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Municipal Responses to Small Batch Manufacturing in New York City and Philadelphia
No full textFor decades, the United States has been experiencing a loss of manufacturing firms and employment. This has been particularly true for cities like New York and Philadelphia. This paper explores ways that New York and Philadelphia municipal governments play a role in the continued deindustrialization of their cities. Through historical trends, and current sector data, as well as business surveys and interviews with municipal and associated organization leaders, this paper identifies the key impediments to small batch urban manufacturing today. Industrial land protection, building stock, financial products, and workforce are key concerns for industrial sectors in both cities. This paper finds the lack of proactive municipal policy and programming in the industry is only exacerbating the loss of manufacturing firms and employees. The paper concludes with six policy recommendations addressing the industrial zoning code, workforce, external communications strategies, and urban production capabilities.M.S., Urban Strategy -- Drexel University, 201
Arts Practice in Preventative and Alternative Programs for Youth
No full textTo address the pertinent need for justice reform in our country to reduce crime and criminal charges, some organizations and programs have turned to the arts as a tool to help at-risk youth. The purpose of this thesis was to examine the role that arts play in diversion-based and preventative-based programs for at-risk-youth. Research showed through the use of arts in these programs, individuals can reduce the risk of becoming involved in the justice system and lower their chances of repeated offenses. Additionally, programs have reported that the use of art in different forms has contributed to helping at-risk youth process their trauma to heal. Findings suggest that more research still needs to be done in order to collect the data that directly links the use of the arts to the success in the programs.M.S., Arts Administration -- Drexel University, 201
Targeting HDAC5 to Improve Cancer Chemotherapy
No full textChemotherapy resistance and dose-limiting adverse effects remain major challenges for tumor management. It has been shown that cytoplasmic translocation of HDAC5 plays a critical role in cell adaptation to metabolic and pathological stress. This is particularly the case in cancer cells where metabolic stress triggers AMPK activation, which leads to phosphorylation and subsequent nuclear export of HDAC5. I hypothesized that chemotherapeutic stress triggers similar adaptive mechanisms as the metabolic stress, thus eliciting innate chemoresistance through cytoplasmic translocation of HDAC5. In this thesis study, I firstly explored the cancer types that may involve cytoplasmic localization of HDAC5, expecting to identify cancer models that may benefit from therapies based on targeting HDAC5 (Chapter II). Using tissue arrays and immunohistochemistry, I investigated the protein level and subcellular localization of HDAC5 and its paralog HDAC4 in normal tissues. Using cancer arrays, I found that HDAC5 expression was significantly higher in tumors originated from cervical, rectal, liver, ovarian, skin, esophageal, lymph, and intestinal carcinomas than corresponding normal tissues. Importantly, in normal cells HDAC5 was predominantly located in the nucleus whereas in cancer cells it was located predominantly in the cytoplasm. Next, I assessed if specific targeting of HDAC5 possesses advantage in safety aspect over other anti-HDAC based strategies (Chapter III). Currently used panHDACi is associated with various adverse effects, among which thrombocytopenia is the most severe, limiting dose and application. I showed that specifically targeting HDAC5 avoided panHDACiassociated thrombocytopenia, which is caused by inhibition of megakaryocyte maturation. I further show that the impairment of megakaryocyte maturation was due to degradation of a key transcription factor GATA-1, but not increased tubulin acetylation. Next, focusing on cancer mechanism, I show that chemotherapy (doxorubicin and cisplatin) stress leads to an increase in cytosolic calcium, which correlates with the activation of CaMKII[delta] kinase, HDAC5 phosphorylation (at S259) and cytoplasmic localization (Chapter IV). Disruption of CaMKII[delta] by either chemical inhibitor, siRNA knockdown or CRISPR/CAS9-based genome editing abolishes chemotherapy-triggered HDAC5 phosphorylation and cytosolic localization, whereas re-expressing a wild type CaMKII[delta] restore the chemotherapy triggered cytoplasmic localization of HDAC5, demonstrating the critical role of CaMKII[delta] in mediating the adaptive pathway. Finally, I evaluated the potential application of HDAC5 inhibition in sensitizing cancer cells to classical chemotherapy drugs (Chapter V). I show that inhibition of HDAC5 sensitizes hepatoma and osteosarcoma cells to doxorubicin and cisplatin, which allowed dose reduction of these drugs dramatically but maintained efficacy. In addition, I show that targeting HDAC5 resensitizes chemoresistant ovarian adenocarcinoma to doxorubicin. Findings from this thesis research pave the way towards the development of HDAC5/CaMKII[delta] inhibitors to sensitize cancer cells to chemotherapy and metabolic therapies, making it possible to reduce doses of classical chemotherapeutical drugs and provide hope to minimize adverse effects on normal tissues.Ph.D., Biological Sciences -- Drexel University, 201
Novel Magnetically Levitated Right Ventricular Assist Device for Pediatric and Adult Patients with Acquired or Congenital Heart Disease
No full textThousands of pediatric and adult patients in the U.S. are diagnosed with congestive heart failure (CHF) secondary to acquired or congenital heart disease. Symptoms of CHF include left-sided heart dysfunction, fluid retention and swelling in lower extremities, weakness, and shortness of breath. A substantial number of these patients also develop right-sided heart failure secondary to the left-sided failure or dysfunction. Strategies to address right ventricular heart failure include pharmacological treatments, which only slow the progression of heart disease, or complete heart transplants. With a lack of donor organs available, mechanical circulatory assist devices are alternative therapeutic options; however, there are few such devices for right ventricular failure in pediatric patients. To address this unmet clinical need, we are developing a new right ventricular assist device (RVAD) or blood pump as a novel treatment strategy for these patients. The axial flow RVAD utilizes third-generation drive technology by incorporating a magnetic suspension to levitate the axial impeller within the pump housing. This magnetically suspended configuration enables the pump to have clearances between rotating and stationary components that are much wider than afforded by conventional mechanical and fluid bearings, thus lowering shear stresses and risk of blood cell damage and clotting. The RVAD consists of five internal fluid domains and bladed regions: inducer, impeller, diffuser and flow straightener. It spans 30 mm in diameter by 60 mm in length. Acting to improve blood flow to the lungs, this RVAD is designed to achieve cardiovascular requirements by generating desired blood flow rates and increased pressures. Numerical simulations of the design were performed using ANSYS computer software to estimate the hydraulic performance of the RVAD. Pressure generation was analyzed over a physiologic blood flow range and varying rotational speeds. In addition to pressure generation, the fluid stress levels, axial and radial fluid forces on the impeller of the RVAD, and power consumption were evaluated. Sufficient pressure rises of 2-142 mmHg were attained for flow rates of 2-6 L/min at rotational speeds 7000-15000 RPM. It was observed that higher flow rates generate lower pressure rises for all speeds, and higher speeds generate increased pressure rises, which follows expected pump trends. For these operating conditions, axial forces were found to be less than 3 N and radial forces less than 1 N. Scalar stresses were less than 425 Pa with residence times less than 600 ms for operating speeds under 12000 RPM. Rotational speeds of 12000 RPM and higher generated high scalar stress values at the trailing edges of the impeller blades. Due to the strong computational data, a prototype of the RVAD was constructed and hydraulically tested. The prototype delivered sufficient pressure rises of 1-126 mmHg for flow rates of 0.1-5 L/min at rotational speeds 6000-14000 RPM with an average deviation of 48% from computational data. These results demonstrated strong pump performance for right ventricular assistance, thus supporting the continued development of this RVAD for pediatric patients with right-sided heart failure.M.S., Biomedical Engineering -- Drexel University, 201
Exploring Structural Identification as a Tool for Characterization of Bridge Substructures
