VictorJuiz/thesis huggingface dataset:
Efficient Terahertz Wave Generation via Second-order Nonlinearity in AlxGa1-xAs Material System

The thesis aimed at generating 1- and 2-THz light in AlxGa1-xAs semiconductor chip through difference frequency generation using chi(2) nonlinearities. The pump and signal wavelengths were targeted around half of the material bandgap. The thesis develops two designs, namely Terahertz Lateral Bragg Reflection Waveguide (THz-LBRW) and Integrated Coplanar Strip (ICPS). The technique employed to achieve the exact phase matching condition in the THz-LBRW is based on engineering the phase velocity of the guided THz mode. The guided THz mode is a Bragg mode where its mode index is tuned to match the group index near the signal wavelength. On the contrary, the ICPS engineers the group index at the signal wavelength; such that, it is decreased to match the mode index of the generated THz light that is guided by coplanar strip. The efficiencies of 25.6[nW/W^2] and 4.9[nW/W^2] were obtained through optimization of the THz-LBRW and ICPS, respectively. Both structures are practical and manufacturable and the thesis presents the fabrication result for the THz-LBRW sample where the linear propagation loss of 10[/cm] was measured. The full fabrication process of the ICPS design is developed and its important partial results are reported.

Keywords: Terahertz
Difference frequency generation
Nonlinear optics
Bragg reflection waveguide
Coplanar strip
GaAs processing
Advisor: Helmy, Amr
Development of a Platform Strain for Production of Adipic Acid Yields Insights into the Localized Redox Metabolism of S. cerevisiae

Adipic acid is a commodity chemical that is currently derived from petroleum and has a global production value of 2.2 billion pounds per annum. Although it is not naturally synthesized, several pathways have been proposed for its biosynthesis from glucose. This work describes efforts to construct a platform strain of S. cerevisiae for production of alpha-ketoglutarate, a TCA cycle intermediate and a metabolite common to several proposed pathways, through cofactor engineering. Specifically, we investigated the disruption of glucose-6-phosphate dehydrogenase (ZWF1) and an aldehyde dehydrogenase (ALD6) gene, key reactions in the generation of cytosolic NADPH, in backgrounds with an interrupted TCA cycle through disruption of succinyl-CoA ligase (LSC2). The resulting strains showed improvements in growth rate and the production of alpha-ketoglutarate, suggesting the mechanism of recovery to be the use of cytosolic NADP(+) dependent isocitrate dehydrogenase for generation of NADPH and thus a coupling of alpha-ketoglutarate production to NADPH synthesis.

Keywords: alpha-ketoglutarate
S. cerevisiae
Metabolic Engineering
Cofactor
Advisor: Mahadevan, Radhakrishnan
Functional Variants of the NADPH Oxidase Genes and iNOS Significantly Contribute to the Development and susceptibility to Very Early Onset Inflammatory Bowel Disease

Very early onset inflammatory bowel disease (VEO-IBD) is characterized by a severe form of IBD diagnosed before the age of 10 years; however, its genetics are not well known nor described. However, it resembles the colitis found in chronic granulomatous disease (CGD) patients, who cannot mount sufficient oxidative burst in phagocytes due to defects in the NADPH oxidase complex. In addition, NOS2, encoding iNOS, which also has anti-microbial properties, has been implicated as important in the disease severity and intestinal tissue damage in IBD patients. Therefore, the role of these genes in VEO-IBD was investigated through genetic association and deep sequencing experiments. A number of novel associations of rare and functional variants with VEO-IBD were found. Upon functional analysis, these variants were found to have implications on gene function and expression. As a result, a large cohort of VEO-IBD is characterized by rare and functional variants important in superoxide and nitric oxide production.

