VictorJuiz/thesis huggingface dataset:
PrP and its Ancestral Relatives ZIP6 and ZIP10 Interact with NCAM1, Altering its Molecular Environment and Post-translational Modifications during Epithelial-to-mesenchymal Transition

The prion protein (PrP) was recently found to be evolutionarily linked to a subfamily of ZIP transporters which possess a PrP-like domain. A member of this subfamily, ZIP6, is of particular interest as separate studies have shown that morpholino knockdowns of ZIP6 or PrP in zebrafish leads to an impairment in gastrulation, a process dependent on epithelial-to-mesenchymal transition (EMT). Furthermore, the neural cell adhesion molecule (NCAM1), a known interactor of PrP, has itself been described as a mediator of EMT. Based on these findings, we hypothesized that both PrP and ZIP6 play crucial roles in the process of EMT by controlling the environment surrounding NCAM. We determined that ZIP6 forms a heteromeric complex with ZIP10 that affects NCAM1â s integration into adhesion complexes while also mediating its phosphorylation during EMT. Meanwhile, PrP was found to have a unique role in controlling the polysialylation of NCAM1 during EMT.

Keywords: epithelial-to-mesenchymal transition
mass spectrometry
ncam
prion protein
ZIP6
Advisor: Schmitt-Ulms, Gerold
Implications of the endothelial cell response in glioblastoma to stimulation by mesenchymal stem cells and ionizing radiation

Heightened angiogenesis is both the pathophysiologic hallmark and the potential cause of therapy resistance for glioblastoma (GBM), a deadly brain tumor. It is thought that mesenchymal stem cells (MSCs) play important roles in neovascularization and tumor progression. We postulated that MSCs protect ECs against radiotherapy, which subsequently enhances tumor angiogenesis, and promotes GBM tumor recurrence following therapy. We therefore sought to establish the in-vitro endothelial cell response to stimulation by MSC condition media and ionizing radiation (IR) treatment. We established the gene expression profiles of endothelial cells in response to IR, MSCs and the combination of both. Within the same gene profiles, we identified a unique gene signature that was highly predictive of response to Bevacizumab for GBM patients. We also demonstrated that MSC increased the viability of ECs in response to IR. Protein analysis in ECs suggested MSC-mediated cell cycle arrest as a mechanism for radio-resistance in ECs.

Advisor: Zadeh, Gelareh
Longitudinal Change in Cognitive Performance of Women Post-Oophorectomy

The impact of estrogen on cognition is well documented throughout the literature (Phillips ; Sherwin, 1992; Berman et al. 1997; Lord et al. 2010) Women with oophorectomy prior to spontaneous menopause have an increased risk of dementia in later years (Sherwin, 1988; Rocca et al., 2007; Phung et al. 2010; Bove et al. 2014). Furthermore, estrogen interacts with the e4 variant of the apolipoprotein E gene (APOE4), a risk factor associated with Alzheimerâ s disease, thereby increasing cognitive decline in an estrogen-depleted state (Stone et al., 1997). This study investigated longitudinal changes in verbal and spatial memory in women with a bilateral salpingo-oophorectomy prior to spontaneous menopause. Our analysis revealed a significant decline with time post-oophorectomy on key measures of verbal memory in the Rey Auditory Verbal Learning (RAVLT) and Verbal Fluency tasks moderated by a deleterious effect of APOE4. This research supports a decline in verbal memory performance following oophorectomy.

Advisor: Einstein, Gillian
Evaluation of a Novel Display Concept for Minimally Invasive Surgery

In minimally invasive surgery, surgeons operate in a small and confined environment with a limited field of view offered by the camera. As a result of this limited field of view, surgeons may insert or maneuver instruments blindly which can lead to patient injury. This thesis evaluates the effectiveness of a bifocal display for addressing this limited field of view. One design parameter of the bifocal display, the detail-to-total ratio, was systematically manipulated while participants completed two tasks, instrument insertion and detailed manipulation, in a contrived minimally invasive surgical environment. The results indicated that the bifocal display significantly improved performance in instrument insertion. In addition, the results highlighted that there existed a trade-off in task performance that was dependent on the detail-to-total ratio. These findings suggest that the bifocal display could be a solution to the limited field of view in minimally invasive surgery.

