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Title: COMPREHENSIVE ANALYSIS OF EXON SKIPPING EDITS WITHIN DYSTROPHIN D20:24 REGIONS
Creator: Niu, Xin
Date: 2020
Description: Exon skipping is a disease modifying therapy that operates at the RNA level. In this strategy, oligonucleotide analog drugs are used to...
Show moreExon skipping is a disease modifying therapy that operates at the RNA level. In this strategy, oligonucleotide analog drugs are used to specifically mask specific exons and prevent them from being included in the mature mRNA. Exon skipping can also be used to restore protein expression in cases where a genetic frameshift mutation has occurred, and this how it is applied to Duchenne muscular dystrophy, DMD. DMD most commonly arises as a result of large exonic deletions that juxtapose flanking exons of incompatible reading frame, which abolishes dystrophin protein expression. This loss leads to the pathology of the disease, which is severe, causing death generally in the second or third decade of life. Here, the primary aim of exon skipping is to restore the reading frame by skipping an exon adjacent to the patient’s original. While restoring some protein expression is good, how removing some region from the middle of protein affects its structure and function is unclear. Complicating this in this case is that the dystrophin gene is very large, containing 79 exons. Many different underlying deletions are knowns, and exon skipping can be applied in many ways. It has previously been shown that many exon-skip edits result in structural perturbations of varying degrees. Very few studies are focused on the protein biophysical study and it is still basically unclear whether and how such editing can be done to minimize such perturbations. In order to provide the solid evidences which prove the significant variation among those cases (especially for the clinically relevant cases) and better understanding the general principles of “what makes a good edit”, we examine a systematic and comprehensive panel of possible exon edits in a region of the dystrophin protein. The domain D20:24 of dystrophin rod region are selected for its entirety which is separated by hinge region (mostly random coiled structure) and addition of other STRs will not disrupt the structure stability. Also D20:24 regions lie in the Hot Spot region II (HS2) which holds the most number of DMD patients. During the comprehensive scan, we identify for the first time, exon edits that appear to maintain structural stability similar to wild-type protein and those clinically relevant edits. Then we figure out the factors that appear to be correlated with the degree of structural perturbation, such as the number of cooperative protein domains, as well as how the edited exon structure interacts with the protein domain structure. Our study is the first systematic and comprehensive scan for an entire multiple STRs domain. This would help us understand the protein nature of various exon skipping edits and provide useful target for clinical treatment. Also the knowledge we learned may be applied to produce more sophisticated CRISPR edits in the future work.
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Title: DEVELOPMENT OF FULLY BIOCOMPATIBLE HYDROGEL NANOPARTICLE FORMULATIONS FOR CONTROLLED-RELEASE DELIVERY OF A WIDE VARIETY OF BIOMOLECULES
Creator: Borges, Fernando Tancredo Pereira
Date: 2020
Description: In recent years, our group has focused on the production of PEGDA-based hydrogel scaffolds and nanoparticles for drug delivery of small...
Show moreIn recent years, our group has focused on the production of PEGDA-based hydrogel scaffolds and nanoparticles for drug delivery of small molecules. However, with recent advances in modern therapeutic treatments, such as protein and genetic engineering, there is an increasing need for the development of drug delivery devices that would be able encapsulate larger molecules. Therefore, the goal of this thesis work was to develop a systematic way to produce fully biocompatible PEGDA-based hydrogel nanoparticle formulations that would be able to encapsulate any size molecule, ranging from small ionic molecules, to peptides and proteins, all the way to large nucleic acids, and deliver it in a controlled manner.The first of part of this work consisted of developing a stable and reproducible process for the production of hydrogel PPi-NPs. Initial studies were done in order to assess the influence of phosphate salts in the polymerization system and it was found that both monophosphate and polyphosphate salts significantly damper the NVP homo-polymerization kinetics, but do not affect the co-polymerization of NVP and PEGDA. Then, emulsion stability studies were done to determine whether phosphate salts affected the stability of the minimeulsion system used in the production of the nanoparticles. Cloud point measurements and droplet size screening measurements showed that by transitioning from a Pi-loaded emulsion system to a PPi-loaded emulsion system, the required HLB of the emulsion shifts by 1.5 points. Upon correction for that shift, a reproducible process for production of PPi-loaded nanoparticles was obtained. A parametric study was then performed to see how the different process parameters affected the different properties of the produced particles. The second part of the work consisted in developing a platform for encapsulation of large to very-large molecules within these hydrogel systems. A new set of equations was developed for better estimation of the interstitial space, available for encapsulation of molecules, of crosslinked polymers that used very high molecular weight crosslinkers and/or high amounts of crosslinker. Upon development of this new set of equations, hydrogel discs were made via photopolymerization in order to validate the equations. By introducing a third monomer, EGA, and varying the molecular weight and concentration of the crosslinker, hydrogels with a wide range of mesh dimensions from 25 to 700 were achieved. These gels were then used to encapsulate 4 different sample molecules of varying molecular weights and size. A new heuristic was developed for encapsulation of non-spherical molecules, where the aspect ratios of the molecule and of the polymer network are considered. By varying the size of the ratios of the dimensions of the hydrogel network to the dimensions of the molecule, significantly different release profiles of small molecules, peptides and oligonucleotides were obtained. Finally, in order to explore different administration routes, the process was transitioning into being fully biocompatible. The organic solvent previously used in the emulsion system was replaced by soybean oil and the surfactants were replaced by a food-grade surfactant, PGPR, to form Bio-Compatible Nanoparticle Emulsions (BCNEs). Qualitative release from the BCNEs was shown. A new method for quantitative measuring of release from BCNE was developed. Release from QK-BCNE was observed up to 46 days, which is unprecedented for sustained-release and revolutionary for the field. A BCNE spreadable ointment formulation was also developed.
