Constraints on the volatile distribution within Shackleton crater at the lunar south pole

Shackleton crater is nearly coincident with the Moon's south pole. Its interior receives almost no direct sunlight and is a perennial cold trap, making Shackleton a promising candidate location in which to seek sequestered volatiles. However, previous orbital and Earth-based radar mapping and orbital optical imaging have yielded conflicting interpretations about the existence of volatiles. Here we present observations from the Lunar Orbiter Laser Altimeter on board the Lunar Reconnaissance Orbiter, revealing Shackleton to be an ancient, unusually well-preserved simple crater whose interior walls are fresher than its floor and rim. Shackleton floor deposits are nearly the same age as the rim, suggesting that little floor deposition has occurred since the crater formed more than three billion years ago. At a wavelength of 1,064 nanometres, the floor of Shackleton is brighter than the surrounding terrain and the interiors of nearby craters, but not as bright as the interior walls. The combined observations are explicable primarily by downslope movement of regolith on the walls exposing fresher underlying material. The relatively brighter crater floor is most simply explained by decreased space weathering due to shadowing, but a one-micrometre-thick layer containing about 20 per cent surficial ice is an alternative possibility.     

Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia

Effective targeted cancer therapeutic development depends upon distinguishing disease-associated 'driver' mutations, which have causative roles in malignancy pathogenesis, from 'passenger' mutations, which are dispensable for cancer initiation and maintenance. Translational studies of clinically active targeted therapeutics can definitively discriminate driver from passenger lesions and provide valuable insights into human cancer biology. Activating internal tandem duplication (ITD) mutations in FLT3 (FLT3-ITD) are detected in approximately 20% of acute myeloid leukaemia (AML) patients and are associated with a poor prognosis. Abundant scientific and clinical evidence, including the lack of convincing clinical activity of early FLT3 inhibitors, suggests that FLT3-ITD probably represents a passenger lesion. Here we report point mutations at three residues within the kinase domain of FLT3-ITD that confer substantial in vitro resistance to AC220 (quizartinib), an active investigational inhibitor of FLT3, KIT, PDGFRA, PDGFRB and RET; evolution of AC220-resistant substitutions at two of these amino acid positions was observed in eight of eight FLT3-ITD-positive AML patients with acquired resistance to AC220. Our findings demonstrate that FLT3-ITD can represent a driver lesion and valid therapeutic target in human AML. AC220-resistant FLT3 kinase domain mutants represent high-value targets for future FLT3 inhibitor development efforts.     

Planar cell polarity signalling couples cell division and morphogenesis during neurulation

Environmental and genetic aberrations lead to neural tube closure defects (NTDs) in 1 out of every 1,000 births. Mouse and frog models for these birth defects have indicated that Van Gogh-like 2 (Vangl2, also known as Strabismus) and other components of planar cell polarity (PCP) signalling might control neurulation by promoting the convergence of neural progenitors to the midline. Here we show a novel role for PCP signalling during neurulation in zebrafish. We demonstrate that non-canonical Wnt/PCP signalling polarizes neural progenitors along the anteroposterior axis. This polarity is transiently lost during cell division in the neural keel but is re-established as daughter cells reintegrate into the neuroepithelium. Loss of zebrafish Vangl2 (in trilobite mutants) abolishes the polarization of neural keel cells, disrupts re-intercalation of daughter cells into the neuroepithelium, and results in ectopic neural progenitor accumulations and NTDs. Remarkably, blocking cell division leads to rescue of trilobite neural tube morphogenesis despite persistent defects in convergence and extension. These results reveal a function for PCP signalling in coupling cell division and morphogenesis at neurulation and indicate a previously unrecognized mechanism that might underlie NTDs.     

A laser frequency comb that enables radial velocity measurements with a precision of 1 cm s(-1)

Searches for extrasolar planets using the periodic Doppler shift of stellar spectral lines have recently achieved a precision of 60 cm s(-1) (ref. 1), which is sufficient to find a 5-Earth-mass planet in a Mercury-like orbit around a Sun-like star. To find a 1-Earth-mass planet in an Earth-like orbit, a precision of approximately 5 cm s(-1) is necessary. The combination of a laser frequency comb with a Fabry-Pérot filtering cavity has been suggested as a promising approach to achieve such Doppler shift resolution via improved spectrograph wavelength calibration, with recent encouraging results. Here we report the fabrication of such a filtered laser comb with up to 40-GHz (approximately 1-A) line spacing, generated from a 1-GHz repetition-rate source, without compromising long-term stability, reproducibility or spectral resolution. This wide-line-spacing comb, or 'astro-comb', is well matched to the resolving power of high-resolution astrophysical spectrographs. The astro-comb should allow a precision as high as 1 cm s(-1) in astronomical radial velocity measurements.     

Schools as Communities: Purveyors of Democratic Values and the Cornerstones of a Public Philosophy

Establishing interdependency and community among people may be the solution to reestablishing or creating a tighter fabric of support for childrens' development, for building cultural democracy and a democratic state. This paper attempts to create a bridge between education and the construction of sustainable democratic communities in education, as a basis for building a public philosophy. Ultimately, sustainable democratic educational communities may address the concerns of today and tomorrow and build sustainable democratic communities in the larger global society.