Optimization of hCFTR lung expression in mice using DNA nanoparticles.

Efficient and prolonged human cystic fibrosis transmembrane conductance regulator (hCFTR) expression is a major goal for cystic fibrosis (CF) lung therapy. A hCFTR expression plasmid was optimized as a payload for compacted DNA nanoparticles formulated with polyethylene glycol (PEG)-substituted 30-mer lysine peptides. A codon-optimized and CpG-reduced hCFTR synthetic gene (CO-CFTR) was placed in a polyubiquitin C expression plasmid. Compared to hCFTR complementary DNA (cDNA), CO-CFTR produced a ninefold increased level of hCFTR protein in transfected HEK293 cells and, when compacted as DNA nanoparticles, produced a similar improvement in lung mRNA expression in Balb/c and fatty acid binding protein promoter (FABP) CF mice, although expression duration was transient. Various vector modifications were tested to extend duration of CO-CFTR expression. A novel prolonged expression (PE) element derived from the bovine growth hormone (BGH) gene 3' flanking sequence produced prolonged expression of CO-CFTR mRNA at biologically relevant levels. A time course study in the mouse lung revealed that CO-CFTR mRNA did not change significantly, with CO-CFTR/mCFTR geometric mean ratios of 94% on day 2, 71% on day 14, 53% on day 30, and 14% on day 59. Prolonged CO-CFTR expression is dependent on the orientation of the PE element and its transcription, is not specific to the UbC promoter, and is less dependent on other vector backbone elements.

The Rural Household Multiple Indicator Survey, data from 13,310 farm households in 21 countries.

The Rural Household Multiple Indicator Survey (RHoMIS) is a standardized farm household survey approach which collects information on 758 variables covering household demographics, farm area, crops grown and their production, livestock holdings and their production, agricultural product use and variables underlying standard socio-economic and food security indicators such as the Probability of Poverty Index, the Household Food Insecurity Access Scale, and household dietary diversity. These variables are used to quantify more than 40 different indicators on farm and household characteristics, welfare, productivity, and economic performance. Between 2015 and the beginning of 2018, the survey instrument was applied in 21 countries in Central America, sub-Saharan Africa and Asia. The data presented here include the raw survey response data, the indicator calculation code, and the resulting indicator values. These data can be used to quantify on- and off-farm pathways to food security, diverse diets, and changes in poverty for rural smallholder farm households.

Mining chemical information from open patents.

Linked Open Data presents an opportunity to vastly improve the quality of science in all fields by increasing the availability and usability of the data upon which it is based. In the chemical field, there is a huge amount of information available in the published literature, the vast majority of which is not available in machine-understandable formats. PatentEye, a prototype system for the extraction and semantification of chemical reactions from the patent literature has been implemented and is discussed. A total of 4444 reactions were extracted from 667 patent documents that comprised 10 weeks' worth of publications from the European Patent Office (EPO), with a precision of 78% and recall of 64% with regards to determining the identity and amount of reactants employed and an accuracy of 92% with regards to product identification. NMR spectra reported as product characterisation data are additionally captured.

The semantic architecture of the World-Wide Molecular Matrix (WWMM).

The World-Wide Molecular Matrix (WWMM) is a ten year project to create a peer-to-peer (P2P) system for the publication and collection of chemical objects, including over 250, 000 molecules. It has now been instantiated in a number of repositories which include data encoded in Chemical Markup Language (CML) and linked by URIs and RDF. The technical specification and implementation is now complete. We discuss the types of architecture required to implement nodes in the WWMM and consider the social issues involved in adoption.

The semantics of Chemical Markup Language (CML): dictionaries and conventions.

The semantic architecture of CML consists of conventions, dictionaries and units. The conventions conform to a top-level specification and each convention can constrain compliant documents through machine-processing (validation). Dictionaries conform to a dictionary specification which also imposes machine validation on the dictionaries. Each dictionary can also be used to validate data in a CML document, and provide human-readable descriptions. An additional set of conventions and dictionaries are used to support scientific units. All conventions, dictionaries and dictionary elements are identifiable and addressable through unique URIs.

The Quixote project: Collaborative and Open Quantum Chemistry data management in the Internet age.

