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Importance Neuroinflammation appears to be a key modulator of disease progression in amyotrophic lateral sclerosis (ALS) and thereby a promising therapeutic target. The CD4+Foxp3+ regulatory T-cells (Tregs) infiltrating into the central nervous system suppress neuroinflammation and promote the activation of neuroprotective microglia in mouse models of ALS. To our knowledge, the therapeutic association of host Treg expansion with ALS progression has not been studied in vivo. Objective To assess the role of Tregs in regulating the pathophysiology of ALS in humans and the therapeutic outcome of increasing Treg activity in a mouse model of the disease. Design, Setting, and Participants This prospective multicenter human and animal study was performed in hospitals, outpatient clinics, and research institutes. Clinical and function assessment, as well as immunological studies, were undertaken in 33 patients with sporadic ALS, and results were compared with 38 healthy control participants who were consecutively recruited from the multidisciplinary ALS clinic at Westmead Hospital between February 1, 2013, and December 31, 2014. All data analysis on patients with ALS was undertaken between January 2015 and December 2016. Subsequently, we implemented a novel approach to amplify the endogenous Treg population using peripheral injections of interleukin 2/interleukin 2 monoclonal antibody complexes (IL-2c) in transgenic mice that expressed mutant superoxide dismutase 1 (SOD1), a gene associated with motor neuron degeneration. Main Outcomes and Measures In patients with ALS, Treg levels were determined and then correlated with disease progression. Circulating T-cell populations, motor neuron size, glial cell activation, and T-cell and microglial gene expression in spinal cords were determined in SOD1G93A mice, as well as the association of Treg amplification with disease onset and survival time in mice. Results The cohort of patients with ALS included 24 male patients and 9 femal

Importance Neuroinflammation appears to be a key modulator of disease progression in amyotrophic lateral sclerosis (ALS) and thereby a promising therapeutic target. The CD4+Foxp3+ regulatory T-cells (Tregs) infiltrating into the central nervous system suppress neuroinflammation and promote the activation of neuroprotective microglia in mouse models of ALS. To our knowledge, the therapeutic association of host Treg expansion with ALS progression has not been studied in vivo. Objective To assess the role of Tregs in regulating the pathophysiology of ALS in humans and the therapeutic outcome of increasing Treg activity in a mouse model of the disease. Design, Setting, and Participants This prospective multicenter human and animal study was performed in hospitals, outpatient clinics, and research institutes. Clinical and function assessment, as well as immunological studies, were undertaken in 33 patients with sporadic ALS, and results were compared with 38 healthy control participants who were consecutively recruited from the multidisciplinary ALS clinic at Westmead Hospital between February 1, 2013, and December 31, 2014. All data analysis on patients with ALS was undertaken between January 2015 and December 2016. Subsequently, we implemented a novel approach to amplify the endogenous Treg population using peripheral injections of interleukin 2/interleukin 2 monoclonal antibody complexes (IL-2c) in transgenic mice that expressed mutant superoxide dismutase 1 (SOD1), a gene associated with motor neuron degeneration. Main Outcomes and Measures In patients with ALS, Treg levels were determined and then correlated with disease progression. Circulating T-cell populations, motor neuron size, glial cell activation, and T-cell and microglial gene expression in spinal cords were determined in SOD1G93A mice, as well as the association of Treg amplification with disease onset and survival time in mice. Results The cohort of patients with ALS included 24 male patients and 9 femal

This paper investigates the lateral vehicle performance when combining torque vectoring with active steering. The left and right front wheels are independently steered with linear actuators, where the steering angles are velocity dependent. The steering angle is combined with a torque vectoring algorithm and the left and right Ackermann ratio is adjusted for high speed turns to maintain tyre traction.

A diamond based microdosimeter prototype featuring a 3D lateral electrode structure was created using laser ablation and active brazing alloys and characterised by means of ion beam induced charge collection measurements and finite element analysis, using Synopsys TCAD simulation package.

A diamond based microdosimeter prototype featuring a 3D lateral electrode structure was created using laser ablation and active brazing alloys and characterised by means of ion beam induced charge collection measurements and finite element analysis, using Synopsys TCAD simulation package.

Objective Pilot study to examine the effect of radiofrequency ablation (RFA) of the lateral palatal fat pad in patients with socially-disruptive snoring. Method Snoring outcomes and complications were compared between a group of patients with treated with RFA ablation of the lateral soft palate fat pad with or without inferior turbinate reduction (8 patients) and another group undergoing inferior turbinate reduction alone (12 patients). Results Snoring loudness and bothersomeness improved in the palate but not inferior turbinate group. Pain was mild and no major complications were observed. Conclusion The study supports RFA ablation of the lateral palatal space as a potential low morbidity procedure for snoring.

This paper quantifies the CO2 emissions embodied in bi-lateral trade between Australia and China using a sectoral input-output model. The results revealed: (1) that China performs lower than Australia in clean technology in the primary, manufacturing, energy sectors due to their overuse of coal and inefficient sectoral production processes, and (2) that China had a 30.94 Mt surplus of bi-lateral CO2 emissions in 2010-2011 and (3) overall global emissions were reduced by 20.19 Mt through Australia-China trade in 2010-2011. The result indicates that the greater the energy efficient a country among the trading partners the lower will be the overall global CO2 emissions. Global emissions decreased mainly because China consumed Australian primary products rather than producing them. Australia is an energy efficient producer of primary products relative to China. The bilateral trade compositions and trade volume played an important role in lowering global emissions and therefore one can view proposed China Australia Free trade Agreement positively in reducing global emissions. However, for the sustainable development, China should strengthen clean energy use and both countries should adopt measures to create an emission trading scheme in order to avoid protectionism in the form of future border price adjustments.

