<p>In this thesis work, two new CO₂-responsive monomers have been synthesized. These amidine-containing monomers were prepared in a simple and effective one-step reaction, giving a very high yield (98.5 %) of product. Furthermore, there was no complicated further purification required to obtain the highly pure product. The CO₂ switchability, conductivity and partitioning of the monomers were measured. It was confirmed that the monomers could be protonated CO₂ in the present of trace amount of water and reversibly switched back and forth to their natural forms by N₂ at room temperature.</p> <p>The polymers having different molecular weights were prepared from one monomer via conventional free radical polymerization method. The polymers also showed the reversible switchability property with CO₂ and N₂ stimuli. This was confirmed by the results of conductivity and partitioning tests. Temperature showed a major influence on the conductivity of the monomer and polymers. The effect of molecular weight on the polymer switchability of was further investigated through conductivity tests and potentiometric titration. The conductivity decreased with the increased molecular weight. The apparent equilibrium constant (pK_a)decreased with the degree of protonation (δ) suggesting that the basicity of the polymers is strongly depended on the value of δ.</p> / Master of Applied Science (MASc)

Nanoparticle-based technologies are an emerging field with the promise to impact a wide range of application areas. However, that potential is somewhat married to a host of research questions that remain to be answered. This work explores the surface modification of magnetic nanoparticles in a controlled fashion to produce hybrid nanoparticle (metal/polymer) systems with different morphologies, understand in-situ behavior of stimuli-responsive polymers grafted to a substrate, and obtain better computational methods for particle-tracking and -deposition. Nanoparticle surface modification was performed using ATRP, obtaining homo-, block-co-, and ‘twoaced/biphasic’ polymer structures on the nanoparticle surfaces. Biphasic Janus nanoparticles (JPs) were formed using a magnetic nanoparticle core and an innovative technique combining non-covalent solid protection with sequential controlled radical polymerization to form the two surface-grafted polymer phases. Surface-confined polymerizations were conducted using pH- and thermo-responsive materials. Poly(methacrylic acid) (PMAA) and a series of (aminoalkyl) methacrylate polymers were used as pH responsive polymers. Additionally, poly(N-isopropylacrylamide) (PNIPAM) was selected as the thermo-responsive material for this study. In-situ characterization techniques, including atomic force microscopy (AFM), dynamic light scattering (DLS), and ellipsometry, were used to evaluate the thermo- and pH-responsiveness of these stimuli responsive materials. A new general-oscillator (GENOSC) model was used to determine swelling ratio, thickness, and optical constant changes in the polymer brush as pH was changed in-situ. AFM was used to study morphological changes due to changes in pH and temperature. Nanoparticle temperature responsiveness was investigated using DLS. A related effort involved the use of computational fluid dynamic (CFD) methods to track (micron-sized) particles in certain geometries, including a human lung morphology. Predicted particle transport and deposition was compared to Lagrangian computational approaches and available experimental data. The Eulerian particle phase modeling method developed resulted in the accurate prediction of both near-wall particle tracking and wall deposition. This Eulerian-Eulerian model is a new tool that has potential for particle tracking in physiological morphologies. This combination of experimental and computational research has led to new nano- and micro-particle surface modification methods and particle transport modeling.