Computational Quantum Chemistry has developed into a powerful, efficient, reliable and increasingly routine tool for exploring the structure and properties of small to medium sized molecules. Many thousands of calculations are performed every day, some offering results which approach experimental accuracy. However, in contrast to other disciplines, such as crystallography, or bioinformatics, where standard formats and well-known, unified databases exist, this QC data is generally destined to remain locally held in files which are not designed to be machine-readable. Only a very small subset of these results will become accessible to the wider community through publication.In this paper we describe how the Quixote Project is developing the infrastructure required to convert output from a number of different molecular quantum chemistry packages to a common semantically rich, machine-readable format and to build respositories of QC results. Such an infrastructure offers benefits at many levels. The standardised representation of the results will facilitate software interoperability, for example making it easier for analysis tools to take data from different QC packages, and will also help with archival and deposition of results. The repository infrastructure, which is lightweight and built using Open software components, can be implemented at individual researcher, project, organisation or community level, offering the exciting possibility that in future many of these QC results can be made publically available, to be searched and interpreted just as crystallography and bioinformatics results are today.Although we believe that quantum chemists will appreciate the contribution the Quixote infrastructure can make to the organisation and and exchange of their results, we anticipate that greater rewards will come from enabling their results to be consumed by a wider community. As the respositories grow they will become a valuable source of chemical data for use by other disciplines in both research and education.The Quixote project is unconventional in that the infrastructure is being implemented in advance of a full definition of the data model which will eventually underpin it. We believe that a working system which offers real value to researchers based on tools and shared, searchable repositories will encourage early participation from a broader community, including both producers and consumers of data. In the early stages, searching and indexing can be performed on the chemical subject of the calculations, and well defined calculation meta-data. The process of defining more specific quantum chemical definitions, adding them to dictionaries and extracting them consistently from the results of the various software packages can then proceed in an incremental manner, adding additional value at each stage.Not only will these results help to change the data management model in the field of Quantum Chemistry, but the methodology can be applied to other pressing problems related to data in computational and experimental science.

OSCAR4: a flexible architecture for chemical text-mining.

The Open-Source Chemistry Analysis Routines (OSCAR) software, a toolkit for the recognition of named entities and data in chemistry publications, has been developed since 2002. Recent work has resulted in the separation of the core OSCAR functionality and its release as the OSCAR4 library. This library features a modular API (based on reduction of surface coupling) that permits client programmers to easily incorporate it into external applications. OSCAR4 offers a domain-independent architecture upon which chemistry specific text-mining tools can be built, and its development and usage are discussed.

Ami - The chemist's amanuensis.

The Ami project was a six month Rapid Innovation project sponsored by JISC to explore the Virtual Research Environment space. The project brainstormed with chemists and decided to investigate ways to facilitate monitoring and collection of experimental data.A frequently encountered use-case was identified of how the chemist reaches the end of an experiment, but finds an unexpected result. The ability to replay events can significantly help make sense of how things progressed. The project therefore concentrated on collecting a variety of dimensions of ancillary data - data that would not normally be collected due to practicality constraints. There were three main areas of investigation: 1) Development of a monitoring tool using infrared and ultrasonic sensors; 2) Time-lapse motion video capture (for example, videoing 5 seconds in every 60); and 3) Activity-driven video monitoring of the fume cupboard environs.The Ami client application was developed to control these separate logging functions. The application builds up a timeline of the events in the experiment and around the fume cupboard. The videos and data logs can then be reviewed after the experiment in order to help the chemist determine the exact timings and conditions used.The project experimented with ways in which a Microsoft Kinect could be used in a laboratory setting. Investigations suggest that it would not be an ideal device for controlling a mouse, but it shows promise for usages such as manipulating virtual molecules.

Chapter 9 Molecular Similarity: Advances in Methods, Applications and Validations in Virtual Screening and QSAR.

This chapter discusses recent developments in some of the areas that exploit the molecular similarity principle, novel approaches to capture molecular properties by the use of novel descriptors, focuses on a crucial aspect of computational models-their validity, and discusses additional ways to examine data available, such as those from high-throughput screening (HTS) campaigns and to gain more knowledge from this data. The chapter also presents some of the recent applications of methods discussed focusing on the successes of virtual screening applications, database clustering and comparisons (such as drug- and in-house-likeness), and the recent large-scale validations of docking and scoring programs. While a great number of descriptors and modeling methods has been proposed until today, the recent trend toward proper model validation is very much appreciated. Although some of their limitations are surely because of underlying principles and limitations of fundamental concepts, others will certainly be eliminated in the future.

Chemical documents: machine understanding and automated information extraction.

Automatically extracting chemical information from documents is a challenging task, but an essential one for dealing with the vast quantity of data that is available. The task is least difficult for structured documents, such as chemistry department web pages or the output of computational chemistry programs, but requires increasingly sophisticated approaches for less structured documents, such as chemical papers. The identification of key units of information, such as chemical names, makes the extraction of useful information from unstructured documents possible.