Development of an Improved Fabrication Method for an Ultrasound-Sensitive Platform for Drug Delivery to Hypoxic Tumor Sites

The efficacy of cancer treatments such as chemotherapy and radiation therapy can be limited by the presence of hypoxic regions within the tumor, leading to poor clinical outcomes. Our group has developed SE61O2¬, a microbubble comprised of a Span 60 (sorbitan monostearate) and water-soluble vitamin E (TPGS) shell with an oxygen gas core, for delivery of oxygen to hypoxic tumor sites. In vivo studies have shown that mice receiving SE61O2 with ultrasound followed by radiation have decreased tumor growth and increased survival, suggesting the potential of SE61O2 to sensitize tumors to radiation therapy. However, the duration of oxygenation after administration of SE61O2 does not last long enough for it to be clinically viable. To increase the duration of oxygenation, our group is investigating lonidamine-loaded SE61O2 (SE61O2-LND), to capitalize on the fact that lonidamine targets tumor metabolism and has been shown to increase sensitivity to radiation therapy. The current fabrication method for SE61O2-LND required the use of methanol and resulted in low drug loading that had high inter-batch variability, leading to a need for an improved methodology. The purpose of this study was to develop an improved fabrication method of SE61¬O2 MBs for drug loading applications. The requirements for drug loaded microbubbles fabricated with the improved methodology are that they needed to meet the minimum acoustic requirements (enhancement ≥ 15 dB and half-life ≥ 1.5 min), have a diameter < 6 µm, be able to support an oxygen gas core, and meet the minimum drug loading requirement of 2 µg/mL. Since TPGS, one of the shell-forming molecules, forms micelles at a low critical micelle concentration, it was hypothesized that we could use these micelles to solubilize lonidamine, as it is a hydrophobic drug, and capitalize on the fact that the concentration of TPGS used to fabricate SE61 is greater than the critical micelle concentration of TPGS. The design resulted in MBs that had acoustic and size properties that met the requirements and that were not significantly different from those made with the standard method. Furthermore, it was found that the TPGS micelle method greatly improved the yield and produced twice as many microbubbles. Initially, it was believed that this may be due to the different fabrication methods resulting in microbubbles with different shell compositions; however, NMR studies showed that the molar ratios of the two surfactants were similar in microbubbles made by either method. Next, Nile red was used as a model hydrophobic drug to assess the loading capabilities of both methods. Drug loading did not affect the acoustic or size properties of the microbubbles for either method. Both methods exceeded the minimum drug loading requirement, but microbubbles made with the TPGS micelle method had loaded twice as much Nile red per batch as the standard method. This could be attributed to the increased microbubble yield attained with the TPGS micelle method. The improved methodology was then applied to lonidamine loading. While the resulting microbubbles met all the necessary requirements, lonidamine loading was lower than expected for the TPGS micelle method based on the Nile red results. This suggests that lonidamine may not intercalate into the TPGS micelles or SE61 microbubble shell the same way Nile red does. Further studies must be completed to characterize lonidamine loading and explore alternative methods for formation of drug loaded micelles.M.S., Biomedical Engineering -- Drexel University, 201

Between Lines: A Critical Multimodal Discourse Analysis of Black Aesthetics in a Vocal Music Therapy Group for Chronic Pain

