58 research outputs found

    Brief of Corporate Law Professors as Amici Curie in Support of Respondents

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    The Supreme Court has looked to the rights of corporate shareholders in determining the rights of union members and non-members to control political spending, and vice versa. The Court sometimes assumes that if shareholders disapprove of corporate political expression, they can easily sell their shares or exercise control over corporate spending. This assumption is mistaken. Because of how capital is saved and invested, most individual shareholders cannot obtain full information about corporate political activities, even after the fact, nor can they prevent their savings from being used to speak in ways with which they disagree. Individual shareholders have no “opt out” rights or practical ability to avoid subsidizing corporate political expression with which they disagree. Nor do individuals have the practical option to refrain from putting their savings into equity investments, as doing so would impose damaging economic penalties and ignore conventional financial guidance for individual investors

    Human Disease-Drug Network Based on Genomic Expression Profiles

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    BACKGROUND: Drug repositioning offers the possibility of faster development times and reduced risks in drug discovery. With the rapid development of high-throughput technologies and ever-increasing accumulation of whole genome-level datasets, an increasing number of diseases and drugs can be comprehensively characterized by the changes they induce in gene expression, protein, metabolites and phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: We performed a systematic, large-scale analysis of genomic expression profiles of human diseases and drugs to create a disease-drug network. A network of 170,027 significant interactions was extracted from the approximately 24.5 million comparisons between approximately 7,000 publicly available transcriptomic profiles. The network includes 645 disease-disease, 5,008 disease-drug, and 164,374 drug-drug relationships. At least 60% of the disease-disease pairs were in the same disease area as determined by the Medical Subject Headings (MeSH) disease classification tree. The remaining can drive a molecular level nosology by discovering relationships between seemingly unrelated diseases, such as a connection between bipolar disorder and hereditary spastic paraplegia, and a connection between actinic keratosis and cancer. Among the 5,008 disease-drug links, connections with negative scores suggest new indications for existing drugs, such as the use of some antimalaria drugs for Crohn's disease, and a variety of existing drugs for Huntington's disease; while the positive scoring connections can aid in drug side effect identification, such as tamoxifen's undesired carcinogenic property. From the approximately 37K drug-drug relationships, we discover relationships that aid in target and pathway deconvolution, such as 1) KCNMA1 as a potential molecular target of lobeline, and 2) both apoptotic DNA fragmentation and G2/M DNA damage checkpoint regulation as potential pathway targets of daunorubicin. CONCLUSIONS/SIGNIFICANCE: We have automatically generated thousands of disease and drug expression profiles using GEO datasets, and constructed a large scale disease-drug network for effective and efficient drug repositioning as well as drug target/pathway identification
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