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Title: Development of Human Brain Atlas Resources
Creator: Qi, Xiaoxiao
Date: 2020
Description: Digital human brain atlases play an increasingly critical role and are widely used in neuroimaging studies such as developing biomarkers,...
Show moreDigital human brain atlases play an increasingly critical role and are widely used in neuroimaging studies such as developing biomarkers, training data for machine learning algorithms, functional connectivity analysis and so on. A brain atlas typically consists of brain templates of different imaging modalities that are representative of individual brains under study in a standard atlas space and semantic labels that delineate brain regions according to the characteristics of the underlying tissue.The IIT Human Brain Atlas project has developed the state-of-the-art diffusion tensor imaging (DTI) template, high angular resolution diffusion imaging (HARDI) template, and anatomical templates for the young adult brain in a standardized space. The probabilistic maps of gray matter (GM) labels and tissue segmentations were also constructed based on the anatomical information of the atlas. This thesis introduced an enhanced T1-weighted template that were developed by combining information from both diffusion and anatomical data. The GM labels and tissue segmentation maps in the standardized space were also improved. Existing white matter (WM) atlases typically lack specificity in terms of brain connectivity. A new approach named regionconnect was developed in this work based on precalculated average healthy adult brain connectivity information stored in standard space in a fashion that allows fast retrieval and integration. This thesis first generated and evaluated the white matter connectome of the IIT Human Brain Atlas v.5.0. Next, the new white matter connectome was used to develop multi-layer, connectivity-based labels for each white matter voxel of the atlas, consistent with the fact that each voxel may contain axons from multiple connections. The regionconnect algorithm was then developed to rapidly integrate information contained in the multi-layer labels across voxels of a white matter region and to generate a list of the most probable connections traversing that region. The regionconnect algorithm as well as the white matter tractogram and connectome, multi-layer, connectivity-based labels, and associated resources developed for the IIT Human Brain Atlas v.5.0 in this work are available at www.nitrc.org/projects/iit. Furthermore, it was well established that use of a young adult atlas in studies of older adults is inappropriate due to the age-related characteristic changes of the brain, resulting in an increasing demand of digital brain atlases for the older adults. To fulfill this demand, a function of fiber orientation distribution (fODF) template that is representative of older adults was developed in a standardized atlas space for studies of white matter of older adult human brains, which built a solid foundation for the development of the white matter resources for the older adults human brain atlas.
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Title: AMPLIFICATION AND PURIFICATION OF RECOMBINANT PRO-DEATH BAXΔ2 PROTEINS FOR STRUCTURE ANALYSIS
Creator: Zhou, Yi
Date: 2020
Description: BaxΔ2 is an isoform of the pro-apoptotic Bax family of proteins, which is an important anti-cancer protein. BaxΔ2 behaves differently from...
Show moreBaxΔ2 is an isoform of the pro-apoptotic Bax family of proteins, which is an important anti-cancer protein. BaxΔ2 behaves differently from Baxα to induce apoptosis. The current computationally predicted model of BaxΔ2 is based on known Baxα structure, which is considered biased. Therefore, the elucidation of the BaxΔ2 crystal structure is critical. The goal of this project was to obtain a sufficient amount of purified recombinant Bax∆2 protein for crystallization. We cloned full-length BaxΔ2 fused with a poly-histidine tag on either N-terminus (His-Bax∆2) or C-terminus (Bax∆2-His) into an inducible bacterial expression vector. We found that His-Bax∆2 proteins were expressed better than Bax∆2-His, which totally inhibit host growth. However, the protein concentration of His-Bax∆2 was still too low to be detected by Coomassie blue staining. To increase His-Bax∆2 expression and avoid cytotoxicity, we further tested different bacterial host cells and applied the chaperone system. However, all attempts could not overcome Bax∆2 cytotoxicity and the protein expression levels were not high enough to be feasible for further large-scale purification. The mechanism underlying how Bax∆2 inhibits bacterial growth is still a mystery because Bax∆2 eukaryotic targets (mitochondria and caspases) do not exist in bacteria. Further experiments are required to explore the mechanism of Bax∆2 cytotoxicity in bacteria, so as to finally optimize and elevate the BaxΔ2 protein yields.
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Title: Development of Microfluidic Platform to Study Insulin Resistance
Creator: Tanataweethum, Nida
Date: 2020
Description: Insulin resistance, a precursor for the development of type 2 diabetes (T2D), propagates among heterologous tissues through dysregulated lipid...
