The glucagon-like peptide 1 receptor (GLP-1R) is a member of the family (or class) B G-protein-co... more The glucagon-like peptide 1 receptor (GLP-1R) is a member of the family (or class) B G-protein-coupled receptor (GPCR). The receptor is a regulator of insulin and a key target in treating Type 2 diabetes mellitus. In this investigation, computational chemistry techniques such as molecular docking were combined with in silico ADME/Tox predictions to determine the position and structure of the allosteric binding site, as well as to examine how the allosteric modulators bind to the binding site. In silico evaluation was used to evaluate the ADME/Tox properties of the allosteric modulators. The findings of the ligand docking studies suggest that the allosteric binding site is situated around the transmembrane (TM) domain TM 6 of the receptor in the active state. ADME/Tox characterisation of the allosteric modulators demonstrate that compounds 1–3 (2,6,7-trichloro-3-(trifluoromethyl)quinoxaline, 1-(5-(4-(tert-butyl)phenyl)-1,3,4-oxadiazol-2-yl)-6,6-dimethyl-3-(methylsulfonyl)-6,7-dihydro...
Wales is one of the world leaders in household waste recycling with a steady recent recycling rat... more Wales is one of the world leaders in household waste recycling with a steady recent recycling rate of ~65%. The Welsh Assembly Government (WAG) set a statutory target of achieving a 70% recycling rate by 2024/25. We reviewed historical trends in waste management in Wales from 2006 to 2020, with a focus on recycling. Authoritative, official data were obtained from WasteDataFlow, an Internet system for municipal waste data reporting by UK local authorities to government. Data are collected quarterly allowing the generation of time series plots, trendlines and like-for-like comparisons between groupings of various characteristics, such as number of separate kerbside collections, income, political preference, and impact of policy changes. Results showed that the approach taken by the WAG to politically prioritise and encourage participation in household recycling has achieved impressive results that contrast starkly with the recycling performance of other UK countries. In Wales, househo...
This review aims firstly to clarify the meanings of key terms and concepts associated with the id... more This review aims firstly to clarify the meanings of key terms and concepts associated with the idea of the transition state, as developed by theoreticians and applied by experimentalist, and secondly to provide an update to the meaning and significance of the transition state in an era when computational simulation, in which complexity is being increasingly incorporated, is commonly employed as a means by which to bridge the realms of theory and experiment. The relationship between the transition state and the potential-energy surface for an elementary reaction is explored, with discussion of the following terms: saddle point, minimum-energy reaction path, reaction coordinate, activated complex, transition structure, intrinsic reaction coordinate, transition vector, transition-state structure, and transition state. Structural information determined by the application of computational methods to simple systems or inferred from empirical studies is critically discussed in the light of various complications. Consequently, the relationship between the transition state and the freeenergy surface for an elementary reaction within a condensed system is explored, with discussion of collective variables, minimum free-energy paths, variational transition-state theory, transmission coefficients, more about reaction coordinates, and equicommittors. It is noted that any visual picture of a transition state is necessarily an average view, and an updated definition of the transition state is proposed.
In 1997, a collection of twenty personal perspectives from eminent chemists was published in Pure... more In 1997, a collection of twenty personal perspectives from eminent chemists was published in Pure and Applied Chemistry to mark the centenary of physical organic chemistry [1]. This Symposium in Print, entitled Physical Organic Chemistry in the 21st Century (POC21C), was organized by the IUPAC Commission on Physical Organic Chemistry, which was chaired at that time by Tom Tidwell, who contributed a historical prologue in which he suggested Stieglitz’s 1899 proposal of carbocations as reaction intermediates as (unwittingly) having given birth to the discipline. The principal authors were Edward Arnett, Daniel Bellus, Ron Breslow, Fulvio Cacace, Jan Engberts, Marye Anne Fox, Ken Houk, Keith Ingold, Alan Katritzky, Ed Kosower, Meir Lahav, Teruaki Mukaiyama, Oleg Nefedov, George Olah, John Roberts, Jean-Michel Savéant, Helmut Schwarz, Andrew Streitwieser, Frank Westheimer, and Akio Yamamoto. Tidwell noted that, whereas they were not all known as physical organic chemists, yet they had a...
International Journal of Environmental Pollution and Remediation, 2017
Seaweeds are established sentinels for metal contamination and are utilised for biomonitoring. Me... more Seaweeds are established sentinels for metal contamination and are utilised for biomonitoring. Metallothionein (MT) is a protein that is induced by metal exposure, and has been widely used as a biomarker for metal pollution. MT has not been reported in spiral wrack (Fucus spiralis), but has been identified in bladder wrack (Fucus vesiculosus), where it has been suggested to be a protective mechanism against metal exposure. This study aimed to evaluate the potential use of MT in F. spiralis as a biomarker for metal pollution for the first time. Samples were collected from Poole Harbour, UK, over a year-long period in 2015. MT and metal concentrations were quantified during winter, spring, summer, and autumn. Linear regression analysis showed few relationships between MT and metal concentrations throughout most seasons. However, during summer, significant positive relationships existed between MT concentrations and iron (R 2 = 0.631), nickel (R 2 = 0.486), tin (R 2 = 0.579), and lead (R 2 = 0.415). Furthermore, MT concentrations were significantly higher in summer than in other seasons. It is possible that for most of the year, metal concentrations in Poole Harbour are not high enough to elicit a MT response in F. spiralis, as it is a metal tolerant species. This suggests that the use of MT as a sensitive biomarker for metal pollution in F. spiralis, at low levels of metal pollution, is limited. However, increased toxicity of metals, and vulnerability of seaweeds to metals, may become pertinent in summer months as metals inhibit photosynthetic processes and growth. This may have caused MT to relate to metal concentrations more closely during summer, as it responds to the increased effects of metals. Therefore, the potential for using MT in F. spiralis as a biomarker for metal pollution may be restricted to summer months in temperate regions, at least at low metal concentrations. Further research is required to fully evaluate the use of MT in Fucus spp., addressing uncertainties of seasonal variation, and MT response in severely polluted environments.
