VictorJuiz/thesis huggingface dataset:
Theory of Charge Transport through Vibrating Molecules
Keywords: charge transport
dissipation
influence functional path integral method
quantum master equation
quantum physics

In this Thesis we study several aspects of charge transport through single molecule junctions. Focusing on the interaction of the electrons with vibrations we devise toy-models which capture the consequences of many-body interactions for transport properties of the junction. We begin with the study of heating, cooling and stability of the molecular bridge. First, the dynamics of the vibrational mode is followed using the master equation. Using this approximate technique, we identify the regimes in which the electronic current is pumping energy into the vibrational mode, or alternatively, absorbing energy from it. An important conclusion of this study is that at large currents, the pumping of energy into vibrations may result in uncontrolled heating, making the structure unstable; Alternatively, at small biases, extraction of energy from vibrations is possible, resulting in a cooling behavior. We extend the model to include a dissipative environment, such as the vibrating backbone of the molecule or the solvent, and demonstrate that dissipation may alleviate structural instability. From the comparison of the behavior of a strongly anharmonic mode (two-level system) with a fully harmonic mode a surprising conclusion is reached: the cooling/heating analysis in both cases produces qualitatively similar results. Finally, we confirm the microscopic equivalent of the Second Law, the charge and energy Fluctuation Theorem, at the level of second order markovian master equation. In order to study exactly the vibration assisted electron transport through a donor-acceptor junction we develop a numerical scheme based on the influence functional path integral (INFPI) and quasi-adiabatic path integral (QUAPI) methods. With this tool, the results obtained with the perturbative kinetic master equation are confirmed validating the approximations used there. We further extend the model to include direct electronic tunneling. Encouraged by the similarity of transport behavior in harmonic and strongly anharmonic junctions, we compare the non-equilibrium Anderson-Holstein model of electron interacting with a harmonic mode to its variant, in which the infinite ladder of the harmonic mode is truncated. In this case, interestingly, the two models show significant differences: strong vibrational anharmonicity does not allow for the Franck-Condon blockade or current hysteresis effects found in the harmonic model. Instead, it introduces a novel many-body off-resonance blockade. We conclude with the study of electronic decoherence due to the interaction with vibrations. To this end, we consider three cases of electronic transport through a molecular junction: fully coherent (rigid molecule), fully dephased and purely inelastic. We demonstrate that the three cases produce characteristic energy profiles and may be distinguished from one another via the measurement of the thermopower.
Foreshortening Leads to Overestimation of Angles
Keywords: depth perception
foreshortening
perception of angles
perspective
slants
surfaces

The hypothesis tested here is that vision's misuse of foreshortening, such as in an optic array's texture gradient, may lead to errors in the perception of angles. While errors may increase with optical slant, they may also be reduced by the use of optic information for the shape of surfaces. The first hypothesis was tested in five experiments. In the first four, observers estimated acute angles between a line receding away from the observer into depth - the z dimension -- and a line oblique to the z-dimension presented on the ground (Experiments 1 and 2) or a wall (Experiments 3 and 4). In Experiment 5, observers estimated angles between a slanted edge of a square platform and an oblique line lying on top of the surface. Foreshortening was increased by increasing the observer-to-target distance along the z-line (Experiments 1-4) and by reducing the distance from the eye to the surface bearing the target (Experiments 2, 4, 5). As expected, target angles were increasingly overestimated with foreshortening in Experiments 1-4. In Experiment 5, target angles on the slanted surface were not overestimated (they were underestimated modestly). Further, geographical slants were overestimated for surfaces. This was true for surfaces covered in different textures (randomly or cardinally oriented texture elements), in line with the foreshortening hypothesis.
The Role of Elongation Factor P in Salmonella enterica serovan Typhimurium Stress Response and Pathogenesis
Keywords: Elongation factor P
Pathogenesis
Salmonella
Stress response
Translation