Show moreInsulin resistance, a precursor for the development of type 2 diabetes (T2D), propagates among heterologous tissues through dysregulated lipid flux, as well as dysregulated glucose production, and secretion of cytokines, adipokines and hepatokines. Although T2D is characterized by systemic insulin resistance, disruption of insulin signaling in the liver and adipose tissue recapitulates many aspects of T2D, including enhance endogenous glucose production as well as defects of insulin action. Mechanistic studies often aim to provide fundamental understanding of the observations from human and animal studies. Due to the complexity of animal models and the multifactorial character of T2D, there is a strong need to develop advanced experimental systems such as in vitro models that can enable the recapitulation of the complex physiology of the in vivo system and enable investigation of the pathological pathways as well as identify novel treatment options. The overall goal of this study was to develop insulin resistant models of adipose tissue and liver to study the metabolic function of each organ as well as to the organ-organ crosstalk. To accomplish this goal, four specific aims were pursued: (1) Establish adipose tissue on-a-chip to study the metabolic function of the adipocytes in flow culture; (2) Develop towards an insulin resistant adipose on-a-chip to study the metabolic function of adipocytes in setting of insulin resistance; (3) Develop insulin resistant liver on-a-chip to investigate the metabolic function of hepatocytes in setting of insulin resistance; (4) Develop adipose-liver on-a-chip in setting of insulin resistance to identify the metabolic interaction between organs.
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Title: Exploiting contextual information for deep learning based object detection
Creator: Zhang, Chen
Date: 2020
Description: Object detection has long been an important research topic in computer vision area. It forms the basis of many applications. Despite the great...
Show moreObject detection has long been an important research topic in computer vision area. It forms the basis of many applications. Despite the great progress made in recent years, object detection is still a challenging task. One of the keys to improving the performance of object detection is to utilize the contextual information from the image itself or from a video sequence. Contextual information is defined as the interrelated condition in which something exists or occurs. In object detection, such interrelated condition can be related background/surroundings, support from image segmentation task, and the existence of the object in the temporal domain for video-based object detection. In this thesis, we propose multiple methods to exploit contextual information to improve the performance of object detection from images and videos.First, we focus on exploiting spatial contextual information in still-image based object detection, where each image is treated independently. Our research focuses on extracting contextual information using different approaches, which includes recurrent convolutional layer with feature concatenation (RCL-FC), 3-D recurrent neural networks (3-D RNN), and location-aware deformable convolution. Second, we focus on exploiting pixel-level contextual information from a related computer vision task, namely image segmentation. Our research focuses on applying a weakly-supervised auxiliary multi-label segmentation network to improve the performance of object detection without increasing the inference time. Finally, we focus on video object detection, where the temporal contextual information between video frames are exploited. Our first research involves modeling short-term temporal contextual information using optical flow and modeling long-term temporal contextual information using convLSTM. Another research focuses on creating a two-path convLSTM pyramid to handle multi-scale temporal contextual information for dealing with the change in object's scale. Our last work is the event-aware convLSTM that forces convLSTM to learn about the event that causes the performance to drop in a video sequence.
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Title: IMAGE-ANALYSIS WITH FIJI PROGRAM ON PERIPHERAL BLOOD MONOCULAR CELLS AFTER CONSUMPTION OF HIGH-FAT, HIGH CARBOHYDRATE MEAL WITH OR WITHOUT ADDITION OF SPICES – A SINGLE-CENTER RANDOMIZED, BLINDED, PLACEBO-CONTROLLED, 4-ARM, 24HR ACUTE CROSSOVER STUDY
Creator: Tsai, Meng Fu
Date: 2020
Description: Chronic low-grade inflammation plays a significant role in developing various chronic diseases, such as cardiovascular disease and type II...
Show moreChronic low-grade inflammation plays a significant role in developing various chronic diseases, such as cardiovascular disease and type II diabetes. Western-type diets characterized by high-fat (saturated fat) and high-carbohydrate (HFHC) calories induce oxidative stress leading to inflammation. Polyphenol rich foods, such as berries, tea, and herbs and spices, have antioxidant properties. Spices have been shown to have anti-inflammatory effects in cell and animal studies; however, data are limited in humans. In the present study, we hypothesized that bioactive polyphenolic compounds in herbs and species would reduce diet-induced inflammation in overweight and obese (OW/OB) individuals. In a randomized, single-blinded 4-arm, 24-h, crossover clinical trial, sixteen OW/OB adults consumed an HFHC meal with and without three herbs and spices combinations, including Italian herbs (rosemary, basil, thyme, oregano, and parsley), cinnamon and pumpkin pie spice (cinnamon, ginger, nutmeg, and allspice) on four separate occasions at least three days apart. Markers of inflammation were assessed before and at 2, 4, 5.5, and 7 hours after meal consumption by tracking nuclear translocation of nuclear factor kappa B (NF-κB), a transcription factor in inflammatory signaling, in human peripheral blood monocular cells (PBMCs) and by measuring plasma interleukin-6 (IL-6), a pro-inflammatory cytokine. Nuclear translocation of NF-κB and the proportion of PBMCs activated were estimated through a new method leveraging machine-learning immunofluorescence image analysis. Metabolic markers were also investigated by RX Daytona automated clinical chemistry analyzer. Statistical analysis was conducted using a statistical package for the social sciences (SPSS) (α<0.05, significance). Preliminary results suggested the pumpkin pie spice mixture may improve inflammatory status. Compared to the control meal, the meal with pumpkin spice reduced nuclear translocation of NF-κB and proportion of PBMCs activation, p=0.007, and p=0.005, respectively. The addition of herbs/spices in HFHC meal had no apparent effect on postprandial glucose, insulin, or IL-6 concentrations compared to the control meal. Increased triglyceride concentrations were suggested after consuming the meal with Italian herbs compared to control (p=0.004). Overall, the results of this research suggested the potential of pumpkin pie spice as having anti-inflammatory effects in the context of a typical western-style eating pattern. A major component of this research was to develop a new method for assessing real-time inflammation in the human body. While the method and data are encouraging, upgrading image resolution and programming will be the subject of future research.