This paper quantifies the CO2 emissions embodied in bi-lateral trade between Australia and China using a sectoral input-output model. The results revealed: (1) that China performs lower than Australia in clean technology in the primary, manufacturing, energy sectors due to their overuse of coal and inefficient sectoral production processes, and (2) that China had a 30.94 Mt surplus of bi-lateral CO2 emissions in 2010-2011 and (3) overall global emissions were reduced by 20.19 Mt through Australia-China trade in 2010-2011. The result indicates that the greater the energy efficient a country among the trading partners the lower will be the overall global CO2 emissions. Global emissions decreased mainly because China consumed Australian primary products rather than producing them. Australia is an energy efficient producer of primary products relative to China. The bilateral trade compositions and trade volume played an important role in lowering global emissions and therefore one can view proposed China Australia Free trade Agreement positively in reducing global emissions. However, for the sustainable development, China should strengthen clean energy use and both countries should adopt measures to create an emission trading scheme in order to avoid protectionism in the form of future border price adjustments.

Concrete-filled steel tubular (CFT) columns are widely used as columns in many structural systems and a common failure mode of such tubular columns is inelastic outward local buckling near a column end. The use of fibre-reinforced polymer (FRP) jackets/wraps for the suppression of such local buckling has recently been proposed and has been proven to possess excellent potential in both retrofit/strengthening and new construction. This paper presents the results of an experimental study into the behaviour of large-scale FRP-confined CFT (CCFT) columns under combined axial compression and lateral loading. The test parameters included the stiffness of the FRP jacket and the loading scenario. The test results showed that the FRP jacket can effectively delay or even prevent outward local buckling at the end of a cantilevered CFT column, leading to significantly improved structural performance under combined constant axial compression and cyclic lateral loading. Compared to monotonic lateral loading, cyclic lateral loading was found to introduce more severe localized deformation near the column end and may lead to earlier FRP rupture within that region.

This paper quantifies the CO2 emissions embodied in bi-lateral trade between Australia and China using a sectoral input-output model. The results revealed: (1) that China performs lower than Australia in clean technology in the primary, manufacturing, energy sectors due to their overuse of coal and inefficient sectoral production processes, and (2) that China had a 30.94 Mt surplus of bi-lateral CO2 emissions in 2010-2011 and (3) overall global emissions were reduced by 20.19 Mt through Australia-China trade in 2010-2011. The result indicates that the greater the energy efficient a country among the trading partners the lower will be the overall global CO2 emissions. Global emissions decreased mainly because China consumed Australian primary products rather than producing them. Australia is an energy efficient producer of primary products relative to China. The bilateral trade compositions and trade volume played an important role in lowering global emissions and therefore one can view proposed China Australia Free trade Agreement positively in reducing global emissions. However, for the sustainable development, China should strengthen clean energy use and both countries should adopt measures to create an emission trading scheme in order to avoid protectionism in the form of future border price adjustments.

The omni-directional vehicle is an innovative vehicle that has an in-wheel steering motor and in-wheel driving motor installed with each wheel. Each wheel of the omni-directional vehicle can be independently controlled so that the vehicle's mobility, handling and stability performance is greatly improved. Various control strategies such as active steering control, direct yaw moment control, and four-wheel drive control have been proposed to improve vehicle handling and stability performance. Most research, however, has only been done for traditional internal combustion vehicles, and the controller performance is constrained by the limitation of the actuators. In recent years, research has looked at the optimal distribution and control of the eight actuators, the steering angle of each wheel and the traction or brake torque of each wheel independently and in real time for an omni-directional vehicle. In this paper, an innovative side-slip angle estimation method developed for an omni-directional vehicle with in-wheel steering motors is applied to construct the side-slip angle controller and to determine the friction limit criteria for the overall control system. Optimal steering and driving actuator distribution and control is developed to improve the yaw rate response and body slip angle response of the vehicle. Finally, simulations are used to validate the proposed control method.

Laboratory model tests have been conducted to investigate the responses of piles subjected to lateral soil movement. The results of a single pile test and four tests on two piles arranged in a row perpendicular to the direction of soil movement are presented. The development of maximum bending moment, maximum shear force, and pile deflection with soil movement and the largest pile response profiles for the single pile and pile groups are compared. Group effect was evaluated using group factor which is defined in terms of the measured maximum bending moment. The major findings are (1) the pile head conditions (free or capped) are insignificant on piles subjected to lateral soil movement when arranged in a row, (2) the group factor decreases as the pile spacing reduces, (3) a linear relationship exists between the maximum bending moment and maximum shear force for both the pile groups and single pile.

