Enhanced Place Name Search Using Semantic Gazetteers

With the increased availability of geospatial data and efficient geo-referencing services, people are now more likely to engage in geospatial searches for information on the Web. Searching by address is supported by geocoding which converts an address to a geographic coordinate. Addresses are one form of geospatial referencing that are relatively well understood and easy for people to use, but place names are generally the most intuitive natural language expressions that people use for locations. This thesis presents an approach, for enhancing place name searches with a geo-ontology and a semantically enabled gazetteer. This approach investigates the extension of general spatial relationships to domain specific semantically rich concepts and spatial relationships. Hydrography is selected as the domain, and the thesis investigates the specification of semantic relationships between hydrographic features as functions of spatial relationships between their footprints. A Gazetteer Ontology (GazOntology) based on ISO Standards is developed to associate a feature with a Spatial Reference. The Spatial Reference can be a GeoIdentifier which is a text based representation of a feature usually a place name or zip code or the spatial reference can be a Geometry representation which is a spatial footprint of the feature. A Hydrological Features Ontology (HydroOntology) is developed to model canonical forms of hydrological features and their hydrological relationships. The classes modelled are endurant classes modelled in foundational ontologies such as DOLCE. Semantics of these relationships in a hydrological context are specified in a HydroOntology. The HydroOntology and GazOntology can be viewed as the semantic schema for the HydroGazetteer. The HydroGazetteer was developed as an RDF triplestore and populated with instances of named hydrographic features from the National Hydrography Dataset (NHD) for several watersheds in the state of Maine. In order to determine what instances of surface hydrology features participate in the specified semantic relationships, information was obtained through spatial analysis of the National Hydrography Dataset (NHD), the NHDPlus data set and the Geographic Names Information System (GNIS). The 9 intersection model between point, line, directed line, and region geometries which identifies sets of relationship between geometries independent of what these geometries represent in the world provided the basis for identifying semantic relationships between the canonical hydrographic feature types. The developed ontologies enable the HydroGazetteer to answer different categories of queries, namely place name queries involving the taxonomy of feature types, queries on relations between named places, and place name queries with reasoning. A simple user interface to select a hydrological relationship and a hydrological feature name was developed and the results are displayed on a USGS topographic base map. The approach demonstrates that spatial semantics can provide effective query disambiguation and more targeted spatial queries between named places based on relationships such as upstream, downstream, or flows through

Process characterization for an updated legacy product

A commercial Chinese Hamster Ovary (CHO) cell culture process was updated using current technologies to improve productivity, ensure consistent product quality, and meet current Health Authority expectations. In order to achieve comparable product quality with the current commercial process, the updated cell culture process has a unique pH drop step. Site- and scale-independent cell culture characterization studies were executed to support this new process. A Critical Quality Attribute (CQA) assessment was performed prior to completion of process characterization because the original product control strategy was developed without formal CQA identification. Since non-CQAs remain part of the product control strategy, they were also considered for process characterization. This work will describe the process characterization approach and results for the updated cell culture process. In addition, an outline on how both CQAs and non-CQAs were considered in the assessment of Critical Process Parameters (CPPs) will be presented

Achieving product quality comparability while making cell culture process changes

Please click Additional Files below to see the full abstract

Strategies for optimizing a cell culture platform to achieve high recombinant protein titer without impacting product quality

Recent advances in cell line development and in the design of culture media have significantly increased both the volumetric and specific productivity of fed batch processes, which is our standard platform technology for synthesis of therapeutic proteins. Cell culture processes are generally simplified when needed as a robust platform technology to meet the imperatives of speedy timelines for early process development and ease of manufacturing. However, both culture media and feeding strategies need to be customized for specific cell lines when there is a need to achieve higher titer due to higher product demand. This presentation will focus on the specific changes that were made in order to enhance the platform cell culture process for achieving much higher titers. A case study will be used to demonstrate that changes made to feeding strategy, feed media and other process parameters have the potential to maximize productivity but also to alter the product quality profile. It is critical to ensure that these process changes do not adversely impact product quality. Strategies used to control the acidic charge variant profile, which was elevated in these enhanced cell culture processes, will be discussed

Achieving product quality targets while maintaining high titer in CHO cell culture processes

Please click Additional Files below to see the full abstract

Process intensification: Case study with a CHO-based monoclonal antibody production process

Standard platform technologies for cell culture processing provide simple and robust strategies to meet rapid timelines for early process development and ease of manufacturing. However, when there is a need to achieve high antibody titers due to high product demand, both culture media and feed strategies must be customized for specific cell lines. Two case studies will describe the strategies employed as part of a process intensification effort to overcome the limitations of a platform Phase III cell culture process. The first case study will demonstrate an intensified fed-batch process development effort performed to maximize production of a CHO-based monoclonal antibody, while maintaining product quality comparability with the original Phase III process. The second case study will describe the evaluation of a concentrated fed-batch process using alternating tangential flow filtration to retain the protein in the bioreactor, and achieve even higher titers in support of the high product demand forecast. These case studies will show that the intensified fed-batch process improved titers by 50%, and the concentrated fed-batch process improved titers by 100% relative to the fed-batch platform

Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors

Production of human mesenchymal stem cells for allogeneic cell therapies requires scalable, cost-effective manufacturing processes. Microcarriers enable the culture of anchorage-dependent cells in stirred-tank bioreactors. However, no robust, transferable methodology for microcarrier selection exists, with studies providing little or no reason explaining why a microcarrier was employed. We systematically evaluated 13 microcarriers for human bone marrow-derived MSC (hBM-MSCs) expansion from three donors to establish a reproducible and transferable methodology for microcarrier selection. Monolayer studies demonstrated input cell line variability with respect to growth kinetics and metabolite flux. HBM-MSC1 underwent more cumulative population doublings over three passages in comparison to hBM-MSC2 and hBM-MSC3. In 100 mL spinner flasks, agitated conditions were significantly better than static conditions, irrespective of donor, and relative microcarrier performance was identical where the same microcarriers outperformed others with respect to growth kinetics and metabolite flux. Relative growth kinetics between donor cells on the microcarriers were the same as the monolayer study. Plastic microcarriers were selected as the optimal microcarrier for hBM-MSC expansion. HBM-MSCs were successfully harvested and characterised, demonstrating hBM-MSC immunophenotype and differentiation capacity. This approach provides a systematic method for microcarrier selection, and the findings identify potentially significant bioprocessing implications for microcarrier-based allogeneic cell therapy manufacture. Large-scale production of human bone-marrow derived mesenchymal stem cells (hBM-MSCs) requires expansion on microcarriers in agitated systems. This study demonstrates the importance of microcarrier selection and presents a systematic methodology for selection of an optimal microcarrier. The study also highlights the impact of an agitated culture environment in comparison to a static system, resulting in a significantly higher hBM-MSC yield under agitated conditions

Stakeholder management reputation and its effects on CEO dismissal and CEO compensation

This dissertation examines the influence of an organization’s reputation for stakeholder management on outcomes relevant to corporate executives. I theorize that organizations develop two distinct reputations for stakeholder management. The first (for ease of exposition) is a reputation for “doing good.” "Do good" stakeholder management reputation is exemplified by organizational actions that are perceived to generate positive spillovers. The second is a reputation for “avoiding harm.” "Avoid harm" stakeholder management reputation is exemplified by organizational actions that are perceived to reduce negative spillovers. I propose that stakeholder management reputation offers a lens through which board members may make sense of a corporate executive’s competencies. This sensemaking process triggers cognitive evaluation processes that influence the type of attributions made about the ability of corporate leaders. These attributions in turn inform the decisions that are made on their behalf. The first study examines the effect of the reputation for stakeholder management on CEO dismissal. I propose that a reputation for "avoid harm" stakeholder management is more beneficial to alleviate the negative effects of poor financial performance on CEO dismissal. The second study examines the effect of the organization’s reputation for stakeholder management on CEO compensation. Here I propose that a reputation for "do good" stakeholder management holds a more positive association with CEO compensation relative to the reputation for "avoid harm" stakeholder management. I also examine the moderating role of firm performance, board independence and information uncertainty. I test these ideas on a sample of S&P-500 firms and the empirical analysis provides partial support for these ideas.Ope

Stakeholder management reputation and its effects on CEO dismissal and CEO compensation

This dissertation examines the influence of an organization’s reputation for stakeholder management on outcomes relevant to corporate executives. I theorize that organizations develop two distinct reputations for stakeholder management. The first (for ease of exposition) is a reputation for “doing good.” "Do good" stakeholder management reputation is exemplified by organizational actions that are perceived to generate positive spillovers. The second is a reputation for “avoiding harm.” "Avoid harm" stakeholder management reputation is exemplified by organizational actions that are perceived to reduce negative spillovers. I propose that stakeholder management reputation offers a lens through which board members may make sense of a corporate executive’s competencies. This sensemaking process triggers cognitive evaluation processes that influence the type of attributions made about the ability of corporate leaders. These attributions in turn inform the decisions that are made on their behalf. The first study examines the effect of the reputation for stakeholder management on CEO dismissal. I propose that a reputation for "avoid harm" stakeholder management is more beneficial to alleviate the negative effects of poor financial performance on CEO dismissal. The second study examines the effect of the organization’s reputation for stakeholder management on CEO compensation. Here I propose that a reputation for "do good" stakeholder management holds a more positive association with CEO compensation relative to the reputation for "avoid harm" stakeholder management. I also examine the moderating role of firm performance, board independence and information uncertainty. I test these ideas on a sample of S&P-500 firms and the empirical analysis provides partial support for these ideas.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste