VictorJuiz/thesis huggingface dataset:
Synthesis and Site-specific Functionalizations of Aziridine-2-Carboxylic Acid-containing Cyclic Peptides
Keywords: Aziridine-2-carboxylic acid
Aziridine aldehydes
Aziridine ring-opening
Cyclic peptides
Site-specific integration

Peptide macrocycles belong to a privileged subclass of compounds, having found applications that range from drug discovery to nanomaterials. However these ring-shaped molecules are difficult, and often impossible to prepare using traditional synthetic methods. As such, a great deal of research has emerged on developing novel solutions to address these challenges in synthesis. Aside from these contemporary strategies, which primarily focus on methods of ring-closure, there still exist few approaches that enable site-specific modification at a late stage of synthesis. We therefore sought to address this paucity through the incorporation of the strained, aziridine-2-carboxylic acid (Azy) residue into the backbone of cyclic tetrapeptides. By way of ring-opening with azide and thiol nucleophiles, we have demonstrated that highly regioselective structural modifications can be accomplished through that generation of macrocycles equipped with a β-amino acid residue. Furthermore, we have capitalized on the reduced amidicity of the distorted aziridine amide bond in the development of a novel backbone modification strategy of an Azy-containing macrocyclic scaffold through the site-specific integration of various amino acid-containing fragments. Our efforts have unveiled a unique trend in the regioselectivity of N-acyl aziridine ring-opening reactions, and we have thus proposed a model to rationalize our findings. Finally, through our experience in the synthesis of Azy-containing derivatives, we have developed a highly scalable and reproducible strategy for the synthesis of elusive dimeric aziridine aldehyde analogues.
The Development of a Sensor to Determine Velocity in Liquid Aluminum
Keywords: Circular Cylinder
Inverse Heat Transfer
Liquid Aluminum
Nusselt Number
Solidification and Melting
Thermal Resistance

This thesis presents two sensor designs to determine velocity of liquid aluminum. These sensors are referred to as Sensor1 and Sensor2 where the principle of operation is based on forced convective heat transfer. Sensor1 is constructed of one material while Sensor2 is comprised of two materials, the geometry of both is that of a circular cylinder. The immersion of the sensor into the flow can be classified as a circular cylinder in liquid aluminum crossflow. A calculation of the localized Nusselt number acting on the surface of the sensor produces an estimate of the magnitude and direction of velocity. The localized Nusselt number estimate is provided by more than one thermocouple temperature measurement from within the sensor. The Sensor1 and Sensor2 concepts were constructed and tested in flowing liquid aluminum and numerical models were developed to study the heat transfer between the liquid and sensor.A peculiarity of this liquid metal system is that aluminum may solidify and subsequently melt onto the surface of the sensors; the solid aluminum is referred to as shell. The growth of the shell depends on various conditions, one examined in this work is the thermal resistance at the Sensor1-aluminum interface. An enthalpy numerical model is used to show that the thermal resistance at the Sensor1-aluminum interface has an important effect on the solidification and melting times of shell. The numerical model is validated with experimental measurements of localized shell solidification and melting times.To estimate the velocity of liquid aluminum the solidification of shell must be suppressed. By incorporating two materials of drastically different thermal properties, various regions of Sensor2 may be treated as lumped systems, this mathematical treatment provides fast estimates of the localized Nusselt number, hence the velocity can be determined in real-time. The modified Nusselt number estimated by Sensor2 is a sum of the thermal resistance from the thermal boundary layer and thermal resistance at the Sensor2-aluminum interface. By numerically modeling the flow of liquid aluminum over the Sensor2 design and by comparing these results to experimental data, the thermal resistance at the Sensor2-aluminum interface is estimated. A technique to determine the magnitude and direction of velocity from the local Nusselt number of the Sensor2 design is presented.
Mapping Organic Molecular Motions with RF Compressed Femtosecond Electron Diffraction
Keywords: Mapping Molecular Motions
Ultrafast Electron Diffraction
Ultrafast Molecular Crystallography
Ultrafast Science
Ultrafast Structure Dynamics