Ballast being an unbounded granular medium spreads laterally when subjected to high-frequency cyclic loading. To reduce lateral movement of ballast and to optimize track performance, rail tracks can be reinforced with geogrid. In this study, a novel large-scale process simulation test (PST) apparatus that can capture the lateral strain variation upon loading is described. Laboratory tests were conducted to explore the deformation and degradation response of both unreinforced and reinforced ballast under high-frequency cyclic loading. Fresh Latite basalt having an average particle size (D50) of 35mm, and geogrids with different aperture sizes were tested. The laboratory experimental results reveal that the ballast deformation (both lateral and vertical) and the breakage during cyclic loading are influenced by the geogrid type and its placement location. Moreover, the lateral strain profiles along the ballast depth have been measured and the geogrid influence zone (GIZ), defined as the distance to which the effect of geogrid in arresting the lateral displacement of ballast exists, has been determined. The GIZ is found to vary from 160mm (4.60D50) to 225mm (6.45D50) depending on the location of the geogrid. In addition, the optimum geogrid position in the track has been identified to be 65mm above the subballast. The test results also exemplify the ability of geogrid to arrest lateral displacement of ballast, reduce settlement and minimize particle degradation under high-frequency cyclic loading.

The upper bound method of plasticity limit analysis is used to estimate the ultimate capacity of laterally loaded long piles. Based on a generic limiting force (or the ultimate soil resistance per unit length) profile, both freehead and fixed-head piles are considered. The current solutions can be reduced to available solutions for some special cases. Design charts may be constructed to estimate the lateral capacity of piles in terms of plastic moment and the parameters describing the limiting force profile.

Ballast being an unbounded granular medium spreads laterally when subjected to high-frequency cyclic loading. To reduce lateral movement of ballast and to optimize track performance, rail tracks can be reinforced with geogrid. In this study, a novel large-scale process simulation test (PST) apparatus that can capture the lateral strain variation upon loading is described. Laboratory tests were conducted to explore the deformation and degradation response of both unreinforced and reinforced ballast under high-frequency cyclic loading. Fresh Latite basalt having an average particle size (D50) of 35mm, and geogrids with different aperture sizes were tested. The laboratory experimental results reveal that the ballast deformation (both lateral and vertical) and the breakage during cyclic loading are influenced by the geogrid type and its placement location. Moreover, the lateral strain profiles along the ballast depth have been measured and the geogrid influence zone (GIZ), defined as the distance to which the effect of geogrid in arresting the lateral displacement of ballast exists, has been determined. The GIZ is found to vary from 160mm (4.60D50) to 225mm (6.45D50) depending on the location of the geogrid. In addition, the optimum geogrid position in the track has been identified to be 65mm above the subballast. The test results also exemplify the ability of geogrid to arrest lateral displacement of ballast, reduce settlement and minimize particle degradation under high-frequency cyclic loading.

The upper bound method of plasticity limit analysis is used to estimate the ultimate capacity of laterally loaded long piles. Based on a generic limiting force (or the ultimate soil resistance per unit length) profile, both freehead and fixed-head piles are considered. The current solutions can be reduced to available solutions for some special cases. Design charts may be constructed to estimate the lateral capacity of piles in terms of plastic moment and the parameters describing the limiting force profile.

Ballast being an unbounded granular medium spreads laterally when subjected to high-frequency cyclic loading. To reduce lateral movement of ballast and to optimize track performance, rail tracks can be reinforced with geogrid. In this study, a novel large-scale process simulation test (PST) apparatus that can capture the lateral strain variation upon loading is described. Laboratory tests were conducted to explore the deformation and degradation response of both unreinforced and reinforced ballast under high-frequency cyclic loading. Fresh Latite basalt having an average particle size (D50) of 35mm, and geogrids with different aperture sizes were tested. The laboratory experimental results reveal that the ballast deformation (both lateral and vertical) and the breakage during cyclic loading are influenced by the geogrid type and its placement location. Moreover, the lateral strain profiles along the ballast depth have been measured and the geogrid influence zone (GIZ), defined as the distance to which the effect of geogrid in arresting the lateral displacement of ballast exists, has been determined. The GIZ is found to vary from 160mm (4.60D50) to 225mm (6.45D50) depending on the location of the geogrid. In addition, the optimum geogrid position in the track has been identified to be 65mm above the subballast. The test results also exemplify the ability of geogrid to arrest lateral displacement of ballast, reduce settlement and minimize particle degradation under high-frequency cyclic loading.

The upper bound method of plasticity limit analysis is used to estimate the ultimate capacity of laterally loaded long piles. Based on a generic limiting force (or the ultimate soil resistance per unit length) profile, both freehead and fixed-head piles are considered. The current solutions can be reduced to available solutions for some special cases. Design charts may be constructed to estimate the lateral capacity of piles in terms of plastic moment and the parameters describing the limiting force profile.

The upper bound method of plasticity limit analysis is used to estimate the ultimate capacity of laterally loaded long piles. Based on a generic limiting force (or the ultimate soil resistance per unit length) profile, both freehead and fixed-head piles are considered. The current solutions can be reduced to available solutions for some special cases. Design charts may be constructed to estimate the lateral capacity of piles in terms of plastic moment and the parameters describing the limiting force profile.

