Investigation of the gas phase reactivity of the 1-adamantyl radical using a distonic radical anion approach

The gas phase reactions of the bridgehead 3-carboxylato-1-adamantyl radical anion were observed with a series of neutral reagents using a modified electrospray ionisation linear ion trap mass spectrometer. This distonic radical anion was observed to undergo processes suggestive of radical reactivity including radical-radical combination reactions, substitution reactions and addition to carbon-carbon double bonds. The rate constants for reactions of the 3-carboxylato-1-adamantyl radical anion with the following reagents were measured ( in units 10(-12) cm(3) molecule(-1) s(-1)): O-18(2) ( 85 +/- 4), NO ( 38.4 +/- 0.4), I-2 ( 50 +/- 50), Br-2 ( 8 +/- 2), CH3SSCH3 ( 12 +/- 2), styrene ( 1.20 +/- 0.03), CHCl3 ( H abstraction 0.41 +/- 0.06, Cl abstraction 0.65 +/- 0.1), CDCl3 ( D abstraction 0.035 +/- 0.01, Cl abstraction 0.723 +/- 0.005), allyl bromide (Br abstraction 0.53 +/- 0.04, allylation 0.25 +/- 0.01). Collision rates were calculated and reaction efficiencies are also reported. This study represents the first quantitative measurement of the gas phase reactivity of a bridgehead radical and suggests that distonic radical anions are good models for the study of their elusive uncharged analogues.

Swelling induced finite strain flexure in a rectangular block of an isotropic elastic material

The deformation of a rectangular block into an annular wedge is studied with respect to the state of swelling interior to the block. Nonuniform swelling fields are shown to generate these flexure deformations in the absence of resultant forces and bending moments. Analytical expressions for the deformation fields demonstrate these effects for both incompressible and compressible generalizations of conventional hyperelastic materials. Existing results in the absence of a swelling agent are recovered as special cases.

