Chemoinformatics Research at the University of Sheffield: A History and Citation Analysis

This paper reviews the work of the Chemoinformatics Research Group in the Department of Information Studies at the University of Sheffield, focusing particularly on the work carried out in the period 1985-2002. Four major research areas are discussed, these involving the development of methods for: substructure searching in databases of three-dimensional structures, including both rigid and flexible molecules; the representation and searching of the Markush structures that occur in chemical patents; similarity searching in databases of both two-dimensional and three-dimensional structures; and compound selection and the design of combinatorial libraries. An analysis of citations to 321 publications from the Group shows that it attracted a total of 3725 residual citations during the period 1980-2002. These citations appeared in 411 different journals, and involved 910 different citing organizations from 54 different countries, thus demonstrating the widespread impact of the Group's work

Equalities in Scotland’s Growth Economic Sectors: Final Report

Aims The purpose of the study was to examine equality issues in Scotland’s growth sectors since baseline research carried out in 2009, focusing on trends in the following protected characteristics: gender; age; disabilities; ethnic minorities; gender reassignment; marital and civil partnership status; maternity and pregnancy; religion and belief; and sexual orientation. Scotland’s growth sectors are identified as: creative industries; energy; financial and business services; food and drink; life sciences; tourism; universities; chemical sciences; construction; engineering; and ICT and digital technologies. Methods The methodology primarily consisted of analysis of a range of datasets, including the Annual Population Survey, (APS) to establish the representation of individuals with protected characteristic in each growth sector; the FAME database, to establish the representation of women, young people and older people among company directors; data from Skills Development Scotland and the Scottish Funding Council on the supply of labour into the growth sectors from the protected characteristics, in terms of Modern Apprenticeship starts, college enrolments and university entrants; and key research published since 2010 on the representation of protected characteristics in the growth sectors and, where available, the factors that are driving this. Information was also collated from a small number of organisations that work with individuals with protected characteristics in order to supplement the desk-based research where there was no or limited data or literature available. Findings The report suggests that no overarching trends can be identified. The representation of individuals with some protected characteristics in the workforce is increasing, but it is declining for others. It also indicates mixed findings on a sector-by-sector basis, with sectors often making progress on the representation of some equalities groups within their workforce whilst experiencing a decline in others. The recession is highlighted as a key factor as, due to the issues faced by many protected characteristics in relation to the labour market, groups such as young people, disabled people and ethnic minorities have experienced disproportionate decreases in employment and increases in unemployment. The creative industries was found to be the sector that is most open to individuals with protected characteristics, while, with the exception of older workers, all groups were found to be underrepresented in the energy sector. Recommendations The report notes that, as the representation of individuals from equalities groups varies across growth sectors, there is a need to customise responses by sector. It is also suggested that in order that individuals from protected characteristics are able to access the good quality employment opportunities that the growth sectors offer, efforts must be made to tackle underrepresentation where it exists and that a key element of this must be to ensure better representation of individuals with protected characteristics on Modern Apprenticeships, and on college or university courses, that lead to careers in these sectors. The report argues that increasing the representation of protected characteristics within the sector is not sufficient, however, and efforts must also be deployed to tackling pay gaps, occupational segregation and the lack of progression into management and leadership roles

Similarity-based data mining in files of two-dimensional chemical structures using fingerprint measures of molecular resemblance

This paper reviews the use of measures of intermolecular similarity for processing databases of chemical structures, which play an important role in the discovery of new drugs by the pharmaceutical industry. The similarity measures considered here are based on the use of a fingerprint representation of molecular structure, where a fingerprint is a vector encoding the presence of fragment substructures in a molecule and where the similarity between pairs of such fingerprints is computed using an association coefficient such as the Tanimoto coefficient. The Similar Property Principle provides the basic rationale for the use of similarity methods in three important chemoinformatics applications—similarity searching, database clustering, and molecular diversity analysis. Similarity searching enables the identification of those molecules in a database that are most similar to a user-defined, biologically active query molecule, with data fusion providing an effective way of combining the results of multiple similarity searches. Cluster analysis, typically using the Jarvis–Patrick, Ward, or divisive k-means clustering methods, enables the cost-effective selection of molecules for biological testing, for property prediction and for investigating database overlap. Molecular diversity analysis, typically using cluster-based, dissimilarity-based, or optimization-based approaches, enables the identification of structurally diverse sets of molecules, so as to ensure that the full chemical space spanned by a database is tested in the search for novel bioactive molecules. © 2011 John Wiley & Sons, Inc. WIREs Data Mining Knowl Discov 2011 1 241–251 DOI: 10.1002/widm.2