Direct mapping of variability in soils can be a complex, time-consuming and costly process. Consequently, maps of geophysical data such as ground penetrating radar (GPR) and electromagnetic induction (EMI) are commonly used as proxies for soil maps, and these geophysical maps are most useful if they relate to variations in plant attributes such as grapevine trunk circumference. This article demonstrates that vine trunk circumference in five pinot noir vineyards is primarily influenced by changes in slope, elevation and aspect. Variability in GPR maps shows mixed correlations with vine trunk circumference data. In contrast, multi-frequency EMI surveys yield soil apparent electrical conductivity data that commonly show significant correlations with variations in vine trunk circumference data, especially when coupled with global positioning system surveys, suggesting that this is the preferred geophysical tool for mapping variability in soils.

As the first part of a sequence focusing on the dynamic response of composite caisson-piles foundations (CCPFs1), this paper develops a simplified method for the lateral response of these foundations. A Winkler model for the lateral vibration of the CCPF is created by joining the two components, the caisson and the pile group, where the four-spring Winkler model is utilized for the caisson and axial-lateral coupled vibration equations are derived for the pile group. For determining the coefficients of the four-spring Winkler model for the caissons, embedded footing impedance is used and a modification on the rotational embedment factor is made for the sake of the geometrical difference between shallow footings and caissons. Comparisons against results from finite element simulations demonstrate the reliability of this modified four-spring Winkler model for caissons in both homogenous and layered soils. The proposed simplified method for the lateral vibration of CCPFs is verified also by 3D finite element modeling. Finally, through an example, the idea of adding piles beneath the caisson is proved to be of great significance to enhance the resistance of the foundation against lateral dynamic loads.

Dissociation of superoxide dismutase 1 dimers is enhanced by glutathionylation, although the dissociation constants reported to date are imprecise. We have quantified the discreet dissociation constants for wild-type superoxide dismutase 1 and six naturally occurring sequence variants, in their unmodified and glutathionylated forms, at the ratios expressed. Unmodified superoxide dismutase 1 variants that shared similar dissociation constants with SOD1WT had disproportionately increased dissociation constants when glutathionylated. This defines a key role for glutathionylation in superoxide dismutase 1 associated familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing neurodegenerative disorder and the majority of ALS is sporadic, where misfolding and aggregation of Cu/Zn-superoxide dismutase (SOD1) is a feature shared with familial mutant-SOD1 cases. ALS is characterized by progressive neurospatial spread of pathology among motor neurons, and recently the transfer of extracellular, aggregated mutant SOD1 between cells was demonstrated in culture. However, there is currently no evidence that uptake of SOD1 into cells initiates neurodegenerative pathways reminiscent of ALS pathology. Similarly, whilst dysfunction to the ER-Golgi compartments is increasingly implicated in the pathogenesis of both sporadic and familial ALS, it remains unclear whether misfolded, wildtype SOD1 triggers ER-Golgi dysfunction. In this study we show that both extracellular, native wildtype and mutant SOD1 are taken up by macropinocytosis into neuronal cells. Hence uptake does not depend on SOD1 mutation or misfolding. We also demonstrate that purified mutant SOD1 added exogenously to neuronal cells inhibits protein transport between the ER-Golgi apparatus, leading to Golgi fragmentation, induction of ER stress and apoptotic cell death. Furthermore, we show that extracellular, aggregated, wildtype SOD1 also induces ER-Golgi pathology similar to mutant SOD1, leading to apoptotic cell death. Hence extracellular misfolded wildtype or mutant SOD1 induce dysfunction to ER-Golgi compartments characteristic of ALS in neuronal cells, implicating extracellular SOD1 in the spread of pathology among motor neurons in both sporadic and familial ALS.

Dissociation of superoxide dismutase 1 dimers is enhanced by glutathionylation, although the dissociation constants reported to date are imprecise. We have quantified the discreet dissociation constants for wild-type superoxide dismutase 1 and six naturally occurring sequence variants, in their unmodified and glutathionylated forms, at the ratios expressed. Unmodified superoxide dismutase 1 variants that shared similar dissociation constants with SOD1WT had disproportionately increased dissociation constants when glutathionylated. This defines a key role for glutathionylation in superoxide dismutase 1 associated familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing neurodegenerative disorder and the majority of ALS is sporadic, where misfolding and aggregation of Cu/Zn-superoxide dismutase (SOD1) is a feature shared with familial mutant-SOD1 cases. ALS is characterized by progressive neurospatial spread of pathology among motor neurons, and recently the transfer of extracellular, aggregated mutant SOD1 between cells was demonstrated in culture. However, there is currently no evidence that uptake of SOD1 into cells initiates neurodegenerative pathways reminiscent of ALS pathology. Similarly, whilst dysfunction to the ER-Golgi compartments is increasingly implicated in the pathogenesis of both sporadic and familial ALS, it remains unclear whether misfolded, wildtype SOD1 triggers ER-Golgi dysfunction. In this study we show that both extracellular, native wildtype and mutant SOD1 are taken up by macropinocytosis into neuronal cells. Hence uptake does not depend on SOD1 mutation or misfolding. We also demonstrate that purified mutant SOD1 added exogenously to neuronal cells inhibits protein transport between the ER-Golgi apparatus, leading to Golgi fragmentation, induction of ER stress and apoptotic cell death. Furthermore, we show that extracellular, aggregated, wildtype SOD1 also induces ER-Golgi pathology similar to mutant SOD1, leading to apoptotic cell death. Hence extracellular misfolded wildtype or mutant SOD1 induce dysfunction to ER-Golgi compartments characteristic of ALS in neuronal cells, implicating extracellular SOD1 in the spread of pathology among motor neurons in both sporadic and familial ALS.