At the heart of the circular economy model is the reorientation of consumer behaviours away from ... more At the heart of the circular economy model is the reorientation of consumer behaviours away from disposing of items before they reach end of their functional life as a step towards resource efficiency and reduction of environmental impacts. One way to facilitate this change is to enable proactive redistribution of electrical and electronic equipment (EEE) with reuse value from urban spaces followed by high quality recycling at end-of-life. We have conducted the first assessment and critical evaluation of a model for the recovery of reusable EEE from a distinct urban mine (DUM) - in this case, a university. The Infrastructure, Service and Behaviour (ISB) model was used as a guide for interventions. EEE recovered from two Halls of Residence at the University of Southampton were characterised and sorted. From the items inspected, 97% was reusable and were donated to participating charities for redistribution via reuse/sale. The results show that an ISB Model system designed using choic...
Isotopic partition-function ratios (IPFRs) computed for transition structures (TSs) of the methyl... more Isotopic partition-function ratios (IPFRs) computed for transition structures (TSs) of the methyl-transfer reaction catalyzed by catechol Omethyltransferase and modeled by hybrid QM/MM methods are analyzed. The ability of smaller Hessians to reproduce trends in α-3 H 3 and 14 C α IPFRs as obtained using the much larger subset QM/MM Hessians from which they are extracted is investigated critically. A 6-atom-extracted Hessian reproduces perfectly the α-T 3 IPFR values from the full-subset Hessians of all the TSs but not the α-14 CIPFRs. Average AM1/OPLS-AA harmonic frequencies and mean-square amplitudes are presented for the 12 normal modes of the α-CH 3 moiety within the active site of several enzymic transition structures, together with QM/MM potential energy scans along each of these modes to assess the degree of anharmonicity. A novel investigation of ponderal effects upon IPFRs suggests that the value for α-14 C tends toward a limiting minimum whereas that for α-T 3 tends toward a limiting maximum as the mass of the rest of the system increases. The transition vector is dominated by motions of atoms within the donor and acceptor moieties and is very well described as a simple combination of Walden-inversion "umbrella" bending and asymmetric stretching of the SC α and C α O bonds. The contribution of atoms of the protein residues Met40, Tyr68, and Asp141 to the transition vector is extremely small. Average valence force constants for the COMT TS show significant differences from early BEBOVIB estimates which were used in support of the compression hypothesis for catalysis. There is no correlation between TS IPFRs and the nonbonded distances for close contacts between the S atom of SAM and Tyr68 or between any of the H atoms of the transferring methyl group and either Met40 or Asp141.
Modeling hyper-dimensional spatial variability is a complex task from both practical and theoreti... more Modeling hyper-dimensional spatial variability is a complex task from both practical and theoretical standpoints. In this paper we develop a method for modeling hyper-dimensional covariance (variogram) structures using the product-sum covariance model initially developed to model spatio-temporal variability. We show that the product-sum model can be used recursively up to an arbitrarily large number of dimensions while preserving relative modeling simplicity and yielding valid covariance models. The method can be used to model variability in anisotropic conditions with multiple axes of anisotropy or when temporal evolution is involved, and thus is applicable to “full anisotropic 3D+time” situations often encountered in environmental sciences. It requires fewer assumptions than the traditional product-sum modeling approach. The new method also presents an alternative to classical approaches to modeling zonal anisotropy and requires fewer parameters to be estimated from data. We prese...
Niemann-Pick disease, type C1 (NPC1) is a lysosomal disease characterized by progressive cerebell... more Niemann-Pick disease, type C1 (NPC1) is a lysosomal disease characterized by progressive cerebellar ataxia. In NPC1, a defect in cholesterol transport leads to endolysosomal storage of cholesterol and decreased cholesterol bioavailability. Purkinje neurons are sensitive to the loss of NPC1 function. However, degeneration of Purkinje neurons is not uniform. They are typically lost in an anterior-to-posterior gradient with neurons in lobule X being resistant to neurodegeneration. To gain mechanistic insight into factors that protect or potentiate Purkinje neuron loss, we compared RNA expression in cerebellar lobules III, VI, and X from control and mutant mice. An unexpected finding was that the gene expression differences between lobules III/VI and X were more pronounced than those observed between mutant and control mice. Functional analysis of genes with anterior to posterior gene expression differences revealed an enrichment of genes related to neuronal cell survival within the pos...
Isotope effects depend upon the polarity of the bulk medium in which a chemical process occurs. I... more Isotope effects depend upon the polarity of the bulk medium in which a chemical process occurs. Implicit solvent calculations with molecule-shaped cavities show that the equilibrium isotope effect (EIE) for heterolysis of the glycosidic bonds in 5′methylthioadenosine and in 2-(p-nitrophenoxy)tetrahydropyran, both in water, are very sensitive in the range 2 ≤ ε ≤ 10 to the relative permittivity of the continuum surrounding the oxacarbenium ion. However, different implementations of nominally the same PCM method can lead to opposite trends being predicted for the same molecule. Computational modeling of the influence of the inhomogeneous effective dielectric surrounding a substrate within the protein environment of an enzymic reaction requires an explicit treatment. The EIE (K H /K D) for transfer of cyclopentyl, cyclohexyl, tetrahydrofuranyl and tetrahydropyranyl cations from water to cyclohexane is predicted by B3LYP/6-31+G(d) calculations with implicit solvation and confirmed by B3LYP/6-31+G(d)/ OPLS-AA calculations with averaging over many explicit solvation configurations. Atomic Hessian analysis, whereby the full Hessian is reduced to the elements belonging to a single atom at the site of isotopic substitution, reveals a remarkable result for both implicit and explicit solvation: the influence of the solvent environment on these EIEs is essentially captured completely by only a 3 × 3 block of the Hessian, although these values must correctly reflect the influence of the whole environment. QM/MM simulation with ensemble averaging has an important role to play in assisting the meaningful interpretation of observed isotope effects for chemical reactions both in solution and catalyzed by enzymes.