Keywords: Genetics
Paediatrics
Gastroenterology
Inflammatory Bowel Disease
Immune Deficiency
Innate Immunity
Paediatric Gastroenterology
Advisor: Muise, Aleixo
A Novel Role of Listeriolysin O in the Exit of Listeria monocytogenes from Host Cells during Infection

Listeria monocytogenes is a Gram-positive human pathogen with a characteristic intracellular life-cycle. Within the host cytoplasm, expression of the cell surface protein ActA allows L. monocytogenes to undergo actin-based motility in the cytosol, leading to formation of actin-rich protrusions at the cell surface which are classically thought to be engulfed by neighbouring cells to facilitate spread. Here, I identify a novel role for Listeriolysin O (LLO) during infection. LLO promotes the release of bacteria-containing protrusions from the host cell, generating membrane-derived vesicles with exofacial phosphatidylserine (PS). These PS-positive structures form in an ActA and LLO-dependent manner, and can be found on the cell surface and in the extracellular media. I demonstrate that the PS-binding receptor TIM-4 contributes to cell-to-cell spread by L. monocytogenes in macrophages in vitro. Thus, L. monocytogenes may promote its dissemination in a host by exposing PS during protrusion formation and exploiting a PS-receptor for engulfment.

Keywords: Listeria
Listeriolysin O
cell-to-cell spread
ActA
Advisor: Brumell, John H.
Identifying Potential Binding Partners of VPS16B and VPS33B in Mammalian Cells

Platelets contain specialized granules that are required for platelet function in hemostasis. These granules are formed in the megakaryocyte precursor, and VPS33B and VPS16B are essential for this process as mutations in them cause arthrogryposis, renal dysfunction and cholestasis syndrome, where platelets lack α-granules. Here, it is shown that VPS33B and VPS16B exist as part of two complexes (480 kDa and 720 kDa). My project entailed the identification of the components of these complexes that could be required for platelet granule biogenesis. It was found that these complexes are distinct from the VPS33A HOPS complex as they are not associated with VPS11 or VPS18, but are formed through self-oligomerization. Yeast three hybrid and co-immunoprecipitation experiments suggest that VPS52, COG5 and ATP6AP2 may interact with VPS33B and VPS16B. In addition, VPS33B and VPS16B likely interact with Rab5 and/or Rab7, but not with Rab11A, based on both GST-pulldown assays and co-immunoprecipitation experiments.

Keywords: megakaryocyte
platelet
VPS33B
VPS16B
VIPAR
SPE-39
alpha granule
Rab5
Yeast hybrid
co-immunoprecipitation
mass spectrometry
electron microscopy
VPS52
COG5
ATP6AP2
ARC syndrome
Arthrogryposis renal dysfunction cholestasis
HOPS
CORVET
KIF5B
MYOIV
SORT1
oligomer
COG1
Rab7
Golgin
Rab11A
Blue native
Y11F
C341R
SF21
Dami
Advisor: Kahr, Walter
An Intranasal Delivery Method for Novel Therapeutics to treat Major Depressive Disorder

A problem in designing drugs that act upon the central nervous system is developing effective delivery methods. Major depressive disorder (MDD) affects 12% of men and 20% of women in the United States, and treatment options are often inadequate. In patients, the interaction between dopamine D1 and D2 receptors is correlated with major depressive disorder. A small peptide that disrupts this interaction can be delivered to brain areas using intranasal delivery. The D1-D2 interfering peptide has an antidepressant effect comparable to imipramine in the forced swimming test (FST), a test for antidepressant efficacy. At doses greater than 5.75 mg/kg, the D1-D2 interfering peptide has antidepressant action in the FST for 2 hours after intranasal administration. The D1-D2 interfering peptide disrupts the D1-D2 receptor interaction in the PFC after intranasal administration. This study provides preclinical support for intranasal administration of the D1-D2 interfering peptide as a new treatment option for MDD.

Keywords: Neuroscience
Major Depressive Disorder
Drug Delivery
Advisor: Liu, Fang
Design and Synthesis of New Scaffolds for Stat5 Inhibition

Signal Transducer and Activator of Transcription (Stat) 5 is a transcription factor that regulates the expression of genes involved in cell survival and proliferation. Hyper-activation of Stat5 is associated with several cancers. This work will discuss our efforts towards developing Stat5 inhibitors based on several scaffolds. One route we have explored involves modifying Stat3 inhibitors in order to produce selectivity for Stat5. The lead identified from this library shows nanomolar activity in vitro and induces leukemia cell death at 5 uM. We have also rigidified the core of the scaffold to improve selectivity. A library of compounds based on the resulting 1,4-benzodiazepine-2,5-dione structure were prepared. This presentation will also include our efforts to develop a new peptidomimetic scaffold based on a peptide sequence that binds to SH2 domains. By using a diverse set of novel scaffolds, we can generate small molecule inhibitors for the study and treatment of Stat5 induced cancers.