This thesis reports on the development of a novel ultrabright femtosecond electron diffraction setup and its application towards monitoring primitive atomic motions during a photoinduced phase transition in an organic molecular crystal. By using the time-dependent electric field of a 3 GHz radio-frequency cylindrical cavity, high flux electron bunches are compressed to a few hundred femtoseconds in duration. A grating-enhanced ponderomotive scattering technique is used to fully characterize the temporal characteristics of the high brightness electron pulses. A minimum temporal instrument response of 420 femtoseconds (full-width-half-maximum) for 200 femtocoulomb electron bunches is reported. The instrument response is limited by the synchronization jitter between the radio-frequency waves and the laser oscillator. To mitigate this problem, a photo-triggered streak camera is used to first characterize the arrival time jitter of the electron pulses and then `time-stamp' the precise arrival time of each individual electron pulse with respect to the laser. This reduces the synchronization contribution to the instrument response time down to 30 femtoseconds RMS (root-mean-square). This new electron source is used to study the molecular dynamics of a photoinduced insulator-to-metal phase transition in the organic crystal (EDO-TTF)
Prognostic Factors in Aneurysmal Subarachnoid Hemorrhage: Pooled Analyses of Individual Patient Data and Development of Novel Risk Scores in Large Cohorts of International Patients
Keywords: Cerebrovascular
Clinical trial
Meta analysis
Outcomes
Risk factors
Subarachnoid hemorrhage

Primary studies reporting prognostic associations in aneurysmal subarachnoid hemorrhage (SAH) are often insufficiently powered, use data of limited representativeness and scarcely examine the added value of prognostic factors above those of other known factors. Hence, considerable knowledge gaps and conflicting results exist in the literature on the nature and extent of prognostic associations in SAH. Prognostic factors have been combined to develop prediction models and risk scores for early outcome prediction after SAH. None is routinely applied in clinical or research settings; some major constraints relate to lack of evidence on the predictive accuracy, reliability and generalizability of reported risk scores. The global aim of this research was to address these challenges and contribute to improved understanding of prognostic associations in SAH by analysing large cohorts of SAH patients reflecting a broad spectrum of settings. Pooled analyses of patient-level data from multiple randomized clinical trials and prospective hospital registries involving 10963 patients demonstrated a strong prognostic effect of admission neurologic status on 3-month outcome according to Glasgow outcome score. Age had a moderate effect on outcome; premorbid hypertension and subarachnoid clot burden on the Fisher scale were weak predictors of outcome. Patient's sex had no independent predictive value. Prognostic effect of aneurysm size and location depended on treatment modality. Novel prognostic scores were developed combining these predictors for early prediction of mortality and unfavorable outcomes at 3 months, and demonstrated adequate performance at bootstrap (AUC: 0.77 - 0.83) and at cross validation. Using 2 nationally representative administrative datasets, socioeconomic status and race/ethnicity were explored as latent prognostic factors in SAH. Multinomial logistic regression analysis demonstrated socioeconomic status, measured as neighborhood income status, was associated with inpatient mortality risk after admission for SAH. The extent of the association could be related to health care system under which treatment was provided. Race/ethnicity was independently associated with inpatient mortality. Patients of Hispanic ethnicity had the best outcomes and Asia/Pacific Islanders experienced the worst outcomes during the inpatient course. This research has provided higher level evidence than prior studies on studied prognostic factors and reliable tools for early prediction of outcome after hospitalization for SAH.
Integrating African Indigenous Science into the Faculties of Higher Education Curriculum in Uganda
Keywords: Anti-colonial education
Indigenous Science
Knowledge hybridization
Traditional Knowledge

This study examines African Indigenous Science (AIS) in higher education in Uganda. To achieve this, I use anticolonial theory and Indigenous knowledge discursive frameworks to situate the subjugation of Indigenous science from the education system within a colonial historical context. These theories allow for a critical examination of the intersection of power relations rooted in the politics of knowledge production, validation, and dissemination, and how this process has become a systemic and complex method of subjugating one knowledge system over the other. I also employ qualitative and autoethnographic research methodologies. Using a qualitative research method, I interviewed 10 students and 10 professors from two universities in Uganda. My research was guided by the following key questions: What is African Indigenous Science? What methodology would help us to indigenize science education in Uganda? How can we work with Indigenous knowledge and anticolonial theoretical discursive frameworks to understand and challenge the dominance of Eurocentric knowledge in mainstream education?My research findings revealed that AIS can be defined in multiple ways, in other words, there is no universal definition of AIS. However, there were some common elements that my participants talked about such as: (a) knowledge by Indigenous communities developed over a long period of time through a trial and error approach to respond to the social, economic and political challenges of their society. The science practices are generational and synergistic with other disciplines such as history, spirituality, sociology, anthropology, geography, and trade among others, (b) a cumulative practice of the use, interactions with and of biotic and abiotic organism in everyday life for the continued existence of a community in its' totality. The research findings also indicate that Indigenous science is largely lacking from Uganda's education curriculum because of the influence of colonial and post-colonial education. Graduates of the colonial education system who are manning education in the country have themselves come to disdain Indigenous knowledge. The major findings from the study were: 1) participants' articulation of Indigenous science; 2) influence of organized religion on African Indigenous Science; 3) dominance of professors' foreign experiences in determining curriculum content; 4) protection of intellectual property rights for Indigenous science; and 5) collaborative research between Indigenous and Western scholars to enhance attitude change toward Indigenous science.
The Genetic and Epigenetic Basis of Posterior Fossa Ependymoma
Keywords: Brain Tumor
Cancer
Ependymoma
Epigenetics
Genetics
Pediatrics