Elongation factor P (EF-P) is a universally conserved bacterial translation factor that resembles a tRNA in both shape and size. It is post-translationally modified by the enzymes PoxA and YjeK to generate the fully active β-lysylated form, which is then hydroxylated by YfcM. EF-P functions to rescue ribosome stalls at difficult-to-translate motifs, such as those encoding multiple prolines. Although EF-P was previously described as an essential gene in E. coli, I successfully generated an efp knockout in Salmonella enterica serovar Typhimurium. The S. Typhimurium efp mutant exhibits pleiotropic phenotypes that overlap with those of the poxA and yjeK mutants. These phenotypes include increased susceptibility to antibiotics and detergents; impaired growth in low osmolarity media; enhanced resistance to the compound S-nitrosoglutathione (GSNO); and reduced motility on soft agar plates. I showed that relatively few cytoplasmic and membrane proteins are differentially expressed in the poxA, yjeK, and efp mutants relative to wild-type S. Typhimurium. Previous work by our lab showed that the S. Typhimurium poxA and yjeK mutants are attenuated in a mouse model of infection. I extended those findings to the efp mutant and further demonstrated that the mutants are defective for invasion, intracellular replication, and Sif formation in HeLa cells. The SPI-2 effector protein SifA is known to be essential for Sif formation and contains a PPP motif. Using translation fusion assays and immunoblotting, I showed that SifA translation is dependent on EF-P and that this dependency is abrogated upon mutation of the PPP motif to PLP. I also observed that efp mutants have reduced SPI-2 gene expression, likely due to the fact that the activity of the OmpR-EnvZ two-component system is impaired. Taken together, my findings identify several novel EF-P targets and shed light on the ways in which loss of EF-P affect the fitness of S. Typhimurium.
Passaged Chondrocytes: A Source of Cells for Cartilage Tissue Engineering
Keywords: Cartilage
Chondrocyte
Dedifferentiated
Osteoarthritis
Redifferentiate
Tissue Engineering

The interest in bioengineered cartilage for the replacement of damaged articular cartilage has gained momentum in recent years. One of the issues limiting clinical translation has been identifying an appropriate cell source. To address this we identified that hyaline cartilage can be formed through the co-culture of a small number of primary articular chondrocytes with twice passaged chondrocytes. Not only were passaged human cells able to redifferentiate, but after separation from the primary cells, maintained their differentiation and formed cartilagenous tissue. This tissue was rich in collagen type II and aggrecan, the major molecules present in hyaline cartilage. There was little collagen type I. Tissue characterization studies demonstrated that redifferentiation was occurring during the first week of culture. Co-culture of primary and passaged cells in side-by-side culture indicated that a soluble factor was responsible for redifferentiation and that direct cell-cell contact was not essential. A serum-free culture system was developed and tissue characterized to confirm that the cells maintained phenotype, in order to be able to examine the secretome. Protein analysis through mass spectrometry and immunohistochemical staining of tissue sections indicated that versican, aggrecan, and types II and XII collagens were accumulated early within the first 3 days, by passaged chondrocytes were redifferentiating and formed cartilage tissue in vitro. This suggested that these molecules may be necessary to provide a microenvironment that supports hyaline cartilage formation. Further study is required to determine if these molecules are also accumulated by passaged human chondrocytes and their role in promoting hyaline cartilage formation. In addition these molecules also may then serve as markers that can be used to identify culture conditions and/or scaffolds that will favour articular cartilage formation by passaged chondrocytes and facilitate rapid screening of culture conditions for chondrogenic inducing potential. Together these studies facilitate the clinical transition of regenerative medicine approaches to cartilage repair.
Assembling Surface Linker Chemistry and Minimization of Biosensor Non-specific Adsorption
Keywords: EMPAS
non-specific adsorption
OEG
short SAM
thiosulfonate
TUBTS

The development of a preparation method for biosensing interface on hydroxylated surfaces is presented in this manuscript. This method involves the use of thiosulfonate-based linkers to construct robust and durable SAMs (Self-Assembling Monolayers) onto hydroxylated surfaces. The resulting SAMs have the ability to chemoselectively immobilize thiol-containing molecules under aqueous condition in a single, straightforward, reliable and coupling-free manner. This method is then implemented in the construction of biosensing interfaces for EMPAS (ElectroMagnetic Piezoelectric Acoustic Sensor) dedicated to the detection of avidin. Efforts were devoted to improving the performance of the biosensing interface by reducing/preventing non-specific adsorption. Improvements were systematically observed with the incorporation of an OEG (Oligo(Ethylene Glycol)) backbone and a diluent (i. e. SAM molecules without a head functional group). The hydroxyl head function and short length of the diluent were crucial in preventing non-specific adsorption. This showed that both enthalpy-driven and entropy-driven mechanisms work in conjunction in order for the surface to achieve high resistance in non-specific adsorption. Expansions of this method to silicon nitride (Si3N4), aluminium nitride (AlN) and gold (Au) were pursued. Lastly, a previously undocumented EMPAS coil circuit design was reported and discussed.
An Investigation of Metallurgical Reactions with Levitated Droplets
Keywords: Decarburization
Levitated droplets
Mass transfer
Silicon refining
Stainless steel
Thermal diffusion