Dissociation of superoxide dismutase 1 dimers is enhanced by glutathionylation, although the dissociation constants reported to date are imprecise. We have quantified the discreet dissociation constants for wild-type superoxide dismutase 1 and six naturally occurring sequence variants, in their unmodified and glutathionylated forms, at the ratios expressed. Unmodified superoxide dismutase 1 variants that shared similar dissociation constants with SOD1WT had disproportionately increased dissociation constants when glutathionylated. This defines a key role for glutathionylation in superoxide dismutase 1 associated familial amyotrophic lateral sclerosis.

Direct mapping of variability in soils can be a complex, time-consuming and costly process. Consequently, maps of geophysical data such as ground penetrating radar (GPR) and electromagnetic induction (EMI) are commonly used as proxies for soil maps, and these geophysical maps are most useful if they relate to variations in plant attributes such as grapevine trunk circumference. This article demonstrates that vine trunk circumference in five pinot noir vineyards is primarily influenced by changes in slope, elevation and aspect. Variability in GPR maps shows mixed correlations with vine trunk circumference data. In contrast, multi-frequency EMI surveys yield soil apparent electrical conductivity data that commonly show significant correlations with variations in vine trunk circumference data, especially when coupled with global positioning system surveys, suggesting that this is the preferred geophysical tool for mapping variability in soils.

Ballast being an unbounded granular medium spreads laterally when subjected to high-frequency cyclic loading. To reduce lateral movement of ballast and to optimize track performance, rail tracks can be reinforced with geogrid. In this study, a novel large-scale process simulation test (PST) apparatus that can capture the lateral strain variation upon loading is described. Laboratory tests were conducted to explore the deformation and degradation response of both unreinforced and reinforced ballast under high-frequency cyclic loading. Fresh Latite basalt having an average particle size (D50) of 35mm, and geogrids with different aperture sizes were tested. The laboratory experimental results reveal that the ballast deformation (both lateral and vertical) and the breakage during cyclic loading are influenced by the geogrid type and its placement location. Moreover, the lateral strain profiles along the ballast depth have been measured and the geogrid influence zone (GIZ), defined as the distance to which the effect of geogrid in arresting the lateral displacement of ballast exists, has been determined. The GIZ is found to vary from 160mm (4.60D50) to 225mm (6.45D50) depending on the location of the geogrid. In addition, the optimum geogrid position in the track has been identified to be 65mm above the subballast. The test results also exemplify the ability of geogrid to arrest lateral displacement of ballast, reduce settlement and minimize particle degradation under high-frequency cyclic loading.

Laboratory model tests have been conducted to investigate the responses of piles subjected to lateral soil movement. The results of a single pile test and four tests on two piles arranged in a row perpendicular to the direction of soil movement are presented. The development of maximum bending moment, maximum shear force, and pile deflection with soil movement and the largest pile response profiles for the single pile and pile groups are compared. Group effect was evaluated using group factor which is defined in terms of the measured maximum bending moment. The major findings are (1) the pile head conditions (free or capped) are insignificant on piles subjected to lateral soil movement when arranged in a row, (2) the group factor decreases as the pile spacing reduces, (3) a linear relationship exists between the maximum bending moment and maximum shear force for both the pile groups and single pile.

Dissociation of superoxide dismutase 1 dimers is enhanced by glutathionylation, although the dissociation constants reported to date are imprecise. We have quantified the discreet dissociation constants for wild-type superoxide dismutase 1 and six naturally occurring sequence variants, in their unmodified and glutathionylated forms, at the ratios expressed. Unmodified superoxide dismutase 1 variants that shared similar dissociation constants with SOD1WT had disproportionately increased dissociation constants when glutathionylated. This defines a key role for glutathionylation in superoxide dismutase 1 associated familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing neurodegenerative disorder and the majority of ALS is sporadic, where misfolding and aggregation of Cu/Zn-superoxide dismutase (SOD1) is a feature shared with familial mutant-SOD1 cases. ALS is characterized by progressive neurospatial spread of pathology among motor neurons, and recently the transfer of extracellular, aggregated mutant SOD1 between cells was demonstrated in culture. However, there is currently no evidence that uptake of SOD1 into cells initiates neurodegenerative pathways reminiscent of ALS pathology. Similarly, whilst dysfunction to the ER-Golgi compartments is increasingly implicated in the pathogenesis of both sporadic and familial ALS, it remains unclear whether misfolded, wildtype SOD1 triggers ER-Golgi dysfunction. In this study we show that both extracellular, native wildtype and mutant SOD1 are taken up by macropinocytosis into neuronal cells. Hence uptake does not depend on SOD1 mutation or misfolding. We also demonstrate that purified mutant SOD1 added exogenously to neuronal cells inhibits protein transport between the ER-Golgi apparatus, leading to Golgi fragmentation, induction of ER stress and apoptotic cell death. Furthermore, we show that extracellular, aggregated, wildtype SOD1 also induces ER-Golgi pathology similar to mutant SOD1, leading to apoptotic cell death. Hence extracellular misfolded wildtype or mutant SOD1 induce dysfunction to ER-Golgi compartments characteristic of ALS in neuronal cells, implicating extracellular SOD1 in the spread of pathology among motor neurons in both sporadic and familial ALS.

