency, I use a symmetrically reduced internal-vector representation for the atomic congurations. Signicant speed-up factor is achieved under controllable accuracy tolerance in the MD simulation on test case of Silicon at dierent temperatures. As the database grows in conguration space, the extrapolative capability systematically increases and QM calculations are nally not needed for simple chemical processes. In the on-the-y ML force calculation scheme, sorting/selecting out the closest data congurations is used to enhance the overall eciency to scale as O(N). The potential application of this methodology for large-scale simulation (e.g. fracture, amorphous, defect), where chemical accuracy and computational eciency are required at the same time, can be anticipated. In the context of fracture simulations, a typical multi-scale system, interesting events happen near the crack tips beyond the description of classical potentials. The simulation results by machine-learning potential derived from a xed database with no enforced QM accuracy inspire a theoretical model which is further used to investigate the atomic bond breaking process during fracture propagation as well as its relation with the initialised vibration modes, crack speed, and bonding structure.