Computational simulation of mechanism and isotope effects on acetal heterolysis as a model for glycoside hydrolysis
Pure and Applied Chemistry, 2019
DFT calculations for the equilibrium isotope effect for deuterium substitution at the anomeric ce... more DFT calculations for the equilibrium isotope effect for deuterium substitution at the anomeric centre Cα in 2-(p-nitrophenoxy)tetrahydropyran with continuum solvation show significant variation in the range of relative permittivity 2 ≤ ε ≤ 10. One-dimensional scans of potential energy (with implicit solvation by water) or of free energy (from QM/MM potentials of mean force with explicit aqueous solvation with a hybrid AM1/OPLS method) for heterolysis of the bond between Cα and the nucleofuge do not show a transition state. A two-dimensional free-energy surface that considers also the distance between Cα and a nucleophilic water indicates a pre-association DN*ANint‡ mechanism with a transition state involving nucleophilic attack upon an ion-pair intermediate, and this is supported by good agreement between the mean values of the calculated and experimental α-D KIEs. However, the magnitudes of the standard deviations about the mean values for the making and breaking C–O bonds suggest ...
Journal of Outdoor and Environmental Education, 2018
This paper describes a quasi-experimental crossover trial of an outdoor adventure program for Yea... more This paper describes a quasi-experimental crossover trial of an outdoor adventure program for Year 9 school students in Australia. Previous studies have reported a range of positive outcomes of outdoor camps and adventure programs, but cautious interpretation of some claims may be warranted due to limitations in research methods. This study examines a purpose-designed, seven-day outdoor adventure program intended to promote positive adjustment in young people. A total of 335 participants (aged 14
Fast fashion' and a 'take, make, dispose' economy are fueling people's accumulation of goods, and... more Fast fashion' and a 'take, make, dispose' economy are fueling people's accumulation of goods, and their willingness to throw these goods away. The end of each University year sees tens of thousands of students clear out their homes, and lives, and move on to pastures new, leaving behind a wake of unwanted clothing, kitchenware and bedding, amongst other 'throwaway' items. Sustainable waste management schemes at higher education institutions (HEIs) are becoming more prominent, and are taking the opportunity to generate positive outcomes from this problem that affects most university cities across the country. This study comprises of an extensive review of HEI reuse schemes as well as the collection of primary data during the planning and running of "Shift Your Stuff", an end-of-term reuse scheme run by Southampton University Students Union (SUSU). The study develops an existing protocol, designed to provide a consistent method of running and analysing an end of term re-use scheme, and refining it to create a methodology which could be easily transferred to other universities. We critically analyse the methods, protocol and key performance indicators (KPIs) which have been used in previous years, and report on the success of this year's project, in comparison to previous years. The KPIs continued to be an effective way of displaying the success of the scheme, with a 92.4% reuse rate-an improvement on the previous year, along with a host of social benefits including the donation of food and clothing to the homeless or deprived and the contribution to groundbreaking heart disease research undertaken by the British Heart Foundation (BHF). These benefits were brought about by the donations themselves, and by the £3,474 raised through the sale of donations. Although the total amount of donations was lower in comparison to previous years, the quality was substantially higher, with a lower percentage of donations having to be sent for disposal. We make a series of suggestions on how to improve the scheme in order make it more effective. For universities to reach their potential in terms of donations, it is recommended that the running of the scheme is handed over to a charitable organisation that is set up for this purpose.
International Journal of Educational Research, 2018
This paper presents a research protocol for a quasi-experimental crossover trial of an outdoor ad... more This paper presents a research protocol for a quasi-experimental crossover trial of an outdoor adventure program for Year 9 school students in Australia. Previous studies have reported a range of positive outcomes of outdoor camps and adventure programs but warrant cautious interpretation due to limitations in research methods typically employed. This study takes place over a period of 36 months and examines a purpose-designed, seven-day outdoor program (camp) intended to promote positive adjustment in young people. Up to 400 participants (ages 14-16 years) will be recruited from across two Victorian secondary schools. Outcome measures include self-reported social and emotional health, and teacher-reported ratings of academic performance and school conduct. Results will be of interest to educators internationally and those involved in improving social and emotional health in adolescents.
New Frontiers on Life Cycle Assessment - Theory and Application [Working Title], 2019
Sub-national governments are increasingly interested in local-level climate change management. Ca... more Sub-national governments are increasingly interested in local-level climate change management. Carbon-(CO 2 and CH 4) and climate-footprints-(Kyoto Basket GHGs) (effectively single impact category LCA metrics, for global warming potential) provide an opportunity to develop models to facilitate effective mitigation. Three approaches are available for the footprinting of sub-national communities. Territorial-based approaches, which focus on production emissions within the geo-political boundaries, are useful for highlighting local emission sources but do not reflect the transboundary nature of sub-national community infrastructures. Transboundary approaches, which extend territorial footprints through the inclusion of key cross boundary flows of materials and energy, are more representative of community structures and processes but there are concerns regarding comparability between studies. The third option, consumption-based, considers global GHG emissions that result from final consumption (households, governments, and investment). Using a case study of Southampton, UK, this chapter develops the data and methods required for a sub-national territorial, transboundary, and consumption-based carbon and climate footprints. The results and implication of each footprinting perspective are discussed in the context of emerging international standards. The study clearly shows that the carbon footprint (CO 2 and CH 4 only) offers a low-cost, low-data, universal metric of anthropogenic GHG emission and subsequent management.
