Rapid quantification of low level polymorph content in a solid dose form using transmission Raman spectroscopy

This proof of concept study demonstrates the application of transmission Raman spectroscopy (TRS) to the non-invasive and non-destructive quantification of low levels (0.62-1.32% w/w) of an active pharmaceutical ingredient's polymorphic forms in a pharmaceutical formulation. Partial least squares calibration models were validated with independent validation samples resulting in prediction RMSEP values of 0.03-0.05% w/w and a limit of detection of 0.1-0.2% w/w. The study further demonstrates the ability of TRS to quantify all tablet constituents in one single measurement. By analysis of degraded stability samples, sole transformation between polymorphic forms was observed while excipient levels remained constant. Additionally, a beam enhancer device was used to enhance laser coupling to the sample, which allowed comparable prediction performance at 60 times faster rates (0.2 s) than in standard mode

The illustris simulation: Public data release

We present the full public release of all data from the Illustris simulation project. Illustris is a suite of large volume, cosmological hydrodynamical simulations run with the moving-mesh code Arepo and including a comprehensive set of physical models critical for following the formation and evolution of galaxies across cosmic time. Each simulates a volume of (106.5 Mpc)3and self-consistently evolves five different types of resolution elements from a starting redshift of z=127 to the present day, z=0. These components are: dark matter particles, gas cells, passive gas tracers, stars and stellar wind particles, and supermassive black holes. This data release includes the snapshots at all 136 available redshifts, halo and subhalo catalogs at each snapshot, and two distinct merger trees. Six primary realizations of the Illustris volume are released, including the flagship Illustris-1 run. These include three resolution levels with the fiducial "full" baryonic physics model, and a dark matter only analog for each. In addition, we provide four distinct, high time resolution, smaller volume "subboxes". The total data volume is ~265 TB, including ~800 full volume snapshots and ~30,000 subbox snapshots. We describe the released data products as well as tools we have developed for their analysis. All data may be directly downloaded in its native HDF5 format. Additionally, we release a comprehensive, web-based API which allows programmatic access to search and data processing tasks. In both cases we provide example scripts and a getting-started guide in several languages: currently, IDL, Python, and Matlab. This paper addresses scientific issues relevant for the interpretation of the simulations, serves as a pointer to published and on-line documentation of the project, describes planned future additional data releases, and discusses technical aspects of the release

‘New and important careers’: how women excelled at the BBC, 1923–1939

From its beginnings in 1923, the BBC employed a sizeable female workforce. The majority were in support roles as typists, secretaries and clerks but, during the 1920s and 1930s, a significant number held important posts. As a modern industry, the BBC took a largely progressive approach towards the ‘career women’ on its staff, many of whom were in jobs that were developed specifically for the new medium of broadcasting. Women worked as drama producers, advertising representatives and Children’s Hour Organisers. They were talent spotters, press officers and documentary makers. Three women attained Director status while others held significant administrative positions. This article considers in what ways it was the modernity and novelty of broadcasting, combined with changing employment possibilities and attitudes towards women evident after the First World War, that combined to create the conditions in which they could excel

A randomised clinical study to determine the effect of a toothpaste containing enzymes and proteins on plaque oral microbiome ecology

The numerous species that make up the oral microbiome are now understood to play a key role in establishment and maintenance of oral health. The ability to taxonomically identify community members at the species level is important to elucidating its diversity and association to health and disease. We report the overall ecological effects of using a toothpaste containing enzymes and proteins compared to a control toothpaste on the plaque microbiome. The results reported here demonstrate that a toothpaste containing enzymes and proteins can augment natural salivary defences to promote an overall community shift resulting in an increase in bacteria associated with gum health and a concomitant decrease in those associated with periodontal disease. Statistical analysis shows significant increases in 12 taxa associated with gum health including Neisseria spp. and a significant decrease in 10 taxa associated with periodontal disease including Treponema spp. The results demonstrate that a toothpaste containing enzymes and proteins can significantly shift the ecology of the oral microbiome (at species level) resulting in a community with a stronger association to health