BACKGROUND: A custom moulded ankle orthosis with hinged joints potentially offers a better control over the subtalar joint and the ankle joint during lateral cutting movements, due to total contact design and increase in material strength. OBJECTIVES: To test the above hypothesis by comparing it to three other available orthoses. STUDY DESIGN: Repeated measures. METHODS: Eight subjects with a history of ankle sprains (Grade 2), and 11 subjects without such history performed lateral cutting movements in four test conditions: 1) non-orthotic, 2) custom-moulded ankle orthosis with hinges, 3) Sport-Stirrup, and 4) elastic ankle sleeve with plastic support. A VICON motion analysis system was used to study the motions at the ankle and subtalar joints. RESULTS: The custom-moulded ankle orthosis significantly lowered the inversion angle at initial contact (p = 0.006) and the peak inversion angle (p = 0.000) during lateral cutting movements in comparison to non-orthotic condition, while the other two orthoses did not. The three orthoses did not affect the plantarflexion motions, which had been suggested by previous studies to be important in shock wave attenuation. CONCLUSIONS: The custom-moulded ankle orthosis with hinges could better control inversion and thus expected to better prevent ankle sprain in lateral cutting movements. CLINICAL RELEVANCE: Custom-moulded ankle orthoses are not commonly used in preventing ankle sprains. This study raises the awareness of the use of custom-moulded ankle orthoses which are expected to better prevent ankle sprains.

The improvement of vibration characteristics of caisson foundation due to the piles added at the bottom is studied. Firstly, dynamic equilibriums for lateral vibration of caisson-pile composite foundation are created through the displacement coordination and internal force equilibrium s at the interface between the two parts of the caisson and piles. Vibration equilibriums for the part of caisson are created by external force balance with the utilization of dynamic Winkler model, and vibration characteristics of the part of piles are defined by the existing literatures. Secondly, the coefficients of dynamic Winkler model in vibration of caisson are studied, and improved expressions are derived. Finally, taking a composite foundation in layered soils as an example, the improving effect of piles under the caisson is observed. This example shows that the piles under the caisson can improve the dynamic performance of the foundation significantly.

'Lateral migration' refers to the application of technologies in a different sector and context from that in which they were originally developed (Pogue and Rampa, 2006). Lorentzen and Pogue (2009) and Jourdan (2010) have proposed that this is most likely to occur when there is: a significant market demand from local producers; local opportunity to test and commission new technologies; a cluster of firms that can support each other and cross fertilize ideas; and a strong base of R&D. In order to investigate these propositions a robust methodology is needed to identify the pathways along which such technology migration occurs and the ways it is facilitated or inhibited. This paper reports on a conceptual and methodological approach to investigate lateral migration of technology from the mining and energy sector in Australia. First, an econometric analysis is used to measure the extent of lateral migration of mining and energy technologies using patent, trade and input-output data sets to provide a quantitative account of which technologies are more successful than others in migrating into other sectors. Second we use a case study approach to investigate the processes that inhibit or facilitate lateral migration.

BACKGROUND: A custom moulded ankle orthosis with hinged joints potentially offers a better control over the subtalar joint and the ankle joint during lateral cutting movements, due to total contact design and increase in material strength. OBJECTIVES: To test the above hypothesis by comparing it to three other available orthoses. STUDY DESIGN: Repeated measures. METHODS: Eight subjects with a history of ankle sprains (Grade 2), and 11 subjects without such history performed lateral cutting movements in four test conditions: 1) non-orthotic, 2) custom-moulded ankle orthosis with hinges, 3) Sport-Stirrup, and 4) elastic ankle sleeve with plastic support. A VICON motion analysis system was used to study the motions at the ankle and subtalar joints. RESULTS: The custom-moulded ankle orthosis significantly lowered the inversion angle at initial contact (p = 0.006) and the peak inversion angle (p = 0.000) during lateral cutting movements in comparison to non-orthotic condition, while the other two orthoses did not. The three orthoses did not affect the plantarflexion motions, which had been suggested by previous studies to be important in shock wave attenuation. CONCLUSIONS: The custom-moulded ankle orthosis with hinges could better control inversion and thus expected to better prevent ankle sprain in lateral cutting movements. CLINICAL RELEVANCE: Custom-moulded ankle orthoses are not commonly used in preventing ankle sprains. This study raises the awareness of the use of custom-moulded ankle orthoses which are expected to better prevent ankle sprains.

The improvement of vibration characteristics of caisson foundation due to the piles added at the bottom is studied. Firstly, dynamic equilibriums for lateral vibration of caisson-pile composite foundation are created through the displacement coordination and internal force equilibrium s at the interface between the two parts of the caisson and piles. Vibration equilibriums for the part of caisson are created by external force balance with the utilization of dynamic Winkler model, and vibration characteristics of the part of piles are defined by the existing literatures. Secondly, the coefficients of dynamic Winkler model in vibration of caisson are studied, and improved expressions are derived. Finally, taking a composite foundation in layered soils as an example, the improving effect of piles under the caisson is observed. This example shows that the piles under the caisson can improve the dynamic performance of the foundation significantly.

