Rapid Quantification of Molecular Diversity for Selective Database Acquisition

There is an increasing need to expand the structural diversity of the molecules investigated in lead-discovery programs. One way in which this can be achieved is by acquiring external datasets that will enhance an existing database. This paper describes a rapid procedure for the selection of external datasets using a measure of structural diversity that is calculated from sums of pairwise intermolecular structural similarities

Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer.

Functional redundancy shared by paralog genes may afford protection against genetic perturbations, but it can also result in genetic vulnerabilities due to mutual interdependency1-5. Here, we surveyed genome-scale short hairpin RNA and CRISPR screening data on hundreds of cancer cell lines and identified MAGOH and MAGOHB, core members of the splicing-dependent exon junction complex, as top-ranked paralog dependencies6-8. MAGOHB is the top gene dependency in cells with hemizygous MAGOH deletion, a pervasive genetic event that frequently occurs due to chromosome 1p loss. Inhibition of MAGOHB in a MAGOH-deleted context compromises viability by globally perturbing alternative splicing and RNA surveillance. Dependency on IPO13, an importin-β receptor that mediates nuclear import of the MAGOH/B-Y14 heterodimer9, is highly correlated with dependency on both MAGOH and MAGOHB. Both MAGOHB and IPO13 represent dependencies in murine xenografts with hemizygous MAGOH deletion. Our results identify MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types and suggest a rationale for targeting the MAGOHB-IPO13 axis in cancers with chromosome 1p deletion

Instrumental performance and results from testing of the BLAST-TNG receiver, submillimeter optics, and MKID arrays

Polarized thermal emission from interstellar dust grains can be used to map magnetic fields in star forming molecular clouds and the diffuse interstellar medium (ISM). The Balloon-borne Large Aperture Submillimeter Telescope for Polarimetry (BLASTPol) flew from Antarctica in 2010 and 2012 and produced degree-scale polarization maps of several nearby molecular clouds with arcminute resolution. The success of BLASTPol has motivated a next-generation instrument, BLAST-TNG, which will use more than 3000 linear polarization sensitive microwave kinetic inductance detectors (MKIDs) combined with a 2.5m diameter carbon fiber primary mirror to make diffraction-limited observations at 250, 350, and 500 $\mu$m. With 16 times the mapping speed of BLASTPol, sub-arcminute resolution, and a longer flight time, BLAST-TNG will be able to examine nearby molecular clouds and the diffuse galactic dust polarization spectrum in unprecedented detail. The 250 $\mu$m detector array has been integrated into the new cryogenic receiver, and is undergoing testing to establish the optical and polarization characteristics of the instrument. BLAST-TNG will demonstrate the effectiveness of kilo-pixel MKID arrays for applications in submillimeter astronomy. BLAST-TNG is scheduled to fly from Antarctica in December 2017 for 28 days and will be the first balloon-borne telescope to offer a quarter of the flight for "shared risk" observing by the community.Comment: Presented at SPIE Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy VIII, June 29th, 201

Visible-light-induced intramolecular charge transfer in the radical spirocyclisation of indole-tethered ynones

Indole-tethered ynones form an intramolecular electron donor-acceptor complex that can undergo visible-light-induced charge transfer to promote thiyl radical generation from thiols. This initiates a novel radical chain sequence, based on dearomatising spirocyclisation with concomitant C-S bond formation. Sulfur-containing spirocycles are formed in high yields using this simple and mild synthetic protocol, in which neither transition metal catalysts nor photocatalysts are required. The proposed mechanism is supported by various mechanistic studies, and the unusual radical initiation mode represents only the second report of the use of an intramolecular electron donor-acceptor complex in synthesis

Chromosomal assembly of the nuclear genome of the endosymbiontbearing trypanosomatid Angomonas deanei

Abstract Angomonas deaneiA. deane

Making Connections - Envisioning Springfield\u27s North End

This work explores a service learning strategy in the context of the senior Urban Design Studio taught in the Department of Landscape Architecture and Regional Planning at the University of Massachusetts Amherst. The primary goal of this project is to stimulate a conversation in the neighborhoods of the North End, to develop green design strategies, to improve services and businesses for residents and the employees of local businesses, and to foster cultural engagement and interaction in the North End that will enhance the vibrancy, resilience, and quality of life of this urban community. Making connections - Envisioning Springfield\u27s North End proposes improved connectivity in a physical, cultural, and social sense will be key to attaining these goals and to engaging and synergizing individuals and community groups in the North End - residents, businesses, schools, churches, employers, and employees. Six sustainable learning and planning principles have emerged from this studio: 1. Input and interaction – Visioning workshops connect campus and community 2. Community-building art - Expression of place and people 3. Healthy living - Urban agriculture and education 4. Urban greenways – Abandoned railways and urban rivers and streams 5. Green infrastructure - Green streets as networks and structural framework 6. Sustainable urban form – Mixed use and pedestrian friendly neighborhood