Flexible prey handling, preference and a novel capture technique in invasive, sub-adult Chinese mitten crabs

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The attached file is the published version of the article

Design and Synthesis of High Affinity Inhibitors of Plasmodium falciparum and Plasmodium vivax N-Myristoyltransferases Directed by Ligand Efficiency Dependent Lipophilicity (LELP)

N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both Plasmodium falciparum and P. vivax NMT and displays activity in vivo against a rodent malaria model. Here we describe the discovery of 34c through optimization of a previously described series. Development, guided by targeting a ligand efficiency dependent lipophilicity (LELP) score of less than 10, yielded a 100-fold increase in enzyme affinity and a 100-fold drop in lipophilicity with the addition of only two heavy atoms. 34c was found to be equipotent on chloroquine-sensitive and -resistant cell lines and on both blood and liver stage forms of the parasite. These data further validate NMT as an exciting drug target in malaria and support 34c as an attractive tool for further optimization

Coral Reef Fish Rapidly Learn to Identify Multiple Unknown Predators upon Recruitment to the Reef

Organisms often undergo shifts in habitats as their requirements change with ontogeny

Bacterial community development in experimental gingivitis.

Current knowledge of the microbial composition of dental plaque in early gingivitis is based largely on microscopy and cultural methods, which do not provide a comprehensive description of oral microbial communities. This study used 454-pyrosequencing of the V1-V3 region of 16S rRNA genes (approximately 500 bp), and bacterial culture, to characterize the composition of plaque during the transition from periodontal health to gingivitis. A total of 20 healthy volunteers abstained from oral hygiene for two weeks, allowing plaque to accumulate and gingivitis to develop. Plaque samples were analyzed at baseline, and after one and two weeks. In addition, plaque samples from 20 chronic periodontitis patients were analyzed for cross-sectional comparison to the experimental gingivitis cohort. All of the healthy volunteers developed gingivitis after two weeks. Pyrosequencing yielded a final total of 344,267 sequences after filtering, with a mean length of 354 bases, that were clustered into an average of 299 species-level Operational Taxonomic Units (OTUs) per sample. Principal coordinates analysis (PCoA) plots revealed significant shifts in the bacterial community structure of plaque as gingivitis was induced, and community diversity increased significantly after two weeks. Changes in the relative abundance of OTUs during the transition from health to gingivitis were correlated to bleeding on probing (BoP) scores and resulted in the identification of new health- and gingivitis-associated taxa. Comparison of the healthy volunteers to the periodontitis patients also confirmed the association of a number of putative periodontal pathogens with chronic periodontitis. Taxa associated with gingivitis included Fusobacterium nucleatum subsp. polymorphum, Lachnospiraceae [G-2] sp. HOT100, Lautropia sp. HOTA94, and Prevotella oulorum, whilst Rothia dentocariosa was associated with periodontal health. Further study of these taxa is warranted and may lead to new therapeutic approaches to prevent periodontal disease.BBSRC Industrial Case Studentship ref no. BB/G01714X/1 in collaboration with GlaxoSmithKline

Chemical Tagging in the Sdss-Iii/Apogee Survey: New Identifications of Halo Stars with Globular Cluster Origins

We present new identifications of five red giant stars in the Galactic halo with chemical abundance patterns that indicate they originally formed in globular clusters. Using data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) Survey available through Sloan Digital Sky Survey (SDSS) Data Release 12, we first identify likely halo giants, and then search those for the well-known chemical tags associated with globular clusters, specifically enrichment in nitrogen and aluminum. We find that 2% of the halo giants in our sample have this chemical signature, in agreement with previous results. Following the interpretation in our previous work on this topic, this would imply that at least 13% of halo stars originally formed in globular clusters. Recent developments in the theoretical understanding of globular cluster formation raise questions about that interpretation, and we concede the possibility that these migrants represent a small fraction of the halo field. There are roughly as many stars with the chemical tags of globular clusters in the halo field as there are in globular clusters, whether or not they are accompanied by a much larger chemically untaggable population of former globular cluster stars