We show that the well-known failure of any single index to capture the diversity and extremes of ... more We show that the well-known failure of any single index to capture the diversity and extremes of El Niño-Southern Oscillation (ENSO) results from the inability of existing indices to uniquely characterize the average longitude of deep convection in the Walker Circulation. We present a simple sea surface temperature (SST)-based index of this longitude that compactly characterizes the different spatial patterns, or flavors of observed and projected ENSO events. It recovers the familiar global responses of temperature, precipitation, and tropical cyclones to ENSO and identifies historical extreme El Niño events. Despite its simplicity, the new longitude index describes the nonlinear relationship between the first two principal components of SST, and unlike previous indices, accounts for background SST changes associated with the seasonal cycle and climate change. The index reveals that extreme El Niño, El Niño Modoki, and La Niña events are projected to become more frequent in the future at the expense of neutral ENSO conditions.
Organisations of all types are significant contributors to international greenhouse gas emissions... more Organisations of all types are significant contributors to international greenhouse gas emissions. The business case for supporting low-carbon practices is gathering pace, alongside the regulatory demands imposed through carbon emission compliance reporting. Despite this, guidance for generating carbon footprints through hybrid environmentally extended input-output analysis is underdeveloped and under-researched. Higher Education Institutions are key components of education systems across the globe, transcending international borders, socio-political regimes and economic systems. As an internationally significant sector beginning to address climate issues through carbon reduction policies on and off the estate, very few research articles have been published that document emissions arising from all directly and indirectly attributable activities. This study outlines a number of key elements to standardise the organisational carbon footprinting process by reconciling and evaluating the methodological steps in six selected internationally reputable guidelines (published by the Global Reporting Initiative, the Carbon Disclosure Project, the United Kingdom's Government Department for Environment, Food and Rural Affairs, the Greenhouse Gas Protocol, the International Standardisation Organisation and the Higher Education Funding Council for England). A systematic review is undertaken which relates the four principles of carbon footprinting (boundary-setting, identification of activities, collecting of data and reporting/verification) to the academic literature. Then, via consultation with university environment managers, a number of recommendations are made to address and improve i) the potential to avoid double-counting, ii) the financial and resource cost of carbon footprinting and iii) the reliability and comparability of data compiled by institutions. We introduce a methodology for a universal, standardised footprinting standard for higher education (that could also apply to all organisations regardless of sector or region) with cutoff criteria that excludes paid-for products and services typically included in the 'Scope 3' proportion of the footprint. In proposing this methodology, carbon footprinting is made more applicable to higher education institutions (since existing standards are designed for generality and for profit-driven organisations) and the practical issues, associated with externally owned data and nonexpert staff, are broadly overcome.
{"__content__"=>"A Nitrido-bridged Heterometallic Ruthenium(IV)/Iron(IV) Phthalocyanine Complex Supported by A Tripodal Oxygen Ligand, [Co(η-CH){P(O)(OEt)}]: Synthesis, Structure, and Its Oxidation to Give Phthalocyanine Cation Radical and Hydroxyphthalocyanine Complexes.", "sup"=>[{"__content__"...
Inorganic chemistry, Jan 6, 2018
Dinuclear iron nitrido phthalocyanine complexes are of interest owing to their applications in ca... more Dinuclear iron nitrido phthalocyanine complexes are of interest owing to their applications in catalytic oxidation of hydrocarbons. While nitrido-bridged diiron phthalocyanine complexes are well documented, the oxidation chemistry of heterodinuclear iron(IV) phthalocyanine nitrides has not been well explored. In this paper we report on the synthesis of a heterometallic Fe/Ru phthalocyanine nitride and its oxidation to yield phthalocyanine cation radical and hydroxyphthalocyanine complexes. Treatment of [Fe(Pc)] (Pc = phthalocyanine dianion) with [Ru(L)(N)Cl] (L = [Co(η-CH){P(O)(OEt)}]) (1) afforded the heterometallic μ-nitrido complex [Cl(L)Ru(μ-N)Fe(Pc)(HO)] (2) that contains an Ru=N = Fe linkage with the Ru-N and Fe-N distances of 1.689(6) and 1.677(6) Å, respectively, and Ru-N-Fe angle of 176.0(4)°. Substitution of 2 with 4- tert-butylpyridine (Bupy) gave [Cl(L)Ru(μ-N)Fe(Pc)(Bupy)]. The cyclic voltammogram of 2 displayed a reversible Pc-centered oxidation couple at +0.18 V versus...
Angewandte Chemie (International ed. in English), Jan 7, 2018
Treatment of CpRuH(PP) (PP=dppm, dppe) with TlPF produced [CpRu(H)(Tl)(PP)]PF . X-ray diffraction... more Treatment of CpRuH(PP) (PP=dppm, dppe) with TlPF produced [CpRu(H)(Tl)(PP)]PF . X-ray diffraction and computational studies suggest that the complexes contain a Ru-H-Tl 3c-2e bond and can be viewed as the first σ-complexes of period 6 main-group hydrides [CpRu{η -(H-Tl)}(PP)]PF or [Tl{η -H-RuCp(PP)}]PF . The complexes can be stored as a solid at room temperature for days without appreciable decomposition, but are unstable in solution and evolved to the trimetallic complexes [{CpRu(PP)} (μ-Tl)]PF .
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 31, 2018
Protease inhibitor monotherapy (PIM) for HIV may exert suboptimal viral control in the central ne... more Protease inhibitor monotherapy (PIM) for HIV may exert suboptimal viral control in the central nervous system. We determined whether cerebral blood flow (CBF) and regional brain volumes were associated with PIM, and whether specific cognitive domains were associated with imaging biomarkers. Cognitive assessment and brain MRI were performed after the final visit of a randomized HIV treatment strategy trial. Participants were virologically suppressed on triple therapy at trial entry and followed for 3-5 years. Thirty-seven patients randomized to ongoing triple therapy and thirty-nine randomized to PIM were studied. Resting CBF and normalized volumes were calculated for brain regions of interest, and correlated with treatment strategy and neuropsychological performance. Mean age was 48.1 years (standard deviation 8.6 years), 63 were male (83%) and 64 were white (84%). Participants had median 8.1 years (interquartile range 6.4, 10.8) of antiretroviral therapy experience and CD4+ counts ...
The glucagon-like peptide 1 receptor (GLP-1R) is a member of the family (or class) B G-protein-co... more The glucagon-like peptide 1 receptor (GLP-1R) is a member of the family (or class) B G-protein-coupled receptor (GPCR). The receptor is a regulator of insulin and a key target in treating Type 2 diabetes mellitus. In this investigation, computational chemistry techniques such as molecular docking were combined with in silico ADME/Tox predictions to determine the position and structure of the allosteric binding site, as well as to examine how the allosteric modulators bind to the binding site. In silico evaluation was used to evaluate the ADME/Tox properties of the allosteric modulators. The findings of the ligand docking studies suggest that the allosteric binding site is situated around the transmembrane (TM) domain TM 6 of the receptor in the active state. ADME/Tox characterisation of the allosteric modulators demonstrate that compounds 1–3 (2,6,7-trichloro-3-(trifluoromethyl)quinoxaline, 1-(5-(4-(tert-butyl)phenyl)-1,3,4-oxadiazol-2-yl)-6,6-dimethyl-3-(methylsulfonyl)-6,7-dihydro...
Wales is one of the world leaders in household waste recycling with a steady recent recycling rat... more Wales is one of the world leaders in household waste recycling with a steady recent recycling rate of ~65%. The Welsh Assembly Government (WAG) set a statutory target of achieving a 70% recycling rate by 2024/25. We reviewed historical trends in waste management in Wales from 2006 to 2020, with a focus on recycling. Authoritative, official data were obtained from WasteDataFlow, an Internet system for municipal waste data reporting by UK local authorities to government. Data are collected quarterly allowing the generation of time series plots, trendlines and like-for-like comparisons between groupings of various characteristics, such as number of separate kerbside collections, income, political preference, and impact of policy changes. Results showed that the approach taken by the WAG to politically prioritise and encourage participation in household recycling has achieved impressive results that contrast starkly with the recycling performance of other UK countries. In Wales, househo...
This review aims firstly to clarify the meanings of key terms and concepts associated with the id... more This review aims firstly to clarify the meanings of key terms and concepts associated with the idea of the transition state, as developed by theoreticians and applied by experimentalist, and secondly to provide an update to the meaning and significance of the transition state in an era when computational simulation, in which complexity is being increasingly incorporated, is commonly employed as a means by which to bridge the realms of theory and experiment. The relationship between the transition state and the potential-energy surface for an elementary reaction is explored, with discussion of the following terms: saddle point, minimum-energy reaction path, reaction coordinate, activated complex, transition structure, intrinsic reaction coordinate, transition vector, transition-state structure, and transition state. Structural information determined by the application of computational methods to simple systems or inferred from empirical studies is critically discussed in the light of various complications. Consequently, the relationship between the transition state and the freeenergy surface for an elementary reaction within a condensed system is explored, with discussion of collective variables, minimum free-energy paths, variational transition-state theory, transmission coefficients, more about reaction coordinates, and equicommittors. It is noted that any visual picture of a transition state is necessarily an average view, and an updated definition of the transition state is proposed.
In 1997, a collection of twenty personal perspectives from eminent chemists was published in Pure... more In 1997, a collection of twenty personal perspectives from eminent chemists was published in Pure and Applied Chemistry to mark the centenary of physical organic chemistry [1]. This Symposium in Print, entitled Physical Organic Chemistry in the 21st Century (POC21C), was organized by the IUPAC Commission on Physical Organic Chemistry, which was chaired at that time by Tom Tidwell, who contributed a historical prologue in which he suggested Stieglitz’s 1899 proposal of carbocations as reaction intermediates as (unwittingly) having given birth to the discipline. The principal authors were Edward Arnett, Daniel Bellus, Ron Breslow, Fulvio Cacace, Jan Engberts, Marye Anne Fox, Ken Houk, Keith Ingold, Alan Katritzky, Ed Kosower, Meir Lahav, Teruaki Mukaiyama, Oleg Nefedov, George Olah, John Roberts, Jean-Michel Savéant, Helmut Schwarz, Andrew Streitwieser, Frank Westheimer, and Akio Yamamoto. Tidwell noted that, whereas they were not all known as physical organic chemists, yet they had a...
International Journal of Environmental Pollution and Remediation, 2017
Seaweeds are established sentinels for metal contamination and are utilised for biomonitoring. Me... more Seaweeds are established sentinels for metal contamination and are utilised for biomonitoring. Metallothionein (MT) is a protein that is induced by metal exposure, and has been widely used as a biomarker for metal pollution. MT has not been reported in spiral wrack (Fucus spiralis), but has been identified in bladder wrack (Fucus vesiculosus), where it has been suggested to be a protective mechanism against metal exposure. This study aimed to evaluate the potential use of MT in F. spiralis as a biomarker for metal pollution for the first time. Samples were collected from Poole Harbour, UK, over a year-long period in 2015. MT and metal concentrations were quantified during winter, spring, summer, and autumn. Linear regression analysis showed few relationships between MT and metal concentrations throughout most seasons. However, during summer, significant positive relationships existed between MT concentrations and iron (R 2 = 0.631), nickel (R 2 = 0.486), tin (R 2 = 0.579), and lead (R 2 = 0.415). Furthermore, MT concentrations were significantly higher in summer than in other seasons. It is possible that for most of the year, metal concentrations in Poole Harbour are not high enough to elicit a MT response in F. spiralis, as it is a metal tolerant species. This suggests that the use of MT as a sensitive biomarker for metal pollution in F. spiralis, at low levels of metal pollution, is limited. However, increased toxicity of metals, and vulnerability of seaweeds to metals, may become pertinent in summer months as metals inhibit photosynthetic processes and growth. This may have caused MT to relate to metal concentrations more closely during summer, as it responds to the increased effects of metals. Therefore, the potential for using MT in F. spiralis as a biomarker for metal pollution may be restricted to summer months in temperate regions, at least at low metal concentrations. Further research is required to fully evaluate the use of MT in Fucus spp., addressing uncertainties of seasonal variation, and MT response in severely polluted environments.
