The Kepler mission discovered 2842 exoplanet candidates with 2 years of data. We provide updates to the Kepler planet candidate sample based upon 3 years (Q1-Q12) of data. Through a series of tests ...to exclude false-positives, primarily caused by eclipsing binary stars and instrumental systematics, 855 additional planetary candidates have been discovered, bringing the total number known to 3697. We provide revised transit parameters and accompanying posterior distributions based on a Markov Chain Monte Carlo algorithm for the cumulative catalogue of Kepler Objects of Interest. There are now 130 candidates in the cumulative catalogue that receive less than twice the flux the Earth receives and more than 1100 have a radius less than 1.5 Rearth. There are now a dozen candidates meeting both criteria, roughly doubling the number of candidate Earth analogs. A majority of planetary candidates have a high probability of being bonafide planets, however, there are populations of likely false-positives. We discuss and suggest additional cuts that can be easily applied to the catalogue to produce a set of planetary candidates with good fidelity. The full catalogue is publicly available at the NASA Exoplanet Archive.
The metabolism of metronidazole was studied in microsomes isolated from livers of human kidney donors. The formation of the major in vivo metabolite, hydroxymetronidazole, proceeded according to ...biphasic kinetics, suggesting the involvement of at least two enzymatic sites. The affinity constant (Km) of the high affinity site ranged from 140 to 320 microM and metabolism at this site contributed more than 75% of the intrinsic clearance. Thus, at therapeutic doses of metronidazole most of the hydroxylation in vivo should be associated with this site. Antipyrine, cimetidine, alpha-naphthoflavone, caffeine, theophylline, mephenytoin, tolbutamide, quinidine, acetone and nifedipine were poor inhibitors of the formation of hydroxymetronidazole by human liver microsomes. Propranolol (500 microM) inhibited the hydroxylation rate by 70%. Phenacetin inhibited metronidazole hydroxylation with a competitive inhibition constant (Ki) of 4-5 microM. However, metronidazole did not inhibit the O-deethylation of phenacetin. It is concluded that cytochromes P450 IA2, IIC9, IIC10, IID6, IIE1 and IIIA3 do not contribute significantly to the high affinity hydroxylation of metronidazole in man.
Anthropogenic pressures on the Earth System have reached a scale where abrupt global environmental change can no longer be excluded. We propose a new approach to global sustainability in which we ...define planetary boundaries within which we expect that humanity can operate safely. Transgressing one or more planetary boundaries may be deleterious or even catastrophic due to the risk of crossing thresholds that will trigger non-linear, abrupt environmental change within continental- to planetary-scale systems. We have identified nine planetary boundaries and, drawing upon current scientific understanding, we propose quantifications for seven of them. These seven are climate change (CO2 concentration in the atmosphere
