PubChem3D: a new resource for scientists

<p>Abstract</p> <p>Background</p> <p>PubChem is an open repository for small molecules and their experimental biological activity. PubChem integrates and provides search, retrieval, visualization, analysis, and programmatic access tools in an effort to maximize the utility of contributed information. There are many diverse chemical structures with similar biological efficacies against targets available in PubChem that are difficult to interrelate using traditional 2-D similarity methods. A new layer called PubChem3D is added to PubChem to assist in this analysis.</p> <p>Description</p> <p>PubChem generates a 3-D conformer model description for 92.3% of all records in the PubChem Compound database (when considering the parent compound of salts). Each of these conformer models is sampled to remove redundancy, guaranteeing a minimum (non-hydrogen atom pair-wise) RMSD between conformers. A diverse conformer ordering gives a maximal description of the conformational diversity of a molecule when only a subset of available conformers is used. A pre-computed search per compound record gives immediate access to a set of 3-D similar compounds (called "Similar Conformers") in PubChem and their respective superpositions. Systematic augmentation of PubChem resources to include a 3-D layer provides users with new capabilities to search, subset, visualize, analyze, and download data.</p> <p>A series of retrospective studies help to demonstrate important connections between chemical structures and their biological function that are not obvious using 2-D similarity but are readily apparent by 3-D similarity.</p> <p>Conclusions</p> <p>The addition of PubChem3D to the existing contents of PubChem is a considerable achievement, given the scope, scale, and the fact that the resource is publicly accessible and free. With the ability to uncover latent structure-activity relationships of chemical structures, while complementing 2-D similarity analysis approaches, PubChem3D represents a new resource for scientists to exploit when exploring the biological annotations in PubChem.</p

Marine Biodiversity in South Africa: An Evaluation of Current States of Knowledge

Continental South Africa has a coastline of some 3,650 km and an Exclusive Economic Zone (EEZ) of just over 1 million km2. Waters in the EEZ extend to a depth of 5,700 m, with more than 65% deeper than 2,000 m. Despite its status as a developing nation, South Africa has a relatively strong history of marine taxonomic research and maintains comprehensive and well-curated museum collections totaling over 291,000 records. Over 3 million locality records from more than 23,000 species have been lodged in the regional AfrOBIS (African Ocean Biogeographic Information System) data center (which stores data from a wider African region). A large number of regional guides to the marine fauna and flora are also available and are listed

REDSHIFT MEASUREMENT and SPECTRAL CLASSIFICATION for eBOSS GALAXIES with the REDMONSTER SOFTWARE

We describe the redmonster automated redshift measurement and spectral classification software designed for the extended Baryon Oscillation Spectroscopic Survey (eBOSS) of the Sloan Digital Sky Survey IV (SDSS-IV). We describe the algorithms, the template standard and requirements, and the newly developed galaxy templates to be used on eBOSS spectra. We present results from testing on early data from eBOSS, where we have found a 90.5% automated redshift and spectral classification success rate for the luminous red galaxy sample (redshifts 0.6 ≲ z ≲ 1.0). The redmonster performance meets the eBOSS cosmology requirements for redshift classification and catastrophic failures and represents a significant improvement over the previous pipeline. We describe the empirical processes used to determine the optimum number of additive polynomial terms in our models and an acceptable δX2rthreshold for declaring statistical confidence. Statistical errors on redshift measurement due to photon shot noise are assessed, and we find typical values of a few tens of km s-1. An investigation of redshift differences in repeat observations scaled by error estimates yields a distribution with a Gaussian mean and standard deviation of μ ∼ 0.01 and σ ∼ 0.65, respectively, suggesting the reported statistical redshift uncertainties are over-estimated by ∼54%. We assess the effects of object magnitude, signal-to-noise ratio, fiber number, and fiber head location on the pipeline's redshift success rate. Finally, we describe directions of ongoing development

Drama as a pedagogical tool for practicing death notification-experiences from Swedish medical students

<p>Abstract</p> <p>Background</p> <p>One of the toughest tasks in any profession is the deliverance of death notification. Marathon Death is an exercise conducted during the fourth year of medical school in northern Sweden to prepare students for this responsibility. The exercise is designed to enable students to gain insight into the emotional and formal procedure of delivering death notifications. The exercise is inspired by Augusto Boal's work around Forum Theatre and is analyzed using video playback. The aim of the study was to explore reflections, attitudes and ideas toward training in delivering death notifications among medical students who participate in the Marathon Death exercise based on forum play.</p> <p>Methods</p> <p>After participation in the Marathon Death exercise, students completed semi-structured interviews. The transcribed interviews were analyzed using the principles of qualitative content analysis including a deductive content analysis approach with a structured matrix based on Bloom's taxonomy domains.</p> <p>Results</p> <p>The Marathon Death exercise was perceived as emotionally loaded, realistic and valuable for the future professional role as a physician. The deliverance of a death notification to the next of kin that a loved one has died was perceived as difficult. The exercise conjured emotions such as positive expectations and sheer anxiety. Students perceived participation in the exercise as an important learning experience, discovering that they had the capacity to manage such a difficult situation. The feedback from the video playback of the exercise and the feedback from fellow students and teachers enhanced the learning experience.</p> <p>Conclusions</p> <p>The exercise, Marathon Death, based on forum play with video playback is a useful pedagogical tool that enables students to practice delivering death notification. The ability to practice under realistic conditions contributes to reinforce students in preparation for their future professional role.</p

Solvolyses of diarylmethyl chlorides. A comprehensive stability scale for diarylcarbenium ions