Priority threat management of invasive plant species in the Lake Eyre Basin

This project is led by scientists in conservation decision appraisal and brings together a group of experts working across the Lake Eyre Basin (LEB). The LEB covers a sixth of Australia, with an array of globally significant natural values that are threatened by invasive plants, among other things. Managers at various levels are investing in attempts to control, contain and eradicate these invasive plant species, under severe time and resources limitations. To date there has been no basin-wide assessment of which weed management strategies and locations provide the best investments for maximising outcomes for biodiversity per unit cost. Further, there has been no assessment of the extent of ecosystem intactness that may be lost without effective invasive plant species management strategies. Given that there are insufficient resources to manage all invasive plant species everywhere, this information has the potential to improve current investment decisions. Here, we provide a prioritisation of invasive plant management strategies in the LEB. Prioritisation was based on cost-effectiveness for biodiversity benefits. We identify the key invasive plant species to target to protect ecosystem intactness across the bioregions of the LEB, the level of investment required and the likely reduction in invasive species dominance gained per dollar spent on each strategy. Our focus is on strategies that are technically and socially feasible and reduce the likelihood that high impact invasive plant species will dominate native ecosystems, and therefore change their form and function. The outputs of this work are designed to help guide decision-making and further planning and investment in weed management for the Basin. Experts in weed management, policy-making, community engagement, biodiversity and natural values of the Basin, attended a workshop and agreed upon 12 strategies to manage invasive plants. The strategies focused primarily on 10 weeds which were considered to have a high potential for broad, significant impacts on natural ecosystems in the next 50 years and for which feasible management strategies could be defined. Each strategy consisted of one or more supporting actions, many of which were spatially linked to IBRA (Interim Biogeographical Regionalisation of Australia) bioregions. The first strategy was an over-arching recommendation for improved mapping, information sharing, education and extension efforts in order to facilitate the more specific weed management strategies. The 10 more specific weed management strategies targeted the control and/or eradication of the following high-impact exotic plants: mesquite, parkinsonia, rubber vine, bellyache bush, cacti, mother of millions, chinee apple, athel pine and prickly acacia, as well as a separate strategy for eradicating all invasive plants from one key threatened ecological community, the GAB (Great Artesian Basin dependant) mound springs. Experts estimated the expected biodiversity benefit of each strategy as the reduction in area that an invasive plant species is likely to dominate in over a 50-year period, where dominance was defined as more than 30% coverage at a site. Costs were estimated in present day terms over 50 years largely during follow up discussions post workshop. Cost-effectiveness was then calculated for each strategy in each bioregion by dividing the average expected benefit by the average annual costs. Overall, the total cost of managing 12 invasive plant strategies over the next 50 years was estimated at $1.7 billion. It was estimated that implementation of these strategies would result in a reduction of invasive plant dominance by 17 million ha (a potential 32% reduction), roughly 14% of the LEB. If only targeting Weeds of National Significance (WONS), the total cost was estimated to be $113 million over the next 50 years. Over the next 50 years, $2.3 million was estimated to eradicate all invasive plant species from the Great Artesian Basin Mound Springs threatened ecological community. Prevention and awareness programs were another key strategy targeted across the Basin and estimated at $17.5 million in total over 50 years. The cost of controlling, eradicating and containing buffel grass were the most expensive, over $1.5 billion over 50 years; this strategy was estimated to result in a reduction in buffel grass dominance of a million ha in areas where this species is identified as an environmental problem. Buffel grass has been deliberately planted across the Basin for pasture production and is by far the most widely distributed exotic species. Its management is contentious, having economic value to many graziers while posing serious threats to biodiversity and sites of high cultural and conservation interest. The strategy for containing and locally eradicating buffel grass was a challenge to cost based on expert knowledge, possibly because of the dual nature of this species as a valued pastoral grass and environmental weed. Based on our conversations with experts, it appears that control and eradication programs for this species, in conservation areas, are growing rapidly and that information on the most cost-effective strategies for this species will continue to develop over time. The top five most cost-effective strategies for the entire LEB were for the management of: 1) parkinsonia, 2) chinee apple, 3) mesquite, 4) rubber vine and 5) bellyache bush. Chinee apple and mother of millions are not WONS and have comparatively small populations within the semi-arid bioregions of Queensland. Experts felt that there was an opportunity to eradicate these species before they had the chance to develop into high-impact species within the LEB. Prickly acacia was estimated to have one of the highest benefits, but the costs of this strategy were high, therefore it was ranked 7th overall. The buffel grass strategy was ranked the lowest (10th) in terms of cost effectiveness. The top five most cost-effective strategies within and across the bioregions were the management of: 1) parkinsonia in the Channel Country, 2) parkinsonia in the Desert Uplands, 3) mesquite in the Mitchell Grass Downs, 4) parkinsonia in the Mitchell Grass Downs, and 5) mother of millions in the Desert Uplands. Although actions for several invasive plant species like parkinsonia and prickly acacia were concentrated in the Queensland part of the LEB, the actions involved investing in containment zones to prevent the spread of these species into other states. In the NT and SA bioregions of the LEB, the management of athel pine, parkinsonia and cacti were the main strategies. While outside the scientific research goals of study, this work highlighted a number of important incidental findings that led us to make the following recommendations for future research and implementation of weed management in the Basin: • Ongoing stakeholder engagement, extension and participation is required to ensure this prioritisation effort has a positive impact in affecting on-ground decision making and planning. • Short term funding for weed management was identified as a major reason for failure of current efforts, hence future funding needs to be secure and ongoing. • Improved mapping and information sharing is essential to implement effective weed management. • Due to uncertainties in the outcomes and impacts of management options, strategies should be implemented as part of an adaptive management program. The information provided in this report can be used to guide investment for controlling high-impact invasive plant species for the benefits of biodiversity conservation. We do not present a final prioritisation of invasive plant strategies for the LEB, and we have not addressed the cultural, socio-economic or spatial components necessary for an implementation plan. Cost-effectiveness depends on the objectives used; in our case we used the intactness of ecosystems as a surrogate for expected biodiversity benefits, measured by the extent that each invasive plant species is likely to dominate in a bioregion. When other relevant factors for implementation are considered the priorities may change and some actions may not be appropriate in some locations. We present the costs, ecological benefits and cost-effectiveness of preventing, containing, reducing and eradicating the dominance of high impact invasive plants through realistic management actions over the next 50 years. In doing so, we are able to estimate the size of the weed management problem in the LEB and provide expert-based estimates of the likely outcomes and benefits of implementing weed management strategies. The priorities resulting from this work provide a prospectus for guiding further investment in management and in improving information availability.

Productive inefficiency analysis and toxic chemical substances in US and Japanese manufacturing sectors

Corporate social responsibility is imperative for manufacturing companies to achieve sustainable development. Under a strong environmental information disclosure system, polluting companies are disadvantaged in terms of market competitiveness, because they lack an environmentally friendly image. The objective of this study is to analyze productive inefficiency change in relation to toxic chemical substance emissions for the United States and Japan and their corresponding policies. We apply the weighted Russell directional distance model to measure companies productive inefficiency, which represents their production technology. The data encompass 330 US manufacturing firms observed from 1999 to 2007, and 466 Japanese manufacturing firms observed from 2001 to 2008. The article focuses on nine high-pollution industries (rubber and plastics; chemicals and allied products; paper and pulp; steel and non-ferrous metal; fabricated metal; industrial machinery; electrical products; transportation equipment; precision instruments) categorized into two industry groups: basic materials industries and processing and assembly industries. The results show that productive inefficiency decreased in all industrial sectors in the United States and Japan from 2001 to 2007. In particular, that of the electrical products industry decreased rapidly after 2002 for both countries, possibly because of the enforcement of strict environmental regulations for electrical products exported to European markets.