The purpose of this study was to gain an understanding of Black clients’ experiences within a music therapy context by exploring the discursive construction of aesthetics demonstrated by Black members of a vocal music therapy (VMT) group for chronic pain. For this purpose, the theoretical framework of critical race theories and Africana womanism guided this study, and a critical multimodal discourse analysis was employed as the primary methodological tool. Three primary research questions guided this study: What were the aesthetic experiences of the Black members of the VMT chronic pain group? What was the role of black lifeworlds (musical representations and cultural representations) in Black clients’ aesthetics experiences? What was the function of Black client aesthetics in the VMT group experience? Secondary data of another research study, namely video data obtained in a clinical trial on the effect of vocal music therapy (VMT) on core outcomes in chronic pain management, served as the primary data source for this analysis. The video data documented an eight-week group VMT treatment program, in which six Black individuals with chronic pain, five females and one male, and one white female participated in vocal music therapy techniques such as toning, group singing, vocal improvisation often accompanied with percussion instruments, song reflection, and deep breathing to address core outcomes of chronic pain. These sessions were facilitated by the white music therapist and principal investigator of the clinical trial and assisted by me, her Black research assistant. This analysis evidenced Black clients’ agency-driven aesthetic exploration of Black language and Black musical representations within a music therapy context. In so doing, the VMT group context is revealed as a racially patterned social activity marked by performances of alterity mobilized through Black participants’ aestheticization of personhood. The analysis detailed the social realities co-constructed by the Black participants vis-à-vis non-monolithic experiences of Black language and Black vernacular music as processed through cultural memory and the inherently subordinate nature of therapy. This was demonstrated in four aesthetic formations: (a) (pre)embodied pain aesthetics, evidenced by participants' portrayals of agency within the intersection of socio-historical, socio-structural, and socio-cultural systems of chronic pain and healthcare disparity discourse; (b) Black language aesthetics, revealed in mono- and cross-racial verbal and prosodic communication; (c) healing aesthetics, delineated by participants' spiritual negotiations within a model of medical music therapy; and (d) musicking aesthetics, detailed by the use and situated meaning of Black musical gestures referentially used within music therapy theory and praxis. These findings detailed Black verbal and musical iconicity, client face-saving practices, individual and collective responses to microaggressions and their impact on the therapeutic process exhibited verbally and nonverbally, in-group tensions, the protective function of spiritual coping, paraxial tensions between medical and culturally centered healing practices, and aesthetic relevance of ethnocentricity within the VMT program. The findings of this analysis detailed the sensorial, relational, imaginal, and political nature of aesthetic discourse and served as the first systematic exploration of aesthetic processes of Black participants in the field of music therapy. Furthermore, this research discussed the widely understudied experience of chronic pain by Black participants, as both physical and psychological phenomena. In so doing, it provided a synthesis of Black client narratives that further contribute to the growing knowledge of culturally responsive clinical practice within music therapy and related healthcare disciplines, as well as the collective discourse of Black bodies within cultural aesthetics, semiotic anthropology, and Africana studies. Given the nature of the findings, implications for future research, clinical practice, and music therapy cultural competence development are provided.Ph.D., Creative Arts in Therapy -- Drexel University, 201

Exploring Chemical Optimization Pathways for HIV-1 Env-Targeting Entry Inhibitors

Entry of HIV-1 virus into human CD4 positive cells is a critical step for infection1. Preventing this entry process is key for therapeutic intervention. Despite advances in AIDS treatment, shortcomings in current Highly Active Anti-Retroviral Therapy (HAART) exist, such as emergent viral resistance and low patient compliance. To date, an anti-HIV-1 vaccine has not been attained. We have previously demonstrated that peptide triazoles (PTs) and their cyclic counterparts (cPTs) effectively compete for human CD4 and co-receptor binding, thus preventing infection2-3. Additionally, cPT derivatives irreversibly inactivate3 HIV-1 virions and are non-cytotoxic2. While previous optimization studies have been performed on lead cPT compounds2, enhancement of potency has been unable to yield IC50 values below 0.1[mu]M (100nM) thus far. In this study, the examination of two chemical routes for improvement of cPT potency against HIV-1 infection were investigated. Changes to the stereochemistry of the peptide backbone were tested in many sequences to yield information about structural tolerance to cPT stereochemistry. Previously, linear PTs were covalently linked4 to a co-receptor inhibitor (coRi) compound developed by collaborators5 to form a potent and synergistic chimera. Thus, the covalent attachment of a cPT to this coRi was attempted via microwave assisted solid phase peptide synthesis. Both pathways presented unique synthetic challenges which were overcome and gave much insight to the process of the solid phase synthesis technique. Neither chemical route resulted in a new lead compound with enhanced potency over the previous generation. Obtaining crystallographic data in future studies would help facilitate interpretation of these results to guide future experiments and syntheses.M.S., Chemistry -- Drexel University, 201

The Role of The Target Audience and Their Preference for Programming in Increasing Subscribers to China's Online Video Website iQiyi

With the advent of China's first streaming video website in 2004, video websites have become the main channels for viewers to watch TV shows, movies and short videos. But behind the industry boom, profitability problems have been a concern for streaming video websites. This thesis examines audience attitudes toward programming on streaming video websites, to find a way to increase iQiyi's number of subscribers. Based on the features of the target audiences for iQiyi, from other literature and the results of a survey, the author provided reasonable suggestions for programming improvement.M.S., Television Management -- Drexel University, 201

A Phenomenological Study: Exploring Academic Equity In Elementary Virtual Classrooms Of A Pennsylvania Cyber Charter School