Advisor: Milgram, Paul
Low-Temperature Ozone Native Oxide – Silicon Nitride Bilayer Passivation of the Silicon Surface

Passivation of crystalline silicon is critical for the development of high efficiency, low cost solar cells. The objective of this project is to advance low temperature passivation of silicon substrates for use in photovoltaics and in particular to investigate the recently reported native oxide – silicon nitride bilayer passivation scheme. Specifically, we report on the passivation of silicon using an ozone ambient native oxide – silicon nitride bilayer where the nanometer thin ozone native oxide layer is grown at low temperatures while the silicon nitride layer is deposited at 400oC. Further, we investigate the chemical composition across the crystalline silicon interface. Advanced ion spectroscopy techniques including medium energy ion spectroscopy (MEIS), elastic recoil detection (ERD), and Rutherford Backscattering (RBS) are used to determine the resulting compositional layers on the silicon surface as well as the hydrogen concentration in both the film and underlying crystalline silicon substrate.

Keywords: Characterization
Hydrogen
Nitride
Passivation
PECVD
Silicon
Advisor: Kherani, Nazir P
The Role of Ventral Hippocampal Projections to the Amygdala on Anxiety Behavior

Anxiety is a natural and adaptive behavioral response that is evoked in anticipation of a threatening situation. In some cases, however, anxiety can be maladaptive, manifesting itself in the absence of a threatening cue. Previous studies showed that the ventral hippocampus and the amygdala have been implicated as being involved in anxiety. However, little is known about how they interact to modulate anxiety behavior. In light of this, experiments were performed to investigate how the ventral hippocampus inputs to the amygdala control anxiety. Specifically, ventral hippocampus axon terminals were modulated optogenetically in freely moving mice on an elevated plus maze test. Results revealed that activating ventral hippocampal inputs to the amygdala leads to an increase in anxiety behavior, whereas the inhibition of the same inputs results in a decrease in anxiety. Thus, our findings suggest that the ventral hippocampal inputs to the amygdala play a role in regulating anxiety.

Keywords: Amygdala
Anxiety
Elevated Plus Maze
Optogenetics
Ventral Hippocampus
Advisor: Kim, Junchul
Early Education and Care Program Quality and Children's Well-being: a Meta-Analysis and Systematic Review of the Early Childhood Environment Rating Scale

The Early Childhood Environment Rating Scale (-Revised) (ECERS/ECERS-R) is the most widely used assessment of global classroom quality in Early Childhood Education and Care programs. Despite prevalent use of the ECERS/ECERS-R in research and applied settings, its impact on child outcomes have not been systematically reviewed. The objective of this study was to evaluate the association between the ECERS/ECERS-R and children’s well-being. Searches of Medline, PsycINFO, ERIC, websites of large datasets and reference sections of all retrieved articles were conducted up to January 2013. Eligible studies provided a statistical link between the ECERS/ECERS-R and child outcomes. Sixty-three empirical studies met our inclusion criteria. All studies were included in the systematic review and 23 could be meta-analyzed. Associations between ECERS/ECERS-R total and factor scores and children’s cognitive, language, math, and social-emotional outcomes are evident but weak. Greater consistency in study methodology is critical in this area of research.

Keywords: Early Childhood Education
ECERS
ECERS-R
Meta-Analysis
Program Quality
Systematic Review
Advisor: Perlman, Michal
The Effect of RGS4 on Autophagic Flux in Min6 Pancreatic Beta Cells

Defective autophagy can lead to dysregulation of metabolic homeostasis. Previous studies in our laboratory have shown that RGS4-overexpressing HEK cells show increased autophagic activity. Herein, we study the potential role of RGS4 as a regulator of autophagy in the Min6 mouse pancreatic beta cell line, via inhibition of Gαi3, an established attenuator of autophagy. Min6 cells exposed to nutrient-deprived conditions undergo autophagic initiation demonstrated by increased expression of autophagy markers. When RGS4-YFP is ectopically expressed in Min6 cells, confocal microscopy imaging revealed colocalization between RGS4-YFP (both wild type and loss-of-function mutants), Gαi3 (RC)-CFP, and autophagy markers including Beclin1-DsRed and Atg12-RFP on intracellular punctae. Despite its colocalization with known regulators of autophagy, RGS4 was apparently unable to modulate the activity of known mediators and markers of autophagic activity (phospho-p76S6K, LC3 II, phospho-Bcl-2). We conclude that Gαi3 and RGS4 are not major factors in the regulation of autophagic flux in Min6 cells.