Relevance of the deletion polymorphisms of the glutathione S-transferases GSTT1 and GSTM1 in pharmacology and toxicology

Although cytosolic glutathione S-transferase (GST) enzymes occupy a key position in biological detoxification processes, two of the most relevant human isoenzymes, GSTT1-1 and GSTM1-1, are genetically deleted (non-functional alleles GSTT1*0 and GSTM1*0) in a high percentage of the human population, with major ethnic differences. The structures of the GSTT and GSTM gene areas explain the underlying genetic processes. GSTT1-1 is highly conserved during evolution and plays a major role in phase-II biotransformation of a number of drugs and industrial chemicals, e.g. cytostatic drugs, hydrocarbons and halogenated hydrocarbons. GSTM1-1 is particularly relevant in the deactivation of carcinogenic intermediates of polycyclic aromatic hydrocarbons. Several lines of evidence suggest that hGSTT1-1 and/or hGSTM1-1 play a role in the deactivation of reactive oxygen species that are likely to be involved in cellular processes of inflammation, ageing and degenerative diseases. There is cumulating evidence that combinations of the GSTM1*0 state with other genetic traits affecting the metabolism of carcinogens (CYP1A1, GSTP1) may predispose the aero-digestive tract and lung, especially in smokers, to a higher risk of cancer. The GSTM1*0 status appears also associated with a modest increase in the risk of bladder cancer, consistent with a GSTM1 interaction with carcinogenic tobacco smoke constituents. Both human GST deletions, although largely counterbalanced by overlapping substrate affinities within the GST superfamily, have consequences when the organism comes into contact with distinct man-made chemicals. This appears relevant in industrial toxicology and in drug metabolism.

Occupational and non-occupational risk factors in bladder cancer patients in an industrialized area located in former East-Germany [Berufliche und außerberufliche Risikofaktoren für das Harnblasenkarzinom in einem ehemaligen Industriegebiet der neuen Bundesländer]

Purpose: Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e.g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1-2 carbon atoms) were investigated. Material and Methods: At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. Results: Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6%) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8%) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). Conclusions: The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis. [Article in German]

Conjugation of carcinogens by 6 class glutathione S-transferases : mechanisms and relevance to variations in human risk

Conjugation of chemicals with glutathione (GSH) can lead to decreased or increased toxicity. A genetic deficiency in the GSH S-transferase μ class gene M1 has been hypothesized to lead to greater risk of lung cancer in smokers. Recently a gene deletion polymorphism involving the human θ enzyme T1 has been described; the enzyme is present in erythrocytes and can be readily assayed. A rat θ class enzyme, 5-5, has structural and catalytic similarity and the protein was expressed in the Salmonella typhimurium tester strain TA1535. Expression of the cDNA vector increased the mutagenicity of ethylene dibromide and several methylene dihalides. Mutations resulting from the known GSH S-transferase substrate 1,2-epoxy-3-(4′nitrophenoxy)propane were decreased in the presence of the transferase. Expression of transferase 5-5 increased mutations when 1,2,3,4-diepoxybutane (butadiene diepoxide), 4-bromo-1,2-epoxybutane, or 1,3-dichloracetone were added. The latter compound is a model for the putative 1,2-dibromo-3-chloropropane oxidation product 1-bromo-3-chloroacetone. These genotoxicity and genotyping assays may be of use in further studies of the roles of GSH S-transferase θ enzymes in bioactivation and detoxication and any changes in risk due to polymorphism.

Enhancement of bacterial mutagenicity of bifunctional alkylating agents by expression of mammalian glutathione s-transferase