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Title: Three Essays on the Internet Economy
Creator: Sun, Yidan
Date: 2024
Description: In an era of digital platforms, the integrity and visibility of consumer reviews, the dynamics of digital advertising markets, and the role of...
Show moreIn an era of digital platforms, the integrity and visibility of consumer reviews, the dynamics of digital advertising markets, and the role of software development kits (SDKs) emerge as pivotal elements shaping user experiences and platform economics. My research spans three distinct but interconnected domains: the impact of safety reviews on Airbnb, the effects of privacy protections on digital advertising markets, and the significance of SDK releases in the evolution of Apple's iOS app market. We find that critical reviews concerning the safety of an Airbnb listing's vicinity influence guest bookings negatively and, therefore, could boost platform revenues if such reviews were obscured, highlighting a misalignment between consumer interests and platform revenue objectives. This effect is more pronounced in low-income and minority neighborhoods, suggesting a nuanced impact on different community segments. In the digital advertising sector, we identify that data frictions disproportionately harm small publishers, especially when associated with smaller ad intermediaries, underscoring the vulnerability of niche players to market and regulatory changes. Lastly, our analysis of the iOS app market reveals the instrumental role of SDK releases in fostering the app ecosystem's growth, independent of the expanding iPhone user base. Together, these findings underscore the complex interplay between consumer feedback, technological advancements, and market dynamics in digital environments, urging a balanced approach that safeguards consumer interests while fostering innovation and equitable market practices.
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Title: Gender Stereotype Biases Within Law Enforcement Clinical Psychological Evaluation
Creator: Porter, Maxwell G.
Date: 2023
Description: Female representation in law enforcement, despite significant improvements in past decades, remains markedly low at approximately 12%. One...
Show moreFemale representation in law enforcement, despite significant improvements in past decades, remains markedly low at approximately 12%. One possible barrier is the clinical psychological evaluation (CPE), a type of individualized assessment used to evaluate the mental or emotional fitness for duty of applicants. The present study examines the presence of potential gender bias in CPE for law enforcement positions by examining self-report personality assessment scores as well as narrative CPE recommendation reports generated by evaluating psychologists. Archival CPE data collected between 2014 through 2019 was obtained from a personnel selection consulting firm for entry-level law enforcement candidates (n = 390). Data included candidate scores on self-report psychological assessments (16PF, IPI-2), candidate background information, and psychologist-generated evaluation reports. A computer-aided text analysis using LIWC-22 was used to measure gender related inferences in the narrative report. Results indicated that (a) women received significantly lower assessor recommendation ratings than men, (b) significant differences in self-report personality scores were observed, however these were limited to a narrow subsection of traits, (c) gender was no longer a significant predictor of CPE outcome after controlling for applicant personality trait scores, and (d) meaningful differences in agency-related inferences in the narrative reports were observed, but it is unclear whether gender stereotypes influenced the reports. Practical implications, study limitations, and directions for future research are discussed.
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Title: Prediction and Control of In-Cylinder Processes in Heavy-Duty Engines Using Alternative Fuels
Creator: Pulpeiro Gonzalez, Jorge
Date: 2024
Description: This Ph.D. thesis focuses on advancing diagnostic techniques and control-oriented models to enhance the efficiency and performance of internal...
Show moreThis Ph.D. thesis focuses on advancing diagnostic techniques and control-oriented models to enhance the efficiency and performance of internal combustion (IC) engines, particularly heavy-duty engines utilizing alternative fuels. The research endeavors to contribute to the field of model-based control of engines through the development and implementation of innovative methodologies. The primary emphasis is on the development of diagnostic methods, control-oriented models and advanced control strategies for compression ignition engines using alternative fuels. The first key topic explores the determination of the Most Representative Cycle for Combustion Phasing Estimation based on cylinder pressure measurements. The method developed extracts crucial information from experimental data obtained from four distinct engines: the heavy-duty single-cylinder GCI engine, the light-duty multi-cylinder diesel engine, a CFR engine, and a single-cylinder light-duty Spark Ignition (SI) engine. This work lays the foundation for precise combustion phasing estimation, a critical parameter for engine control. The second major contribution involves the development of control-oriented models for Variable Geometry Turbochargers (VGT) and inter-coolers. Two models are established: a data-driven turbocharger model and an empirical inter-cooler model. These models are meticulously calibrated and validated using experimental data from a multi-cylinder light-duty diesel engine, providing valuable insights into the behavior of these components under varying conditions. The outcomes contribute to facilitate predictive control of engine air systems. The third core aspect of the thesis revolves around Model Predictive Control of Combustion Phasing in heavy-duty compression-ignition engines utilizing alternative fuels. A combustion phasing and engine load model is derived from experimental data and incorporated into an MPC framework. The MPC strategy is subsequently tested in the heavy-duty GCI test cell and compared against a conventional Proportional-Integral-Derivative (PID) control strategy. The results showcase the effectiveness of the MPC approach in achieving precise control of combustion phasing, demonstrating its potential for optimizing engine performance. In summary, this Ph.D. thesis contributes significantly to the field of engine controls by advancing diagnostic techniques, control-oriented models, and implementing a cutting-edge MPC-based control strategy for compression ignition engines using alternative fuels. The research findings not only enhance the understanding of in-cylinder processes but also pave the way for more efficient and sustainable heavy-duty engines using alternative fuels.
