Genetic contribution to white matter hyperintensity burden in early- and late-onset ischemic stroke patients

Thesis (M.A.)--Boston UniversityWhite matter hyperintensity volume (WMHV) is associated with greater risk of ischemic stroke, and discovery of genetic markers of increased WMHV may contribute to improved stroke risk prediction models, leading to novel stroke prevention strategies, especially in high-risk individuals. These genetic markers may have a greater effect in early-onset stroke patients due to their shorter exposure to environmental factors, or play a protective role in late-onset stroke patients. In a genome-wide study designed to discover single nucleotide polymorphisms (SNPs) associated with white matter hyperintensity burden in early- and late-onset stroke patients, approximately nine million SNPs were ascertained in 781 subjects, whose age, sex, WMHV, and history of hypertension, hyperlipidemia, and tobacco use were also determined. Association analyses in three subpopulations (patients with early-onset stroke, patients with average age of stroke onset, and patients with late-onset stroke) provided lists of SNPs associated with WMHV, and these SNPs were used to calculate genetic risk (GR) scores for each subject. Single-variable linear regression was used to identify which of the baseline characteristics were nominally significant, for inclusion in multivariable regression models with and without the effect contributed by the GR scores. We found that GR scores calculated using SNPs discovered in patients with early-onset stroke significantly predicted of white matter burden in patients with average age of stroke onset, and that GR scores calculated with a panel of SNPs discovered in patients with average age of stroke onset predicted WMHV in patients with late-onset stroke. Furthermore, our findings suggest a different genetic mechanism for increased WMHV in early-onset stroke patients

Immuno-Anti-Infective Drug Design Using BioAI

According to the World Health Organization, antibiotic resistance is one of the biggest threats to global health, food security, and development today. A growing number of infections, like Methicillin-resistant Staphylococcus aureus, are becoming harder to treat as the antibiotics used to treat them become less effective. As a result, the primary concern for infections in the hospital setting is due to the S. aureus’s growing resistance to antibiotics. Therefore, in response to this global health threat, our project focuses on furthering the research in developing a drug that S. aureus will not develop resistance to. In this paper, we assess NPY-Y2 as a potential immuno-anti-infective drug target to prevent the activation of Sortase A on S. aureus. We have shown that NPY-Y2 is a potential drug target; however, further invasion assay experiments need to be conducted for more reliable verification. In a larger scheme, our hope is that the approach of this research will allow for the development of other anti-infective drugs for other bacteria

An Information-Based Theory of International Currency

This paper develops an information-based theory of international currency based on search frictions, private trading histories, and imperfect recognizability of assets. Using an open-economy search model with multiple competing currencies, the value of each currency is determined without requiring agents to use a particular currency to purchase a country's goods. Strategic complementarities in portfolio choices and information acquisition decisions generate multiple equilibria with different types of payment arrangements. While some inflation can benefit the country issuing an international currency, the threat of losing international status puts an inflation discipline on the issuing country. When monetary authorities interact in a simple policy game, the temptation to inflate can lead optimal policy to deviate from the Friedman rule. A calibration of the generalized model shows that for the U.S. dollar, the welfare cost of losing international status ranges from 1.3% to 2.1% of GDP per year

An Information-Based Theory of International Currency

This paper develops an information-based theory of international currency based on search frictions, private trading histories, and imperfect recognizability of assets. Using an open-economy search model with multiple competing currencies, the value of each currency is determined without requiring agents to use a particular currency to purchase a country's goods. Strategic complementarities in portfolio choices and information acquisition decisions generate multiple equilibria with different types of payment arrangements. While some inflation can benefit the country issuing an international currency, the threat of losing international status puts an inflation discipline on the issuing country. When monetary authorities interact in a simple policy game, the temptation to inflate can lead optimal policy to deviate from the Friedman rule. A calibration of the generalized model shows that for the U.S. dollar, the welfare cost of losing international status ranges from 1.3% to 2.1% of GDP per year

DynGO: a tool for visualizing and mining of Gene Ontology and its associations

BACKGROUND: A large volume of data and information about genes and gene products has been stored in various molecular biology databases. A major challenge for knowledge discovery using these databases is to identify related genes and gene products in disparate databases. The development of Gene Ontology (GO) as a common vocabulary for annotation allows integrated queries across multiple databases and identification of semantically related genes and gene products (i.e., genes and gene products that have similar GO annotations). Meanwhile, dozens of tools have been developed for browsing, mining or editing GO terms, their hierarchical relationships, or their "associated" genes and gene products (i.e., genes and gene products annotated with GO terms). Tools that allow users to directly search and inspect relations among all GO terms and their associated genes and gene products from multiple databases are needed. RESULTS: We present a standalone package called DynGO, which provides several advanced functionalities in addition to the standard browsing capability of the official GO browsing tool (AmiGO). DynGO allows users to conduct batch retrieval of GO annotations for a list of genes and gene products, and semantic retrieval of genes and gene products sharing similar GO annotations. The result are shown in an association tree organized according to GO hierarchies and supported with many dynamic display options such as sorting tree nodes or changing orientation of the tree. For GO curators and frequent GO users, DynGO provides fast and convenient access to GO annotation data. DynGO is generally applicable to any data set where the records are annotated with GO terms, as illustrated by two examples. CONCLUSION: We have presented a standalone package DynGO that provides functionalities to search and browse GO and its association databases as well as several additional functions such as batch retrieval and semantic retrieval. The complete documentation and software are freely available for download from the website

Money and Credit as Means of Payment: A New Monetarist Approach

This paper studies the choice of payment instruments in a simple model where both money and credit can be used as means of payment. We endogenize the acceptability of credit by allowing retailers to invest in a costly record-keeping technology. Our framework captures the two-sided market interaction between consumers and retailers, leading to strategic complementarities that can generate multiple steady-state equilibria. In addition, limited commitment makes debt contracts self-enforcing and yields an endogenous upper bound on credit use. So long as record-keeping is imperfect, money and credit coexist for a range of nominal interest rates. Our model captures the dependence of debt limits on monetary policy and explains how hold-up problems in technological adoption prevent retailers from accepting credit as consumers continue to coordinate on cash usage. With limited commitment, changes in monetary policy generate multiplier effects in the credit market due to complementarities between consumer borrowing and the adoption of credit by merchants

A comparison study on algorithms of detecting long forms for short forms in biomedical text

<p>Abstract</p> <p>Motivation</p> <p>With more and more research dedicated to literature mining in the biomedical domain, more and more systems are available for people to choose from when building literature mining applications. In this study, we focus on one specific kind of literature mining task, i.e., detecting definitions of acronyms, abbreviations, and symbols in biomedical text. We denote acronyms, abbreviations, and symbols as short forms (SFs) and their corresponding definitions as long forms (LFs). The study was designed to answer the following questions; i) how well a system performs in detecting LFs from novel text, ii) what the coverage is for various terminological knowledge bases in including SFs as synonyms of their LFs, and iii) how to combine results from various SF knowledge bases.</p> <p>Method</p> <p>We evaluated the following three publicly available detection systems in detecting LFs for SFs: i) a handcrafted pattern/rule based system by Ao and Takagi, ALICE, ii) a machine learning system by Chang et al., and iii) a simple alignment-based program by Schwartz and Hearst. In addition, we investigated the conceptual coverage of two terminological knowledge bases: i) the UMLS (the Unified Medical Language System), and ii) the BioThesaurus (a thesaurus of names for all UniProt protein records). We also implemented a web interface that provides a virtual integration of various SF knowledge bases.</p> <p>Results</p> <p>We found that detection systems agree with each other on most cases, and the existing terminological knowledge bases have a good coverage of synonymous relationship for frequently defined LFs. The web interface allows people to detect SF definitions from text and to search several SF knowledge bases.</p> <p>Availability</p> <p>The web site is <url>http://gauss.dbb.georgetown.edu/liblab/SFThesaurus</url>.</p

Optimal Monetary and Fiscal Policy with Migration in a Currency Union

We develop an open economy model of a currency union with frictional goods markets and costly migration to study optimal monetary and fiscal policy for the union. Households finance consump- tion with a common currency and can migrate across regions given regional differences in goods market characteristics and microstructure. Equilibrium is generically inefficient due to regional spillovers from migration. While monetary policy alone cannot correct this distortion, fiscal policy can help by taxing or subsidizing at the regional level. When households of only one region can migrate, optimal policy entails a deviation from the Friedman rule and a production subsidy (tax) if there is underinvestment (overinvestment) in migration. Optimal policy when households from both region can migrate is the Friedman rule and zero taxes in both regions