Ependymomas are childhood brain tumors that occur throughout the central nervous system, but are most common in the hindbrain, also known as the posterior fossa (PF). Current standard therapy comprises maximal safe surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Despite histological similarity, ependymomas from throughout the neuroaxis likely comprise multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa ependymomas, termed Group A and B. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis at recurrence, and death as compared to Group B patients. In spite of balanced genomes observed in Group A PF ependymoma, whole-genome and whole-exome sequencing of 47 PF ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants (SNVs). While devoid of recurrent SNVs and focal copy number aberrations, poor prognosis Group A ependymomas exhibit a CpG island methylator phenotype (CIMP). Transcriptional silencing driven by CpG methylation converges exclusively on targets of the polycomb repressive complex 2 (PRC2) that represses expression of differentiation genes through tri-methylation of H3K27. Group A-CIMP+ PF ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically de-regulated but genetically bland.
Dynamic Thermo-mechanical Phase-field Models for Martensitic Transformations in Shape Memory Alloys
Keywords: Isogeometric analysis
Martensitic transformations
Phase-field model
Shape memory alloys
Thermo-elasticity
Twinning

Shape memory alloys (SMAs) exhibit complex microstructures and non-linear hysteretic behaviors that arise from a strong interaction between mechanical and thermal phenomena. It is imperative to couple the thermal physics and the mechanical dynamics to study the influence of such coupling on the mechanical properties of SMA systems, including nanostructures. However, the majority of phase-field models in the literature related to SMAs account for structural physics only. With the aim to incorporate thermal physics, in this thesis, first the 2D and 3D dynamic fully coupled thermo-mechanical phase-field models are developed based on the strain-based order parameters. The developed models are highly nonlinear, strongly hysteretic with fourth-order spatial differential terms, which impose several computational challenges. Secondly, to overcome these computational challenges, a numerical formulation based on the isogeometric analysis is developed for a straightforward solution to the fourth-order differential equations using continuously differentiable non-uniform rational B-splines (NURBS).Several numerical examples of microstructure evolution in SMA systems, in particular nanostructures of different geometries, under temperature and stress induced loadings illustrated the flexibility, accuracy and robustness of the developed numerical formulation. The numerical simulations revealed a significant impact of the temperature dynamics on mechanical properties of SMAs. The developed models successfully captured experimentally observed mechanical and thermal hysteresis phenomena, local non-uniform phase transformations and corresponding non-uniform temperature and deformations distributions. The predicted microstructure evolution is in qualitative agreement with the results reported in the literature. The material properties of austenite and martensite phases are different, as observed experimentally during phase transformations. However, the majority of macroscale non-isothermal phase-field models in the literature related to SMAs account only for uniform material properties of different phases. Therefore, the new 1D and 3D macroscale non-isothermal phase-field models incorporating the phase dependent properties are developed in this thesis for a better description of hysteresis phenomena in SMAs. Specifically, the non-linear thermo-mechanical phase dependent material properties are incorporated via the compliance variable as a function of local scalar phase order parameter and stress state. The simplicity of the proposed 1D and 3D non-isothermal phase-field models allowed efficient numerical implementations.
Computing the Zeta Function of Two Classes of Singular Curves
Keywords: cryptography
p-adic cohomology
point counting
singular varieties
zeta function