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Title: Extremal and Enumerative Problems on DP-Coloring of Graphs
Creator: Sharma, Gunjan
Date: 2024
Description: Graph coloring is the mathematical model for studying problems related to conflict-free allocation of resources. DP-coloring (also known as...
Show moreGraph coloring is the mathematical model for studying problems related to conflict-free allocation of resources. DP-coloring (also known as correspondence coloring) of graphs is a vast generalization of classic graph coloring, and many more concepts of colorings studied in the past 150+ years. We study problems in DP-coloring of graphs that combine questions and ideas from extremal, structural, probabilistic, and enumerative aspects of graph coloring. In particular, we study (i) DP-coloring Cartesian products of graphs using the DP-color function, the DP coloring counterpart of the Chromatic polynomial, and robust criticality, a new notion of graph criticality; (ii) Shameful conjecture on the mean number of colors used in a graph coloring, in the context of list coloring and DP-coloring; and (iii) asymptotic bounds on the difference between the chromatic polynomial and the DP color function, as well as the difference between the dual DP color function and the chromatic polynomial, in terms of the cycle structure of a graph. These results respectively give an upper bound and a lower bound on the chromatic polynomial in terms of DP colorings of a graph.
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Title: Agency and Pathway Thinking as Mediators of The Relationship Between Caregiver Burden And Life Satisfaction Among Family Caregivers Of People With Parkinson’s Disease: An Application Of Snyder’s Hope Theory
Creator: Springer, Jessica Gabrielle
Date: 2024
Description: In the United States, there are 47.9 million caregivers providing care to family members with disabilities. Those providing care to someone...
Show moreIn the United States, there are 47.9 million caregivers providing care to family members with disabilities. Those providing care to someone who has Parkinson’s Disease (PD), a complex degenerative movement disorder, may have a unique caregiving experience, given that disease-related factors (e.g. motor and non-motor symptoms) can contribute to worsening caregiver burden and life satisfactions (LS). PD has an increasing incidence of 90,000 new cases per year, likely resulting in an increased need for caregivers. Caregiving research frequently focuses on the mediators between caregiver burden and LS including social support, coping skills, and appraisals. Research that has specifically focused on caregivers of people with PD (Pw/PD) is significantly limited. Hope is a “positive motivational characteristic comprised of agency and pathways thinking that can help facilitate drive towards one’s goal while also serving as a buffer against negative events” (Snyder et al.,1991). The goal of this study is to understand Snyder’s hope theory as it relates to caregiver burden and LS for caregivers of Pw/PD. Specifically, we hypothesized that (a) caregiver burden will be negatively correlated with agency thinking, pathways thinking, and LS among caregivers of Pw/PD. In addition, pathways thinking, and agency thinking will be positively associated with LS, and (b) agency thinking, and pathways thinking will mediate the relationship between caregiver burden and LS among caregivers of Pw/PD. The study sample consisted of 249 caregivers of Pw/PD who completed an online anonymous questionnaire. Correlations between agency and pathways thinking, LS, caregiver burden, and sociodemographic factors were evaluated. A parallel mediation analysis was run to evaluate the mediating roles of pathways and agency thinking in the relationship between caregiver burden and LS. Results indicated that LS was significantly and negatively correlated with caregiver burden. LS was significantly and positively correlated with both pathways and agency thinking. Pathways thinking had no indirect effect on the relationship of caregiver burden on LS. Agency thinking had a negative, indirect effect on the relationship suggesting that agency thinking partially mediated the relationship between caregiver burden and LS. Clinical implications and future directions are discussed.
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Title: In situ EXAFS studies of novel Palladium-based anode catalysts for direct ethanol and formic acid fuel cells
Creator: Su, Ning
Date: 2024
Description: In this work we made nanoscale uniform deposition of Pd based anode catalyst on the transition metal Au (with atomic ratio Pd:Au=1:10) support...
Show moreIn this work we made nanoscale uniform deposition of Pd based anode catalyst on the transition metal Au (with atomic ratio Pd:Au=1:10) support of direct liquid ethanol fuel cells (DLEFCs) and direct liquid formic acid fuel cells (DLFAFCs). Synthesizing with uniform dispersion and catalyst nanoparticle dimensions understand the role of Pd reaction on its support in the direct EOR (ethanol oxidation reaction) and FOR (formic acid reaction) pathways, we performed in situ Pd K-edge X-ray absorption spectroscopy measurements as a function of potential using a custom-designed flow cell with the catalyst deposited on the glassy carbon window. We did in-situ EXAFS to better understand the reaction mechanism of Pd1@Au10 anode catalyst with EOR and AOR in nanoscale. Compared EOR with FOR electrochemical performance showed Pd@Au&C played better in ethanol than HCOOH and more stable which the the current density can reach up to 1216.25 mA·mg-1 Pd of EOR with Pd1@Au10&C in 1M KOH+1M EtOH (CH3CH2OH) on the ethanol fuel cells (DLEFCs), and 3.56 times higher of the EOR current compared with commercial Pd@C
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Title: The Voderettes: Gender, Labor, and Techno-Utopia at the 1939 New York World's Fair
Creator: Simon, Sara M. B.
