Making Evaluation Work

Outlines how evaluation has been integrated into grantmaking practices, since the foundation embarked upon a new approach to the field of youth development in 2000

Trusting in Change

Describes the background to a series of changes that led the foundation, beginning in 2000, to implement a new grantmaking approach

Giving While Living: The Beldon Fund Spend-Out Story

Provides insight into the challenges, advantages, and practical implications of a limited-life foundation. Offers strategies, advice, and lessons learned on how spending out affects program strategy, staffing, asset management, and grantee relations

Looking Back: Influencing, Networking, Facilitating

A ten-year retrospective of the Funders' Network for Smart Growth and Livable Communities, based on a series of interviews among members and a review of materials generated over the years

Chemiluminescence from osmium(ii) complexes with phenanthroline, diphosphine and diarsine ligands

The reaction of various [Os(L)2(L′)]2+ complexes (where L and L′ are phenanthroline, diphosphine or diarsine ligands) and organic reducing agents after chemical or electrochemical oxidation of the reactants produces an emission of light corresponding to MLCT transitions. In certain instances, the emission was greater than that of [Ru(bipy)3]2+, but the relative signals were dependent on many factors, including reagent concentration, mode of oxidation, reducing agent and the sensitivity of the photodetector over the wavelength range

Asteroid exploration and utilization

The Earth is nearing depletion of its natural resources at a time when human beings are rapidly expanding the frontiers of space. The resources possessed by asteroids have enormous potential for aiding and enhancing human space exploration as well as life on Earth. Project STONER (Systematic Transfer of Near Earth Resources) is based on mining an asteroid and transporting raw materials back to Earth. The asteroid explorer/sample return mission is designed in the context of both scenarios and is the first phase of a long range plan for humans to utilize asteroid resources. Project STONER is divided into two parts: asteroid selection and explorer spacecraft design. The spacecraft design team is responsible for the selection and integration of the subsystems: GNC, communications, automation, propulsion, power, structures, thermal systems, scientific instruments, and mechanisms used on the surface to retrieve and store asteroid regolith. The sample return mission scenario consists of eight primary phases that are critical to the mission

Clock-Comparison Tests of Lorentz and CPT Symmetry in Space

Clock-comparison experiments conducted in space can provide access to many unmeasured coefficients for Lorentz and CPT violation. The orbital configuration of a satellite platform and the relatively large velocities attainable in a deep-space mission would permit a broad range of tests with Planck-scale sensitivity.Comment: 4 page

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

Identification of an Allosteric Small-Molecule Inhibitor Selective for the Inducible Form of Heat Shock Protein 70

Inducible Hsp70 (Hsp70i) is overexpressed in a wide spectrum of human tumors and its expression correlates with metastasis, poor outcomes, and resistance to chemotherapy in patients. Identification of small molecule inhibitors selective for Hsp70i could provide new therapeutic tools for cancer treatment. In this work, we used fluorescence-linked enzyme chemoproteomic strategy (FLECS) to identify HS-72, an allosteric inhibitor selective for Hsp70i. HS-72 displays the hallmarks of Hsp70 inhibition in cells, promoting substrate protein degradation and growth inhibition. Importantly, HS-72 is selective for Hsp70i over the closely related constitutively active Hsc70. Studies with purified protein show HS-72 acts as an allosteric inhibitor, reducing ATP affinity. In vivo HS-72 is well-tolerated, showing bioavailability and efficacy, inhibiting tumor growth and promoting survival in a HER2+ model of breast cancer. The HS-72 scaffold is amenable to resynthesis and iteration, suggesting an ideal starting point for a new generation of anticancer therapeutics targeting Hsp70i