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

Ligand-based virtual screening using a genetic algorithm with data fusion

Substructural analysis provides a simple and effective way of ranking the 2D fingerprints representing the molecules in a database upon the basis of weights that denote a substructural fragment’s contribution to the overall activity or inactivity of a molecule. A substructural analysis method has been described recently that is based on the use of a genetic algorithm (GA), with the resulting sets of weights proving to be more effective for ligand-based virtual screening than existing approaches. However, the inherently non-deterministic nature of a GA means that different runs are likely to result in different sets of weights and hence in variations in the effectiveness of screening. This paper describes the use of data fusion to combine the rankings generated in multiple GA runs, and demonstrates that the resulting fused rankings are markedly superior to GA runs on average, and in some cases can even exceed the performance of the very best individual GA run

Observed variability of the North Atlantic current in the Rockall Trough from four years of mooring measurements

The Rockall Trough is one of the main conduits for warm Atlantic Water to the Nordic Seas. Ocean heat anomalies, originating from the eastern subpolar gyre, are known to influence Arctic sea ice extent, marine ecosystems, and continental climate. Knowledge of the transport through this basin has previously been limited to estimates from hydrographic sections which cannot characterise the intra‐annual and multi‐annual variability. As part of the Overturning in the Subpolar North Atlantic Programme (OSNAP), a mooring array was deployed in the Rockall Trough in order to obtain the first continuous measurements of transport. Here, we define the methodology and the errors associated with estimating these transports. Results show a 4‐year mean northward transport of 6.6 Sv (1 Sv = 106 m3/s) by the North Atlantic Current (NAC) in the east and interior of the Rockall Trough (2014‐2018). A mean transport of ‐2.0 Sv (southward) is observed in the west of the basin, which could be part of a recirculation around the Rockall Plateau. The 90‐day low‐pass filtered transport shows large sub‐annual and inter‐annual variability (‐1.6 Sv to 9.1 Sv), mostly resulting from changes in the mid‐basin geostrophic transport. Satellite altimetry reveals the periods of low and high transport are associated with significant changes in the Rockall Trough circulation. There is a detectable seasonal signal, with the greatest transport in spring and autumn

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

Rapid export of waters formed by convection near the Irminger Sea's western boundary

The standard view of the overturning circulation emphasizes the role of convection, yet for waters to contribute to overturning, they must not only be transformed to higher densities but also exported equatorward. From novel mooring observations in the Irminger Sea (2014–2016), we describe two water masses that are formed by convection and show that they have different rates of export in the western boundary current. Upper Irminger Sea Intermediate Water appears to form near the boundary current and is exported rapidly within 3 months of its formation. Deep Irminger Sea Intermediate Water forms in the basin interior and is exported on longer time scales. The subduction of these waters into the boundary current is consistent with an eddy transport mechanism. Our results suggest that light intermediate waters can contribute to overturning as much as waters formed by deeper convection and that the export time scales of both project onto overturning variability. Plain Language Summary The deep ocean can regulate the Earth's climate by storing carbon and heat. At high latitudes, waters are cooled by the atmosphere and sink, but they can only be successfully stored in the deep ocean if they are exported toward the equator. In this study, we analyze new mooring observations in the Irminger Sea to investigate the cooling and export of high‐latitude waters. In addition to the well‐documented waters that are cooled in the center of the Irminger Sea, we find that saltier waters are cooled near the western boundary current. Both of these water types make it into boundary current and are exported. Our observations are consistent with the dynamics of swirling eddy motions. The eddy transport process is more effective for the waters cooled near the boundary current, implying that cooling near boundary currents may be more important for the climate than has been appreciated to date

Discovery of TUG-770: a highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist for treatment of type 2 diabetes

Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing

‘I already have a culture.’ Negotiating competing grand and personal narratives in interview conversations with new study abroad arrivals

In an interview with a postgraduate student about her intercultural experience of recently arriving for study abroad, it was found that the two researchers and the student were engaged in a mutual exploration of cultural identity. The in- terview events became conversational and took the form of small culture formation on the go in which each participant employed diverse narratives to project, make sense of and negotiate expression of cultural identity. The stu- dent shifted between personal narratives drawn from her particular cultural trajectories and splintered from grand narratives of nation and global position- ing, between non- essentialist threads and essentialist blocks. The researchers learned from her and intervened to facilitate shifts to non-essentialist threads, drawing on narratives from their own personal cultural trajectories, but some- times also falling into essentialist blocks splintered from grand narratives. The roles of ideology and competing essentialist and non-essentialist discourses of culture were implicit in these negotiations, as were the personal agency of the student as she responded to the constraining conflicts, structures and hierarchies encountered through the events she spoke about. Rather than providing a picture of intercultural assimilation and integration, interculturality is revealed as a hesitant and searching negotiation, sometimes of vulnerability, wrong-footedness and occasional assault on identity

Irminger Sea is the center of action for subpolar AMOC variability

Significant societally important climate impacts can be caused by changes in the strength of the Atlantic Meridional Overturning Circulation (AMOC) at higher latitudes. Focusing on variability and long-term change of the subpolar North Atlantic (SPNA)—a key AMOC action center—and using eastern OSNAP array observations, we identify a distinct density and sea-surface height signature of the AMOC strength in the Irminger Sea (2014–2018), reinforced and extended with an ocean reanalysis (1993–2018). Reconstruction of AMOC variability using Irminger Sea density shows strong control by the North Atlantic Oscillation on subpolar overturning on multiple timescales, achieved via the gyre circulation and waters from the Labrador Sea. Furthermore, the observed decrease of Irminger Sea density since the mid-twentieth century (1950–2019) is suggestive of a long-term AMOC weakening of 2.2 Sv or 13%, however, this trend remains statistically insignificant due to the large interannual and decadal variability of the SPNA

Robust ferromagnetism in the compressed permanent magnet Sm2Co17

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPThe compound Sm2CO17 displays magnetic properties amenable to permanent magnet applications owing to both the 3d electrons of Co and the 4f electrons of Sm. The long-standing description of the magnetic interactions between the Sm and Co ions implies a truly ferromagnetic configuration, but some recent calculations challenge this axiom, suggesting at least a propensity for ferrimagnetic behavior. We have used high-pressure synchrotron x-ray techniques to characterize the magnetic and structural properties of Sm2Co17 to reveal a robust ferromagnetic state. The local Sm moment is at most weakly affected by compression, and the ordered moments show a surprising resilience to volumetric compressions of nearly 20%. Density functional theory calculations echo the magnetic robustness of Sm2Co17.9010112FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2013/14338-3We graciously thank K. Visbeck for assistance with DAC preparation and C. Kenney-Benson for assistance with setup at the Advanced Photon Source. This work was performed under LDRD (Tracking Code 12-ERD-013) and under the auspices of the US Department of Energy by Lawrence Livermore National Laboratory (LLNL) under Contract No. DE-AC52-07NA27344. L. S. I. Veiga is supported by FAPESP (SP-Brazil) under Contract No. 2013/14338-3. Portions of this work were performed at Sector 4 and at HPCAT (Sector 16), Advanced Photon Source (APS), Argonne National Laboratory. HPCAT operations are supported by DOE-NNSA under Award No. DE-NA0001974 and DOE-BES under Award No. DE-FG02-99ER45775, with partial instrumentation funding by NSF. APS is supported by DOE-BES, under Contract No. DE-AC02-06CH11357. Beamtime was provided by the General User Proposal system and the Carnegie DOE-Alliance Center (CDAC). Identification of commercial materials or equipment does not imply recommendation or endorsement by the National Institute of Standards and Technology, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose