What Has Carbamazepine Taught Crystal Engineers?

The antiepilepsy drug carbamazepine is one of the most studied pharmaceuticals in the world. The rich story of its solid forms, cocrystals, and formulation is a microcosm of the topical world of pharmaceutical materials. Understanding carbamazepine has required time, money, and dedication from numerous researchers and pharmaceutical companies worldwide. This wealth of knowledge provides the opportunity to reflect on progress within the crystal engineering field in general. This Perspective covers the extensive solid form landscape of carbamazepine and applies these examples to discuss and answer fundamental questions in the discipline. The story encompasses screening methods, computational solid form discovery, the power and influence of crystal engineering in understanding and controlling crystals and the amorphous state, and the environmental legacy of modern pharmaceuticals. This broad but in-depth analysis of carbamazepine is a vehicle into modern crystal engineering, not only in its own right but across the spectrum of organic materials science and pharmaceutical formulation. Discoveries of carbamazepine demonstrate the potential richness in the materials chemistry of every drug

Pre-integrated structures for Space Station Freedom

An in-space construction (erectable) approach to assembling Freedom is planned but the increasing complexity of the station design along with a decrease in shuttle capability over the past several years has led to an assembly sequence that requires more resources (EVA, lift, volume) than the shuttle can provide given a fixed number of flights. One way to address these issues is to adopt a pre-integrated approach to assembling Freedom. A pre-integrated approach combines station primary structure and distributed systems into discrete sections that are assembled and checked out on the ground. The section is then launched as a single structural entity on the shuttle and attached to the orbiting station is then launched as a single structural entity on the shuttle and attached to the orbiting station with a minimum of EVA. The feasibility of a pre-integrated approach to assembling Freedon is discussed. The structural configuration, packaging, and shuttle integration of discrete pre-integrated elements for Freedom assembly are discussed. It is shown that the pre-integrated approach to assembly reduces EVA and increases shuttle margin with respect to mass, volume, and center of gravity limits when compared to the baseline Freedom assembly sequence

Identifying Verticillium dahliae resistance in strawberry through disease screening of multiple populations and image based phenotyping

© 2019 Cockerton, Li, Vickerstaff, Eyre, Sargent, Armitage, Marina-Montes, Garcia-Cruz, Passey, Simpson and Harrison. Verticillium dahliae is a highly detrimental pathogen of soil cultivated strawberry (Fragaria x ananassa). Breeding of Verticillium wilt resistance into commercially viable strawberry cultivars can help mitigate the impact of the disease. In this study we describe novel sources of resistance identified in multiple strawberry populations, creating a wealth of data for breeders to exploit. Pathogen-informed experiments have allowed the differentiation of subclade-specific resistance responses, through studying V. dahliae subclade II-1 specific resistance in the cultivar “Redgauntlet” and subclade II-2 specific resistance in “Fenella” and “Chandler.” A large-scale low-cost phenotyping platform was developed utilizing automated unmanned vehicles and near infrared imaging cameras to assess field-based disease trials. The images were used to calculate disease susceptibility for infected plants through the normalized difference vegetation index score. The automated disease scores showed a strong correlation with the manual scores. A co-dominant resistant QTL; FaRVd3D, present in both “Redgauntlet” and “Hapil” cultivars exhibited a major effect of 18.3% when the two resistance alleles were combined. Another allele, FaRVd5D, identified in the “Emily” cultivar was associated with an increase in Verticillium wilt susceptibility of 17.2%, though whether this allele truly represents a susceptibility factor requires further research, due to the nature of the F1 mapping population. Markers identified in populations were validated across a set of 92 accessions to determine whether they remained closely linked to resistance genes in the wider germplasm. The resistant markers FaRVd2B from “Redgauntlet” and FaRVd6D from “Chandler” were associated with resistance across the wider germplasm. Furthermore, comparison of imaging versus manual phenotyping revealed the automated platform could identify three out of four disease resistance markers. As such, this automated wilt disease phenotyping platform is considered to be a good, time saving, substitute for manual assessment

An introduction to Graph Data Management

A graph database is a database where the data structures for the schema and/or instances are modeled as a (labeled)(directed) graph or generalizations of it, and where querying is expressed by graph-oriented operations and type constructors. In this article we present the basic notions of graph databases, give an historical overview of its main development, and study the main current systems that implement them

tRNA is a new target for cleavage by a MazF toxin

Toxin-antitoxin (TA) systems play key roles in bacterial persistence, biofilm formation and stress responses. The MazF toxin from the Escherichia coli mazEF TA system is a sequence- and single-strand-specific endoribonuclease, and many studies have led to the proposal that MazF family members exclusively target mRNA. However, recent data indicate some MazF toxins can cleave specific sites within rRNA in concert with mRNA. In this report, we identified the repertoire of RNAs cleaved by Mycobacterium tuberculosis toxin MazF-mt9 using an RNA-seq-based approach. This analysis revealed that two tRNAs were the principal targets of MazF-mt9, and each was cleaved at a single site in either the tRNAPro14 D-loop or within the tRNALys43 anticodon. This highly selective target discrimination occurs through recognition of not only sequence but also structural determinants. Thus, MazF-mt9 represents the only MazF family member known to target tRNA and to require RNA structure for recognition and cleavage. Interestingly, the tRNase activity of MazF-mt9 mirrors basic features of eukaryotic tRNases that also generate stable tRNA-derived fragments that can inhibit translation in response to stress. Our data also suggest a role for tRNA distinct from its canonical adapter function in translation, as cleavage of tRNAs by MazF-mt9 downregulates bacterial growth

The HST/ACS Coma Cluster Survey. II. Data Description and Source Catalogs

The Coma cluster was the target of a HST-ACS Treasury program designed for deep imaging in the F475W and F814W passbands. Although our survey was interrupted by the ACS instrument failure in 2007, the partially completed survey still covers ~50% of the core high-density region in Coma. Observations were performed for 25 fields that extend over a wide range of cluster-centric radii (~1.75 Mpc) with a total coverage area of 274 arcmin^2. The majority of the fields are located near the core region of Coma (19/25 pointings) with six additional fields in the south-west region of the cluster. In this paper we present reprocessed images and SExtractor source catalogs for our survey fields, including a detailed description of the methodology used for object detection and photometry, the subtraction of bright galaxies to measure faint underlying objects, and the use of simulations to assess the photometric accuracy and completeness of our catalogs. We also use simulations to perform aperture corrections for the SExtractor Kron magnitudes based only on the measured source flux and half-light radius. We have performed photometry for ~73,000 unique objects; one-half of our detections are brighter than the 10-sigma point-source detection limit at F814W=25.8 mag (AB). The slight majority of objects (60%) are unresolved or only marginally resolved by ACS. We estimate that Coma members are 5-10% of all source detections, which consist of a large population of unresolved objects (primarily GCs but also UCDs) and a wide variety of extended galaxies from a cD galaxy to dwarf LSB galaxies. The red sequence of Coma member galaxies has a constant slope and dispersion across 9 magnitudes (-21<M_F814W<-13). The initial data release for the HST-ACS Coma Treasury program was made available to the public in 2008 August. The images and catalogs described in this study relate to our second data release.Comment: Accepted for publication in ApJS. A high-resolution version is available at http://archdev.stsci.edu/pub/hlsp/coma/release2/PaperII.pd