Date: 2024
Description: This thesis explores the labor demands of the Voder, the electrical speech synthesis machine developed by Bell Labs to be a major component of...
Show moreThis thesis explores the labor demands of the Voder, the electrical speech synthesis machine developed by Bell Labs to be a major component of AT&T's 1939 New York World's Fair exhibit. With the United States emerging from the Great Depression, and with political tensions escalating across the globe, the paper situates the Voder's labor demands within the historical context of the fair. Specifically, I explore the decision to have young women operate the Voder, the intricacies of the machine cloaked by the warm presence of its highly-skilled female operator. Using archival records from Bell Labs engineers, the paper exposes the previously unacknowledged engineering contributions of Voder operators in the years before the fair. These young women not only influenced major decisions about the Voder's mechanics but also gave early credence to the notion that developing a performance with the machine could make for a thrilling fair exhibit. Moreover, the paper argues that at the fair itself, AT&T and Bell Labs executives used the Voder operators to normalize a new vision of a technological utopia that relied heavily and conspicuously on the infrastructural labor of women. Given the Voder's legacy, as a tool that laid critical groundwork for voice encryption technology, the paper adds important context to the historical record, highlighting the young women at the heart of the machine.
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Title: Three-Dimensional Co-Culture Systems for Vascularization of Cardiac Tissue
Creator: Rodriguez Arias, Jessica A.
Date: 2023
Description: Myocardial Infarction (MI) is the partial or complete blockage of blood flow to the myocardial tissue resulting in damage and therefore loss...
Show moreMyocardial Infarction (MI) is the partial or complete blockage of blood flow to the myocardial tissue resulting in damage and therefore loss of heart function. In the U.S. every 40 seconds, someone will suffer from MI and the only available treatment is medication to treat the symptoms of heart function loss, but do not treat the underlying cause. Some attempts to treat the underlying cause have arisen in the last decades including cell-based therapies or tissue engineering therapies such as spheroid-based cardiac patches that have shown to be promising. Improvement in the mechanical properties to create suturable engineered tissues remain to be improved for ease of implantation purposes. Cell-laden hydrogel scaffolds can provide improved mechanical properties compared to biomaterial free cell-based therapies but need to allow for vascularization of the engineered tissue. Thus, the goal of this thesis is to provide preliminary studies for the use of a cell adhesive, proteolytically degradable PEG hydrogel scaffold that eventually would be used as an invitro model to evaluate engineered tissue vascularization for cardiac tissue engineering. To construct this model, important cell spheroid parameters on vascular invasion in 3D culture were investigated including the total number of cells/spheroid, the supporting cell for endothelial cells. In order to scale-up scaffolds to size of clinically relevant dimensions, a multilayered hydrogel construct visible light free-radical polymerization approach encapsulating vascular spheroids in multiple layers was also investigated. Results indicate that a total cell number of 5000 cells/spheroid aggregate were feasible due to cell sourcing. In addition, co-cultures of endothelial and mesenchymal stem cells led to maximized vascular invasion of the spheroids compared to fibroblast/endothelial co-culture and endothelial monoculture of spheroids in the hydrogel. Finally, the extent of vascularization of spheroids in each layer of the multilayered hydrogel constructs varied due to the observed differences in mechanical properties and swelling ratio of each layer due to incomplete polymerization of layers. This study demonstrated the importance of support cells and hydrogel mechanical properties in promoting vascularization of spheroid which serves as basis for building cell-laden hydrogel scaffolds for vascularization for cardiac tissues.
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Title: ENLARGED PERIVASCULAR SPACES IN COMMUNITY-BASED OLDER ADULTS
Creator: Javierre Petit, Carles
Date: 2020
Description: Enlarged perivascular spaces (EPVS) have been associated with aging, increased stroke risk, decreased cognitive function and vascular dementia...
Show moreEnlarged perivascular spaces (EPVS) have been associated with aging, increased stroke risk, decreased cognitive function and vascular dementia. Furthermore, recent studies have investigated the links of EPVS with the glymphatic system (GS), since perivascular spaces are thought to play a major role as the main channels for clearance of interstitial solutes from the brain. However, the relationship of EPVS with age-related neuropathologies is not well understood. Therefore, more conclusive studies are needed to elucidate specific relationships between EPVS and neuropathologies. After demonstration of their neuropathologic correlates, detailed assessment of EPVS severity could provide as a potential biomarker for specific neuropathologies.In this dissertation, our focus was twofold: to develop a fully automatic EPVS segmentation model via deep learning with a set of guidelines for model optimization, and to evaluate both manual and automatic assessment of EPVS severity to investigate the neuropathologic correlates of EPVS, and their contribution to cognitive decline, by combining ex-vivo brain magnetic resonance imaging (MRI) and pathology (from autopsy) in a large community-based cohort of older adults. This project was structured as follows. First, a manual approach was used to assess neuropathologic and cognitive correlates of EPVS burden in a large dataset of community-dwelling older adults. MR images from each participant were rated using a semiquantitative 4-level rating scale, and a group of identified EPVS was histologically evaluated. Two groups of participants in descending order of average cognitive impairment were defined based and studied. Elasticnet regularized ordinal logistic regression was used to assess the neuropathologic correlates of EPVS burden in each group, and linear mixed effects models were used to investigate the associations of EPVS burden with cognitive decline. Second, a fully automatic EPVS segmentation model was implemented via deep learning (DL) using a small dataset of 10 manually segmented brain MR images. Multiple techniques were evaluated to optimize performance, mainly by implementing strategies to reduce model overfitting. The final segmentation model was evaluated in an independent test set and the performance was validated with an expert radiologist. Third, the DL segmentation model was used to segment and quantify EPVS. Quantified EPVS (qEPVS) were evaluated by combining ex-vivo MRI, pathology, and longitudinal cognitive evaluation. EPVS quantification allowed to study qEPVS both in the whole brain and regionally. Two different qEPVS metrics were studied. Elastic-net regularized linear regression was used to assess the neuropathologic correlates of qEPVS within each region of interest (ROI) under study, and linear mixed effects models were used to investigate the associations of qEPVS with cognitive decline. Finally, a preliminary study investigated the longitudinal associations of qEPVS with time. The DL segmentation model was re-trained using 4 in-vivo MR images. EPVS were segmented and quantified in a large longitudinal cohort where each participant was imaged at multiple timepoints. Factors that influenced segmentation performance across timepoints were evaluated, and linear mixed effects models controlling for these factors were used to investigate the associations of qEPVS with time.