BACKGROUND: A custom moulded ankle orthosis with hinged joints potentially offers a better control over the subtalar joint and the ankle joint during lateral cutting movements, due to total contact design and increase in material strength. OBJECTIVES: To test the above hypothesis by comparing it to three other available orthoses. STUDY DESIGN: Repeated measures. METHODS: Eight subjects with a history of ankle sprains (Grade 2), and 11 subjects without such history performed lateral cutting movements in four test conditions: 1) non-orthotic, 2) custom-moulded ankle orthosis with hinges, 3) Sport-Stirrup, and 4) elastic ankle sleeve with plastic support. A VICON motion analysis system was used to study the motions at the ankle and subtalar joints. RESULTS: The custom-moulded ankle orthosis significantly lowered the inversion angle at initial contact (p = 0.006) and the peak inversion angle (p = 0.000) during lateral cutting movements in comparison to non-orthotic condition, while the other two orthoses did not. The three orthoses did not affect the plantarflexion motions, which had been suggested by previous studies to be important in shock wave attenuation. CONCLUSIONS: The custom-moulded ankle orthosis with hinges could better control inversion and thus expected to better prevent ankle sprain in lateral cutting movements. CLINICAL RELEVANCE: Custom-moulded ankle orthoses are not commonly used in preventing ankle sprains. This study raises the awareness of the use of custom-moulded ankle orthoses which are expected to better prevent ankle sprains.

BACKGROUND: A custom moulded ankle orthosis with hinged joints potentially offers a better control over the subtalar joint and the ankle joint during lateral cutting movements, due to total contact design and increase in material strength. OBJECTIVES: To test the above hypothesis by comparing it to three other available orthoses. STUDY DESIGN: Repeated measures. METHODS: Eight subjects with a history of ankle sprains (Grade 2), and 11 subjects without such history performed lateral cutting movements in four test conditions: 1) non-orthotic, 2) custom-moulded ankle orthosis with hinges, 3) Sport-Stirrup, and 4) elastic ankle sleeve with plastic support. A VICON motion analysis system was used to study the motions at the ankle and subtalar joints. RESULTS: The custom-moulded ankle orthosis significantly lowered the inversion angle at initial contact (p = 0.006) and the peak inversion angle (p = 0.000) during lateral cutting movements in comparison to non-orthotic condition, while the other two orthoses did not. The three orthoses did not affect the plantarflexion motions, which had been suggested by previous studies to be important in shock wave attenuation. CONCLUSIONS: The custom-moulded ankle orthosis with hinges could better control inversion and thus expected to better prevent ankle sprain in lateral cutting movements. CLINICAL RELEVANCE: Custom-moulded ankle orthoses are not commonly used in preventing ankle sprains. This study raises the awareness of the use of custom-moulded ankle orthoses which are expected to better prevent ankle sprains.

The improvement of vibration characteristics of caisson foundation due to the piles added at the bottom is studied. Firstly, dynamic equilibriums for lateral vibration of caisson-pile composite foundation are created through the displacement coordination and internal force equilibrium s at the interface between the two parts of the caisson and piles. Vibration equilibriums for the part of caisson are created by external force balance with the utilization of dynamic Winkler model, and vibration characteristics of the part of piles are defined by the existing literatures. Secondly, the coefficients of dynamic Winkler model in vibration of caisson are studied, and improved expressions are derived. Finally, taking a composite foundation in layered soils as an example, the improving effect of piles under the caisson is observed. This example shows that the piles under the caisson can improve the dynamic performance of the foundation significantly.

The improvement of vibration characteristics of caisson foundation due to the piles added at the bottom is studied. Firstly, dynamic equilibriums for lateral vibration of caisson-pile composite foundation are created through the displacement coordination and internal force equilibrium s at the interface between the two parts of the caisson and piles. Vibration equilibriums for the part of caisson are created by external force balance with the utilization of dynamic Winkler model, and vibration characteristics of the part of piles are defined by the existing literatures. Secondly, the coefficients of dynamic Winkler model in vibration of caisson are studied, and improved expressions are derived. Finally, taking a composite foundation in layered soils as an example, the improving effect of piles under the caisson is observed. This example shows that the piles under the caisson can improve the dynamic performance of the foundation significantly.

Phase imaging in atomic force microscopy (AFM) is a useful technique for determining dissipative tip-sample interactions related to changes in the material surface properties such as local stiffness or adhesion. In this work, we applied both phase imaging and phase spectroscopy measurements to conducting polymer (polypyrrole) doped with either hyaluronic acid or chondroitin sulfate. As observed in previous studies, phase-separated regions correlating with the characteristic nodular topography of polypyrrole and attributed to crystalline (doped) and amorphous (undoped) regions were observed. However, through additional phase spectroscopy measurements, we show that the phase-separated regions can arise due to variation in attractive and repulsive tip-sample interactions across the polymer surface. We show that these attractive and repulsive interactions are dependent on the redox state and degree of doping and suggest that they are related to phase separation of the polymer surface charge and/or energy. The latter may have implications for these materials when under investigation in a fluid, or biological, environment. For example, such surface variations will play a role in electrostatic forces, which in turn can influence protein and cellular interactions. 2012 American Chemical Society.