Keywords: Stat5
leukemia
cancer
medicinal chemistry
1,4-benzodiazepine-2,5-dione
Advisor: Gunning, Patrick
A Narrative Inquiry into Critical Learning Strategies in the Ontario High School Dramatic Arts Curriculum

The purpose of this study was to identify and apply critical learning strategies to the design of social justice lesson plans for the dramatic arts, followed by reflections upon the process. The major research question to be answered was “How can we integrate critical learning theories into the curriculum of Ontario high school drama curriculum?” To arrive at the answer to this question, the study addressed four sub-questions: Why is it important to integrate critical learning theories into the curriculum of high school drama classes? Which teaching strategies support critical learning curriculum? What are some examples of past efforts to integrate critical learning theories into the curriculum of high school drama classes? What are some examples of future possibilities for implementing critical learning theories into the curriculum of Ontario high school drama classes? The chosen methodology was narrative inquiry.

Keywords: dramatic arts curriculum critical theory
narrative inquiry
Advisor: Cameron, Linda
The Influence of Drama and Dance on Urban Elementary Students Critical Engagement with Questions of Social Justice and Equity

What is the influence of drama and dance on urban elementary students' critical engagement of questions of social justice/equity? This Masters thesis explores a critical participatory process drama unit as implemented, co-created and reflected upon in a Junior classroom. This paper asks what influence this kind of teaching has on critical thinking. I reflect on my subject position in terms of gender, race and class, and the positions of my students and their communities through an auto-ethnographic examination of dance and process drama practice and by documenting and examining the influence of this approach on critical pedagogy, grounded in research in an urban grade 5 classroom. This thesis contributes to the growing body of knowledge around why arts-based learning contributes to the skills and pedagogies that aid learners with a strong sense of equity and social justice.

Keywords: drama
critical pedagogy
urban education
dance
elementary
Advisor: Cameron, Linda
Pragmatism and Teaching Philosophy: An Inquiry into Truth, Relativism and Practice

When applied to problems in teaching philosophy, pragmatism improves philosophical teaching. It does so by deflating and clarifying the meaning of its problems and providing ways to understand and evaluate their effects on students and teachers. Problems of truth, relativism and teaching practice are investigated and the extent to which the pragmatic attitude ameliorates some of their central issues is shown. The net results of the thesis are: 1. It does not matter philosophically if there is an essence to truth as far as education is concerned, 2. Relativism is not a problem to be explained away but an opportunity to meaningfully improve philosophical teaching, and 3. A pragmatic attitude deflates some of the central problems in teaching philosophy and gives rise to new possibilities for educational experiences. Pragmatism improves teaching philosophy and assists in its necessary reorientation towards a practice that is future-oriented and embedded within the context of life.

Keywords: Pragmatism
Teaching Philosophy
Truth
Relativism
Pedagogy
Advisor: Bredo, Eric
Norris, Trevor
The Role of the Legionella Collagen-like Protein in Legionella pneumophila Biofilm Formation, Environmental Dissemination and Pathogenicity

The Legionella collagen-like protein (Lcl) of Legionella pneumophila is an adhesin involved in multiple processes during the lifecycle of L. pneumophila. Among these processes is the sedimentation and auto-aggregation of L. pneumophila. Lcl potentiates the infection of amoeba species by facilitating contact and adhesion to its host, allowing the pathogen to replicate, disseminate and persist in the environment. Lcl dependent auto- aggregation requires divalent cations, suggesting it may occur in the natural habitat of L. pneumophila. In addition to its role in sedimentation, Lcl mediates biofilm production of L. pneumophila. The Lcl encoding gene, lpg2644 is polymorphic among clinical isolates, and the number of collagenous repeats is positively correlated to biofilm production and clinical prevalence. This study underscores the role of Lcl in human infection by contributing to environmental dissemination and persistence, thereby increasing the likelihood of encountering human hosts.