At the heart of the circular economy model is the reorientation of consumer behaviours away from ... more At the heart of the circular economy model is the reorientation of consumer behaviours away from disposing of items before they reach end of their functional life as a step towards resource efficiency and reduction of environmental impacts. One way to facilitate this change is to enable proactive redistribution of electrical and electronic equipment (EEE) with reuse value from urban spaces followed by high quality recycling at end-of-life. We have conducted the first assessment and critical evaluation of a model for the recovery of reusable EEE from a distinct urban mine (DUM) - in this case, a university. The Infrastructure, Service and Behaviour (ISB) model was used as a guide for interventions. EEE recovered from two Halls of Residence at the University of Southampton were characterised and sorted. From the items inspected, 97% was reusable and were donated to participating charities for redistribution via reuse/sale. The results show that an ISB Model system designed using choic...
Isotopic partition-function ratios (IPFRs) computed for transition structures (TSs) of the methyl... more Isotopic partition-function ratios (IPFRs) computed for transition structures (TSs) of the methyl-transfer reaction catalyzed by catechol Omethyltransferase and modeled by hybrid QM/MM methods are analyzed. The ability of smaller Hessians to reproduce trends in α-3 H 3 and 14 C α IPFRs as obtained using the much larger subset QM/MM Hessians from which they are extracted is investigated critically. A 6-atom-extracted Hessian reproduces perfectly the α-T 3 IPFR values from the full-subset Hessians of all the TSs but not the α-14 CIPFRs. Average AM1/OPLS-AA harmonic frequencies and mean-square amplitudes are presented for the 12 normal modes of the α-CH 3 moiety within the active site of several enzymic transition structures, together with QM/MM potential energy scans along each of these modes to assess the degree of anharmonicity. A novel investigation of ponderal effects upon IPFRs suggests that the value for α-14 C tends toward a limiting minimum whereas that for α-T 3 tends toward a limiting maximum as the mass of the rest of the system increases. The transition vector is dominated by motions of atoms within the donor and acceptor moieties and is very well described as a simple combination of Walden-inversion "umbrella" bending and asymmetric stretching of the SC α and C α O bonds. The contribution of atoms of the protein residues Met40, Tyr68, and Asp141 to the transition vector is extremely small. Average valence force constants for the COMT TS show significant differences from early BEBOVIB estimates which were used in support of the compression hypothesis for catalysis. There is no correlation between TS IPFRs and the nonbonded distances for close contacts between the S atom of SAM and Tyr68 or between any of the H atoms of the transferring methyl group and either Met40 or Asp141.
Modeling hyper-dimensional spatial variability is a complex task from both practical and theoreti... more Modeling hyper-dimensional spatial variability is a complex task from both practical and theoretical standpoints. In this paper we develop a method for modeling hyper-dimensional covariance (variogram) structures using the product-sum covariance model initially developed to model spatio-temporal variability. We show that the product-sum model can be used recursively up to an arbitrarily large number of dimensions while preserving relative modeling simplicity and yielding valid covariance models. The method can be used to model variability in anisotropic conditions with multiple axes of anisotropy or when temporal evolution is involved, and thus is applicable to “full anisotropic 3D+time” situations often encountered in environmental sciences. It requires fewer assumptions than the traditional product-sum modeling approach. The new method also presents an alternative to classical approaches to modeling zonal anisotropy and requires fewer parameters to be estimated from data. We prese...
Niemann-Pick disease, type C1 (NPC1) is a lysosomal disease characterized by progressive cerebell... more Niemann-Pick disease, type C1 (NPC1) is a lysosomal disease characterized by progressive cerebellar ataxia. In NPC1, a defect in cholesterol transport leads to endolysosomal storage of cholesterol and decreased cholesterol bioavailability. Purkinje neurons are sensitive to the loss of NPC1 function. However, degeneration of Purkinje neurons is not uniform. They are typically lost in an anterior-to-posterior gradient with neurons in lobule X being resistant to neurodegeneration. To gain mechanistic insight into factors that protect or potentiate Purkinje neuron loss, we compared RNA expression in cerebellar lobules III, VI, and X from control and mutant mice. An unexpected finding was that the gene expression differences between lobules III/VI and X were more pronounced than those observed between mutant and control mice. Functional analysis of genes with anterior to posterior gene expression differences revealed an enrichment of genes related to neuronal cell survival within the pos...
Isotope effects depend upon the polarity of the bulk medium in which a chemical process occurs. I... more Isotope effects depend upon the polarity of the bulk medium in which a chemical process occurs. Implicit solvent calculations with molecule-shaped cavities show that the equilibrium isotope effect (EIE) for heterolysis of the glycosidic bonds in 5′methylthioadenosine and in 2-(p-nitrophenoxy)tetrahydropyran, both in water, are very sensitive in the range 2 ≤ ε ≤ 10 to the relative permittivity of the continuum surrounding the oxacarbenium ion. However, different implementations of nominally the same PCM method can lead to opposite trends being predicted for the same molecule. Computational modeling of the influence of the inhomogeneous effective dielectric surrounding a substrate within the protein environment of an enzymic reaction requires an explicit treatment. The EIE (K H /K D) for transfer of cyclopentyl, cyclohexyl, tetrahydrofuranyl and tetrahydropyranyl cations from water to cyclohexane is predicted by B3LYP/6-31+G(d) calculations with implicit solvation and confirmed by B3LYP/6-31+G(d)/ OPLS-AA calculations with averaging over many explicit solvation configurations. Atomic Hessian analysis, whereby the full Hessian is reduced to the elements belonging to a single atom at the site of isotopic substitution, reveals a remarkable result for both implicit and explicit solvation: the influence of the solvent environment on these EIEs is essentially captured completely by only a 3 × 3 block of the Hessian, although these values must correctly reflect the influence of the whole environment. QM/MM simulation with ensemble averaging has an important role to play in assisting the meaningful interpretation of observed isotope effects for chemical reactions both in solution and catalyzed by enzymes.
