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  • 1. DePolo, Kelsey Architecture to Support a Transient America

    MARCH, University of Cincinnati, 2021, Design, Architecture, Art and Planning: Architecture

    The United States' labor market is shifting towards temporary gig work, advancing communications technologies are eliminating the need for people to meet in shared physical spaces, and global warming threatens the longevity and livability of cities and towns around the world. In the future, it will be increasingly unnecessary and even ill-advised for humans to attempt to settle permanently in one location, yet the transient populations that currently exist in America are already insufficiently supported by the infrastructural systems in place. This paper examines the successes and failures of these systems as a means of evaluating the validity of any proposed or existing architecture meant to support a mobile society. The nature of this society is considered as well: how do the inherent needs of a nomadic, propertyless culture differ from those of a sedentary, land-owning culture, and how can the two co-exist within a landscape that has been striated by centuries of development? With these concepts in mind, past flawed predictions of future societies of highly-mobile peoples and the architectures proposed to accommodate them are also studied to determine why they failed to become reality. Through these studies, this paper also attempts to answer whether a highly-formalized architectural construct is even the correct tool to support a transient society with diverse needs and reasons for adopting a nomadic lifestyle.

    Committee: Edward Mitchell M.Arch (Committee Chair); Vincent Sansalone M.Arch. (Committee Member) Subjects: Architecture
  • 2. Poudel, Prabesh Security Vetting Of Android Applications Using Graph Based Deep Learning Approaches

    Master of Science (MS), Bowling Green State University, 2021, Computer Science

    Along with the immense popularity of Android applications, the Android ecosystem is under constant threat of malware attacks. This issue warrants developing efficient tools to detect malware apps. There is a large body of work in the literature that has applied static analysis for malware detection. For instance, one popular idea has been to extract API-calls from the app code and then to use those API-calls as artifacts to train machine learning models to classify malware and benign apps. However, most of this line of work does not incorporate the true execution sequence of the API-calls, and thus misses out to capture a potentially rich signature. Furthermore, while evaluating the vetting accuracy, many of the prior work report their primary results on a randomly selected test set that are not spatially consistent (malware percentage in the test set approximating real-world scenario) and/or temporally consistent (having correct time split of train and test data) which artificially inflates the performance of the model. In this thesis, we explore if tracking the true sequence of the API-calls improves the effectiveness of the vetting process and present results ranging from testing on a random test set to a spatially and temporally consistent test set. We perform deep learning-based malware classification using a graph that we name API sequence graph which preserves the true sequence of API calls. The experiments show that our best performing model achieves AuPRC ranging from 0.977 to 0.86 and an F1-score of 0.955 to 0.83 depending on the consistency of the test set. The results show that our best-performing model, based on the true sequence of API calls, outperforms a quasi-sequence-based model.

    Committee: Sankardas Roy Ph.D. (Advisor); Jong Kwan Lee Ph.D. (Committee Member); Qing Tian Ph.D. (Committee Member) Subjects: Computer Science
  • 3. Reza, Katebi Nuclear Outbursts in the Centers of Galaxies

    Doctor of Philosophy (PhD), Ohio University, 2019, Physics and Astronomy (Arts and Sciences)

    This dissertation consists of two parts. In the first part, we focus on studying the nuclear outbursts in the centers of galaxies and their nature in order to better understand the behavior of central Super Massive Black Holes (SMBHs) and their interaction with the surrounding environment, and to better understand the accretion disk structure. Nuclear outbursts can be better understood by studying the changes in the broad emission lines and the underlying continuum. We quantify the properties of these nuclear outbursts using multi-wavelength observations including optical, ultraviolet, and X-rays from MDM Observatory, the Sloan Digital Sky Survey, Swift, and Magellan. Some of these nuclear outbursts are linked to Tidal Disruption Events (TDEs) and nuclear supernovae (SNs), while a number of these events are proposed to be a rare phenomenon called “changing-look” Active Galactic Nuclei (AGN). These types of AGNs have been observed to optically transition from type 1 to type 2 and vice versa on timescales of months to years, where broad emission lines such as Hα and Hβ appeared or disappeared followed by an increase or decrease in the continuum light. We investigate two transient events called PS1-13cbe and PS1-10cdq that were observed during outburst by the PS1 survey in 2013 and 2010, respectively. We investigate TDE, SN, and AGN activity as the three possible scenarios for the nature of these events. In the case of PS1- 3cbe, we conclude that “changing-look” behavior caused by thermal accretion disk instabilities is the most plausible explanation for the outburst. However, in the case of PS1-10cdq, we favor the tidal disruption scenario because of the structure of the lightcurve and spectral evolution. In the second part of this dissertation, we focus on galaxy morphology prediction using a newly designed neural network called “Capsule Networks”. We automate the process of morphology prediction and eliminate the need for feature engineering and heavy data preposses (open full item for complete abstract)