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Title: Unraveling the Factors Affecting Virus Adhesion to Food Contact Materials and Virus-Virus Interaction – A Nanoscopic Study
Creator: Guo, Ao
Date: 2020
Description: Food safety is a worldwide issue nowadays since pathogens cause diseases, even death. Human enteric viruses are a major cause of non-bacterial...
Show moreFood safety is a worldwide issue nowadays since pathogens cause diseases, even death. Human enteric viruses are a major cause of non-bacterial foodborne gastroenteritis. In the United States, they are the most life-threatening pathogenic agents for the foodborne illnesses. The fecal-oral route is responsible for the attachment and transmission of such foodborne pathogens, which lead to contamination of food-contact materials (FCMs) during food preparation, enhancing the risk of transmission. The interaction between viruses and contact surface is the source of virus adhesion.Due to lack of knowledge on virus adhesion to various FCMs, this thesis aims to reveal the key factors that mediate the virus-FCM and virus-virus interactions in order to effectively prevent virus infection or spread. The objectives are (1) to identify the physical and chemical features of a material surface that affect virus adhesion to determine an optimal FCM, (2) to reduce virus adhesion via nanofabrication of a material’s surface; (3) to investigate the effect of thermal inactivation (heat treatment) on virus-virus interaction toward the establishment of a non-culture-based infectivity assay for laboratory assessment of the effectiveness of disinfection methods. In this study, virus adhesion on various FCMs, including glass, polyvinyl chloride (PVC), polyethylene (PE) and graphite which have been widely used in food storages, food packages and utensil handling during food preparations, was investigated. Male-specific coliphage (MS2) was used as a virus surrogate of the highly infectious human enteric virus with similar physiochemical properties. Atomic force microscopy (AFM) was predominantly used in quantitative analyses of the strength of MS2 adhesion to various food-contact surfaces. Dynamic light scattering (DLS) was applied in MS2 dimensional analysis in aqueous suspension. Moreover, surface modification, such as nanofabrication, was employed to create controllable surface textures to reduce virus adhesion on FCM. Thermal inactivation was employed as a disinfection method. A comparative study was carried out to differentiate the active and inactivated MS2 in the virus-FCM and the virus-virus interactions. The results of this examination indicate that a material’s surface property, such as topography, hydrophobicity and surface charge, contributed to virus adhesion in aqueous phase at neutral pH (=7.4). Each surface feature played a distinctive role; however, the combined effect as well as the chemical signature of a virion’s surface determined the virus-FCM interaction. A delicate control of a surface’s chemical affinity and physical feature is expected to effectively reduce/interfere virus adhesion. It was also discovered that thermally inactivated MS2 particles became larger, softer, and more hydrophobic. These properties can be utilized in developing a non-culture-based assay to assess the effectiveness of disinfection methods for human enteric viruses, which can hardly be cultured in laboratory.
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Title: BIG DATA AS A SERVICE WITH PRIVACY AND SECURITY
Creator: Hou, Jiahui
Date: 2020
Description: With the increase of data production sources like IoT devices (e.g., smartwatches, smartphones) and data from smart home (health sensor,...
Show moreWith the increase of data production sources like IoT devices (e.g., smartwatches, smartphones) and data from smart home (health sensor, energy sensors), truly mind-boggling amounts of data are generated daily. Building a big data as a service system, that combines big data technologies and cloud computing, will enhance the huge value of big data and tremendously boost the economic growth in various areas. Big data as a service has evolved into a booming market, but with the emergence of larger privacy and security challenges. Privacy and security concerns limit the development of big data as a service and increasingly become one of the main reasons why most data are not shared and well utilized. This dissertation aims to build a new incrementally deployable middleware for the current and future big data as a service eco-system in order to guarantee privacy and security. This middleware will retain privacy and security in the data querying and ensure privacy preservation in data analysis. In addition, emerging cloud computing contributes to providing valuable services associated with machine learning (ML) techniques. We consider privacy issues in both traditional queries and ML queries (i.e., ML classification) in this dissertation. The final goal is to design and develop a demonstrable system that can be deployed in the big data as a service system in order to guarantee the privacy of data/ service owners as well as users, enabling secure data analysis and services.Firstly, we consider a private dataset composed of a set of individuals, and the data is outsourced to a remote cloud server. We revisit the classic query auditing problem in the outsourcing scenario. Secondly, we study privacy preserving neural network classification where source data is randomly partitioned. Thirdly, we concern the privacy of confidential training dataset and models which are typically trained in a centralized cloud server but publicly accessible, \ie online ML-as-a-Service (MLaaS). Lastly, we consider the offline MLaaS systems. We design, implement, and evaluate a secure ML framework to enable MLaaS on clients' edge devices, where a ``encrypted'' ML models are stored locally.