Polymeric nanoparticles have a wide range of applications, particularly as drug delivery and diagnostic agents, and tannins have been regarded as a promising building block for redox and pH responsive systems. Tannins are a class of naturally occurring polyphenols commonly produced by plants and are found in many of our consumables like teas, spices, fresh fruits, and vegetables. Many of the health benefits associated with these foods are a result of their high tannin contents and the many different types of tannins found in various plants have demonstrated therapeutic potentials for conditions ranging from cardiovascular disease and diabetes to ulcers and cancer. Diets rich in tannins have been associated with lower blood pressure in patients with hypertension. The plurality of phenols in tannins also makes them powerful antioxidants and as a result, there is a lot of interest in taking advantage of their self-assembling abilities to make redox and pH responsive drug delivery systems. However, the benefit of natural tannins is limited by their instability in physiological conditions. Furthermore, there is limited control over molecular weight and reactivity of the phenolic content of plant extracts. Herein we report the novel synthesis of pseudotannins with control over molecular weight and reactivity of phenolic moieties. These pseudotannins have can form nanoscale interpolymer complexes under physiological conditions and have demonstrated antioxidative potential. Furthermore, pseudotannin IPCs have been shown to be responsive to physiologically relevant oxidation as well as the ability to easily incorporate cell targeting peptides, fluorescent tags, and MRI contrast agents. The work presented here describes how pseudotannins would be ideally suited to minimally invasive techniques for diagnosing atherosclerotic plaques and targeting triple negative breast cancer. We demonstrate that pseudotannin can very easily and quickly form nanoscale particles that are small enough to be uptaken into mammalian cells. Furthermore, by self-assembling with gadolinium, pseudotannins can effectively attenuate the signal of gadolinium based MRI contrast agents. This in conjunction with oxidation responsive decomplexation could be a viable option for diagnosing the severity and risk of rupture of atherosclerotic plaques. Also, we demonstrate that pegylated compounds can easily be incorporated into pseudotannin nanoparticles to impart cell targeting functionality. The subsequent uptake of pseudotannin nanoparticles into breast cancer cells demonstrated the ability to increase their sensitivity to UV radiation. The creation of synthetic tannin-like polymers leads to directly to making a variety of self-assembling, stimuli responsive, and bioactive nanoparticles well-suited for various biomedical applications. / Bioengineering

We study the optimal resource portfolio for a price-setter firm under a consumer choice model with supply and demand risks. The firm sells two products that are vertically differentiated, and has the option to invest in both dedicated and flexible resources. Our objective is to understand the effectiveness of the two hedging mechanisms, resource flexibility and demand management through production differentiation, under demand and supply risks. We show that the presence of consumer-driven substitution does not always reduce the need for the firm to offer differentiated products. In particular, when the firm faces demand risk and differential production costs, it might invest in the flexible resource and offer differentiated products for a wider range of parameters. Interestingly, more uncertainty (in the form of additional supply risk) does not always make the firm more eager to adopt a hedging mechanism. This depends on the relationship between resource risks, product attributes, and resource investment costs. On the other hand, when the firm invests in the flexible resource, this never completely replaces the dedicated resources, and always results in a "diverse" resource portfolio. While this happens in the supply risk setting mainly due to resource diversification advantage, it also happens in the demand risk setting due to the vertical differentiation between the products. Finally, in the absence of differential production costs, demand management by itself (without resource flexibility) becomes powerful enough to hedge against the demand risk, but not the supply risk, due to the additional resource diversification benefit of the flexible resource in the latter setting. / Ph. D.

The synthesis of a variety of novel functionalized polymers using living polymerization techniques to achieve functional and stimuli responsive coatings on silica surfaces are described. Since microscopic features on a surface influence the overall wetting properties of the surface, a systematic investigation of the influence of polymer architecture on the microscopic characteristics of the modified surfaces was studied using silane-functionalized linear and novel star-branched polystyrene (PS). Star-branched modifiers provide functional and relatively well-defined model systems for probing surface properties compared to ill-defined highly branched systems and synthetically challenging dendrimers. Using these simple star-shaped macromolecules it was shown that the topographies of the polymer-modified surfaces were indeed influenced by the polymer architecture. A model explaining the observed surface features was proposed. A living polymerization strategy was also used to synthesize centrally functionalized amphiphilic triblock copolymers. The amphiphilic copolymers exhibited stimuli responsive changes in surface hydrophobicity. In spite of multiple solvent exposures, the copolymer films remained stable on the surface indicating that the observed changes in surface properties were due to selective solvent induced reversible rearrangement of the copolymer blocks. The chemical composition of the copolymers was tailored in order to tune the response time of the surface anchored polymer chains. Thus, the polymer coatings were used to reversibly change the surface polarities in an on-demand fashion and could find possible applications as smart adhesives, sensors and reusable membrane devices. In contrast to the afore-mentioned covalent modification approach, which often leads to permanent modification of surfaces, renewable surfaces exhibiting "universal" adhesion properties were also obtained through non-covalent modification. By employing hydrogen bonding interactions between DNA bases, surfaces functionalized with adenine groups were found to reversibly associate with thymine-functionalized polymers. This study describing the solvato-reversible polymer coating was the first demonstration on silica surfaces. A systematic investigation of the influence of surface concentration of the multiple hydrogen bonding groups and their structure on the extent of polymer recognition by the modified surfaces is also discussed. / Ph. D.

Peptide-based biomaterials have gained much interest in various applications in drug delivery and tissue engineering in recent years, in large part due to their typically excellent biocompatibility and biodegradability. Composed of different amino acids, peptides can be designed with numerous sequences, providing flexibility and tunability in biomaterials. Peptides are easy to modify with small molecule drugs, inorganic components, and polymer chains to access multiple functions and tune properties relevant to biology and medicine. Stimuli-responsive peptide-based biomaterials can respond to environmental stimuli, such as light and ultrasound, in addition to local environmental factors, such as temperature, enzyme activity, and pH. Under environmental changes, these materials can be triggered to release therapeutic payloads, change conformations, or induce self-assembly in the target sites. In this work, I introduce the design, synthesis, and potential applications of several stimuli-responsive peptide-based biomaterials. The first half of this dissertation is based on enzyme-responsive, peptide-based biomaterials as extracellular matrix (ECM) mimics in tissue engineering. We synthesized linear and dendritic elastin-like peptides (ELPs) as crosslinkers and conjugated them with hyaluronic acid (HA) to form hydrogels. Trypsin was used as the enzyme trigger for cleaving the C-terminal lysine and to study how crosslinker topology affects enzymatic degradation. Hydrogels with dendritic ELPs degraded more slowly than linear ELPs, providing a novel strategy to tune the degradation rate of hydrogels as ECM mimics by the molecular design of crosslinker topology. Building on this peptide-polysaccharide platform for synthetic ECM design, we subsequently prepared hydrogels embedded with bioactive cryptic sites. These novel polymeric hydrogels mimicked native ECM cryptic sites by using depsipeptides that undergo an enzyme-triggered molecular rearrangement, "switching" from a non-functional epitope to a bioactive sequence. Mass spectrometry, 1H and 13C NMR spectroscopy, and fluorescence studies were applied to track structural changes in the peptide. SEM was used to image these polymer-peptide hybrid hydrogels. Finally, in vitro studies were conducted to evaluate cell interactions with the hydrogels. Switch peptide-modified alginate hydrogels showed increased cell adhesion upon induction of enzymatic activity, which provided a "gain of function" of the synthetic ECM. Critically, enzymes associated with the cells themselves could trigger the peptide switch and change in synthetic ECM behavior. With knowledge of stimuli-responsive peptide-based biomaterials applied in tissue engineering, I then studied how this system could be used in drug delivery by designing peptide-hydrogen sulfide (H2S) donor conjugates (PHDCs). H2S is a gasotransmitter that is produced endogenously, which has been explored in recent years with many potential therapeutical applications. We studied H2S release profiles in dual-enzyme-responsive PHDCs, with a further investigation into PHDC–Fe2+ complexes for potential tumor treatments via chemodynamic therapy. The PHDC–Fe2+ complexes were examined in a C6 glioma cell line, exhibiting an improved cell-killing effect compared with controls, by inducing toxic hydroxyl radical generation (•OH) via a Fenton reaction. To this end, we further discovered how side chains influence self-assembling nanostructures, H2S release profiles, and biological activities via three constitutionally isomeric PHDCs. Different morphologies and varied H2S release rates were observed, paving the way for tuning the properties of PHDCs by simple changes in molecular design. Finally, this dissertation discloses conclusions and future directions on stimuli-responsive peptide-based biomaterials using similar platforms with different designs in the drug delivery and tissue engineering fields. / Doctor of Philosophy / Peptides, short sequences of two or more amino acids linked by chemical bonds, are smaller versions of proteins. Forming naturally in nature, peptides are promising candidates in the design of biocompatible and biodegradable materials. To make these peptide-based materials "smart", certain sequences or functional groups are installed in the peptides, making them responsive to environmental changes, or stimuli. These external stimuli include light, ultrasound, temperature, enzyme activity, and pH changes. In this work, we have explored the design and synthesis of stimuli-responsive peptide-based biomaterials and their potential applications in tissue engineering and drug delivery. The first half of this dissertation focuses on the design and synthesis of two enzyme-responsive, peptide-based materials that function as extracellular matrix (ECM) mimics. The ECM is a three-dimensional microenvironment where cells reside, providing structural support and adhesive anchor points for cells. In the first system, we synthesized peptide-polysaccharide hydrogels with different peptide crosslinkers, comparing