    Committee: Ryan Chornock Dr (Advisor); Prakash Madappa Dr (Committee Member); Shields Joseph Dr (Committee Member); Bunescu Razvan Dr (Committee Member) Subjects: Astronomy; Astrophysics; Physics
  • 4. Gervais, Kristen Evaluation of a biodegradable thermogel polymer for intraocular delivery of cyclosporine A to prevent posterior capsule opacification

    Master of Science, The Ohio State University, 2017, Comparative and Veterinary Medicine

    Purpose: To utilize a thermosensitive hydrogel (thermogel) polymer to achieve sustained release of cyclosporine A (CsA) for targeted destruction of lens epithelial cells (LEC) and reduction of posterior capsule opacification (PCO) after cataract surgery. Part I of the study evaluated the drug delivery system in an ex vivo canine model of PCO, while Part II evaluated intraocular delivery in an in vivo rabbit model. Methods. A PLGA-PEG-PLGA thermogel polymer was formulated to release CsA ([300µg/mL]) or vehicle (ethanol). PART I: Extracapsular cataract extraction and intraocular lens (IOL) placement were performed in 24 canine cadaver globes. Lens capsule explants with residual LEC were treated with 200µL of CsA-eluting (n=12) or vehicle-eluting (n=12) thermogel and maintained in culture. Posterior capsule coverage by LEC was graded following 7 (n=8), 14 (n=6), or 28 (n=10) days of treatment. Following histology, LEC were manually quantified via light microscopy from capsules treated for 28-days. CsA concentration in culture media was quantified by tandem liquid chromatography-mass spectrometry (LC-MS/MS) at each time point. Differences in percent posterior capsule coverage and LEC counts were analyzed by the student's t-test with Welch's correction. PART II: Phacoemulsification cataract surgery and IOL placement were performed in 10 adult rabbits (20 eyes). Ten left eyes served as negative controls and were treated with viscoelastic material only. Five right eyes were treated with 200µL CsA-eluting thermogel polymer, and five right eyes were treated with vehicle-eluting thermogel polymer. Clinical ophthalmic examination parameters and PCO grading were performed daily for 6 days post-operatively, and then weekly until the termination of the study at 49 days. Aqueous humor samples were analyzed for CsA concentration at day 6 post-operatively. Following euthanasia, globes were collected and analyzed histologically for degree of PCO formation and any evidence of ocular t (open full item for complete abstract)

    Committee: Heather Chandler (Advisor) Subjects: Pharmacology; Veterinary Services
  • 5. Steiner, Jessica Characterization of sterility and germline defects caused by Smed-boule RNA-interference