Keywords: Legionella pneumophila
biofilm
attachment
aggregation
Advisor: Guyard, Cyril
Improvement of Binaural Hearing in Long Sequential Bilateral Cochlear Implantation

Providing children with bilateral cochlear implants after many years of unilateral hearing leads to asymmetric hearing and a persistent mismatch in auditory development in the central auditory pathways. These abnormalities were evident when we compared auditory evoked responses from each of the two ears at the level of brainstem, cortex, loudness perception, and identifying binaural cues. We asked whether the asymmetry in auditory development could be resolved by asking the children to wear the second device alone for periods of time during the day (aural patching). Even though children did adhere to aural patching, they did not do it for the requested amount of time. Furthermore, changes occurred at the level of the brainstem and cortex which were not related to the aural patching regimen, suggesting that the aural patching cannot reverse the abnormal plasticity produced by several years of unilateral hearing with the first cochlear implant.

Keywords: bilateral cochlear implant
aural patching
children
asymmetrical hearing
sequential bilateral cochlear implantation
binaural hearing
Advisor: Gordon, Karen Ann
Development of Sustainable Ultra-high Strength Concretes

The influence of constituent materials and curing regimes on compressive strength characterization of sustainable ultra-high strength concrete (SUHSC) was researched employing a standard mortar mixer and a non-vibration consolidation method. High intrinsic strength of fillers and reactive particles enhanced compressive strength. While the effect of the type of silica fume was negligible, the increase of the content of silica fume improved compressive strength. Use of combination of different sized limestone powders was effective in modifying the particle size distributions of SUHSC. Water content of the mixtures was an important parameter, but it was not the dominant influencing factor. An increase in the content of cement did not necessarily lead to the improvement of compressive strength. Elevated curing temperature, compared with ambient curing temperature, enhanced the compressive strength, and there was no strength decline at later ages.

Keywords: sustainable
concrete
ultra-high strength
Advisor: Hooton, Douglas
Exploring the Possibility of Changes in SIRT1 Activity in Lipotoxicity-mediated β-cell Dysfunction

Within the β-cell, there is evidence that sirtuin 1 (SIRT1), a key regulator of nutrient metabolism, plays a beneficial role on insulin secretion. Excess circulating fat, as seen in obesity, has been shown to be detrimental to β-cell function (“β-cell lipotoxicity”); an effect that may involve decreased SIRT1 activity. Consequently, SIRT1 activation may have a beneficial role on β-cell function in conditions of nutrient excess. Here we attempted to mitigate lipotoxicity induced β-cell dysfunction in vivo using pharmacological and genetic models of SIRT1 activation. Through hyperglycaemic clamps, we found that lipotoxicity resulted in significant β-cell dysfunction as expected in both models. SIRT1 activation, which did not affect β-cell function in the absence of fat, resulted in partial protection from the fat-induced β-cell dysfunction. These results suggest that the mechanisms of lipotoxicity-induced β-cell dysfunction include changes in SIRT1 activity.

Keywords: Lipotoxicity
Pancreatic Beta Cells
Sirtuins
Advisor: Giacca, Adria
Immortalization of MIP-GFP Neurons from the Hypothalamus and Neuronal Cell Types from Human Islet Isolates

The mouse insulin I promoter construct was developed to eliminate the unintended hypothalamic activity seen in the rat insulin II promoter. Given the importance of the hypothalamus in the maintenance of energy homeostasis, the specificity of this construct must be validated. To investigate the possible promoter activity within the hypothalamus, primary hypothalamic cultures of fluorescent reporter mice were immortalized and sorted. The resulting mHypoA-MIP/GFP cell lines confirmed the activity of the promoter within hypothalamic neurons and act as representative neuronal models. Initial characterization has determined the insulin responsive nature of these NPY neurons. Limited in vivo validations have confirmed the NPY nature of these neurons but were unable to pinpoint their localization within the hypothalamus. Subsequently, the technology utilized was adapted to attempt to generate immortalized human islet cells with limited success. The newly generated cell models can be utilized to refine the promoter construct and human islet immortalization process.

