Effect of Wavefront Error on 10^-7 Contrast Measurements

We have measured a contrast of 6.5 {center_dot} 10{sup -8} from 10-25{lambda}/D in visible light on the Extreme Adaptive Optics testbed using a shaped pupil for diffraction suppression. The testbed was designed with a minimal number of high-quality optics to ensure low wavefront error and uses a phase shifting diffraction interferometer for metrology. This level of contrast is within the regime needed for imaging young Jupiter-like planets, a primary application of high-contrast imaging. We have concluded that wavefront error, not pupil quality, is the limiting error source for improved contrast in our system

Characterizing the Adaptive Optics Off-Axis Point-Spread Function - I: A Semi-Empirical Method for Use in Natural-Guide-Star Observations

Even though the technology of adaptive optics (AO) is rapidly maturing, calibration of the resulting images remains a major challenge. The AO point-spread function (PSF) changes quickly both in time and position on the sky. In a typical observation the star used for guiding will be separated from the scientific target by 10" to 30". This is sufficient separation to render images of the guide star by themselves nearly useless in characterizing the PSF at the off-axis target position. A semi-empirical technique is described that improves the determination of the AO off-axis PSF. The method uses calibration images of dense star fields to determine the change in PSF with field position. It then uses this information to correct contemporaneous images of the guide star to produce a PSF that is more accurate for both the target position and the time of a scientific observation. We report on tests of the method using natural-guide-star AO systems on the Canada-France-Hawaii Telescope and Lick Observatory Shane Telescope, augmented by simple atmospheric computer simulations. At 25" off-axis, predicting the PSF full width at half maximum using only information about the guide star results in an error of 60%. Using an image of a dense star field lowers this error to 33%, and our method, which also folds in information about the on-axis PSF, further decreases the error to 19%.Comment: 29 pages, 9 figures, accepted for publication in the PAS

A cell based high-throughput screening approach for the discovery of new inhibitors of respiratory syncytial virus

Background: Human respiratory syncytial virus (hRSV) is a highly contagious pathogen and is the most common cause of bronchiolitis and pneumonia for infants and children under one year of age. Worldwide, greater than 33 million children under five years of age are affected by hRSV resulting in three million hospitalizations and 200,000 deaths. However, severe lower respiratory tract disease may occur at any age, especially among the elderly or those with compromised cardiac, pulmonary, or immune systems. There is no vaccine commercially available. Existing therapies for the acute infection are ribavirin and the prophylactic humanized monoclonal antibody (Synagis® from MedImmune) that is limited to use in high risk pediatric patients. Thus, the discovery of new inhibitors for hRSV would be clinically beneficial. Results: We have developed and validated a 384-well cell-based, high-throughput assay that measures the cytopathic effect of hRSV (strain Long) in HEp-2 cells using a luminescent-based detection system for signal endpoint (Cell Titer Glo®). The assay is sensitive and robust, with Z factors greater than 0.8, signal to background greater than 35, and signal to noise greater than 24. Utilizing this assay, 313,816 compounds from the Molecular Libraries Small Molecule Repository were screened at 10 μM. We identified 7,583 compounds that showed greater than 22% CPE inhibition in the primary screen. The top 2,500 compounds were selected for confirmation screening and 409 compounds showed at least 50% inhibition of CPE and were considered active. We selected fifty-one compounds, based on potency, selectivity and chemical tractability, for further evaluation in dose response and secondary assays Several compounds had SI50 values greater than 3, while the most active compound displayed an SI50 value of 58.9. Conclusions: A robust automated luminescent-based high throughput screen that measures the inhibition of hRSV-induced cytopathic effect in HEp-2 cells for the rapid identification of potential inhibitors from large compound libraries has been developed, optimized and validated. The active compounds identified in the screen represent different classes of molecules, including aryl sulfonylpyrrolidines which have not been previously identified as having anti-hRSV activity

(S)-N-(2,5-Dimethylphenyl)-1-(quinoline-8-ylsulfonyl)pyrrolidine-2-carboxamide as a Small Molecule Inhibitor Probe for the Study of Respiratory Syncytial Virus Infection

A high-throughput, cell-based screen was used to identify chemotypes as inhibitors for human respiratory syncytial virus (hRSV). Optimization of a sulfonylpyrrolidine scaffold resulted in compound 5o that inhibited a virus-induced cytopathic effect in the entry stage of infection (EC50 = 2.3 ± 0.8 µM) with marginal cytotoxicity (CC50 = 30.9 ± 1.1 µM) and reduced viral titer by 100-fold. Compared to ribavirin, sulfonylpyrrolidine 5o demonstrated an improved in vitro potency and selectivity index

Three Keys to Success for Principals (and Their Teachers)

This is the author's accepted manuscript, post peer-review. The publisher's official version is available at: http://dx.doi.org/10.1080/00228958.2008.10516527.What is successful leadership and how can leadership concepts be applied to schools? Hundreds of books and articles and a plethora of executive seminars describe what leadership is and propose strategies for what effective leaders do. Most of these writings and presentations, however, focus on business, with much less information available about how to lead schools. In addition, there is a diversity of opinions about what makes leaders effective. This article suggests that it is possible to extract, reframe, and apply the best of what is known about leadership to help principals be more successful. Moreover, if principals are successful, teachers also are positioned to be successful, with the ultimate impact being successful student learning