Collection-Level Subject Access in Aggregations of Digital Collections: Metadata Application and Use

Problems in subject access to information organization systems have been under investigation for a long time. Focusing on item-level information discovery and access, researchers have identified a range of subject access problems, including quality and application of metadata, as well as the complexity of user knowledge required for successful subject exploration. While aggregations of digital collections built in the United States and abroad generate collection-level metadata of various levels of granularity and richness, no research has yet focused on the role of collection-level metadata in user interaction with these aggregations. This dissertation research sought to bridge this gap by answering the question “How does collection-level metadata mediate scholarly subject access to aggregated digital collections?” This goal was achieved using three research methods: • in-depth comparative content analysis of collection-level metadata in three large-scale aggregations of cultural heritage digital collections: Opening History, American Memory, and The European Library • transaction log analysis of user interactions, with Opening History, and • interview and observation data on academic historians interacting with two aggregations: Opening History and American Memory. It was found that subject-based resource discovery is significantly influenced by collection-level metadata richness. The richness includes such components as: 1) describing collection’s subject matter with mutually-complementary values in different metadata fields, and 2) a variety of collection properties/characteristics encoded in the free-text Description field, including types and genres of objects in a digital collection, as well as topical, geographic and temporal coverage are the most consistently represented collection characteristics in free-text Description fields. Analysis of user interactions with aggregations of digital collections yields a number of interesting findings. Item-level user interactions were found to occur more often than collection-level interactions. Collection browse is initiated more often than search, while subject browse (topical and geographic) is used most often. Majority of collection search queries fall within FRBR Group 3 categories: object, concept, and place. Significantly more object, concept, and corporate body searches and less individual person, event and class of persons searches were observed in collection searches than in item searches. While collection search is most often satisfied by Description and/or Subjects collection metadata fields, it would not retrieve a significant proportion of collection records without controlled-vocabulary subject metadata (Temporal Coverage, Geographic Coverage, Subjects, and Objects), and free-text metadata (the Description field). Observation data shows that collection metadata records in Opening History and American Memory aggregations are often viewed. Transaction log data show a high level of engagement with collection metadata records in Opening History, with the total page views for collections more than 4 times greater than item page views. Scholars observed viewing collection records valued descriptive information on provenance, collection size, types of objects, subjects, geographic coverage, and temporal coverage information. They also considered the structured display of collection metadata in Opening History more useful than the alternative approach taken by other aggregations, such as American Memory, which displays only the free-text Description field to the end-user. The results extend the understanding of the value of collection-level subject metadata, particularly free-text metadata, for the scholarly users of aggregations of digital collections. The analysis of the collection metadata created by three large-scale aggregations provides a better understanding of collection-level metadata application patterns and suggests best practices. This dissertation is also the first empirical research contribution to test the FRBR model as a conceptual and analytic framework for studying collection-level subject access.

Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors

Adoptive immunotherapy and oncolytic virotherapy are two promising strategies for treating primary and metastatic malignant brain tumors. We demonstrate the ability of adoptively transferred tumor-specific T cells to rapidly mediate the clearance of established brain tumors in several mouse models. Similar to the clinical situation, tumor recurrences are frequent and result from immune editing of tumors. T cells can eliminate antigen-expressing tumor cells but are not effective against antigen loss variant (ALV) cancer cells that multiply and repopulate a tumor. We show that the level of tumor antigen present affects the success of adoptive T cell therapy. When high levels of antigen are present, tumor stromal cells such as microglia and macrophages present tumor peptide on their surface. As a result, T cells directly eliminate cancer cells and cross-presenting stromal cells and indirectly eliminate ALV cells. We were able to show the first direct evidence of tumor antigen cross-presentation by CD11b+ stromal cells in the brain using soluble, high-affinity T cell receptor monomers. Strategies that target brain tumor stroma or increase antigen shedding from tumor cells leading to increased crosspresentation by stromal cells may improve the clinical success of T cell adoptive therapies. We evaluated one potential strategy to complement adoptive T cell therapy by characterizing the oncolytic effects of myxoma virus (MYXV) in a syngeneic mouse brain tumor model of metastatic melanoma. MYXV is a rabbit poxvirus with strict species tropism for European rabbits. MYXV can also infect mouse and human cancer cell lines due to signaling defects in innate antiviral mechanisms and hyperphosphorylation of Akt. MYXV kills B16.SIY melanoma cells in vitro, and intratumoral injection of virus leads to robust, selective and transient infection of the tumor. We observed that virus treatment recruits innate immune cells iii to the tumor, induces TNFα and IFNβ production in the brain, and results in limited oncolytic effects in vivo. To overcome this, we evaluated the safety and efficacy of co-administering 2C T cells, MYXV, and neutralizing antibodies against IFNβ. Mice that received the triple combination therapy survived significantly longer with no apparent side effects, but eventually relapsed. Based on these findings, methods to enhance viral replication in the tumor and limit immune clearance of the virus will be pursued. We conclude that myxoma virus should be further explored as a vector for transient delivery of therapeutic genes to a tumor to enhance T cell responses.