Recently, we inserted the plasmid vector pKK233-2 containing rat GSH S-transferase (GST) 5-5 cDNA into Salmonella typhimurium TA1535 and found that these bacteria [GST 5-5(+)] expressed the protein and produced mutations when ethylene or methylene dihalides were added [Thier, R., Taylor, J. B., Pemble, S. E., Ketterer, B., Persmark, M., Humphreys, W. G., and Guengerich, F. P. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 8576-8580]. After exposure to the known GST 5-5 substrate 1,2-epoxy-3-(4′-nitrophenoxy)propane, the GST 5-5(+) strain showed fewer mutants than the bacteria transfected with the cDNA clone in a reverse orientation [GST 5-5(-)], suggesting a protective role of GST 5-5. However, mutations were considerably enhanced in the GST 5-5(+) strain [as compared to GST 5-5(-)] when 1,2,3,4-diepoxybutane (butadiene diepoxide) or 1,2-epoxy-4-bromobutane was added. The GST 5-5(+) and GST 5-5(-) bacterial stains showed similar responses to 1,2-epoxypropane, 3,4-epoxy-1-butene, and 1,4-dibromobutane. The results suggest that some bifunctional activated butanes are transformed to mutagenic products through GSH conjugation. We also found that the GST 5-5(+) strain showed enhanced mutagenicity with 1,4-dibromo-2,3-epoxybutane, 1,2-epoxy-3-bromopropane (epibromohydrin), and (±)-1,4-dibromo-2,3-dihydroxybutane. The possibility was considered that a 5-membered thialonium ion may be involved in the mutagenicity. Model thialonium compounds were rather stable to hydrolysis in aqueous solution at pH 7.4 and slowly alkylated 4-(4-nitrobenzyl)pyridine. The presence of a hydroxyl group β to the sulfur did not enhance reactivity. Mechanisms involving episulfonium ions are considered more likely. Potential oxidation products of the toxic pesticide 1,2-dibromo-3-chloropropane (DBCP) were also considered in this system. DBCP itself gave rather similar results in the two strains. Others have reported that oxidation of DBCP is required for mutagenicity, along with GST-catalyzed GSH conjugation [Simula, T. P., Glancey, M. J., Söderlund, E. J., Dybing, E., and Wolf, C. R. (1993) Carcinogenesis 14, 2303-2307]. The putative oxidation product 1,2-dibromopropional did not show a difference between the two strains. However, 1,3-dichloroacetone, a model for the putative oxidation product 1-bromo-3-chloroacetone, was considerably more mutagenic in the GST 5-5(+) strain.

Human glutathione S-transferase T1-1 enhances mutagenicity of 1,2-dibromoethane, dibromomethane and 1,2,3,4-diepoxybutane in Salmonella typhimurium

The rat theta class glutathione S-transferase (GST) 5-5 has been shown to affect the mutagenicity of halogenated alkanes and epoxides. In Salmonella typhimurium TA1535 expressing the rat GST5-5 the number of revertants was increased compared to the control strain by CH2Br2, ethylene dibromide (EDB) and 1,2,3,4-diepoxybutane (BDE); in contrast, mutagenicity of 1,2-epoxy-3-(4'-nitrophenoxy)propane (EPNP) was reduced. S.typhimurium TA1535 cells were transformed with an expression plasmid carrying the cDNA of the human theta ortholog GST1-1 either in sense or antisense orientation, the latter being the control. These transformed bacteria were utilized for mutagenicity assays. Mutagenicity of EDB, BDE, CH2Br2, epibromohydrin and 1,3-dichloroacetone was higher in the S.typhimurium TA1535 expressing GSTT1-1 than in the control strain. The expression of active enzyme did not affect the mutagenicity of 1,2-epoxy-3-butene or propylene oxide, GSTT1-1 expression reduced the mutagenicity of EPNP. Glutathione S-transferase 5-5 and GSTT1-1 modulate genotoxicity of several industrially important chemicals in the same way. Polymorphism of the GSTT1 locus in humans may therefore cause differences in cancer susceptibility between the two phenotypes.

Soft tissue human thigh and buttock finite element model to simulate vehicle seat cushion indentation

Accurate modelling of automotive occupant posture is strongly related to the mechanical interaction between human body soft tissue and flexible seat components. This paper presents a finite-element study simulating the deflection of seat cushion foam and supportive seat structures, as well as human buttock and thigh soft tissue when seated. The thigh-buttock surface shell model was based on 95th percentile male subject scan data and made of two layers, covering thin to moderate thigh and buttock proportions. To replicate the effects of skin and fat, the neoprene rubber layer was modelled as a hyperelastic material with viscoelastic behaviour. The analytical seat model is based on a Ford production seat. The result of the finite-element indentation simulation is compared to a previous simulation of an indentation with a hard shell human model of equal geometry, and to the physical indentation result. We conclude that SAE composite buttock form and human-seat indentation of a suspended seat cushion can be validly simulated.