    Master of Science (MS), Wright State University, 2016, Biological Sciences

    Evolutionarily conserved molecular processes involved in construction of the germline and embryonic development are essential for the procreation of many species. Infertility affects 15% of couples in the world and can be caused by dysfunctions during egg and sperm development, anatomic defects, as well as faulty embryonic development. Although there are some infertility disorders that are genetically defined, such as Turner and Klinefelter syndromes, many clinical infertility cases are diagnosed as idiopathic due to the lack of understanding of basic fertility mechanisms. Schmidtea mediterranea is a freshwater planarian species that has the ability to regenerate complete organisms, including germ cells and reproductive structures, from small tissue fragments containing pluripotent somatic stem cells. The developmental plasticity of planarians provides a wonderful opportunity to investigate the molecular mechanisms behind the differentiation and development of specialized cells, including gametes. Smed-boule encodes for an RNA-binding protein and is the most ancestral member of the Deleted in AZoospermia (DAZ) gene family. DAZ family genes function in different aspects of germ cell development and fertility in species ranging from sea anemone to humans. Whole-mount in situ hybridization experiments revealed Smed-boule expression is enriched in the testes and ovaries of planarian flatworms. Interestingly, Smed-boule RNA-interference (RNAi) planarians lost the ability to produce gametes, yet still were able to deposit sterile egg capsules. Virgin Smed-boule(RNAi) and control planarians maintained in isolation also continuously produced sterile egg capsules. Altogether these results demonstrate that egg capsule production in S. mediterranea occurs independently of ovulation, fertilization, and mating events. In addition, detailed analysis of gametogenesis defects revealed that Smed-boule functions at different stages during male and female germline development. These (open full item for complete abstract)

    Committee: Labib Rouhana Ph.D. (Advisor); David Goldstein Ph.D. (Committee Chair); Scott Baird Ph.D. (Committee Member); Mill Miller Ph.D. (Committee Member) Subjects: Biology; Developmental Biology
  • 6. Brash, Breanna The Effect of Trypan Blue on Posterior Capsule Opacification in an Ex Vivo Canine Model

    Master of Science, The Ohio State University, 2016, Comparative and Veterinary Medicine

    Purpose. To determine if trypan blue (TB) reduces lens epithelial (LEC) or corneal endothelial cell viability. Methods. Tissue was harvested from canine cadavers. Cultured LECs were treated with TB at 0, 0.05, 0.1, 0.2, or 0.3% for 30, 60, or 120 seconds. Cell morphology was evaluated and an LDH viability assay performed. Cultured LECs were treated with 0 and 0.3% TB for 120 seconds and an apoptosis assay was performed to assess caspase-3 activity. To evaluate the effects of TB on ex vivo PCO, following mock cataract surgery, lens capsules were treated with 0 and 0.3% TB at the above times and maintained in culture for two weeks. Capsules were monitored for changes in cell density and morphology; histology was performed at experimental completion. Corneal endothelial cells were treated with 0 and 0.3% TB for 120 seconds and an LDH viability assay performed. Results. TB did not significantly reduce LEC density. While TB-treated LECs demonstrate higher rates of cell death compared to vehicle control, the difference was not significant. Induction of apoptotic signaling was found in TB-treated LEC cultures. Ex vivo PCO formation was not significantly different in any treatment group. Endothelial cells treated with TB or vehicle showed no significant differences in cell death. Conclusions. TB induced low levels of LEC death via apoptotic signaling cascades but was not effective at reducing ex vivo PCO formation. TB did not induce endothelial cell death. Funded by ACVO Vision for Animals Foundation grant (VAF2014-01). Trypan blue provided by Acrivet.

    Committee: David Wilkie DVM, MS, DACVO (Advisor); Anne Gemensky-Metzler DVM, MS, DACVO (Committee Member); Eric Miller DVM, MS, DACVO (Committee Member); Heather Chandler PHD (Committee Member) Subjects: Medicine; Ophthalmology; Veterinary Services
  • 7. Hydeman, Laura "Induction of Autophagy-Mediated Lens Epithelial Cell Death Using Cyclosporine A to Prevent Posterior Capsule Opacification"