The study of gas-metal interactions has industrial significance in metallurgical processes. Despite the vast production volume, the high temperature kinetics of these processes are far from fully understood. The difficulty in accounting for the effects brought by the large temperature gradients that commonly exist between gas and liquid metal phases remains a major challenge. It is therefore essential to understand and quantify the influence of these conditions on mass transfer during metallurgical reactions. In the production of stainless steel, one of the main objectives is to minimize oxidative loss of valuable alloying elements such as chromium during the decarburization process. Carbon dioxide has a lower oxidizing potential compared to oxygen gas, and could provide a potential solution to the problem of alloy loss during the oxidation refining of stainless steel. From an economic standpoint, in order to fully utilize the advantages associated with using CO
(In)Humanity on Trial: On the Ground Perceptions of International Criminal Tribunals
Keywords: Africa
Europe
human rights
international criminal law
transitional justice and reconciliation
war crimes and genocide

The purpose of this dissertation is to understand how international criminal tribunals (ICTs) are received in different contexts. The dissertation is driven by the following puzzle: Why has there often been a negative response to international criminal tribunals (ICTs) in local communities that have been victim to the crimes that these institutions are prosecuting? I examine this puzzle through local responses to the International Criminal Tribunal for former Yugoslavia (ICTY) in Bosnia and Herzegovina (BiH) and Serbia, and the International Criminal Tribunal for Rwanda (ICTR) in Rwanda. The findings are based on three research trips to each country, including nine consecutive months of fieldwork in Rwanda and six consecutive months of fieldwork in BiH and Serbia, and over 136 successful semi-structured and open-ended interviews with a variety of local actors. My data suggest that the two ad hoc tribunals were not successful at establishing themselves as legitimate and credible mechanisms of transitional justice. The locals in each country believed that they were not the primary beneficiaries of ICTs, and that that the ICTs paid insufficient attention to the dynamics between tribunal demands and proceedings, and political events on the ground. My findings show that, first, in each case, local actors in power - those connected to past regimes who were responsible for the 1990s atrocities, and those who were part of new regimes - adapted well to the conditions set by ICTs, manipulating the tribunals for their own political goals and influencing the perception of these institutions among the local populations. Second, ICTs had a serious impact on domestic politics, feeding into power struggles between domestic and international actors and between factions on the ground. This outcome had significant implications for political transitions in the three countries, many of which were unintended and contrary to the aims and expectations of the tribunals.
On the Nature of Allosteric Interactions at the M2 Muscarinic Receptor
Keywords: allosteric modulators
cooperativity
G protein coupled receptors
mechansitic modelling
molecular dynamics
Muscarinic receptors

G protein-coupled receptors (GPCRs) are allosteric machines that constitute the largest family of membrane bound receptors. Members of the family 1a GPCRs such as the M2 muscarinic cholinergic receptor transduce the binding of an extracellular ligand to an intracellular messenger. The size of the receptor that participates in signalling is debated and as such the mechanism of signalling is uncertain. In addition, each of these receptors possess two distinct but conformationally linked sites, an orthosteric site and an allosteric site which engage in a process of allosteric modulation; the mechanism of which is also uncertain. For modulation, debate centers on the roles of electrostatic repulsion, steric hindrance and conformational stability. For signalling, the differences in these effects at monomers and oligomers on modulation are unexplored. Here we have explored the role of monomers and oligomers on modulation in kinetic studies and at equilibrium. Allosteric ligands slow orthosteric ligand kinetics and the time required for equilibration. This prolonged incubation is typically not considered in presumed equilibrium measurements that rationalise modulation in terms of monomers. Binding at equilibrium, however, reveal multiphasic effects which identify varying types of interactions and the oligomeric nature of the receptor. These interactions can be categorised into two types of allosteric modulation: inter-molecular, which occurs between an allosteric site at one receptor and the orthosteric site at another; intra-molecular, which occurs between the allosteric and orthosteric sites of the same receptor. Inter-molecular effects suggest a conformational interplay among receptors which was demonstrated by a FRET based probe, engineered mutants and kinetic-based mechanistic models. Inter-molecular effects and conformational stability, as examined by molecular dynamics, account for varied types of allosteric modulation (i.e., positive and negative) and may underlie high-affinity binding of allosteric ligands. Intra-molecular effects appear to result from electrostatic repulsion between highly charged ligands that engage in steric hindrance. The net result tends to negative allosteric modulation and low-affinity binding of allosteric modulators. Overall, binding of allosteric ligands at equilibrium identify that the M2 muscarinic receptor is a tetramer and the oligomer, not a monomer, allows for the various types of allosteric modulation.
Maternal and Perinatal Health of Refugees in Ontario: A Population-based Perspective
Keywords: perintal epidemiology
refugee health
social disparities

