Shannon Bradshaw

Zinc-finger Nucleases as a Novel Therapeutic Strategy for Targeting Hepatitis B Virus DNAs

Hepatitis B virus (HBV) chronically infects 350-400 million people worldwide and causes >1 million deaths yearly. Current therapies prevent new viral genome formation, but do not target pre-existing viral genomic DNA, thus curing only approximately 1/2 of patients. We targeted HBV DNA for cleavage using zinc-finger nucleases (ZFNs), which cleave as dimers. Co-transfection of our ZFN pair with a target plasmid containing the HBV genome resulted in specific cleavage. After 3 days in culture, 26% of the target remained linear, whereas approximately10% was cleaved and misjoined tail-to-tail. Notably, ZFN treatment decreased levels of the hepatitis C virus pregenomic RNA by 29%. A portion of cleaved plasmids are repaired in cells, often with deletions and insertions. To track misrepair, we introduced an XbaI restriction site in the spacer between the ZFN sites. Targeted cleavage and misrepair destroys the XbaI site. After 3 days in culture, approximately 6% of plasmids were XbaI-resistant. Thirteen of 16 clones sequenced contained frameshift mutations that would lead to truncations of the viral core protein. These results demonstrate, for the first time, the possibility of targeting episomal viral DNA genomes using ZFNs.

Reference Directed Indexing: Redeeming Relevance for Subject Search in Citation Indexes

Citation indexes are valuable tools for research, in part because they provide a means with which to measure the relative impact of articles in a collection of scientific literature. Recent efforts demonstrate some value in retrieval systems for citation indexes based on measures of impact. However, such approaches use weak measures of relevance, ranking together a few useful documents with many that are frequently cited but irrelevant. We propose an indexing technique that joins measures of relevance and impact in a single retrieval metric. This approach, called Reference Directed Indexing (RDI) is based on a comparison of the terms authors use in reference to documents. Initial retrieval experiments with RDI indicate that it retrieves documents of a quality on par with current ranking metrics, but with significantly improved relevance.

Supporting on-line resource discovery in the context of ongoing tasks with proactive software assistants

We present ongoing work on systems aimed at improving a users awareness of resources available to them on the Internet and in intranets. First, we briefly describe Watson, a system that proactively retrieves documents from on-line repositories that are potentially useful in the context of a task, allowing the user to quickly become aware of document resources available in on-line information repositories. Next, we describe I2I, an extension of Watson that builds communities of practice on the fly, based on the work that its users do, so that users with similar goals and interests can discover each other and communicate both synchronously and asynchronously. Both Watson and I2I operate given some knowledge of the users current task, gleaned automatically from the behavior of users in software tools. As a result, the systems can provide users with useful resources in the context of the work that they are performing. We argue that the systems can foster a greater sense of awareness of the resources available, while minimizing the effort required to discover them.

Guiding people to information: providing an interface to a digital library using reference as a basis for indexing

We describe Rosetta, a digital library system for scientific literature. Rosetta makes it easy for people to find the information for which they are looking even when using short, imprecise queries. Rosetta indexes research articles based on the way they have been described when cited in other documents. The concise descriptions that occur in citations are similar to the short queries people typically form when searching; therefore, citations make a better basis for indexing than do the words used within a research article itself. Using this indexing technique we are able to provide a user interface that presents users with an automatically generated directory of the information space surrounding a query. Our objective with this interface is to present people with the information for which they have asked as well as the information for which they may have intended to ask.

Clustering for opportunistic communication

We describe ongoing work on I2I, a system aimed at fostering opportunistic communication among users viewing or manipulating content on the Web and in productivity applications. Unlike previous work in which the URLs of Web resources are used to group users visiting the same resource, we present a more general framework for clustering work contexts to group users together that accounts for dynamic content and distributional properties of Web accesses which can limit the utility URL based systems. In addition, we describe a method for scaffolding asynchronous communication in the context of an ongoing task that takes into account the ephemeral nature of the location of content on the Web. The techniques we describe also nicely cover local files in progress, in addition to publicly available Web content. We present the results of several evaluations that indicate systems that use the techniques we employ may be more useful than systems that are strictly URL based.

Jabberwocky: you don't have to be a rocket scientist to change slides for a hydrogen combustion lecture

In designing Jabberwocky—a speech-based interface to Microsoft PowerPoint—we have tried to go beyond simple commands like “Next slide, please” and make a tool that aids speakers as they present and even learns as they rehearse their presentations. Jabberwocky looks at the contents of the slides, extracting key words and phrases and associating them with their places in the presentation. By listening for these phrases (and synonymous phrases derived using syntactic rules) Jabberwocky is able to follow along with the presentation, switching slides at the appropriate moments. In this paper, we discuss the implementation of this system—a component of our Intelligent Classroom project—and look at how we are using it.

Network arts: exposing cultural reality

In this article, we explore a new role for the computer in art as a reflector of popular culture. Moving away from the static audio-visual installations of other artistic endeavors and from the traditional role of the machine as a computational tool, we fuse art and the Internet to expose cultural connections people draw implicitly but rarely consider directly. We describe several art installations that use the World Wide Web as a reflection of cultural reality to highlight and explore the relations between ideas that compose the fabric of our every day lives.

Automatically indexing documents: content vs. reference

Authors cite other work in many types of documents. Notable among these are research papers and web pages. Recently, several researchers have proposed using the text surrounding citations (references) as a means of automatically indexing documents for search engines, claiming that this technique is superior to indexing documents based on their content [1,2]. While we ourselves have made this claim, we acknowledge that little empirical data has been presented to support it. Therefore, in the limited space available we present a terse overview of a study comparing reference to content as bases for indexing documents. This study indicates that reference identifies the value of documents more accurately and with a greater diversity of language than content.

Search Engine-Crawler Symbiosis: Adapting to Community Interests

Web crawlers have been used for nearly a decade as a search engine component to create and update large collections of documents. Typically the crawler and the rest of the search engine are not closely integrated. If the purpose of a search engine is to have as large a collection as possible to serve the general Web community, a close integration may not be necessary. However, if the search engine caters to a specific community with shared focused interests, it can take advantage of such an integration. In this paper we investigate a tightly coupled system in which the crawler and the search engine engage in a symbiotic relationship. The crawler feeds the search engine and the search engine in turn helps the crawler to better its performance. We show that the symbiosis can help the system learn about a community’s interests and serve such a community with better focus.

Annotation consensus: implications for passage recommendation in scientific literature

We present a study of the degree to which annotations overlap when several researchers read the same set of scientific articles. Our objective is to determine whether there is sufficient evidence to suggest that information about which passages initial readers tend to annotate might be used to recommend important passages to later readers of the same material. We found that readers exhibit a high degree of overlap in the passages they annotate, that these passages account for a small but significant fraction of the total document, and that such passages are distributed throughout a document rather than concentrated in the same few sections in each paper (e.g., the results section). These findings indicate that work on developing a passage recommendation model based on annotation is warranted.