Motivated by applications to cryptography, for over a decade mathematicians have successfully used p-adic cohomological methods to compute the zeta functions of various classes of varieties defined over finite fields. In all instances, the varieties considered had smooth representations in either affine or projective space.In this thesis, two non-smooth situations are introduced: the case of superelliptic curves with singular points that are rational over the field of definition, and the case of nodal projective plane curves. In each case we present, assuming the characteristic is fixed, a polynomial-time algorithm which computes the zeta function the curve, and we provide the results of an implementation in MAGMA. The case of singular superelliptic curves extends a method of Gaudry and Gurel, and the case of nodal projective curves extends a method of Kedlaya, Abbott, and Roe.
Femtosecond Electron Diffraction and Spectroscopic Studies of a Solid State Organic Chemical Reaction
Keywords: Crystallography
Diarylethene
Electron DIffraction
Solid State Organic Reaction
Transient Absorption Spectroscopy
Ultrafast

Photochromic diarylethene molecules are excellent model systems for studying electrocyclic reactions, in addition to having important technological applications in optoelectronics. The photoinduced ring-closing reaction in a crystalline photochromic diarylethene derivative was fully resolved using the complementary techniques of transient absorption spectroscopy and femtosecond electron crystallography. These studies are detailed in this thesis, together with the associated technical developments which enabled them. Importantly, the time-resolved crystallographic investigation reported here represents a highly significant proof-of-principle experiment. It constitutes the first study directly probing the molecular structural changes associated with an organic chemical reaction with sub-picosecond temporal and atomic spatial resolution -- to follow the primary motions directing chemistry.In terms of technological development, the most important advance reported is the implementation of a radio frequency rebunching system capable of producing femtosecond electron pulses of exceptional brightness. The temporal resolution of this newly developed electron source was fully characterized using laser ponderomotive scattering, confirming a 435 +/- 75 fs instrument response time with 0.20 pC bunches. The ultrafast spectroscopic and crystallographic measurements were both achieved by exploiting the photoreversibility of diarylethene. The transient absorption study was first performed, after developing a novel robust acquisition scheme for thermally irreversible reactions in the solid state. It revealed the formation of an open-ring excited state intermediate, following photoexcitation of the open-ring isomer with an ultraviolet laser pulse, with a time constant of approximately 200 fs. The actual ring closing was found to occur from this intermediate with a time constant of 5.3 +/- 0.3 ps. The femtosecond diffraction measurements were then performed using multiple crystal orientations and a large number of different samples. To analyse the results, an innovative method was developed in which the apparently complex ring-closing reaction is distilled down to a small number of basic rotations. Immediately following photoexcitation, sub-picosecond structural changes associated with the formation of the intermediate are observed. The rotation of the thiophene rings is identified as the key motion. Subsequently, on the few picosecond time scale, the time-resolved diffraction patterns are observed to converge towards those associated with the closed-ring photoproduct. The formation of the closed-ring molecule is thus unambiguously witnessed.
Three Essays on the Individual, Task-, and Context-related Factors Influencing the Organizational Behaviour of Volunteers
Keywords: Nonprofit management
Volunteering

This dissertation examines how various individual, task-, and context-related factors influence important volunteering outcomes. Using data sourced from a large international aid and development agency in the United Kingdom, the three studies that follow explore the organizational behaviour of volunteers and highlight several initiatives that nonprofit organizations can introduce in order to motivate and retain their volunteers.In the first chapter, I present a moderated mediation model where I show that prosocially motivated volunteers dedicate more time to volunteering. The study results further show that volunteer engagement fully mediates the relationship between the value motive and volunteer time, and that the strength of the mediated effect varies as a function of volunteers' commitment to beneficiaries. These findings provide a new perspective on the link between volunteers' motivation and active participation in volunteer activities.The second chapter presents a framework for understanding the processes through which volunteers' perceived impact on beneficiaries influences their turnover intentions and time spent volunteering. The results show that volunteers who perceive that their work impacts beneficiaries (1) report lower intentions to leave their volunteer organization due to their commitment to that organization; and (2) dedicate more time to volunteering because they are committed to the beneficiaries of their work. These findings make a significant contribution to volunteering research by uncovering two different mechanisms that explain how the positive consequences of perceived impact on beneficiaries may unfold.Finally, the third chapter presents a mediation model that explains how an organizational support framework promotes organizational commitment in volunteers. Specifically, the results show that training and paid staff support promote higher levels of volunteers' organizational commitment due to increases in volunteers' perceptions of role clarity and self-efficacy. Importantly, this study illustrates how volunteer managers can use two management practices that are under their control to maximize the commitment of volunteers.