The transfer RNA gene downstream from the HMR locus in S. cerevisiae functions as part of a boundary (barrier) element that restricts the spread of heterochromatic gene silencing into the downstream region of chromosome III. A genetic screen for identifying additional genes that, when mutated, allow inappropriate spreading of silencing from HMR through the tRNA gene was performed. YTA7, a gene containing bromodomain and ATPase homologies, was identified multiple times. Previously, others had shown that the bromodomain protein Bdf1p functions to restrict silencing at yeast euchromatinheterochromatin boundaries; therefore we deleted nonessential bromodomain-containing genes to test their effects on heterochromatin spreading. Deletion of RSC2, coding for a component of the RSC chromatin-remodeling complex, resulted in a significant spread of silencing at HMR. Since the bromodomain of YTA7 lacks a key tyrosine residue shown to be important for acetyllysine binding in other bromodomains, we confirmed that a GST-Yta7p bromodomain fusion was capable of binding to histones in vitro. Epistasis analysis suggests that YTA7 and the HMR-tRNA function independently to restrict the spread of silencing, while RSC2 may function through the tRNA element. Our results suggest that multiple bromodomain proteins are involved in restricting the propagation of heterochromatin at HMR.

1049ward referring clinicians and other health care providers in an effort to optimize patient care in radiology [1,2].In this study, we performed a quality improvement initiative with the goal of reducing the number of unindicated dual-phase head CT examinations by educating referring physicians and radiology faculty about the ACR Appropriateness Criteria. Previous quality initiative studies involving clinical decision support in radiology have focused on either volume reduction [3][4][5] or adherence to ACR Appropriateness Criteria [6,7]. Both approaches have limitations. Quality initiatives that focus explicitly on reducing the number of examinations via utilization management systems often fail to show improved quality of patient care [3][4][5]. Those that focus on adherence to ACR Appropriateness Criteria may result in more appropriate choices of imaging studies, and there-A recent national focus on patient safety and an increasing awareness of the unsustainable expansion of health care costs have served as a rallying cry for the radiology community, which has responded with an increased emphasis on delivering the best possible care to patients in the most efficient manner possible. To achieve and maintain this standard, the American Board of Radiology has mandated systemic practice quality improvement. An important element of practice quality improvement is the American College of Radiology (ACR) Appropriateness Criteria; first developed in 1993, the ACR Appropriateness Criteria provide scientific guidelines regarding the most appropriate use of radiology examinations. The guidelines delineate the best use of radiologic examinations based on evidence-based medicine and are targeted to-OBJECTIVE. During this study, we instituted a phased quality improvement initiative designed to educate referring clinicians and departmental radiologists about the recommendations of the American College of Radiology (ACR) Appropriateness Criteria for dual-phase (without and with contrast material) head CT examinations. The primary aims of the study were to evaluate whether the quality improvement initiative was associated with an improvement in ACR Appropriateness Criteria appropriateness ratings and a reduction in the number of unindicated dual-phase head CT examinations performed. A secondary aim was to assess the impact of the quality improvement initiative on health care costs. MATERIALS AND METHODS.This study included-with the exception of the examinations performed during a 3-month training period-all single-and dual-phase head CT examinations performed of adult patients at a tertiary care medical center from January 2009 through October 2011. Both inpatients and outpatient examinations were included. There were no exclusion criteria.RESULTS. Implementation of the initiative enhanced patient safety and reduced health care costs by achieving a significant reduction (p = 0.006) in the number of unindicated dual-phase head CT examinations performed from a median number of 40 per month to 17 per month.CONCLUSION. Although ...

To develop improved strategies for gene transfer to hematopoietic cells, we have explored targeted gene transfer using molecular conjugate vectors (MCVs). MCVs are constructed by condensing plasmid DNA containing the gene of interest with polylysine (PL), PL linked to a replication-incompetent adenovirus (endosomolytic agent), and PL linked to streptavidin for targeting with biotinylated ligands. In this report, we compare gene transfer to K562 cells by using the previously described transferrin-targeted MCV (Trans-MCV) to a novel transferrin-targeted MCV. In the novel MCV, the transferred gene (luciferase) is in the genome of recombinant replication-incompetent adenovirus (recMCV), which also acts as the endosomolytic agent. The level of luciferase gene expression was fivefold higher in K562 cells transfected with Trans-recMCV than in cells transfected with Trans-MCV. Furthermore, targeted transfection with recMCV resulted in prolonged luciferase expression that declined 14 to 20 days after transfection, in comparison with Trans-MCV, where luciferase expression declined by 4 to 8 days. Moreover, targeted transfection of K562 cells with the Trans-recMCV resulted in persistent luciferase gene expression for 6 months. Analysis of luciferase gene expression in K562 single-cell clones that were subcloned 5 weeks after transfection with Trans-recMCV showed that 35 to 50% of the single-cell clones had intermediate to high levels of luciferase gene expression that was stable for 6 months, with the remaining clones showing low or no luciferase gene expression. Stable gene expression was associated with integration of adenovirus sequences into genomic DNA.