No full textInsufficient information on existing bridge substructures and foundations poses significant challenges for structural condition evaluation and can cause significant uncertainties for the safety and serviceability of bridges. Characterization and condition evaluation of bridges substructures and foundations will not only help to decrease the vulnerability to natural hazards, but it could also provide opportunities for their reuse with considerable benefits. In this thesis, the feasibility of leveraging structural identification techniques to characterize bridge substructures and foundations is studied. The challenges and limitations of implementing structural identification on bridge substructure characterization are also explored. In addition, the counter measurements for these challenges are also investigated. A 3-span simply supported bridge located in Mossy, WV is used as a case study. Multi-Reference Impact Testing is applied to this bridge with two different sensor layouts designed to investigate different unknowns of the bridge substructure, and to increase spatial information to be leveraged in the following study. Modal analysis and finite element model updating techniques are used to comprehend the uncertainties and conditions of the substructure. An updated finite element model for this structure provides valuable information for bridge condition assessment and proves how structural identification is a viable tool for the case considered. Several difficulties of implementing structural identification on this bridge substructure is also discussed including: (a) identifying substructure modes from Experimental Modal Analysis results; (b) identifying unknown variables with parameter coupling effect (between foundation depth and SSI); (c) mode pairing during automated FEM calibration process. A physical scaled bridge model is designed and studied to provide more flexibility to explore the application of structural identification on the bridge substructures. The scaled bridge model is designed as a scaled phenomenological model considering similitude requirements and distortions. Three experimentation cases are designed for EMA on the scaled bridge model: a case where aluminum bearings are installed with bolts to connect superstructure and substructure, a case where rubber bearings are installed with bolts and a case where rubber bearings are installed with epoxy. Based on the study on the scaled bridge model, structural identification shows the potential to characterize bridge substructures. The counter measurements for the major challenges met in the WV bridge study are explored and verified in the study for the scaled bridge model. In addition, recommendations for the application of structural identification on real bridge substructures are given based on the results presented in this thesis.Ph.D., Civil engineering -- Drexel University, 201
Biomaterial-Mediated Control Over Macrophage Behavior for Tissue Regeneration
No full textMacrophages, the primary cell of the immune response, and fibroblasts, the major producers of extracellular matrix (ECM), have significant roles in wound healing and the foreign body response to implanted biomaterials. Macrophages are known to exhibit a spectrum of unique phenotypes in response to their environment; M1 macrophages, are associated with increased inflammation and initiating angiogenesis, while M2a macrophages have been associated with anti-inflammatory behavior and extracellular matrix deposition. Temporal control of macrophage phenotype from M1 to M2a has been shown to be critical in normal wound healing. On the other hand, dysregulated macrophage behavior has been associated with detrimental pathologies including chronic wounds and fibrosis. Therefore, the development of immunomodulatory biomaterials that can harness the natural immune response for repair and healing, hold significant promise for future of regenerative medicine. While it's appreciated that macrophages may hold the key to aberrant healing outcomes, it is not well understood how they direct pro-healing outcomes, especially within the context of a biomaterial implant. Therefore, the overall goals of this work were to 1. thoroughly characterize macrophage-biomaterial interactions and macrophage-fibroblast interactions further our understanding of how these cells may influence functional tissue regeneration, and 2. Utilize a model drug-eluting biomaterial to directly assess the role of M2a macrophages in tissue regeneration. To accomplish these goals, I investigated how macrophages change their behavior in response to 'successful', commercially- available wound matrices in vitro. Collectively, these studies showed that four commercially-available wound matrices evaluated pro-inflammatory macrophage behavior (more M1-like) and that direct contact (as opposed to soluble factors) of macrophages with a bioactive (i.e. containing cells and proteins) wound matrix was critical for reducing inflammation in pro-inflammatory macrophages. Next, I investigated the effects of macrophage-secreted signals on fibroblast behavior and matrix formation in vitro and employed model drug-eluting biomaterials to develop an M2a-promoting hydrogel to directly assess the role of M2a macrophages in the foreign body response in vivo. Together, these studies illustrated that M1 and M2a macrophage-derived signals