Doctor of Philosophy, The Ohio State University, 2017, Biomedical Sciences

Immune suppression is a hallmark of cancer that has gained recent unprecedented attention following dramatic responses with new immune based therapies. Many therapeutic strategies are employed to reverse suppression and utilize our natural biological defense against cancerous cells. The beauty of which, is demonstrated as a non-chemotherapeutic method for durable clinical benefit and potentially, a cure. Attunement of anti-tumor immunity rests largely on provocation of adaptive immunity and the ability of T cells to remember non-self and self-dangerous signals. The naive to effector T cell transition, accomplished through stimulation of the T cell receptor and co-stimulation through CD28, is critical for the development of this response. Presented here are two strategies in a B cell malignancy, Chronic Lymphocytic Leukemia (CLL), aimed at attunement of this T cell co-stimulatory node by influencing surrounding biological players. The first component of this dissertation identifies Cytotoxic T Lymphocyte Antigen 4 (CTLA-4), an antagonist of CD28, as a potential therapeutic target on tumor cells. Despite clinical utility in targeting CTLA-4 on T cells, its function on non-T cells remains unaddressed, especially in the context of therapy. We define an immunosuppressive role for tumor expressed CTLA-4 in CLL. A majority of primary CLL samples were intracellularly CTLA-4+. Co-culture with activated T cells induced surface expression of CTLA-4 on CLL B cells. CTLA-4 expression on CLL cell lines Mec1 and OSU-CLL decreased expression of the cognate ligand, CD80, on CD80+ cells with rescue upon CTLA-4 blockade. Co-culture of CTLA-4+ Mec1 and CTLA-4+ primary CLL cells with CD80-GFP+ cells revealed transfer of CD80-GFP into primary CLL and Mec1 cells, consistent with the ability of CTLA-4+ T cells to trans-endocytose CD80. Additionally, co-culture of T cells with Mec1 CTLA-4+ cells decreased IL2 production, signifying reduced co-stimulation. Finally, the role of CTLA-4 on (open full item for complete abstract)

Committee: Natarajan Muthusamy PhD, DVM (Advisor); John Byrd MD (Advisor); Virginia Sanders PhD (Committee Member); Gregory Lesinski PhD (Committee Member) Subjects: Biomedical Research; Immunology

Master of Science, The Ohio State University, 2010, Computer Science and Engineering

Presently, The Ohio State University (OSU) routinely uses email and websites to communicate with students. These approaches do not provide real-time communication and they also contribute to a student's current information overload. Under the present system students cannot receive immediate and cost-effective notification of emergencies or upcoming campus events. One instance of the above problem occurs while new and prospective students are presented with a great deal of information during orientation programs on campus. This is burdensome for tour guides, who must remember all this information, and is also prone to error. For instance, they might lead a group of students past the recently renovated library but might forget to mention the renovations. Connected Campus (CC) provides a new platform that enables free, instantaneous communication. CC sends push notifications via OSU Wireless to students' mobile devices, each of which is uniquely tied to an OSU username (name.n), and is free for use by any OSU affiliate. CC comprises of a mobile device application, which receives the notifications, and a web application, which transmits them. CC thus overcomes the limitations of existing university communication systems and also satisfies the need for a cost-effective, real-time communication platform. From a student perspective, it is desirable to simply receive pushed information on a mobile device than having to reach out and pull the information from email or the web. The pushed information will be transmitted as short notifications to quickly capture student's attention and deliver content. Orientation leaders can distribute CC-equipped mobile devices to new and prospective students. As they pass a particular location on campus with OSU Wireless access, the CC server can send push notifications to student's devices informing them about that building's purposes, policies, and upcoming events, based on the location details sent from the device. This reduces the b (open full item for complete abstract)

Committee: Dr. Dong Xuan PhD (Advisor); Dr. Feng Qin PhD (Committee Member) Subjects: Computer Science; School Administration

Master of Science (M.S.), University of Dayton, 2011, Civil Engineering

Geographical information systems (GIS) can be useful in gathering information for soil properties especially at the preliminary design phases of projects. However, the usefulness and accuracy of the GIS analysis depend on the database that it relies on. The database becomes usually more populated around metropolitan areas or major cities, simply because of the increased need for infrastructure to serve larger population in and around these cities. A total of 255 consolidation test data collected from numerous transportation projects in the State of Ohio were analyzed, corrected for sample disturbance using Schmertmann's correction, and entered into a GIS database for analysis. The analyses indicate that reasonably accurate compression index (Cc) values can be obtained both in metropolitan areas and statewide. This thesis presents the database, the uses of GIS with spreadsheets to analyze the data, and several compression index correlations developed for Ohio soils.

Committee: Omer Bilgin PhD, PE (Advisor) Subjects: Civil Engineering; Engineering; Geographic Information Science; Geological; Geology; Geotechnology; Information Technology; Sedimentary Geology; Soil Sciences; Transportation; Transportation Planning

Doctor of Philosophy, Case Western Reserve University, 2010, Chemistry

A novel exo-selective [CN+C+CC] 1,3-dipolar cycloaddition catalyzed by Cu(I)-phosphine ligand complex has been developed for ring formation using a chiral glycyl sultam exerting powerful stereochemical control with an aldehyde and an activated olefin. It is the best exo-selective condition so far reported that is suitable for use with a variety of aliphatic aldehydes. This method has great potential in natural product synthesis for the construction of tri- or tetra-substituted pyrrolidine rings bearing an α- aliphatic chain. A new synthetic route to kaitocephalin, a glutamate receptor antagonist, has been designed featuring a disubstituted pyrrolidine as the key intermediate. An auxiliarycontrolled [CN+C+CC] 1,3-dipolar cycloaddition followed by removal of auxiliary and sulfone was employed to synthesize 2,5-disubstituted pyrrolidines. The key intermediate disubstituted pyrrolidine was prepared in 10 steps and 4% overall yield. Acylation at C4 introduced the C1-C3 moiety and afforded an important precursor to kaitocephalin bearing a complete carbon skeleton in 8% unoptimized yield.

Committee: Anthony J. Pearson PhD (Advisor); John Protasiewicz PhD (Committee Chair); Gregory Tochtrop PhD (Committee Member); Geneviève Sauvé PhD (Committee Member); Yanming Wang PhD (Committee Member) Subjects: Organic Chemistry

Master of Science, The Ohio State University, 2013, Electrical and Computer Engineering

Highly scaled III-V compound semiconductors, particularly n-In0,53Ga0,47As in conjunction with a suitable high-¿ dielectric, has been regarded as a promising channel material for high performance metal-oxide-semiconductor field effect transistors (MOSFETs). The high intrinsic electron mobility and small band gap of n-In0,53Ga0,47As offers the possibility of developing MOSFETs with higher drive currents at low operation voltages. However, the high density of interface states (Dit) at the high-¿/n-In0,53Ga0,47As interface degrades the device performance. Therefore, accurate and quantitative characterization of the interface states is an important issue in the continued development of high quality interfaces to track changes induced by processing and growth optimization. This work demonstrates that high Dit concentrations from high-¿/semiconductor interfaces can be accurately characterized using constant capacitance deep level transient spectroscopy and low temperature C-V (LTCV) method. This is compared with the conductance method, which underestimates Dit magnitude and shows energy dependent distribution.

Committee: Steven Ringel (Advisor); Siddharth Rajan (Committee Member) Subjects: Electrical Engineering