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The use of RNAi to silence gene expression has recently provided a novel means to screen for genes important to cell physiology. More recently, new reagents that lead to the specific and enhanced silencing of individual genes have been developed. Thus, the combined use of RNAi, in conjunction with the enhanced specificity of siRNAs, offers a powerful approach to evaluate the function of individual genes within cells. The objective of this proposal is to test the utility of the combined use of RNAi and gene silencing enhanced siRNAs (esiRNA) in the study of the molecular mechanism of T-cell activation and differentiation. The central hypothesis of this proposal is that siRNAs can be utilized to perform a gene function test within a cell, and in particular within the context of the T-cell activation and differentiation pathway. The rationale for the proposed research is that once this technology is developed, the ability to silence genes within a cell will open up an entire new area of molecular and cellular biology, especially in the area of immune system biology. Once developed, the approach will be useful in further defining the molecular events involved in T-cell activation and differentiation, and in the development of new immunotherapeutic strategies. A single such strategy has the potential to be beneficial to individuals suffering from numerous debilitating diseases that are mediated by dysregulated immune function.The New York Times reports a new scandal in the Obama administration: members of the IRS are being accused of improperly targeting conservative groups and taxpayers for years. “A federal investigation into the IRS handling of applications by politically conservative groups for tax-exempt status has reached a new stage, according to two people familiar with the investigation,” the New York Times writes. “The inquiry involves employees in Cincinnati who may have improperly scrutinized applications by conservative groups during a 2012 election year.” That investigation is being conducted by the Department of Justice, and the Times names one person as a key target: Mark Everson, a “top official in the Cincinnati office.” As the Times notes, Everson has been involved in a number of matters involving the Internal Revenue Service since at least 2003. In 2011, he was involved in the “sensitive case” involving the IRS targeting of Tea Party groups. Back in 2009, he was involved in an audit of a California vineyard, which was deemed “grossly negligent” and thus gave the IRS “authority to impose a civil penalty” of up to $10,000.


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