    Master of Science, The Ohio State University, 2014, Vision Science

    Cataracts are the leading cause of blindness throughout the world, and cataract surgery is the most common ophthalmic surgery performed in America. Posterior capsule opacification (PCO) is the leading complication following cataract surgery. During routine cataract surgery, lens fibers and lens epithelial cells (LEC) found on the anterior capsule are removed. However, due to surgical constraints it is impossible to remove all LEC. The remaining LEC eventually proliferate and migrate around and behind the intraocular lens implant causing a progressive reduction in vision. This opacification of the posterior lens capsule following cataract surgery is known as PCO. The only current treatment for PCO is Nd-YAG capsulotomy, in which a laser is utilized to remove the LEC from the posterior capsule of the lens. However, this procedure has complications including damage to the intraocular lens, cystoid macular edema, intra-ocular pressure spikes, and retinal detachments. This procedure is also difficult to perform in children, is costly, and is not widely available in rural areas and under-developed countries. Several surgical and pharmacologic procedures have been implemented to reduce the incidence of PCO; however, PCO can still occur in up to 50% of adults and 100% of children and canines following cataract surgery. Recent research has used Cyclosporine-A (CsA) to prevent PCO formation ex vivo. In the present study, it was determined that 10 µg/mL CsA for 7 days was the necessary dose needed to prevent PCO formation in an ex vivo extra-capsular cataract surgery model using cadaveric canine lenses. The mechanism whereby LEC death occurs was subsequently evaluated using transmission electron microscopy, western blots for microtubule associated light chain 3 (LC3) protein, and immunofluorescence (specifically targeting LC3, F-actin, and acridine orange). Specific results included the presence of double-membrane autophagosomes, increased expression of LC3-II, accumulation (open full item for complete abstract)

    Committee: Heather Chandler PhD (Advisor) Subjects: Ophthalmology
  • 8. Gaurav, Rahul Development of a Novel Method for the Identification of Human B Cells Producing Antibodies against Staphylococcus aureus Type 8 Capsule

    Master of Science in Biological Sciences, Youngstown State University, 2014, Department of Biological Sciences and Chemistry

    Staphylococcus aureus infections are the primary cause of nosocomial infections worldwide. Increasing antibiotic resistance in S. aureus requires the development of alternative treatment methods. It has been shown that mice injected with homologous antibodies against Staphylococcus aureus had much lower fatality, when compared to control mice infected with S. aureus. Although mouse monoclonal antibodies against S. aureus have been developed, injection into human subjects results in the production of human anti-murine antibodies in the host. The long term goal of this project is the production of human antibodies against S. aureus. Towards this goal, S. aureus type 8 (Wright strain) was grown in Columbia broth containing 2% sodium chloride, harvested and autoclave. It was then treated with nucleases, pronase and sodium periodate and the carbohydrate purified using DEAE ion exchange chromatography and Sephadex S-300 size-exclusion chromatography. The purified sample contained reducing carbohydrate that was reactive with capsule specific antibodies, but no detectable protein or teichoic acid. Biotin hydrazide was used to biotinylate the carbohydrate sample and binding of anti-capsular antibodies to the biotinylated product was tested using an ELISA. We found that the use of PBS + 0.05% Tween-20 + 0.1% BSA as the sample buffer caused false positive results, which was rectified by the use of casein based sample buffer. In these studies, we have developed an ELISA which can be used to test antibody binding to biotinylated capsular carbohydrate.

    Committee: Diana Fagan PhD (Advisor); David Asch PhD (Committee Member); Jonathan Caguiat PhD (Committee Member) Subjects: Biology; Cellular Biology; Immunology; Microbiology
  • 9. Marshall, Joanna The O-Antigen Capsule of Salmonella Typhimurium in Acute and Chronic Infection

    Doctor of Philosophy, The Ohio State University, 2013, Integrated Biomedical Science Graduate Program

    Salmonella Typhimurium, similarly to other enteric pathogens, produce a group IV O-antigen (O-ag) capsule exhibiting structural resemblance to the lipopolysaccharide (LPS). Polysaccharide capsules are known virulence factors of many bacterial pathogens, facilitating evasion of immune recognition and systemic dissemination during acute infection. Capsular polysaccharides can also aid establishment of chronic infection and environmental spread of disease by increasing bacterial surface adherence, self-aggregation and resistance to stress, all of which are critical steps in the continued cycle of infection. In this work, we sought to further characterize the O-ag capsule, a recently described surface polysaccharide of Salmonella Typhimurium. We have established that functional surface assembly of the O-ag capsule shares several common enzymatic pathways with lipopolysaccharide (LPS) biosynthesis and that disruption of the O-ag capsule does not interfere with production of LPS. Whole cell imaging has revealed heterogeneous capsular expression within sessile and biofilm bacterial populations and indicates that capsular expression may shield recognition of the LPS O-ag by specific antibodies. Additionally, we have observed that absence of the O-ag capsule results in dysregulated surface expression of highly immunostimulatory phase I flagellin (FliC) and increases bacterial susceptibility to killing by human serum. Due to their high level of attenuation, strains lacking the alternative RNA polymerase sigma factor RpoS have been extensively investigated for possible future inclusion in a live vaccine strain and the currently licensed live-attenuated vaccine strain for Salmonella Typhi TY21A is RpoS-deficient. Efforts to produce attenuated vaccines with RpoS-deficient phenotypes have focused on achieving a balance of attenuation and immunogenicity, reporting that a lack of systemic replication of rpoS mutants necessitates multiple doses of greater than 10^10CFU to achi (open full item for complete abstract)