Numerical optimization of soft-mold aided co-curing process of advanced grid-stiffened composite structures

The co-curing process for advanced grid-stiffened (AGS) composite structure is a promising manufacturing process, which could reduce the manufacturing cost, augment the advantages and improve the performance of AGS composite structure. An improved method named soft-mold aided co-curing process which replaces the expansion molds by a whole rubber mold is adopted in this paper. This co-curing process is capable to co-cure a typical AGS composite structure with the manufacturer’s recommended cure cycle (MRCC). Numerical models are developed to evaluate the variation of temperature and the degree of cure in AGS composite structure during the soft-mold aided co-curing process. The simulation results were validated by experimental results obtained from embedded temperature sensors. Based on the validated modeling framework, the cycle of cure can be optimized by reducing more than half the time of MRCC while obtaining a reliable degree of cure. The shape and size effects of AGS composite structure on the distribution of temperature and degree of cure are also investigated to provide insights for the optimization of soft-mold aided co-curing process.

Combining the diaza-Diels-Alder reaction and palladium-catalyzed aminations to prepare amino-substituted porphyrins

A strategy to tackle the synthesis of azoporphyrins with unsubstituted terminal meso positions was investigated. It comprised the combination of diaza-Diels–Alder (DADA) reaction of 1,3-dienes with dialkyl azodicarboxylates, decarboxylative hydrolysis of the bis(carbamates), palladium-catalyzed amination of bromoporphyrin precursors, and retro-DADA reactions to release the ultimate targets. The somewhat confused historical results on the DADA reactions of 1,3-cyclohexadiene were clarified, but the hydrolyses yielded extremely air-sensitive amines which decomposed completely in minutes via autooxidation and retro-DADA reaction. With anthracene or 2,3-dimethyl-1,3-butadiene as the diene, the synthesis of azoporphyrin was not achieved but three amino-substituted porphyrins were obtained in moderate yields under mild conditions. The X-ray crystal structures of several of the intermediates and the final aminoanthracene-porphyrin nickel(II) complex were determined.

Determination of tricyclazole in water using solid phase extraction and liquid chromatography

A method for determination of tricyclazole in water using solid phase extraction and high performance liquid chromatography (HPLC) with UV detection at 230nm and a mobile phase of acetonitrile:water (20:80, v/v) was developed. A performance comparison between two types of solid phase sorbents, the C18 sorbent of Supelclean ENVI-18 cartridge and the styrene-divinyl benzene copolymer sorbent of Sep-Pak PS2-Plus cartridge was conducted. The Sep-Pak PS2-Plus cartridges were found more suitable for extracting tricyclazole from water samples than the Supelclean ENVI-18 cartridges. For this cartridge, both methanol and ethyl acetate produced good results. The method was validated with good linearity and with a limit of detection of 0.008gL-1 for a 500-fold concentration through the SPE procedure. The recoveries of the method were stable at 80% and the precision was from 1.1-6.0% within the range of fortified concentrations. The validated method was also applied to measure the concentrations of tricyclazole in real paddy water.

A new method for the in vivo identification of mechanical properties in arteries from cine MRI images: Theoretical framework and validation

Quantifying the stiffness properties of soft tissues is essential for the diagnosis of many cardiovascular diseases such as atherosclerosis. In these pathologies it is widely agreed that the arterial wall stiffness is an indicator of vulnerability. The present paper focuses on the carotid artery and proposes a new inversion methodology for deriving the stiffness properties of the wall from cine-MRI (magnetic resonance imaging) data. We address this problem by setting-up a cost function defined as the distance between the modeled pixel signals and the measured ones. Minimizing this cost function yields the unknown stiffness properties of both the arterial wall and the surrounding tissues. The sensitivity of the identified properties to various sources of uncertainty is studied. Validation of the method is performed on a rubber phantom. The elastic modulus identified using the developed methodology lies within a mean error of 9.6%. It is then applied to two young healthy subjects as a proof of practical feasibility, with identified values of 625 kPa and 587 kPa for one of the carotid of each subject.

Experimental measurement of the mechanical properties of carotid atherothrombotic plaque fibrous cap

Eleven carotid atherothrombotic plaque samples were harvested from patients. Three samples that were highly calcified were discarded, while eight yielded results. The elastic properties of the material were estimated by fitting the measured indentation response to finite element simulations. The methodology was refined and its accuracy quantified using a synthetic rubber. The neo-Hookean form of the material model gave a good fit to the measured response of the tissue. The inferred shear modulus μ was found to be in the range 7-100 kPa, with a median value of 11 kPa. A review of published materials data showed a wide range of material properties for human atherothrombotic tissue. The effects of anisotropy and time dependency in these published results were highlighted. The present measurements were comparable to the static radial compression tests of Lee et al, 1991 [Structure-dependent dynamic behaviour of fibrous caps from human atherosclerotic plaques. Circulation 83, 1764-1770].