Cyber schools have experienced exponential increases in enrollment across the United States in recent years. While research shows the potential for academic equity in cyber schools to educate students who may have faced struggles in a traditional school setting, we lack a clear understanding of the factors that contribute to that potential equity. The purpose of this phenomenological research study was to describe the lived experiences of elementary cyber school teachers to explore their perceptions, conceptualization, development, and implementation of academic equity in their elementary virtual classrooms. This study explored the experiences of four elementary virtual classroom teachers of a single cyber charter school in Southeastern Pennsylvania to grasp the essence of their perceptions, conceptualization, development, and implementation of academic equity in their virtual classroom setting. The data gathered was comprised of semi-structured interviews, observations, and artifact review. First cycle In Vivo coding and second cycle Descriptive coding revealed five emergent themes, producing key findings. Results and interpretations revealed the following: (a) Families seek alternative learning environments for their children in order for students facing challenges in traditional classroom settings to feel safe and supported according to their individual needs; (b) The parent(s)/guardian must be an integral part of the K-5 virtual classroom experience in order for students to engage and fully access the equitable opportunities offered in the virtual classroom; (c) Leveraging relationships between and among students, parents, and faculty is critical in order to maintain engagement of the family and to improve the capacity of the teachers' equitable instruction; (d) Flexibility in schedule and approach is an indispensable component of a successful virtual program in order for teachers to prioritize collaboration and extensive differentiated planning; (e) Differentiating instruction is a necessary part of the planning and delivery of virtual classroom instruction in order to meet the needs of the diverse students. Conclusions rendered insights to the four research questions. Recommendations to enhance and increase equitable access and opportunity in cyber charter schools were included and comprised of the following: (a) recommendations to the Cyber Charter School; (b) recommendations to cyber charter schools overall; and (c) recommendations for practice and recommendations for additional research.Ed.D., Educational Leadership and Management -- Drexel University, 201

Structural Characterization and Introduction of Biomimetic Proteoglycans in Temporomandibular Joint Pain

Temporomandibular Joint disorders (TMJD) are the second-most common source of orofacial pain with 33% of adults having at least one TMJ disorder symptom. A significant subset of patients with TMJD develop osteoarthritis (OA), a progressive pathology characterized by intraarticular inflammation and fibrocartilage degeneration. Specific indications of osteoarthritic development are reorganization of collagen and loss of proteoglycans such as aggrecan. Loss of proteoglycans cause a decrease in tissue hydration, joint lubrication, and compromised compressive mechanics. Recent research suggests these structural changes are identifiable early within the pericellular matrix of the tissue. The goal of this thesis was to evaluate the use of a novel biomimetic proteoglycan (BPG) as a treatment during early stages of TMJ osteoarthritis. BPGs have similar composition and properties to naturally occurring proteoglycans, but resist enzymatic degradation associated with hostile, osteoarthritic tissue environments. We initially established there is pericellular reorganization of collagen VI and aggrecan in joint overloading rat models of tunable TMJ pain, with more robust structural outcomes in joints exposed to 3.5N, resembling chronic pain, versus those exposed to 2N, representing acute pain. This established motivation to introduce BPG to this animal model. With ex-vivo diffusion of the biomimetic into TMJs from the acute and chronic pain models, we characterized BPG distribution and localization within the tissue matrix and found modulation between non-loaded, 2N, and 3.5N loaded TMJs. Further, we identified a functional role of BPGs to influence matrix mechanics of TMJ fibrocartilage. Together, these findings bridge the inflammatory and catabolic cascades of TMJ pain to tissue structural outcomes and provide a first look into the use of biomimetic proteoglycans as a way restore proteoglycans lost during early TMJ osteoarthritis known to induce associated symptomatic pain.M.S., Biomedical Engineering -- Drexel University, 201

Navigating the Hallways: A Dance/Movement Therapy Method for Adolescents in Schools

This thesis will describe the development of a dance/movement therapy method catered towards adolescents in a school setting that experience anxiety and chaos while in the classroom. The literature review addresses adolescent development, adolescents "at-risk", anxiety, identity development, and applications for dance/movement therapists working with adolescents. The method itself is a multi-step, somatic experience to help mitigate the symptoms of anxiety. Often, chaos occurs in the classroom. For adolescents with added exposure to violence, aggression, and abuse, classrooms become undesirable environments and increase levels of student’s anxiety. The method, "Navigating the Hallways" begins with body awareness to identify triggers that lead to anxiety. It is followed by four pathways, co-created with the therapist, to support the student’s ability to emotionally regulate, and to calm down enough to return to the classroom. This author looks at ways to provide students with body-based techniques to reduce anxiety that can then be utilized more independently or in coordination with other students in need. This author reflects on the process of developing this method and how relationships with the students aided in her growth as a dance/movement therapist.M.A., Dance/Movement Therapy and Counseling -- Drexel University, 201