significantly reduced the fiber diameter of fibroblast-derived deposition in vitro relative to other macrophage phenotypes. While clinically relevant macrophage-derived signals (M1+M2a and M1->M2a) returned fibroblast matrix fiber diameter to the in vitro baseline. IL4+IL13-releasing hydrogel resulted in a significant reduction in leukocyte recruitment 21 days relative to the Blank hydrogel control, suggesting an increased presence of other key ECM-producing cells. Alternatively, these results may also imply that IL4+IL13 hydrogels may change the quality and composition of ECM surrounding a biomaterial or at the tissue-biomaterial interface. Interestingly and in contrast to pilot data, the IL4+IL13 hydrogel yielded minimal differences in gene expression and histological outcomes compared the Blank control. Collectively, these preliminary and somewhat inconclusive in vivo results are likely due to technical challenges there were discovered in the in vivo experimental design. A final validation study showed that the IL4+IL13 hydrogels that were originally implanted within the same mouse as the Blank controls were likely releasing enough drug to have an impact on the outcomes of the Blank controls. Preliminary data from the validation study yielded a robust response of the IL4+IL13 hydrogel relative to the Blank control at the Day 3 time point. Future work will focus on elucidating the long-term effects of these IL4+IL13 hydrogels on ECM deposition. This work is critical for understanding how transient control of macrophage behavior is directly linked to tissue repair and regeneration outcomes. Due to the importance of macrophage behavior in all tissues, this project has the potential to translate into a myriad of other fields, especially those in which abnormal inflammation prevent tissue repair or regeneration.Ph.D., Biomedical Engineering -- Drexel University, 201
Detection of Hypoxia in Humans
No full textHumans exposed to high altitude or high acceleration conditions for prolonged periods of time often exhibit hypoxic symptoms. The commencement of physiological and cognitive changes due to the onset of hypoxia may not be immediately apparent to the exposed individual. These changes can go unrecognized for minutes and even hours; and may lead to serious performance degradation or complete incapacitation. Despite interest in the detection of hypoxia, existing detection methodologies have limited scope of reliable performance in the field. This research investigates the underlying physiological and cognitive signals under environments prone to development of hypoxic symptoms. Attention is focused toward developing temporal models for physiological signals, state-augmented Kalman filters, and designing of hypoxia detection frameworks. These frameworks utilize parallel fusion architectures that use Bayesian decision criteria to combine local decisions from ensembles of raw physiological, cognitive, and environmental signals, along with outputs of local classifier/detectors trained using machine learning techniques, to provide reliable hypoxia detection.Ph.D., Electrical Engineering -- Drexel University, 201
The Impact of Response to Intervention/Multi-Tiered System of Supports for Literacy on Student Outcomes in a Pennsylvania Elementary School: A Quasi-Experimental Cohort Study
No full textThe Response to Intervention/Multi-Tiered System of Supports (RtI/MTSS) framework for literacy is a tiered instructional framework that is intended to improve the reading achievement of all students. In addition, RtI/MTSS can also be used as a methodology for Specific Learning Disability (SLD) identification. The purpose of this study was to examine the potential impact of a state-approved, fidelity-driven RtI/MTSS framework for literacy on student outcomes within one public elementary school in Pennsylvania. The intention of this study was to add to the existing research on RtI/MTSS while focusing on a framework that is aligned with the Pennsylvania Department of Education (PDE) guidelines. This quasi-experimental cohort study compared a historical, Pre-RtI/MTSS Implementation Cohort of kindergarten through second grade (K-2) students to a Full-RtI/MTSS Implementation Cohort of K-2 students across several end-of-year outcomes, including Dynamic Indicators of Basic Early Literacy Skills (DIBELS) Composite and Subscale Scores, student tier placement, special education referral rates, and SLD identification rates. Findings suggested that differences in reading achievement between the cohorts depended upon grade level. Kindergarteners enrolled during Full-RtI/MTSS Implementation had significantly higher mean end-of-year DIBELS scores across all measures, and more of these students met end-of-year benchmark goals. In first grade, the Full-RtI/MTSS Cohort earned higher mean end-of-year