Eleven donor substituted diarylmethyl chlorides have been solvolyzed in ethanol. The rate constants, determined at 25°C, and additional ethanolysis data taken from the literature have been connected with solvolvsis rate constants, determined in other solvents, to construct a stability scale for 74 diarylcarbenium ions, covering a rate range of> 1012. Correlation equations are given which allow the calculation of solvolysis rates in other solvents, of equilibrium constants, and of rate constants for reactions involving diarylcarbenium ions

Defining language impairments in a subgroup of children with autism spectrum disorder

Autism spectrum disorder (ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment (SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.M01 RR00533 - NCRR NIH HHS; R01 DC10290 - NIDCD NIH HHS; U19 DC03610 - NIDCD NIH HH

Threat-sensitive anti-predator defence in precocial wader, the northern lapwing Vanellus vanellus

Birds exhibit various forms of anti-predator behaviours to avoid reproductive failure, with mobbing—observation, approach and usually harassment of a predator—being one of the most commonly observed. Here, we investigate patterns of temporal variation in the mobbing response exhibited by a precocial species, the northern lapwing (Vanellus vanellus). We test whether brood age and self-reliance, or the perceived risk posed by various predators, affect mobbing response of lapwings. We quantified aggressive interactions between lapwings and their natural avian predators and used generalized additive models to test how timing and predator species identity are related to the mobbing response of lapwings. Lapwings diversified mobbing response within the breeding season and depending on predator species. Raven Corvus corax, hooded crow Corvus cornix and harriers evoked the strongest response, while common buzzard Buteo buteo, white stork Ciconia ciconia, black-headed gull Chroicocephalus ridibundus and rook Corvus frugilegus were less frequently attacked. Lapwings increased their mobbing response against raven, common buzzard, white stork and rook throughout the breeding season, while defence against hooded crow, harriers and black-headed gull did not exhibit clear temporal patterns. Mobbing behaviour of lapwings apparently constitutes a flexible anti-predator strategy. The anti-predator response depends on predator species, which may suggest that lapwings distinguish between predator types and match mobbing response to the perceived hazard at different stages of the breeding cycle. We conclude that a single species may exhibit various patterns of temporal variation in anti-predator defence, which may correspond with various hypotheses derived from parental investment theory

A hazard analysis method for systematic identification of safety requirements for user interface software in medical devices

© Springer International Publishing AG (outside the US) 2017. Formal methods technologies have the potential to verify the usability and safety of user interface (UI) software design in medical devices, enabling significant reductions in use errors and consequential safety incidents with such devices. This however depends on comprehensive and verifiable safety requirements to leverage these techniques for detecting and preventing flaws in UI software that can induce use errors. This paper presents a hazard analysis method that extends Leveson’s System Theoretic Process Analysis (STPA) with a comprehensive set of causal factor categories, so as to provide developers with clear guidelines for systematic identification of use-related hazards associated with medical devices, their causes embedded in UI software design, and safety requirements for mitigating such hazards. The method is evaluated with a case study on the Gantry-2 radiation therapy system, which demonstrates that (1) as compared to standard STPA, our method allowed us to identify more UI software design issues likely to cause use-related hazards; and (2) the identified UI software design issues facilitated the definition of precise, verifiable safety requirements for UI software, which could be readily formalized in verification tools such as Prototype Verification System (PVS).- U.S. Food and Drug Administration(NORTE-01-0145-FEDER-000016)Sandy Weininger (FDA), Scott Thiel (Navigant Consulting, Inc.), Michelle Jump (Stryker), Stefania Gnesi (ISTI/CNR) and the CHI+MED team (www.chi-med.ac.uk) provided useful feedback and inputs. Paolo Masci’s work is supported by the North Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement, and by the European Regional Development Fund (ERDF) within Project “NORTE-01-0145-FEDER-000016”.info:eu-repo/semantics/publishedVersio

The FIELDS Instrument Suite for Solar Probe Plus: Measuring the Coronal Plasma and Magnetic Field, Plasma Waves and Turbulence, and Radio Signatures of Solar Transients.

NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products

Fast 3D shape screening of large chemical databases through alignment-recycling

<p>Abstract</p> <p>Background</p> <p>Large chemical databases require fast, efficient, and simple ways of looking for similar structures. Although such tasks are now fairly well resolved for graph-based similarity queries, they remain an issue for 3D approaches, particularly for those based on 3D shape overlays. Inspired by a recent technique developed to compare molecular shapes, we designed a hybrid methodology, alignment-recycling, that enables efficient retrieval and alignment of structures with similar 3D shapes.</p> <p>Results</p> <p>Using a dataset of more than one million PubChem compounds of limited size (< 28 heavy atoms) and flexibility (< 6 rotatable bonds), we obtained a set of a few thousand diverse structures covering entirely the 3D shape space of the conformers of the dataset. Transformation matrices gathered from the overlays between these diverse structures and the 3D conformer dataset allowed us to drastically (100-fold) reduce the CPU time required for shape overlay. The alignment-recycling heuristic produces results consistent with <it>de novo </it>alignment calculation, with better than 80% hit list overlap on average.</p> <p>Conclusion</p> <p>Overlay-based 3D methods are computationally demanding when searching large databases. Alignment-recycling reduces the CPU time to perform shape similarity searches by breaking the alignment problem into three steps: selection of diverse shapes to describe the database shape-space; overlay of the database conformers to the diverse shapes; and non-optimized overlay of query and database conformers using common reference shapes. The precomputation, required by the first two steps, is a significant cost of the method; however, once performed, querying is two orders of magnitude faster. Extensions and variations of this methodology, for example, to handle more flexible and larger small-molecules are discussed.</p