their enzymatic degradation performance to evaluate how peptide topology (architecture) influences degradation. A more branched topology led to a slower hydrogel degradation rate. To introduce biofunctionality into the ECM mimics, we embedded the second system with a "switchable" peptide sequence, which transformed from a non-functional peptide into a functional, bioactive epitope after being triggered by an enzyme. The functional peptide after the switch provided cell adhesion and increased cell spreading. The latter half of this dissertation explores the possibility of stimuli-responsive peptide-based biomaterials in drug delivery. We designed peptides that release hydrogen sulfide (H2S), a signaling gas is commonly known for its foul smell and toxicity, and studied the biological behaviors in cells. The peptide-H2S donor conjugates (PHDCs) were activated by the enzyme legumain, which cancer cells overproduce, leading to H2S release. With the combined treatment with Fe2+, the PHDC-Fe2+ system reduced cancer cell viability due to the high amount of hydroxyl radicals (•OH) generated by the Fenton reaction. This system may be a potential design platform for precise tumor treatments.

<p dir="ltr">American society’s increase in ethnic textures, interracial tension, immigrants, religion, gender, disability, ability, and students who speak languages other than English as their first language prolongs the pedagogical challenges teachers encounter in the classroom due to diversity. This study explored the experiences of secondary social studies teachers as curricular-instructional gatekeepers implementing culturally responsive pedagogy in times of socio-political tensions in the United States. The teacher as curricular-instructional gatekeeper framework guided this research. By adopting a qualitative multiple-case study, I utilized interviews with four teachers, two hundred hours of classroom observation, and document analysis as data sources. The findings revealed that the social studies gatekeepers’ culturally responsive practices amidst the present socio-political tensions included exposing diverse perspectives to diverse students, leveraging culturally diverse learners’ lived experiences, diversifying instructional methodologies for diverse learners, and confronting stereotypes in a culturally diverse classroom. Moreover, I discovered that present happenings influence culturally responsive practices by presenting difficulty in exposing specific topics to diverse learners, limiting classroom participation for responsive teaching, increasing workload in planning responsive lessons, and becoming a better teacher in a culturally diverse classroom. I recommend that further research should be conducted to explore the role of teacher education programs in preparing pre-service or in-service teachers to implement culturally responsive practices, how the multiple identities of in-service social studies teachers interplay to influence their implementation of culturally responsive practices, and how professional development training offered to in-service social studies teachers prepare them to implement culturally responsive practices amidst the growing legislation in the United States.</p>

School cultures, curriculum, and instruction are too often created through a monocultural lens, which excludes Black and Latino/a/x students both socially and academically, and perpetuates the false notion that these students are inherently less capable of achieving academic success when compared to their White counterparts. This is visible across all content areas, but especially in secondary science, technology, engineering, and mathematics (STEM) classes, which means that our Black and Latino/a/x students are continually denied preparation for the critical, high demand careers in the STEM field. Just as critical, with the dominance of White teachers in the classroom, out Black and Latino/a/x students often do not have access to teachers who share their lived experiences or who understand the nuances of their home cultures. However, teachers and school instructional leaders can change course by focusing their efforts to develop a rich cultural consciousness, and by focusing on the utilization of culturally responsive pedagogy (CRP) and related instructional strategies with great intentionality in the classroom. This mixed method, single site, exploratory case study was conducted to examine Black and Latino/a/x students' perceptions of their culturally responsive STEM teachers' cultural consciousness, and culturally responsive STEM teachers' perceptions of culturally responsive practices and their Black and Latino/a/x academic abilities. The results provide a clear discrepancy between STEM teacher and Black and Latino/a/x student perspectives that emphasizes a tension between them. This tension must be further explored and highlights a critical need for STEM specific professional development that encompasses both culturally responsive practices and opportunities to develop a critical consciousness.