Keywords: MIP
insulin promoter
hypothalamus
islet neurons
Advisor: Belsham, Denise
A Blind Baud-rate CDR and Zero-forcing Adaptive DFE for an ADC-based Receiver

This thesis describes two design ideas in the area of ADC-based receivers. The first contribution of thesis is a 10Gb/s blind baud-rate CDR. The blind baud-rate operation, which is made possible by using a 2UI integrate-and-dump filter, creates intentional ISI in adjacent bit periods. The blind samples are interpolated to recover center-of-the-eye samples for a speculative Mueller-Muller PD and a 2-tap DFE operation. The 65nm CMOS test chip has a measured high-frequency jitter tolerance of 0.19UIPP at -/+300ppm of frequency offset. The second contribution of this thesis is a digital zero-forcing adaptive DFE. The DFE coefficients are calculated by correlating data samples with the recovered bits. Simulations show that the adaptive taps converge to the ISI values on the pulse response of the data signal. The CDR and adaptive 2-tap DFE have a high-frequency jitter tolerance of 0.28UIPP when simulated at 10Gb/s with an 8" FR4 channel.

Keywords: high-speed signalling
clock and data recovery
CDR
ADC-Based CDR
blind-sampling CDR
Mueller-Muller PD
baud-rate CDR
decision feedback equalizer
zero-forcing DFE
adaptive DFE
Advisor: Sheikholeslami, Ali
Algorithms for Base Station Assignment in Heterogeneous Cellular Networks

This thesis aims to find out the base station (BS) assignment strategy which achieves load balancing in heterogeneous networks from the proportional fairness perspective. There are mainly three contributions in this thesis. First, for the BS assignment problem under fixed transmit power, a dual pricing approach called the dual coordinate descent is proposed, which achieves near-optimal solution and is suitable for distributed implementation. Further, this method is modified to apply to the orthogonal frequency-division multiplexing (OFDM) case. Second, for the joint BS assignment and power control problem, this thesis offers the outside incorporation method. This method is shown to be more practical than another novel approach in this thesis. Third, for the joint BS assignment and beamforming problem, this thesis proposes a two-stage method. This approach has comparable performance and low computational complexity as compared to the algorithm in the existing literature.

Keywords: base station assignment
heterogeneous networks
Advisor: Yu, Wei
Generating C-peptide Humanized Mice

Type 1 diabetes is primarily caused by the loss of insulin producing beta-cells. Future therapies based on transplantation of in vitro generated beta-cells hold great promise for providing a cure. The development of such treatments heavily relies on the use of mouse models. However, insulin expressed from transplanted, mouse derived beta-cells cannot be differentiated from the host in allograft studies. ELISA can distinguish mouse and human C-peptide, a biomarker of insulin secretion. This project aims to create a humanized C-peptide mouse line that could be used to distinguish insulin production in allograft transplantation studies, or differentiate expression from the two mouse insulin genes. Humanized C-peptide insulin 1 chimeras have been generated and an insulin 2 founder has been identified. Following germline transmission, the lines will be crossed to obtain double homozygous humanized C-peptide mice. These animals will be an invaluable resource in allogeneic beta-cell transplants and in monitoring insulin allele expression.

Keywords: Mouse model
Gene targeting
Advisor: Nagy, Andras
Measuring the Time-dependent Thermal Preference of Caenorhabditis elegans in a Novel Droplet Assay

I am interested in precisely quantifying the process of thermal memory acquisition and decay in Caenorhabditis elegans under varying association conditions. I have developed a novel droplet-based assay to observe arrays of individual animals swimming in a spatial thermal gradient. By tracking the worm’s center-of-mass, I can compile a detailed map of its movements in a single droplet and show that worms will perform thermotaxis. The change in thermal preference over time (thermotaxis index), can be measured over multiple hours. By shifting worms to different temperatures for different times with and without food I can measure negative and positive association rates. Notably, my results demonstrate that C. elegans: can negatively associate a temperature with starvation; can be perturbed genetically to abolish negative association; processes positive and negative associative learning with multiple time scales.

Keywords: C. elegans
Thermotaxis
Learning
Advisor: Ryu, William