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Title: Investigating anti-biofilm and anti-persister activities of natural compounds and antimicrobial proteins
Creator: Jin, Xing
Date: 2020
Description: Bacterial biofilm formation is frequently involved in the development of chronic infectious diseases. Inhibiting biofilms is challenging due...
Show moreBacterial biofilm formation is frequently involved in the development of chronic infectious diseases. Inhibiting biofilms is challenging due to their tolerance against conventional antibiotics which are not effective to penetrating biofilm matrix to kill the cells residing in biofilms. Metabolically dormant cells known as persisters are also not eradicated by antibiotic treatment. Therefore, novel antimicrobial drugs that can kill non-growing persisters or inhibit biofilms are needed urgently. Here, we investigate the anti-biofilm and anti-persister activities of new drug candidates including plant extracts, fatty acids and colicins. We firstly screened 50 different plant extracts on enterohemorrhagic E. coli and Listeria monocytogenes, and identified Cancavalia ensiformis-derived lectin Concanavalin A (ConA) inhibits biofilm formation of enterohemorrhagic E. coli and Listeria monocytogenes by binding to carbohydrates on bacterial cell surface. Biofilm results support that ConA lectin can be applied for developing anti-adherent and anti-biofilm agents to control biofilms. Also, fatty acids may be promising candidates as anti-persister or anti-biofilm agents, because some fatty acids exhibit antimicrobial effects. We screened a fatty acid library consisting of 65 different fatty acid molecules for altered persister formation. We found that undecanoic acid, lauric acid, and N-tridecanoic acid inhibited E. coli persister cell formation including enterohemorrhagic E. coli EDL933. These fatty acids were all medium chain saturated forms. Furthermore, the fatty acids repressed EHEC biofilm formation (for example, by 8-fold for lauric acid) without having antimicrobial activity. This study demonstrates that medium chain saturated fatty acids can serve as anti-persister and anti-biofilm agents that may be applied to treat bacterial infections. Colicins, a type of antimicrobial bacteriocins, are considered as a viable alternative of conventional antibiotics due to their unique cell killing mechanisms that can damage cells by pore-forming on the cell membrane, nuclease activity, and cell wall synthesis inhibition. In this study, we utilized cell-free protein synthesis to produce colicins with different modes of action. We optimized the production yield and activity of colicins in cell-free system. Also, we tested effect of cell-free produced colicins on persister cell formation and biofilm formation. We illustrated that colicins kill persister cells and biofilm cells. Moreover, colicins produced from the engineered probiotic E. coli cells, which can be used as a living medicine, specifically and significantly eradicate target biofilms without affecting other bacterial population. Colicins have great potential to be an antibiotic alternative, and engineered probiotic E. coli is a potential candidate for engineered bacterial therapeutics.
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Title: DIAGNOSING AND TREATING ADHD: CLINICIAN CHARACTERISTICS, METHODS OF DIAGNOSIS, DIAGNOSTIC RATES, AND TREATMENT RECOMMENDATIONS
Creator: Haak, Christopher Luke
Date: 2019
Description: Attention-deficit/hyperactivity disorder (ADHD) is one of the top five most common referrals among all neuropsychologists (Sweet et al. 2015)...
Show moreAttention-deficit/hyperactivity disorder (ADHD) is one of the top five most common referrals among all neuropsychologists (Sweet et al. 2015) and continues to elicit public and professional concern about over-diagnosis in children (Sciutto & Eisenberg, 2007) and under-diagnosis in adults (Asheron et al., 2012; Kooji et al., 2010). In recent years, the prevalence of ADHD has increased (Polanczyk et al., 2007 & 2014, Thomas et al., 2015). It is unclear what is driving these changes though changes in criteria may be playing a role (van de Voort et al., 2014). Further, there has been little research on whether professional training, beliefs, and practice factors can influence the likelihood to diagnose ADHD. The purpose of this study was to examine the extent to which neuropsychologists’ professional characteristics, training, and beliefs about ADHD diagnosis and treatment influence their likelihood to diagnose ADHD. The study also evaluated whether there are differences in assessing and treating ADHD based upon the client population focus (child, lifespan, or adult) of neuropsychologists. Participants in this study were 106 neuropsychologists from across the United States and Canada who were recruited through neuropsychology listservs to participate in an online survey. Results indicated that population focus was associated with significant differences in approach to diagnosing and treating ADHD, with child- and lifespan-focused neuropsychologists reporting higher rates of ADHD diagnosis. Additionally, having a higher percent of clinical cases in which ADHD is a referral question and greater self-reported adherence to following full diagnostic criteria for making a diagnosis were associated with higher ADHD diagnostic rates, controlling for age, gender, ethnicity, and other professional characteristics. This study is among the first to examine specific clinician factors impacting diagnostic rates and its findings have several implications for practice and research.
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