In the United States corn is one of the leading agricultural products and one of the top exports. The majority of U.S corn is grown in the Midwestern region of the U.S. known as the Corn Belt where the bacterial disease Stewart's Wilt reduces crop yield. Pantoea stewartii subsp. stewartii (Pss) is transmitted into corn via the corn flea beetle insect vector, Chaetocnema pulicaria. As the beetle feeds on the corn plant leaves, Pss deposited in beetle feces enter the leaf through lesions. The early stage of Pss infection begins in the mesophyll apoplast of the corn leaf where a type III secretion system (T3SS) and its associated effectors induce water soaking (WS) and nutrient release. Ultimately, Pss will enter the plant xylem apoplast (will be referred to as the xylem) and use quorum sensing (QS) to initiate a lifestyle shift. Within the xylem, Pss grows to high cell density and secretes exopolysaccharide (EPS), forming a biofilm which eventually obstructs water transport, leading to wilting and necrosis. Previous Tn-Seq experiments provided insights into genes that are essential for in planta survival, including the master transcriptional regulator, Leucine-responsive Regulatory Protein (Lrp). To better understand the role of Lrp when Pss inhabits the xylem, RNA-Seq experiments comparing Pss wild-type and ∆lrp strains grown in planta were conducted to ascertain differential gene expression. The RNA-Seq data was further analyzed using DESeq2 and validated using qRT-PCR methods. Following validation, the Pss genome was annotated using Blast2GO software and genes upregulated and downregulated by Lrp were linked with biological processes. Lrp was found to be involved in regulating capsule biosynthesis and nitrogen-associated assimilation and metabolism during Pss survival in the xylem. This provides further insight into how Pss contends with harmful host defense compounds and extracts scarce nutrients present in the in planta xylem environment. A corn xylem fluid extraction method was developed that has enabled more physiologically relevant growth experiments to be conducted in vitro. Extracted xylem fluid was used to grow Pss wild-type and ∆lrp mutant strains as monocultures to observe any differences in growth patterns in different growth media. When grown separately in xylem fluid or Luria-Bertani (LB) medium, the Pss wild-type and ∆lrp mutant strains grew at similar rates and to final cell densities . The Pss ∆lrp mutant strain greatly outcompeted the wild type when grown together in LB medium. However, when the two Pss strains were growth together in xylem fluid, a shift in relative competition was observed, providing evidence of the wild type slightly outcompeting the ∆lrp mutant. Analysis of the composition of extracted xylem fluid through metabolomics will help define the nutrients specifically utilized by Pss in planta. Altogether, the outcome of these research projects was to provide pertinent discoveries to contribute to understanding the mechanisms used by Pss to survive in the corn xylem environment. Broadly, increased understanding of Pss pathogenesis may translate to understanding pathogenesis mechanisms in other bacterial wilt-disease causing plant pathogens. / Master of Science / Corn is a significant agricultural product and export in the United States. This important crop is used as a food source for humans, a primary nutrient source of livestock, and a major ingredient for corn-based industries manufacturing commodities such as culinary additives, biofuels, and preservatives. Certain bacteria are greatly beneficial to plants, able to increase their overall health and growth, while other bacteria share a more insidious relationship with plants and cause disease. The research discussed in this thesis focuses on the bacterial pathogen Pantoea stewartii subspecies stewartii (Pss), the causal agent of Stewart's wilt disease in corn. Pss grows inside the plant xylem (vascular tissues which distribute water throughout the plant) and forms a biofilm that causes plant wilt leading to lower crop yield and