Computational simulation of mechanism and isotope effects on acetal heterolysis as a model for glycoside hydrolysis
Pure and Applied Chemistry, 2019
DFT calculations for the equilibrium isotope effect for deuterium substitution at the anomeric ce... more DFT calculations for the equilibrium isotope effect for deuterium substitution at the anomeric centre Cα in 2-(p-nitrophenoxy)tetrahydropyran with continuum solvation show significant variation in the range of relative permittivity 2 ≤ ε ≤ 10. One-dimensional scans of potential energy (with implicit solvation by water) or of free energy (from QM/MM potentials of mean force with explicit aqueous solvation with a hybrid AM1/OPLS method) for heterolysis of the bond between Cα and the nucleofuge do not show a transition state. A two-dimensional free-energy surface that considers also the distance between Cα and a nucleophilic water indicates a pre-association DN*ANint‡ mechanism with a transition state involving nucleophilic attack upon an ion-pair intermediate, and this is supported by good agreement between the mean values of the calculated and experimental α-D KIEs. However, the magnitudes of the standard deviations about the mean values for the making and breaking C–O bonds suggest ...
Journal of Outdoor and Environmental Education, 2018
This paper describes a quasi-experimental crossover trial of an outdoor adventure program for Yea... more This paper describes a quasi-experimental crossover trial of an outdoor adventure program for Year 9 school students in Australia. Previous studies have reported a range of positive outcomes of outdoor camps and adventure programs, but cautious interpretation of some claims may be warranted due to limitations in research methods. This study examines a purpose-designed, seven-day outdoor adventure program intended to promote positive adjustment in young people. A total of 335 participants (aged 14
Fast fashion' and a 'take, make, dispose' economy are fueling people's accumulation of goods, and... more Fast fashion' and a 'take, make, dispose' economy are fueling people's accumulation of goods, and their willingness to throw these goods away. The end of each University year sees tens of thousands of students clear out their homes, and lives, and move on to pastures new, leaving behind a wake of unwanted clothing, kitchenware and bedding, amongst other 'throwaway' items. Sustainable waste management schemes at higher education institutions (HEIs) are becoming more prominent, and are taking the opportunity to generate positive outcomes from this problem that affects most university cities across the country. This study comprises of an extensive review of HEI reuse schemes as well as the collection of primary data during the planning and running of "Shift Your Stuff", an end-of-term reuse scheme run by Southampton University Students Union (SUSU). The study develops an existing protocol, designed to provide a consistent method of running and analysing an end of term re-use scheme, and refining it to create a methodology which could be easily transferred to other universities. We critically analyse the methods, protocol and key performance indicators (KPIs) which have been used in previous years, and report on the success of this year's project, in comparison to previous years. The KPIs continued to be an effective way of displaying the success of the scheme, with a 92.4% reuse rate-an improvement on the previous year, along with a host of social benefits including the donation of food and clothing to the homeless or deprived and the contribution to groundbreaking heart disease research undertaken by the British Heart Foundation (BHF). These benefits were brought about by the donations themselves, and by the £3,474 raised through the sale of donations. Although the total amount of donations was lower in comparison to previous years, the quality was substantially higher, with a lower percentage of donations having to be sent for disposal. We make a series of suggestions on how to improve the scheme in order make it more effective. For universities to reach their potential in terms of donations, it is recommended that the running of the scheme is handed over to a charitable organisation that is set up for this purpose.
International Journal of Educational Research, 2018
This paper presents a research protocol for a quasi-experimental crossover trial of an outdoor ad... more This paper presents a research protocol for a quasi-experimental crossover trial of an outdoor adventure program for Year 9 school students in Australia. Previous studies have reported a range of positive outcomes of outdoor camps and adventure programs but warrant cautious interpretation due to limitations in research methods typically employed. This study takes place over a period of 36 months and examines a purpose-designed, seven-day outdoor program (camp) intended to promote positive adjustment in young people. Up to 400 participants (ages 14-16 years) will be recruited from across two Victorian secondary schools. Outcome measures include self-reported social and emotional health, and teacher-reported ratings of academic performance and school conduct. Results will be of interest to educators internationally and those involved in improving social and emotional health in adolescents.
New Frontiers on Life Cycle Assessment - Theory and Application [Working Title], 2019
Sub-national governments are increasingly interested in local-level climate change management. Ca... more Sub-national governments are increasingly interested in local-level climate change management. Carbon-(CO 2 and CH 4) and climate-footprints-(Kyoto Basket GHGs) (effectively single impact category LCA metrics, for global warming potential) provide an opportunity to develop models to facilitate effective mitigation. Three approaches are available for the footprinting of sub-national communities. Territorial-based approaches, which focus on production emissions within the geo-political boundaries, are useful for highlighting local emission sources but do not reflect the transboundary nature of sub-national community infrastructures. Transboundary approaches, which extend territorial footprints through the inclusion of key cross boundary flows of materials and energy, are more representative of community structures and processes but there are concerns regarding comparability between studies. The third option, consumption-based, considers global GHG emissions that result from final consumption (households, governments, and investment). Using a case study of Southampton, UK, this chapter develops the data and methods required for a sub-national territorial, transboundary, and consumption-based carbon and climate footprints. The results and implication of each footprinting perspective are discussed in the context of emerging international standards. The study clearly shows that the carbon footprint (CO 2 and CH 4 only) offers a low-cost, low-data, universal metric of anthropogenic GHG emission and subsequent management.