    Committee: John Gunn PhD (Advisor); Robert Munson PhD (Committee Member); Jesse Kwiek PhD (Committee Member); Daniel Wozniak PhD (Committee Member) Subjects: Biomedical Research; Microbiology; Molecular Biology
  • 10. Mulye, Minal Delineating the Immune Mechanisms Required by Murine Neutrophils and Macrophages for Clearance of Burkholderia pseudomallei, the Causative Agent of Melioidosis

    Doctor of Philosophy (PhD), University of Toledo, 2013, College of Medicine

    Infection of susceptible hosts by the encapsulated Gram-negative bacterium Burkholderia pseudomallei (Bp) causes melioidosis, with septic patients attaining mortality rates greater than or equal to 40%. Due to its high infectivity through inhalation and lack of effective therapies, Bp is considered as a potential bioweapon. Thus, there is great interest in identifying immune effectors important in Bp clearance. Our goal was to compare the relative abilities of murine macrophages and neutrophils to clear Bp in vitro, as well as determine the importance of serum opsonins. Our studies showed that murine macrophages and neutrophils were inherently unable to clear unopsonized Bp or the related relatively-avirulent acapsular bacterium B. thailandensis (Bt). Opsonization of Bp with complement or specific antibodies increased uptake by macrophages, but did not promote clearance, although antibody-binding enhanced complement deposition. However, complement opsonization of Bp resulted in enhanced uptake and rapid killing by neutrophils. Bp killing was linked with rapid induction of reactive oxygen species by neutrophils infected with Bp opsonized with a threshold level of complement deposition (greater than or equal to 5% serum in our system). Addition of Bp-specific antibodies enhanced complement deposition, but antibodies alone were unable to elicit clearance by neutrophils. Macrophages are only observed to efficiently clear Bp after pre-activation with IFN-gamma, which is independent of serum opsonization. These studies indicated that murine macrophages were inefficient in clearing even opsonized Bp unless pre-activated with IFN-gamma, and suggested the requirement of a Th1 response for macrophages to effectively clear Bp. Conversely; neutrophils appeared to efficiently clear serum-opsonized Bp. These findings provide important insight regarding the cell types and immune mediators that should be targeted for melioidosis-related therapies.

    Committee: R. Mark Wooten (Advisor); Robert Blumenthal (Committee Chair); Viviana Ferreira (Committee Member); Jason Huntley (Committee Member); Marcia McInerney (Committee Member) Subjects: Immunology; Microbiology
  • 11. Karargyris, Alexandros A Novel Synergistic Diagnosis Methodology for identifying Abnormalities in Wireless Capsule Endoscopy videos

    Doctor of Philosophy (PhD), Wright State University, 2010, Computer Science and Engineering PhD

