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

Choice-free Stone duality

The standard topological representation of a Boolean algebra via the clopen sets of a Stone space requires a nonconstructive choice principle, equivalent to the Boolean Prime Ideal Theorem. In this paper, we describe a choice-free topological representation of Boolean algebras. This representation uses a subclass of the spectral spaces that Stone used in his representation of distributive lattices via compact open sets. It also takes advantage of Tarski’s observation that the regular open sets of any topological space form a Boolean algebra. We prove without choice principles that any Boolean algebra arises from a special spectral space X via the compact regular open sets of X; these sets may also be described as those that are both compact open in X and regular open in the upset topology of the specialization order of X, allowing one to apply to an arbitrary Boolean algebra simple reasoning about regular opens of a separative poset. Our representation is therefore a mix of Stone and Tarski, with the two connected by Vietoris: the relevant spectral spaces also arise as the hyperspace of nonempty closed sets of a Stone space endowed with the upper Vietoris topology. This connection makes clear the relation between our point-set topological approach to choice-free Stone duality, which may be called the hyperspace approach, and a point-free approach to choice-free Stone duality using Stone locales. Unlike Stone’s representation of Boolean algebras via Stone spaces, our choice-free topological representation of Boolean algebras does not show that every Boolean algebra can be represented as a field of sets; but like Stone’s representation, it provides the benefit of a topological perspective on Boolean algebras, only now without choice. In addition to representation, we establish a choice-free dual equivalence between the category of Boolean algebras with Boolean homomorphisms and a subcategory of the category of spectral spaces with spectral maps. We show how this duality can be used to prove some basic facts about Boolean algebras

The retroflection of part of the East Greenland Current at Cape Farewell

The East Greenland Current (EGC) and the smaller East Greenland Coastal Current (EGCC) provide the major conduit for cold fresh polar water to enter the lower latitudes of the North Atlantic. They flow equatorward through the western Irminger Basin and around Cape Farewell into the Labrador Sea. The surface circulation and transport of the Cape Farewell boundary current region in summer 2005 is described. The EGCC merges with Arctic waters of the EGC to the south of Cape Farewell, forming the West Greenland Current. The EGC transport decreases from 15.5 Sv south of Cape Farewell to 11.7 Sv in the eastern Labrador Sea (where the water becomes known as Irminger Sea Water). The decrease in EGC transport is balanced by the retroflection of a substantial proportion of the boundary current (5.1 Sv) into the central Irminger Basin; a new pathway for fresh water into the interior of the subpolar gyre

Space-Time Clustering and Correlations of Major Earthquakes

Earthquake occurrence in nature is thought to result from correlated elastic stresses, leading to clustering in space and time. We show that occurrence of major earthquakes in California correlates with time intervals when fluctuations in small earthquakes are suppressed relative to the long term average. We estimate a probability of less than 1% that this coincidence is due to random clustering.Comment: 5 pages, 3 figures. Submitted to PR

High-Efficiency MOSFET-based MMC Design for LVDC Distribution Systems

LVDC distribution networks have the potential to release larger capacity without having to upgrade the existing cables. One of the main challenges of LVDC networks is the extra customer-end DC-AC conversion stage. This paper proposes and evaluates a 5-level Si MOSFET-based MMC as a promising alternative to the conventional 2-level IGBT-based converter. This is due to the comparatively higher efficiency, power quality and reliability, and reduced EM emissions. A comprehensive analysis of a Si MOSFET 5-level MMC converter design is performed to investigate the suitability of the topology for LVDC applications. Detailed theoretical analysis of the 5-level MMC is presented, with simulated and experimental results to demonstrate circuit performance. To suppress the AC circulating current, especially the dominant 2nd harmonics, this paper presents a double line-frequency PI with orthogonal imaginary axis control method. Comparison of simulation and experimental results with those for double line-frequency PR control shows that the proposed PI controller has better performance. In addition, it is simpler to implement and more immune to sampling/discretisation errors

Is EC class predictable from reaction mechanism?

We thank the Scottish Universities Life Sciences Alliance (SULSA) and the Scottish Overseas Research Student Awards Scheme of the Scottish Funding Council (SFC) for financial support.Background: We investigate the relationships between the EC (Enzyme Commission) class, the associated chemical reaction, and the reaction mechanism by building predictive models using Support Vector Machine (SVM), Random Forest (RF) and k-Nearest Neighbours (kNN). We consider two ways of encoding the reaction mechanism in descriptors, and also three approaches that encode only the overall chemical reaction. Both cross-validation and also an external test set are used. Results: The three descriptor sets encoding overall chemical transformation perform better than the two descriptions of mechanism. SVM and RF models perform comparably well; kNN is less successful. Oxidoreductases and hydrolases are relatively well predicted by all types of descriptor; isomerases are well predicted by overall reaction descriptors but not by mechanistic ones. Conclusions: Our results suggest that pairs of similar enzyme reactions tend to proceed by different mechanisms. Oxidoreductases, hydrolases, and to some extent isomerases and ligases, have clear chemical signatures, making them easier to predict than transferases and lyases. We find evidence that isomerases as a class are notably mechanistically diverse and that their one shared property, of substrate and product being isomers, can arise in various unrelated ways. The performance of the different machine learning algorithms is in line with many cheminformatics applications, with SVM and RF being roughly equally effective. kNN is less successful, given the role that non-local information plays in successful classification. We note also that, despite a lack of clarity in the literature, EC number prediction is not a single problem; the challenge of predicting protein function from available sequence data is quite different from assigning an EC classification from a cheminformatics representation of a reaction.Publisher PDFPeer reviewe

MACiE: a database of enzyme reaction mechanisms.

SUMMARY: MACiE (mechanism, annotation and classification in enzymes) is a publicly available web-based database, held in CMLReact (an XML application), that aims to help our understanding of the evolution of enzyme catalytic mechanisms and also to create a classification system which reflects the actual chemical mechanism (catalytic steps) of an enzyme reaction, not only the overall reaction. AVAILABILITY: http://www-mitchell.ch.cam.ac.uk/macie/.EPSRC (G.L.H. and J.B.O.M.), the BBSRC (G.J.B. and J.M.T.—CASE studentship in association with Roche Products Ltd; N.M.O.B. and J.B.O.M.—grant BB/C51320X/1), the Chilean Government’s Ministerio de Planificacio´n y Cooperacio´n and Cambridge Overseas Trust (D.E.A.) for funding and Unilever for supporting the Centre for Molecular Science Informatics.application note restricted to 2 printed pages web site: http://www-mitchell.ch.cam.ac.uk/macie

PhD students, interculturality, reflexivity, community and internationalisation

Interviews with a small group of doctoral students at a British university indicate that the students feel that the programme provides an environment within which they develop interculturality through reflexive engagement with the PhD community and in some cases with the participants in their research. Significant here is that they are interpretivist, constructivist qualitative researchers within a larger university community of qualitative researchers where there is a shared reflexivity that is at the core of interculturality. They also bring with them existing cultural complexity with which to engage, build on, make reflexive sense of and resolve in this experience. This complexity which they all share make it difficult to consider them differently as 'international' or 'home' students, which are revealed as inappropriately divisive labels within an intercultural community. Where there are apparent issues with English as a second or other language among some of the students, it is realised that this represents a broader struggle, shared with all students, regarding self-expression in writing. These findings demand cultural belief in whatever backgrounds the students come from. This belief impacts on how we understand internationalisation and the nature of academic knowledge and process

Rapid communication of upper‐ocean salinity anomaly to deep waters of the Iceland Basin indicates an AMOC short‐cut

The mooring observations of the Overturning in the Subpolar North Atlantic Program reveal a significant freshening of the Iceland Scotland overflow waters that did not involve the Nordic Seas, the source of the dense Deep North Atlantic Water (Devana et al., 2021, https://doi.org/10.1029/2021GL094396). Their study suggests that this freshening at depth in the Iceland Basin stems from the largest upper-ocean freshening event in 120 years that rapidly communicated through entrainment with the Iceland Scotland Overflow Waters. This communication, which is very likely driven by strong wintertime heat losses, strongly adds to our thinking that the progression of this extreme freshening event is providing us with a natural tracer that is helping to identify and understand key processes that determine the strength and variability of the overturning circulation and its sensitivity to ongoing climate change. Continued monitoring of the overturning in the North Atlantic is therefore necessary