DIBELS scores in Nonsense Word Fluency (NWF), but Oral Reading Fluency (ORF) and Composite Scores were comparable between cohorts. More growth from beginning-of-year to middle-of-year was noted in Full-RtI/MTSS kindergarteners and first graders, while their Pre-RtI counterparts took longer to show gains into the second half of the year. No significant differences in literacy outcomes were found between cohorts in second grade, and a large proportion of second graders in both cohorts showed a need for intensive intervention at the end of the year based on ORF tier placement. No differences were found between cohorts in special education outcomes. Implications for future research include expanding the analysis of data in a longitudinal manner to include multiple school years, including qualitative methods in comprehensive program evaluation, and considering how other factors, such as demographic variables and the implementation of tiered behavioral support systems, might impact student outcomes as well.Ed.D., Educational Leadership and Management -- Drexel University, 201
Solution Processing and Optical Properties of 2D Transition Metal Carbides (MXenes)
No full textPotentially the largest family of 2D materials, known as transition metal carbides and/or nitrides (MXenes), have a chemical formula of Mn+1XnTx, where M represents a transition metal (Ti, Mo, Nb, V, Cr, etc.), X is either carbon and/or nitrogen, and Tx represents surface terminations. The diversity in composition offers a plethora of structures and chemistries to investigate. The first discovered MXene, titanium carbide, has shown unique light-matter interactions enabling applications such as electromagnetic interference shielding, wireless communication, photothermal therapy, and as a transparent conducting electrode. Combining the optical properties with ease in processing, high electronic conductivity and mechanical strength, MXenes have the characteristics necessary to develop as optical materials, however the solution processing routes to achieve controlled nanoparticle dispersions and quality thin films are not optimized and only a few compositions have been explored. This dissertation focuses on the development of colloidal solution processing approaches, including size selection, and stability control, of carbide MXenes in various solvents, fabrication of MXene films of optical quality, and characterization of the optical properties of MXenes in the colloidal and solid state. Control of the MXene dispersion allowed for the preparation of a range of MXene compositions, varying M and n, exhibiting an unusually broad and visually striking color spectrum. The origin of the color variation, spectroscopic information from the ultraviolet to the near infrared, and a relationship between the optical spectra and the electronic properties is examined. Under the assumption that it is possible to change the optical features, optical property tuning is explored by the change in surface chemistry, modification of the composition by alloying, and the application of an electric charge through electrochemical charge injection. Using the spectroscopic details provided throughout this dissertation, a few optoelectronic applications of MXenes are demonstrated, expanding the opportunities for research on this family of optically active materials.Ph.D., Materials Science and Engineering -- Drexel University, 201
The Westernization of the Japanese Garden
No full textIn 1894, Japan decided to share the art of the Japanese garden with Western civilization at the first World’s Fair held in the United States. The event took place in San Francisco, California and featured a hybrid Japanese garden — one that combined different styles of garden design into one intricate display nestled in a make-shift bazaar. The garden was so well received that it became a staple attraction of San Francisco and inspired the creation of other American Japanese gardens in the 19th and 20th centuries. These spaces have each developed their own representation of Japanese garden design and have overcome obstacles involving their unique climate and sourcing accurate materials, as well as financial burdens to ensure they provide the most culturally sensitive depiction. After speaking with the managers of seven different American Japanese gardens, I’ve found that, though they receive no additional funding from their local or state government, they prioritize cultural authenticity and use the resources at their disposal to make their gardens a learning opportunity for their surrounding communities. Some gardens receive more resources than others and are able to portray the Japanese garden more realistically; however, each organization approaches the subject with respect and with eventual growth in mind.M.S., Arts Administration -- Drexel University, 201