Keywords: Atg12
autophagy
Beclin1
LC3
Min6 cells
mTOR
Advisor: Heximer, Scott P
Investigating the Role of the Small GTPase Rab25a during Zebrafish Epiboly

The earliest morphogenetic event during zebrafish development is epiboly, defined as the thinning and spreading of a multilayered cell sheet. In a coordinated manner, the epithelial enveloping layer (EVL), deep cells, and yolk syncytial layer all undergo epiboly to close the blastopore. Despite epiboly being essential for development, its molecular control is not well understood. rab25a encodes a small GTPase involved in cellular trafficking in epithelial cells. rab25a was identified as a gene that may be important for epiboly. Loss of rab25a resulted in delayed epiboly and defects suggestive of reduced cell adhesion and impaired trafficking. rab25a is expressed exclusively in the EVL during epiboly but surprisingly, deep cells were more delayed than EVL cells. Additional work showed that deep cell epiboly could be rescued by restoring Rab25a expression to the EVL. My analysis provides evidence for a novel role for EVL-deep cell signaling to mediate epiboly movements.

Keywords: Danio Rerio
Enveloping Layer
Epiboly
Rab25a
Small GTPase
Zebrafish
Advisor: Bruce, Ashley E
Novel Gluconeogenesis Regulators for Anti-diabetic Drug Repurposing using Transgenic Zebrafish pck1 Reporters

Phosphoenolpyruvate carboxykinase is an enzyme that catalyzes the rate-limiting step of gluconeogenesis and is encoded by the pck1 gene. High levels of pck1 gene expression are associated with type 2 diabetes. The main goal of the present study is to identify compounds that can modulate pck1 expression. Furthermore, the knowledge gained from this study can streamline the process of identifying regulators by high-throughput screening in the future. A luminescent zebrafish reporter Tg(pck1:luc2) was used to screen the NIH Clinical Collections library containing 727 small molecules. Four leads were identified and validated using the fluorescence reporters Tg(pck1:Venus) and Tg(pck1:eGFP) as well as endogenous pck1 expression using quantitative PCR, where they down-regulated pck1 expression in larval zebrafish. One of the validated compounds (levofloxacin) altered glucose metabolism in adult zebrafish as determined by glucose tolerance tests. Methods were also established for efficient screening of future chemical libraries to identify novel anti-diabetic therapeutics.

Keywords: drug repurposing
gluconeogenesis
zebrafish
Advisor: Wen, Xiao-Yan
Investigating the Role of microRNAs in Human Congenital Hepatic Fibrosis

Congenital Hepatic Fibrosis (CHF) is histologically characterized by increased profile of dilated biliary tracts and progressive periportal fibrosis. We describe for the first time the change in microRNA expression pattern in human CHF liver tissues using miRNA-sequencing analysis. The expression pattern of miRNAs in the CHF patient liver is distinguishable from that of normal and other typical forms of hepatic fibrosis by differential analysis. We have isolated, for the first time, diseased biliary epithelial cells from patients with human Congenital Hepatic Fibrosis using Laser Capture Micro-dissection. We verified that the dysregulated miRNA in CHF whole liver were also dysregulated in diseased cholangiocytes. In silico target prediction of candidate miRNAs shows that molecular pathways that are associated with CHF were under the regulation of dysregulated miRNA targets. These results may provide insight into a regulatory network of miRNAs with crucial functional roles in the disease pathology of CHF.

Keywords: ARPKD
Cholangiocytes
Congenital Hepatic Fibrosis
Differential Expression
microRNA
RNA Sequencing
Advisor: Rosenblum, Norman D
The Effect of Simulated Human Salivary Enzymes and Matrix Metalloproteinase (MMP) Inhibition on the Degradation and Fracture Toughness of the Self-etched Resin-dentin Interface

Background: Oral esterase activities and dentinal matrix metalloproteinases (MMPs) contribute to interfacial degradation of composite restorations, compromising structural integrity, and increasing risk of secondary caries. Hypothesis: MMP inhibition modulates simulated human salivary esterase (SHSE) accelerated degradation of mechanical performance parameters for composite-dentin bonds achieved via self-etched adhesives. Objective: Assess the effect of SHSE and MMP inhibition on biostability, interfacial fracture toughness (FT), and failure mode (FM) for self-etched resin-dentin interfaces. Materials and Methods: FT and FM analyses were performed on mini short-rod FT specimens (N=10/group), prepared with Easy Bond, with and without MMP inhibition (galardin), after incubation for 0, 7, 30, 90, or 180 days in phosphate buffered saline (PBS) or SHSE. Results and Conclusions: FM shifts into the composite/adhesive vs. hybrid-layer after longer incubation periods. Despite higher amounts of the degradation marker, Bis-hydroxy-propoxy-phenyl-propane, collected from SHSE vs. PBS (p