Unexpected Gelators with Unforeseen Properties: A Spectroscopic Investigation of Alanine-Based Self-Assembling Hydrogels

Self-assembly of biomolecules is a prominent issue explored in biomedical, biophysical, and biomaterial research. Understanding how and why certain peptides/proteins prefer to self-assemble into larger networks can reveal the mechanism of amyloid formation and assist in bottom-up designs of supramolecular structures like gels and nanotubes. Hydrogels formed by polypeptides could be much-favored tools for drug delivery and other biotechnical applications due to their main ingredients being biodegradable. However, the gelation of peptides in aqueous solution is generally thought to require a minimal length of the peptide chain, as well as distinct sequences of hydrophilic and hydrophobic residues. This biodegradability and cheap manufacturing costs are increased for shorter peptides, but a high degree of hydrophobicity or aromaticity was deemed necessary. Contrary to expectation, it was discovered that cationic glycyl-alanyl-glycine (GAG) in ethanol/water mixtures forms a gel comprised of network spanning fibrils several 100 μm long. To explore how ethanol solvation and solvent-peptide interactions prepare the system for aggregation and fibrillization, we utilized amide I band profiles along with J-coupling constants and chemical shift from NMR measurements to observe conformational changes of the alanine residue caused by the addition of ethanol. We propose that GAG accumulates on the ethanol/water interface, which would increase the effective chemical potential of the peptide and thus would facilitate its self-assembly. We first focused our investigation of the gelation phase on 220 mM GAG in 55 mol% ethanol/45 mol% water. Rheology shows that under optimal conditions, the storage modulus is 106 Pa. UVCD, VCD and IR measurements, supported by DFT calculations, suggested that the underlying structure of the fibrils is dependent on the formation temperature of the fibrils and that it is not solely comprised of β-sheets. It was determined through annealing cycles that the fibrillar aggregates are not the thermodynamically preferred structure. Instead, amorphous aggregates were formed and stable. At short incubation times, the reformed gels are weakened suggesting the strength of the gel and melting temperature can be easily tuned. A phase diagram was constructed by systematically adjusted the amount of GAG dissolved into different ethanol/water mixtures. We observed that the gel phase is stabilized by increasing the ethanol fraction more so than by an increase of the peptide concentration. UVCD was utilized to determine the melting temperature of all formed gels to add a third dimension to the phase diagram.Ph.D., Chemistry -- Drexel University, 201

Factors Contributing to the Success of the Chinese Documentary Industry

Although Chinese documentary has established a solid foundation and formed a relatively stable situation after decades of development, it still occupies a small market share in the Chinese television and online media industry. Also, the overall revenues of the Chinese documentary industry are not yet able to cover the costs of production. This thesis explored and examined the characteristics, distribution methods, and revenue streams that are helpful in increasing the viewership and revenue of Chinese documentaries. A survey focused on Chinese documentary viewers was conducted for this thesis, investigating the audiences' viewing preferences and habits, as well as their related consuming behaviors. Complementary data were collected from published reports of Chinese documentary, related statistical reports, and related database. The results showed that the characteristics of a documentary that primarily attract Chinese viewers are the combination of traditional culture and humanistic spirit present in the work, the capability to provoke meditation on reality and human nature, and well-scripted and compatible narration. With the increasing number of Chinese Internet users and the change of audiences' viewing habits from TV to digital media, digital distribution has played an increasingly important role in the distribution of Chinese documentary and the increase of its viewership. Developing documentary derivatives, on the other hand, is a practical strategy to extend the lifeline of Chinese documentary and bring more long-term revenue to the industry.M.S., Television Management -- Drexel University, 201

When a Child is Sick: Helping Young Patients Cope in a Hospital Setting

The purpose of this project was to develop a method to build coping skills and lessen anxiety for school-aged children suffering from a medical illness requiring an extended hospital stay. Relevant literature was reviewed in order to support creation of the method. The literature review included articles and research including anxiety in general and in a pediatric medical setting, coping in general and in pediatric medical settings, various aspects relating to a hospital stay, other creative and alternative therapies, and dance/movement therapy. The method was intended to use three phases (breath work, choice and control, and ritual ending) to expand coping abilities for a more expansive coping repertoire and work on the expansion of an emotion understanding. I additionally used the research and literature to reflect on the creation of the method, the implications of the method, and the results of the method.M.A., Dance/Movement Therapy and Counseling -- Drexel University, 201