Refugee women and their newborns are suspected to experience greater risk of adverse maternal and perinatal health outcomes. However, little systematic refugee-specific research has been done. This dissertation poses the research question - "are refugee immigrant women and their newborns at higher risk of adverse maternal and perinatal outcomes compared to 1) non-refugee immigrant and 2) non-immigrant women?" Large population-based immigration (1985-2010) and hospitalizations databases (2002-2010) from Ontario, Canada were used (all women eligible for health insurance). The first manuscript examined severe maternal morbidity (SMM) and SMM subtypes among refugee immigrants compared to both non-refugee immigrants and non-immigrants. The rate of any SMM was elevated among refugees (n=30,420) compared to non-refugee immigrants (n=235,540) (adjusted rate ratios (ARR)=1.22, 95% confidence interval: 1.09-1.36) and non-immigrants (n=878,709) (ARR=1.34 (1.23-1.47)). HIV (SMM subtype) among refugees was 8 and 17 times that of non-refugee immigrants and non-immigrants, respectively. The SMM rate among refugees was no longer elevated when deliveries with HIV were excluded. The second manuscript examined the risk of severe neonatal morbidity (SNM) among neonates born to refugees compared to those of non-refugee immigrants and non-immigrants. SNM risk among non-sponsored refugees (i.e., asylum seekers) was also compared to that of sponsored refugees (i.e., government, privately sponsored). The risk of severe neonatal morbidity was significantly higher among newborns of refugee compared to non-refugee immigrants (ARR=1.10 (1.03-1.17)) but lower in comparison to non-immigrants (ARR=0.94 (0.89-0.99)). There was no difference by sponsorship status. The objective of the third manuscript was to determine if the relationship between refugee status and risk of preterm birth (PTB) was modified by secondary (migration to another country prior to Canada) or primary (direct to Canada) migration. A secondary objective was to examine whether this relationship varied by maternal region of birth. Secondary refugees and primary refugees experienced a significantly higher cumulative probability of PTB (22-31, 32-36, ≥37 weeks) compared to their secondary and primary non-refugee counterparts (adjusted cumulative odds ratio (ACOR) =1.59 (1.25-2.01) and ACOR=1.12 (1.02-1.23)), respectively. These associations were also significant for Asian immigrants. This dissertation makes a substantial contribution towards understanding the health and the determinants of health of refugee immigrant mothers and their infants in Canada.
Towards Solid-phase Nucleic Acid Hybridization Assays on a Paper-based Platform and Within Channel Microfluidics Using Quantum Dots as Donors in Fluorescence Resonance Energy Transfer
Keywords: Fluorescence resonance energy transfer
Microfluidics
Nucleic acid detection
Paper-based assays
Quantum dots

The work described herein has explored solid-phase transduction of nucleic acid hybridization on platforms composed of paper substrates, and also glass surfaces within glass/polydimethylsiloxane microfluidic channels. Single-stranded probe oligonucleotides were conjugated to quantum dots (QDs), and the QDs were immobilized to the solid substrates. The QDs served as donors in fluorescence resonance energy transfer (FRET). Hybridization of solution-phase targets with the probes brought acceptor dye in close proximity to the surface of immobilized QDs, triggering a FRET-sensitized emission from the acceptor dye for ratiometric transduction of nucleic acid hybridization. Chemical modifications of the paper and glass surfaces were developed to immobilize the QD-probe conjugates. Assays with both the paper and glass platforms exhibited fast hybridization kinetics with complete signal development within minutes. For the channel microfluidic experiments, the quantification of target was determined from the spatial length of the microfluidic channel that provided an optical emission indicative of the presence of hybrids. For the paper-based QD-FRET assays, quantification was based on the magnitude of donor and acceptor photoluminescence intensities. The intensity of emission from the paper-based assays was determined using an epifluorescence microscope, and also a consumer digital camera. A novel signal enhancement strategy for QD-FRET transduction was demonstrated on paper substrates. Drying compacted the paper and increased the optical cross-talk of QD-FRET probes to enhance emission intensity. Multiplexed detection of two oligonucleotide targets with excellent mismatch discrimination was demonstrated by implementation of two different QD-dye FRET pairs. Both assay platforms offered a detection limit in the femtomole range, and additional isothermal target amplification allowed target detection in the zeptomole range. The work in this thesis demonstrates that integration of the QD-FRET transduction method with microscale fluidic platforms provides for analytical figures of merit that are sufficient to warrant development of field portable and point-of-care nucleic acid diagnostic applications.