    Wireless Capsule Endoscopy (WCE) is a new technology that allows medical personnel to view the gastrointestinal (GI) mucosa. It is a swallowable miniature capsule device the size of a pill that transmits thousands of screenshots of the digestive tract to a wearable receiver. When the procedure finishes the video is uploaded to a workstation for viewing. Capsule Endoscopy has been established as a tool to identify various gastrointestinal (GI) conditions, such as blood-based abnormalities, polyps, ulcers, Crohn's disease in the small intestine, where the classical endoscopy is not regularly used. As of 2009 the market is dominated by Given Imaging Inc. capsule (PillCam SB). More than 300,000 capsules have been sold since 2001 when it was first introduced. The company provides a software package (RAPID) to view the WCE video, offering a bleeding detector feature based on red color. It provides a position estimator of the capsule inside the digestive tract. Additionally its multi-view feature gives a simultaneous view of two or four consecutive video frames in multiple windows. Finally a library of reference images (RAPID Atlas) is provided so that the user can have easy access to on-screen case images. Although the company's software is a useful tool, the viewing of a WCE video is still a time consuming process (~ 2 hours), even for experienced gastroenterologists. In addition, the company's software has serious limitations (35% bleeding detection) and no capability of detecting polyps or ulcers according to gastroenterologists. Therefore, the need for computer aided model-methodology with robust detection performance on various conditions (blood, polyps, ulcers, etc) is clearly obvious. Thus, our research studies have been successfully carried out on: a) the automatic detection of malignant intestinal features like polyps, bleeding, and abnormal regions (tumors); b) finding the boundaries of the digestive organs; and c) reducing the viewing-examination time with a (open full item for complete abstract)

    Committee: Nikolaos Bourbakis PhD (Advisor); Soon Chung PhD (Committee Member); Thomas Hangartner PhD (Committee Member); Yong Pei PhD (Committee Member); Marios Pouagare PhD (Committee Member) Subjects: Computer Science
  • 12. Xia, Shijing Experimental and Computational Studies for Various Organic Systems

    Doctor of Philosophy, The Ohio State University, 2008, Chemistry

    The electronic properties and the thermodynamic preferences for O2 addition to various tetrathiatriarylmethyl (TAM)-type triarylmethyl (trityl) radicals were experimentally and theoretically investigated. The radicals' stability in the presence of O2 and biological milieu was also experimentally assessed. Results showed that H substitution on the aromatic ring affects the trityl radical's stability and may lead to substitution reactions in cellular systems. We proposed that this degradation process involves an arylperoxyl radical that can further decompose to alcohol or quinone products. Computational approaches were also being used to search for spin probes with improved stability and enhanced chemical and biological properties.A signature absorbance at 392 nm, which is generated from acetonitrile solutions of N-hydroxypyridin-2-thione in the presence of trans-stilbene, was used in competitive laser flash photolysis (LFP) experiments to determine rate constants of reactions for hydroxyl radical with sixteen different benzene derivatives. Structure-reactivity relationships for these reactions were derived. Computational studies were employed to reveal the details of these reactions. The tautomerism and photochemistry of N-hydroxypyridones (NHPs) and N-hydroxy-pyridinethiones (NHPTs) were also studied theoretically in order to find some potential radical precursors or probes for hydroxyl radical reactions with aromatics. To avoid the problems typically encountered in the measurement of rate constants of superoxide radical trapping by nitrones, a more straightforward approach, stopped-flow UV methodology, has been developed by using KO2 as a direct source of superoxide radical. The absolute rate constants for the reactions of superoxide radical anion with five different spin traps were measured experimentally. The conformational and IR spectroscopic studies of several novel capsules were studied computationally. The theoretical data rationalized the experimental resul (open full item for complete abstract)

    Committee: Christopher Hadad (Advisor); Robert Coleman (Committee Member); David Hart (Committee Member) Subjects: Chemistry
  • 13. Taljan, Kyle Investigations of Anatomical Connectivity in the Internal Capsule of Macaques with Diffusion Magnetic Resonance Imaging

    Master of Science in Biomedical Engineering, Cleveland State University, 2011, Fenn College of Engineering

    Understanding anatomical connectivity is crucial for improving outcomes of deep brain stimulation surgery. Tractography is a promising method for noninvasively investigating anatomical connectivity, but connections between subcortical regions have not been closely examined by this method. As many connections to subcortical regions converge at the internal capsule (IC), we investigate the connectivity through the IC to three subcortical nuclei (caudate, lentiform nucleus, and thalamus) in 6 macaques. We show that a statistical correction for a known distance-related artifact in tractography results in large changes in connectivity patterns. Our results suggest that care should be taken in using tractography to assess anatomical connectivity between subcortical structures.

    Committee: Cameron McIntyre PhD (Committee Chair); Ken Sakaie PhD (Advisor); Nolan Holland PhD (Committee Member) Subjects: Biomedical Engineering
  • 14. Lutz, Elizabeth Effects of Modified Cyclosporine A on Posterior Capsule Opacification Formation and Corneal Endothelial Cell Viability in an Ex Vivo Model

    Master of Science, The Ohio State University, 2013, Comparative and Veterinary Medicine

    PURPOSE: To determine the effects of modified Cyclosporine A (SCY-641) on canine lens epithelial cell (LEC) and corneal endothelial cell viability and formation of posterior capsule opacification (PCO) ex vivo. MATERIALS AND METHODS: Lens capsules and corneas were harvested from canine cadaver eyes. Lens capsules were randomly assigned to one of three treatment groups: 0 µg/mL SCY-641 (n=6), 20 µg/mL SCY-641 (n=9), or 40 µg/mL SCY-641 (n=9) and were treated for 7 days before processing for routine H&E staining. Additional lens capsules were treated for 7 days with 0 or 40 µg/mL SCY-641 (n=6), subsequently incubated in culture media without SCY-641 for 21 additional days, and were processed for routine H&E staining. Corneas (n=7 per group) were randomly assigned to one of three control groups (no treatment, balanced salt solution, mitomycin-C) or to one of three treatment groups (20, 40, or 100 µg/mL SCY-641). Corneas were treated for 180 minutes prior to staining and microscopic evaluation. RESULTS: Lens capsules treated with 0 µg/mL SCY-641 had complete PCO formation by 7 days, and capsules that were maintained for 28 total days were wrinkled with confluent LECs. Capsules that received 20 µg/mL SCY-641 had a moderate number of LECs remaining following 7 days of treatment. Capsules treated with 40 µg/mL SCY-641 had few to no LECs present by 7 days. Capsules that received 40 µg/mL SCY-641 and were maintained for 28 days had progressive loss of LECs without any LEC regrowth. Corneal endothelial cell viability was not decreased in corneas acutely exposed to 20, 40, or 100 µg/mL of SCY-641. CONCLUSIONS: Treatment with SCY-641 resulted in decreased LEC viability in a dose-dependent fashion ex vivo, with higher doses causing greater cytotoxicity; 40 µg/mL of SCY-641 was most effective at removing LECs from the capsule and preventing long-term LEC regrowth. SCY-641 was not acutely toxic to the corneal endothelium at concentrations up to 100 µg/mL. SCY-641 m (open full item for complete abstract)

    Committee: David Wilkie (Advisor); Heather Chandler (Advisor); Anne Gemensky-Metzler (Committee Member) Subjects: Animal Diseases; Animal Sciences; Animals; Biomedical Research; Cellular Biology; Experiments; Health; Health Care; Medicine; Ophthalmology; Pharmaceuticals; Surgery; Veterinary Services
  • 15. Yang, Jung In Vivo Studies of the Foreign Body Reaction to Biomedical Polymers

    Master of Sciences, Case Western Reserve University, 2013, Biomedical Engineering

    The in vivo foreign body reaction on biomaterials regarding development of foreign body giant cells and formation of fibrous capsules was studied. The first study (chapter II) discusses the development of foreign body reaction with specific lymphocytic immunodeficient mice mainly targeting IL-4 (interleukin-4) cytokine. The experiment consisted of in vivo subcutaneous implants of polyether urethane (PEU) and polyethylene terephthalate (PET) in immunodeficient mice strains. Analysis on polymer surfaces using quantitative calculations such as percent fusion, cell density, and nuclei density described the development of foreign body reaction on biomaterial surface. In addition qualitative assessment was implemented to also describe the development of foreign body reaction that provided similar characterization to the quantitative calculations. The second study (chapter III) focuses on the fibrous capsule formation around biomaterials. Electrospun nanofibers poly(e-caprolactone-co-ethylethylene phosphate) coupled with collagen type I siRNA were subcutaneously implanted. A significant decrease in fibrous capsule thickness at weeks 2 and 4 were shown compared to the control nanofibers.

    Committee: James Anderson M.D., PhD (Advisor); Horst von Recum PhD (Committee Member); Roger Marchant PhD (Committee Member) Subjects: Biomedical Engineering