We show that the well-known failure of any single index to capture the diversity and extremes of ... more We show that the well-known failure of any single index to capture the diversity and extremes of El Niño-Southern Oscillation (ENSO) results from the inability of existing indices to uniquely characterize the average longitude of deep convection in the Walker Circulation. We present a simple sea surface temperature (SST)-based index of this longitude that compactly characterizes the different spatial patterns, or flavors of observed and projected ENSO events. It recovers the familiar global responses of temperature, precipitation, and tropical cyclones to ENSO and identifies historical extreme El Niño events. Despite its simplicity, the new longitude index describes the nonlinear relationship between the first two principal components of SST, and unlike previous indices, accounts for background SST changes associated with the seasonal cycle and climate change. The index reveals that extreme El Niño, El Niño Modoki, and La Niña events are projected to become more frequent in the future at the expense of neutral ENSO conditions.
Organisations of all types are significant contributors to international greenhouse gas emissions... more Organisations of all types are significant contributors to international greenhouse gas emissions. The business case for supporting low-carbon practices is gathering pace, alongside the regulatory demands imposed through carbon emission compliance reporting. Despite this, guidance for generating carbon footprints through hybrid environmentally extended input-output analysis is underdeveloped and under-researched. Higher Education Institutions are key components of education systems across the globe, transcending international borders, socio-political regimes and economic systems. As an internationally significant sector beginning to address climate issues through carbon reduction policies on and off the estate, very few research articles have been published that document emissions arising from all directly and indirectly attributable activities. This study outlines a number of key elements to standardise the organisational carbon footprinting process by reconciling and evaluating the methodological steps in six selected internationally reputable guidelines (published by the Global Reporting Initiative, the Carbon Disclosure Project, the United Kingdom's Government Department for Environment, Food and Rural Affairs, the Greenhouse Gas Protocol, the International Standardisation Organisation and the Higher Education Funding Council for England). A systematic review is undertaken which relates the four principles of carbon footprinting (boundary-setting, identification of activities, collecting of data and reporting/verification) to the academic literature. Then, via consultation with university environment managers, a number of recommendations are made to address and improve i) the potential to avoid double-counting, ii) the financial and resource cost of carbon footprinting and iii) the reliability and comparability of data compiled by institutions. We introduce a methodology for a universal, standardised footprinting standard for higher education (that could also apply to all organisations regardless of sector or region) with cutoff criteria that excludes paid-for products and services typically included in the 'Scope 3' proportion of the footprint. In proposing this methodology, carbon footprinting is made more applicable to higher education institutions (since existing standards are designed for generality and for profit-driven organisations) and the practical issues, associated with externally owned data and nonexpert staff, are broadly overcome.
{"__content__"=>"A Nitrido-bridged Heterometallic Ruthenium(IV)/Iron(IV) Phthalocyanine Complex Supported by A Tripodal Oxygen Ligand, [Co(η-CH){P(O)(OEt)}]: Synthesis, Structure, and Its Oxidation to Give Phthalocyanine Cation Radical and Hydroxyphthalocyanine Complexes.", "sup"=>[{"__content__"...
Inorganic chemistry, Jan 6, 2018
Dinuclear iron nitrido phthalocyanine complexes are of interest owing to their applications in ca... more Dinuclear iron nitrido phthalocyanine complexes are of interest owing to their applications in catalytic oxidation of hydrocarbons. While nitrido-bridged diiron phthalocyanine complexes are well documented, the oxidation chemistry of heterodinuclear iron(IV) phthalocyanine nitrides has not been well explored. In this paper we report on the synthesis of a heterometallic Fe/Ru phthalocyanine nitride and its oxidation to yield phthalocyanine cation radical and hydroxyphthalocyanine complexes. Treatment of [Fe(Pc)] (Pc = phthalocyanine dianion) with [Ru(L)(N)Cl] (L = [Co(η-CH){P(O)(OEt)}]) (1) afforded the heterometallic μ-nitrido complex [Cl(L)Ru(μ-N)Fe(Pc)(HO)] (2) that contains an Ru=N = Fe linkage with the Ru-N and Fe-N distances of 1.689(6) and 1.677(6) Å, respectively, and Ru-N-Fe angle of 176.0(4)°. Substitution of 2 with 4- tert-butylpyridine (Bupy) gave [Cl(L)Ru(μ-N)Fe(Pc)(Bupy)]. The cyclic voltammogram of 2 displayed a reversible Pc-centered oxidation couple at +0.18 V versus...
Angewandte Chemie (International ed. in English), Jan 7, 2018
Treatment of CpRuH(PP) (PP=dppm, dppe) with TlPF produced [CpRu(H)(Tl)(PP)]PF . X-ray diffraction... more Treatment of CpRuH(PP) (PP=dppm, dppe) with TlPF produced [CpRu(H)(Tl)(PP)]PF . X-ray diffraction and computational studies suggest that the complexes contain a Ru-H-Tl 3c-2e bond and can be viewed as the first σ-complexes of period 6 main-group hydrides [CpRu{η -(H-Tl)}(PP)]PF or [Tl{η -H-RuCp(PP)}]PF . The complexes can be stored as a solid at room temperature for days without appreciable decomposition, but are unstable in solution and evolved to the trimetallic complexes [{CpRu(PP)} (μ-Tl)]PF .
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 31, 2018
Protease inhibitor monotherapy (PIM) for HIV may exert suboptimal viral control in the central ne... more Protease inhibitor monotherapy (PIM) for HIV may exert suboptimal viral control in the central nervous system. We determined whether cerebral blood flow (CBF) and regional brain volumes were associated with PIM, and whether specific cognitive domains were associated with imaging biomarkers. Cognitive assessment and brain MRI were performed after the final visit of a randomized HIV treatment strategy trial. Participants were virologically suppressed on triple therapy at trial entry and followed for 3-5 years. Thirty-seven patients randomized to ongoing triple therapy and thirty-nine randomized to PIM were studied. Resting CBF and normalized volumes were calculated for brain regions of interest, and correlated with treatment strategy and neuropsychological performance. Mean age was 48.1 years (standard deviation 8.6 years), 63 were male (83%) and 64 were white (84%). Participants had median 8.1 years (interquartile range 6.4, 10.8) of antiretroviral therapy experience and CD4+ counts ...
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Papers by Ian Williams