Keywords: Biodegradaion
Esterase
Fracture Toughness
Matrix metalloproteinase (MMPs)
Resin-dentin interface
Self-etch adhesive
Advisor: Finer, Yoav
Haptoglobin 2-2 is Associated with Presence and Progression of MRI Depicted Carotid Intraplaque Hemorrhage

Intraplaque hemorrhage (IPH) is a source of free hemoglobin that binds the haptoglobin protein and forms a complex cleared by tissue macrophages. There are three haptoglobin genotypes: Hp1-1, Hp2-2 and Hp1-2. The Hb-Hp2-2 complex has a lower affinity for macrophages, resulting in vascular oxidative burden. We hypothesized that Hp2-2 patientsâ failure to clear hemoglobin results in a greater prevalence and progression of IPH. Eighty patients with advanced vascular disease (>30% carotid stenosis) underwent carotid MRI. IPH was quantified using the VesselMass software. Haptoglobin was genotyped and phenotyped using established protocols. Logistic and longitudinal regression analyses were performed. Hp2-2 patients had a significantly higher prevalence of baseline IPH (p=0.02). Longitudinal analysis of 35 IPH positive carotids indicated a significant progression of IPH volume over time in Hp2-2 patients (p=0.003). Therefore, Hp2-2 patients had a significantly higher prevalence and progression of carotid IPH. Hp2-2 genotype may be a biomarker of IPH and can identify at-risk populations for more targeted imaging investigations.

Keywords: Atherosclerosis
Biomarker
Haptoglobin
Intraplaque Hemorrhage
MRI
Advisor: Moody, Alan
Elucidating the Roles of TCAP-1 on Glucose Transport and Muscle Physiology

Teneurin C-terminal associated peptide (TCAP)-1 is a cleavable bioactive peptide on the carboxy terminus of teneurin proteins. Previous findings indicate that the primary role of TCAP-1 may be to regulate metabolic optimization in the brain by increasing the efficiency of glucose transport and energy utilization. The findings show that TCAP-1 administration in rats results in a 20-30% decrease in plasma glucose levels and an increase in 18F-2-deoxyglucose uptake into the cortex. In vitro, TCAP-1 also induces 3H-deoxyglucose transport into hypothalamic neurons via an insulin-independent manner. This is correlated with an increase in membrane GLUT3 immunoreactivity. A previously deduced pathway by which TCAP-1 signals in vitro was used to establish a link between the MEK-ERK1/2 pathway and glucose uptake as well as a connection between the MEK-ERK1/2 and AMPK pathways. Immunoreactivity studies indicate that the TCAP-1 system exists in muscle and may play a part in skeletal muscle metabolism and physiology.

Keywords: Endocrinology
Glucose
Metabolism
Muscle
Peptide
Physiology
Advisor: Lovejoy, David A
Synthesis, Size-selective Separation and Characterization of Colloidally Stable, Water-soluble Silicon Nanocrystals

In the field of silicon nanocrystals (ncSi), polydispersity, pH-independent aqueous colloidal stability, near-infrared (NIR) to visible photoluminescence tunability and cytotoxicity present significant challenges in the elucidation of important size-dependent physical, chemical, and biological properties. This thesis outlines some contributions towards understanding and addressing these challenges with special consideration towards biological fluorescent cell labelling. We begin by demonstrating the synthesis of polydisperse ncSi functionalized with 10-undecenoic acid (ncSi:UDA) which are size-separated using two different size-separation methods: size-selective precipitation and sucrose density gradient ultracentrifugation. Further improvements are then made on the pH-independent colloidal stability of ncSi:UDA by coupling the carboxylic acid terminus to poly(ethylene glycol) (ncSi:UDAPEG). Finally, the colloidal stability of NIR-emitting ncSi:UDA is investigated through the synthesis and hydrolysis of ethyl 10-undecenoate-functionalized ncSi (ncSi:EUD).

Keywords: Quantum dots
Silicon Nanocrystals
Size-selective separation
Advisor: Ozin, Geoffrey A.
Development of a Generic Controller Interface Program NICON for Multi-degrees of Freedom PSD Hybrid Simulation

Substructure hybrid simulation has been widely applied to investigate structural behavior under earthquake event. In this simulation technique, critical components of a structure are physically modelled as experimental specimens, and the rest of the structure is numerically modeled in a computer. This study presents a generic network interface and control program for controllers (NICON) which can be used in most common actuator configurations for substructure hybrid simulation. An algorithm is implemented in the program which allows coordinate conversion between a numerical model's Cartesian coordinate system and actuators' strokes in one to three dimensions. This study verifies the algorithm by comparing actuator stroke commands generated from NICON with theoretical predictions for most common actuator configurations. It then validates the algorithm by comparing the displacement commands from NICON with measurements obtained from a Multi-axial shaking table (MAST). Finally, suggestions for future study are listed at the end.

Advisor: Kwon, Oh-Sung
Towards Red Light Control of Ion Channel Blockers

Photoswitchable ion channel blockers reported previously have proven effective for modulating the activity of voltage-gated potassium (KV) channels. One limitation of previously reported azobenzene-based blockers was that the wavelength needed to promote trans-to-cis isomerization ranged from ultraviolet (UV) to blue. Light in this wavelength range poorly penetrates tissues and is cytotoxic, which limits the utility of these photoswitchable compounds for in vivo studies of KV channel activity. We designed, synthesized and ran preliminary patch-clamp experiments on analogous ion channel blockers bearing the tetra-ortho-methoxy (TOM) substitution pattern to bathochromically shift the absorption spectrum to permit long-wavelength photo-control. In combination with a bis-para-amino functionality, these blockers can form azonium ions under physiological conditions, which absorb red light strongly and undergo trans-to-cis isomerization. Red-light effectively penetrates tissues, allowing for in vivo studies of biological systems. We also report synthesis and initial characterization of a novel, further red-shifted dioxane ortho-methoxy (DOM) azobenzene substitution pattern.

Advisor: Woolley, G. Andrew
Evaluation and Optimization of Cellulose and PVDF Membranes for Application in Membrane Bioreactors and Vacuum Membrane Distillation for Water and Wastewater Treatment

As water sources around the world are depleted, there is an increasing need for advanced treatment systems that can produce high-quality effluent for discharge or reuse. In this thesis, cellulose membranes were used in a bench-scale membrane bioreactor with the intention of developing a membrane that is inexpensive and made from renewable resources. The cellulose membranes were able to remove suspended solids during multi-day filtrations, but suffered from severe fouling. The membranes developed in this study are unique, as they are manufactured using a papermaking process instead of conventional casting processes. Next, a bench-scale vacuum membrane distillation system was tested using salt solutions, surface water, and MBR effluent as feed solutions. With all feed solutions, this system could produce a permeate with low conductivity and dissolved solids, and free of coliforms. Combining these two systems provides an option for water reuse which has not been previously studied.

Keywords: Cellulose
Membrane Bioreactor
Membrane Distillation
Wastewater
Water
Advisor: Farnood, Ramin R
Investigating the Role of NRG1β/ErbB4 Signalling in LTP

Synaptic plasticity is the fundamental feature of the mammalian brain that enables learning and memory. One main form of activity-dependent, lasting increase in synaptic transmission termed LTP is observed at the hippocampal CA1 and mediated by the NMDARs. Schizophrenia susceptibility pathway NRG1β/ErbB4 has been implicated in physiological, as well as aberrant, regulation of NMDAR function. Prevention of LTP induction is the consensus phenomenology observed in studies involving exogenous application of NRG1β on acute hippocampal slice preparations. Recent efforts demonstrated that NRG1β-mediated suppression of LTP involves the inhibition of nonreceptor tyrosine kinase Src; however; the exact mechanism remains controversial. After observing no effect of NRG1β application on LTP, I carried out a step-wise interrogation NRG1β/ErbB4 ligand-receptor pair. In this thesis, I present evidence for an experimental-condition-dependent downregulation of ErbB4 expression; this finding bears important implications for experimental design, in addition to broadening our understanding of the mechanisms governing NRG1β/ErbB4 signalling.

Keywords: LTP
NMDAR
NRG1
Synapse
Advisor: Salter, Michael W