A comparison of clinical pharmacodynamics of different administration schedules of oral topotecan (Hycamtin)

Prolonged exposure to topotecan in in vitro and in vivo experiments has yielded the highest antitumor efficacy. An oral formulation of topotecan with a bioavailability of 32-44% in humans enables convenient prolonged administration. Pharmacokinetic/pharmacodynamic relationships from four Phase I studies with different schedules of administration of oral topotecan in 99 adult patients with malignant solid tumors refractory to standard forms of chemotherapy were compared. Topotecan was administered as follows: (a) once daily (o.d.) for 5 days every 21 days (29 patients); (b) o.d. for 10 days every 21 days (19 patients); (c) twice daily (b.i.d.) for 10 days every 21 days (20 patients); and (d) b.i.d. for 21 days every 28 days (31 patients). Pharmacokinetic analysis was performed in 55 patients using a validated high-performance liquid chromatographic assay and noncompartmental pharmacokinetic me

College of Puget Sound: A Dream Realized

History of the College written by President Todd.https://soundideas.pugetsound.edu/pugetsoundhistoricaltext/1012/thumbnail.jp

Hydrogen Bonding Effects in Anion Binding Calixarenes

A series of disubstituted urea, thiourea and dansyl amide calix[4]arene based anion receptors have been prepared and characterised by X-ray crystallography. The structures show a fine balance of intramolecular urea α-tape, and ureacalixarene phenolic oxygen atom hydrogen bonding patterns. Both motifs are in competition with the anion binding behaviour of the compounds in solution

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

EvryFlare. I. Long-term Evryscope Monitoring of Flares from the Cool Stars across Half the Southern Sky

We search for superflares from 4068 cool stars in 2+ yr of Evryscope photometry, focusing on those with high-cadence data from both Evryscope and the Transiting Exoplanet Survey Satellite (TESS). The Evryscope array of small telescopes observed 575 flares from 284 stars, with a median energy of 1034.0 erg. Since 2016, Evryscope has enabled the detection of rare events from all stars observed by TESS through multi-year, high-cadence continuous observing. We report around twice the previous largest number of 1034 erg high-cadence flares from nearby cool stars. We find eight flares with amplitudes of 3+ g′ magnitudes, with the largest reaching 5.6 mag and releasing 1036.2 erg. We observe a 1034 erg superflare from TOI-455 (LTT 1445), a mid-M with a rocky planet candidate. We measure the superflare rate per flare-star and quantify the average flaring of active stars as a function of spectral type, including superflare rates, flare frequency distributions, and typical flare amplitudes in g′. We confirm superflare morphology is broadly consistent with magnetic reconnection. We estimate starspot coverage necessary to produce superflares, and hypothesize maximum allowed superflare energies and waiting times between flares corresponding to 100% coverage of the stellar hemisphere. We observe decreased flaring at high Galactic latitudes. We explore the effects of superflares on ozone loss to planetary atmospheres: we observe one superflare with sufficient energy to photodissociate all ozone in an Earth-like atmosphere in one event. We find 17 stars that may deplete an Earth-like atmosphere via repeated flaring. Of the 1822 stars around which TESS may discover temperate rocky planets, we observe 14.6% ± 2% emit large flares

Bright Opportunities for Atmospheric Characterization of Small Planets: Masses and Radii of K2-3 b, c, and d and GJ3470 b from Radial Velocity Measurements and Spitzer Transits

We report improved masses, radii, and densities for four planets in two bright M-dwarf systems, K2-3 and GJ3470, derived from a combination of new radial velocity and transit observations. Supplementing K2 photometry with follow-up Spitzer transit observations refined the transit ephemerides of K2-3 b, c, and d by over a factor of 10. We analyze ground-based photometry from the Evryscope and Fairborn Observatory to determine the characteristic stellar activity timescales for our Gaussian Process fit, including the stellar rotation period and activity region decay timescale. The stellar rotation signals for both stars are evident in the radial velocity data and is included in our fit using a Gaussian process trained on the photometry. We find the masses of K2-3 b, K2-3 c, and GJ3470 b to be 6.48, 2.14, and 12.58 M ⊕, respectively. K2-3 d was not significantly detected and has a 3σ upper limit of 2.80 M ⊕ . These two systems are training cases for future TESS systems; due to the low planet densities (ρ < 3.7 g cm -3 ) and bright host stars (K < 9 mag), they are among the best candidates for transmission spectroscopy in order to characterize the atmospheric compositions of small planets

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signal-to-noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO's first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far. © 2017 American Physical Society