OBJECTIVE To quantify the frequency and seriousness of adverse events in non-oncology phase I studies with healthy participants. DESIGN Meta-analysis of individual, healthy volunteer level data. SETTING Phase I studies with healthy volunteers conducted between September 2004 and March 2011 at Pfizer's three dedicated phase I testing sites in Belgium, Singapore, and the United States. These ...

We report here the purification and mechanistic characterization of a 5′-3′ exonuclease associated with DNA polymerase R from the yeast Saccharomyces cereVisiae. Earlier, we identified a 5′ f 3′ exonuclease activity that copurified with yeast DNA polymerase R-primase in a multiprotein complex [Biswas, E. E., et al. (1993) Biochemistry, 32, 3020-3027]. Peptide sequence analysis of the purified 4...

We present high refractive index optical metamaterials assembled via a microfluidic evaporation technique. This technique enables fabrication of truly three-dimensional bulk samples from a suspension of nanoparticles with a number of layers well in excess of 600, surpassing rival techniques by at least an order of magnitude. In addition to their large dimensions, the assembled metamaterials sho...

3-Amino-1,2,4-benzotriazine 1,4-dioxide (SR4233, WIN59075, tirapazamine, 1) is a clinically promising antitumor agent that requires bioreductive activation, selectively kills oxygen-deficient cells, and is believed to derive its biological activity from DNA cleavage. Using a xanthine-xanthine oxidase enzyme system as a one-electron reductant to activate 1 for DNA cleavage, it has been found tha...

American Shad Alosa sapidissima in the Hudson River, New York, and coastwide have shown major long-term declines. A possible contributing factor is commercial fisheries that harvest this population outside of the Hudson River estuary. Using previously published and new reference microsatellite data from 33 baseline populations, our goals were (1) to estimate the proportion of Hudson River Ameri...

Effective conservation of Cutthroat Trout Oncorhynchus clarkii lineages native to the Rocky Mountains will require estimating effects of multiple stressors and directing management toward the most important ones. Recent analyses have focused on the direct and indirect effects of a changing climate on contemporary ranges, which are much reduced from historic ranges owing to past habitat loss and...

Evaluating aquatic habitats is an important component of many ecological studies and natural resource assessments, but traditional habitat evaluations are time and labor intensive and do not provide continuous data. Side-scan sonar (SSS) can provide a low-cost method that collects continuous aquatic habitat data. We used SSS mapping to quantify suitable spawning substrate available toWalleye Sa...

Reliable fish condition estimates help managers better understand ecosystem population dynamics. Therefore, our study objectives were to measure seasonal changes in percent dry weight and energy density (physiological-based measures of condition) of stream-dwelling Appalachian Brook Trout Salvelinus fontinalis, field-validate bioelectrical impedance analysis (BIA) models, and compare reliabilit...

Tournament displacement, stockpiling near release points, and handling stress are major concerns for managers of sport fisheries in the southeastern USA. We examined the effects of transport distance and tournament handling stress on dispersal of 40 Largemouth BassMicropterus salmoides via telemetry from May 2012 to September 2013 in the Albemarle Sound system of eastern North Carolina. Largemo...

We perform second-harmonic generation (SHG) microscopy with circularly polarized (CP) light to measure chirality of individual twistedcross gold nanodimers. The chiral signatures, based on different SHG response for the two CP components of incident light, are clearly visible even with off-resonance excitation. The SHG responses of individual nanodimers are found to vary by about a factor of fi...