even plant death. Previous research on Pss identified important genes for successful Pss survival inside the corn plant xylem. One of those genes codes for the Leucine-responsive Regulatory Protein (Lrp). Using a combination of experimental (RNA-Seq) and computational (bioinformatics) analyses, Lrp was found to control other genes related in biological process important for living inside the plant, necessary for the metabolism of available nutrients and production the protect slime layer within biofilm. By better understanding the key bacterial genes needed for Pss to grow inside the xylem, new disease intervention strategies can be developed to disrupt these genes and impede the ability of the bacterium to infect the plant. A second part of this research project was to develop a method for extracting corn xylem fluid from the plant. Using this extracted xylem fluid, experiments could be conducted in the laboratory to study Pss growth in more detail. The original strain of Pss (wild type) was grown separately and in combination with a Pss mutant lacking the Lrp gene in the extracted xylem fluid. Both strains grew similarly in the xylem fluid, but the wild type slightly outcompeted the mutant strain when they were grown in competition. Future work in the lab will use extracted xylem fluid to determine its precise nutrient composition and the development of synthetic xylem fluid that will enable a more detailed analysis of mechanisms used by Pss to grow in the xylem. Work on Pss serves as a model for the study of other bacterial wilt-disease causing pathogens.

<p dir="ltr">The development of feeding skills is essential for infant health, growth, and family well-being. Despite the importance of this skill, relatively little is known about the development of independent solid feeding skills relative to other body systems – like vocalizations – or external factors including caregivers or the feeding environment. The purpose of this preliminary study was to examine the relationship between feeding skills, vocalizations, and caregiver feeding responsiveness at the same point in 6-8-month-old infants. We conducted this study remotely in order to obtain the most accurate assessment of infant skills and include diverse infant feeding experiences within their own home environments. Twenty-five typically developing – low-risk – infants and a pilot group of ten infants at increased risk for feeding and communication disorders completed the study, along with their caregivers. Infants were categorized as “at-risk” if they spent time in the Neonatal Intensive Care Unit. We collected feeding data through caregiver-recorded videos of typical mealtimes, vocalization measures from daylong audio recordings, and responsiveness assessments from video-conferencing interviews with caregivers and the mealtime feeding videos. In our sample, it was feasible to use these remote data collection methods, and we obtained high inter- and intra-rater reliability for all measures (> 90%). In our preliminary study, we found that infants in the low- and at-risk groups demonstrated different oral motor feeding skills. In hierarchical regression models, the interaction between risk group and utterance duration was the most significant predictor of oral motor feeding skills, while neither vocalization measure was strongly related to eating efficiency. In the opposite direction, feeding skills were not predictive of either normalized child vocalization count or utterance duration. Relative to caregiver feeding responsiveness, we found that caregiver feeding responsivity alone did not predict feeding or vocalization measures. Responsivity in combination with weeks of feeding experience and medical risk group was related to oral motor feeding skill but not related to vocalization measures. Overall, this study provided initial evidence that feeding skills develop as a dynamic system, influenced by multiple within-child and external factors, and future research is warranted on the influence of these factors on feeding and communication skill development.</p>