Toward an internally consistent astronomical distance scale

Accurate astronomical distance determination is crucial for all fields in astrophysics, from Galactic to cosmological scales. Despite, or perhaps because of, significant efforts to determine accurate distances, using a wide range of methods, tracers, and techniques, an internally consistent astronomical distance framework has not yet been established. We review current efforts to homogenize the Local Group's distance framework, with particular emphasis on the potential of RR Lyrae stars as distance indicators, and attempt to extend this in an internally consistent manner to cosmological distances. Calibration based on Type Ia supernovae and distance determinations based on gravitational lensing represent particularly promising approaches. We provide a positive outlook to improvements to the status quo expected from future surveys, missions, and facilities. Astronomical distance determination has clearly reached maturity and near-consistency.Comment: Review article, 59 pages (4 figures); Space Science Reviews, in press (chapter 8 of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Age

Weakly nonlinear dynamics in noncanonical Hamiltonian systems with applications to fluids and plasmas

A method, called beatification, is presented for rapidly extracting weakly nonlinear Hamiltonian systems that describe the dynamics near equilibria for systems possessing Hamiltonian form in terms of noncanonical Poisson brackets. The procedure applies to systems like fluids and plasmas in terms of Eulerian variables that have such noncanonical Poisson brackets, i.e., brackets with nonstandard and possibly degenerate form. A collection of examples of both finite and infinite dimensions is presented

Advancing biological understanding and therapeutics discovery with small-molecule probes

Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the NIH launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines but also highlight the need to innovate the science of therapeutic discovery

Re-exploration of the PHCCC Scaffold: Discovery of Improved Positive Allosteric Modulators of mGluR4

[Image: see text] This paper describes a detailed structure−activity relationship (SAR) analysis of the metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulator, (−)-N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC). We have now developed compounds with improved potency and efficacy; in addition, compounds are presented that show selectivity for mGluR4 versus the other mGluR subtypes