The use of heat and chemical penetration enhancers to increase the follicular delivery of erythromycin to the skin

Copyright © 2019. Published by Elsevier B.V.The effect of heat on the follicular absorption of drugs into the skin has not previously been investigated. In comparison to drug delivery across the continuous stratum corneum (SC), follicular absorption is known to be relatively rapid and therefore the use of short durations of heat may be particularly useful for enhancing drug delivery to the hair follicles, as well as being practical for patients to use. In this study erythromycin has been used as a model drug and the combined use of heat and chemical penetration enhancers was found to be able to synergistically increase the penetration of erythromycin into human skin via the follicular route. Moreover durations of heat application as short as 10 min in combination with particular enhancer systems were found to be sufficient to significantly increase erythromycin delivery to the skin. Overall the data indicate that the use of heat with chemical penetration enhancers offers a potentially valuable strategy for delivering drugs via the follicular route.Peer reviewedFinal Accepted Versio

In-vitro antioxidant and anti-inflamatory activities of Pituranthos chloranthus and Artemisia vulgaris from Tunisia

Pituranthos chloranthus and Artemisia vulgaris L. are two of the most important aromatic and medicinal species from the Apiaceae and Asteraceae families, respectively. They are traditionally used in certain pathologies in which inflammatory processes are involved. The present study investigates the potential of aqueous extracts of Tunisian P. chloranthus and A. vulgaris as a natural alternative source of antioxidant and anti-inflammatory activities using in-vitro techniques. The antioxidant activities of aqueous extracts were evaluated through several assays: capacity for scavenging free radicals (ABTS, DPPH, hydroxyl, superoxide, nitric oxide); and total antioxidant capacity by ferric reducing power activity and inhibition of lipid peroxidation by thiobarbituric acid reactive species (TBARS) method. The anti-inflammatory activity was evaluated through the lipoxygenase (LOX) inhibitory activity. P. chloranthos aqueous extract presented higher concentration of total phenols than A. vulgaris extract, nevertheless higher capacity for scavenging ABTS, superoxide, hydroxyl. and NO free radicals. In the presence of liver homogenate, both extracts had poorer antioxidant activity than in the remaining lipid substrates. P. chloranthos extract had a higher ability for inhibiting lipoxygenase twice higher than A. vulgaris, while it had lower capacity for reducing Fe3+ than P. chloranthos extract. Our results suggest that there are differences of antioxidant activity between both samples, but also the strength for inhibiting the oxidation is highly dependent on the method used.info:eu-repo/semantics/publishedVersio

S = 3 Ground State for a Tetranuclear Mn^(IV)₄O₄ Complex Mimicking the S₃ State of the Oxygen Evolving Complex

The S₃ state is currently the last observable intermediate prior to O–O bond formation at the oxygen-evolving complex (OEC) of Photosystem II, and its electronic structure has been assigned to a homovalent Mn^(IV)₄ core with an S = 3 ground state. While structural interpretations based on the EPR spectroscopic features of the S₃ state provide valuable mechanistic insight, corresponding synthetic and spectroscopic studies on tetranuclear complexes mirroring the Mn oxidation states of the S₃ state remain rare. Herein, we report the synthesis and characterization by XAS and multifrequency EPR spectroscopy of a Mn^(IV)₄O₄ cuboidal complex as a spectroscopic model of the S₃ state. Results show that this Mn^(IV)₄O₄ complex has an S = 3 ground state with isotropic ⁵⁵Mn hyperfine coupling constants of −75, −88, −91, and 66 MHz. These parameters are consistent with an αααβ spin topology approaching the trimer–monomer magnetic coupling model of pseudo-octahedral Mn^(IV) centers. Importantly, the spin ground state changes from S = 1/2 to S = 3 as the OEC is oxidized from the S₂ state to the S₃ state. This same spin state change is observed following oxidation of the previously reported Mn^(III)Mn^(IV)₃O₄ cuboidal complex to the Mn^(IV)₄O₄ complex described here. This sets a synthetic precedent for the observed low-spin to high-spin conversion in the OEC

Similarity-based virtual screening using 2D fingerprints

This paper summarises recent work at the University of Sheffield on virtual screening methods that use 2D fingerprint measures of structural similarity. A detailed comparison of a large number of similarity coefficients demonstrates that the well-known Tanimoto coefficient remains the method of choice for the computation of fingerprint-based similarity, despite possessing some inherent biases related to the sizes of the molecules that are being sought. Group fusion involves combining the results of similarity searches based on multiple reference structures and a single similarity measure. We demonstrate the effectiveness of this approach to screening, and also describe an approximate form of group fusion, turbo similarity searching, that can be used when just a single reference structure is available