'Lateral migration' refers to the application of technologies in a different sector and context from that in which they were originally developed (Pogue and Rampa, 2006). Lorentzen and Pogue (2009) and Jourdan (2010) have proposed that this is most likely to occur when there is: a significant market demand from local producers; local opportunity to test and commission new technologies; a cluster of firms that can support each other and cross fertilize ideas; and a strong base of R&D. In order to investigate these propositions a robust methodology is needed to identify the pathways along which such technology migration occurs and the ways it is facilitated or inhibited. This paper reports on a conceptual and methodological approach to investigate lateral migration of technology from the mining and energy sector in Australia. First, an econometric analysis is used to measure the extent of lateral migration of mining and energy technologies using patent, trade and input-output data sets to provide a quantitative account of which technologies are more successful than others in migrating into other sectors. Second we use a case study approach to investigate the processes that inhibit or facilitate lateral migration.

Phase imaging in atomic force microscopy (AFM) is a useful technique for determining dissipative tip-sample interactions related to changes in the material surface properties such as local stiffness or adhesion. In this work, we applied both phase imaging and phase spectroscopy measurements to conducting polymer (polypyrrole) doped with either hyaluronic acid or chondroitin sulfate. As observed in previous studies, phase-separated regions correlating with the characteristic nodular topography of polypyrrole and attributed to crystalline (doped) and amorphous (undoped) regions were observed. However, through additional phase spectroscopy measurements, we show that the phase-separated regions can arise due to variation in attractive and repulsive tip-sample interactions across the polymer surface. We show that these attractive and repulsive interactions are dependent on the redox state and degree of doping and suggest that they are related to phase separation of the polymer surface charge and/or energy. The latter may have implications for these materials when under investigation in a fluid, or biological, environment. For example, such surface variations will play a role in electrostatic forces, which in turn can influence protein and cellular interactions. 2012 American Chemical Society.

Phase imaging in atomic force microscopy (AFM) is a useful technique for determining dissipative tip-sample interactions related to changes in the material surface properties such as local stiffness or adhesion. In this work, we applied both phase imaging and phase spectroscopy measurements to conducting polymer (polypyrrole) doped with either hyaluronic acid or chondroitin sulfate. As observed in previous studies, phase-separated regions correlating with the characteristic nodular topography of polypyrrole and attributed to crystalline (doped) and amorphous (undoped) regions were observed. However, through additional phase spectroscopy measurements, we show that the phase-separated regions can arise due to variation in attractive and repulsive tip-sample interactions across the polymer surface. We show that these attractive and repulsive interactions are dependent on the redox state and degree of doping and suggest that they are related to phase separation of the polymer surface charge and/or energy. The latter may have implications for these materials when under investigation in a fluid, or biological, environment. For example, such surface variations will play a role in electrostatic forces, which in turn can influence protein and cellular interactions. 2012 American Chemical Society.

'Lateral migration' refers to the application of technologies in a different sector and context from that in which they were originally developed (Pogue and Rampa, 2006). Lorentzen and Pogue (2009) and Jourdan (2010) have proposed that this is most likely to occur when there is: a significant market demand from local producers; local opportunity to test and commission new technologies; a cluster of firms that can support each other and cross fertilize ideas; and a strong base of R&D. In order to investigate these propositions a robust methodology is needed to identify the pathways along which such technology migration occurs and the ways it is facilitated or inhibited. This paper reports on a conceptual and methodological approach to investigate lateral migration of technology from the mining and energy sector in Australia. First, an econometric analysis is used to measure the extent of lateral migration of mining and energy technologies using patent, trade and input-output data sets to provide a quantitative account of which technologies are more successful than others in migrating into other sectors. Second we use a case study approach to investigate the processes that inhibit or facilitate lateral migration.

Hybrid FRP-concrete-steel double-skin tubular columns (hybrid DSTCs) are a new form of hybrid columns developed at The Hong Kong Polytechnic University. They consist of an outer tube made of fibre reinforced polymer (FRP) and an inner tube made of steel, with the space between filled with concrete. In these hybrid DSTCs, the three constituent materials are optimally combined to achieve several advantages not available with existing forms of columns, including their superior corrosion and seismic performance. This paper presents the test results of a series of large-scale hybrid DSTCs subjected to combined axial and cyclic lateral loads, with an emphasis on the effect of a high strength concrete infill. All column specimens had a circular section with a diameter of 300 mm and a height of 1350 mm (from the point of lateral loading to the top surface of the stiff RC footing). The parameters examined include the concrete strength, the confinement stiffness of the GFRP tube and the axial load ratio. The test results showed that these hybrid DSTCs possess excellent ductility and hence excellent seismic resistance even when high strength concrete with a cylinder compressive strength of around 120 MPa is used.

This study surveys current international institutional cooperation to strengthen the implemetation of multilateral environment agreements (MEAs) by means of interlinkages between their compliance mechanisms. Ultimately, this should create synergies that increase the efficiency of implementation.

This study surveys current international institutional cooperation to strengthen the implemetation of multilateral environment agreements (MEAs) by means of interlinkages between their compliance mechanisms. Ultimately, this should create synergies that increase the efficiency of implementation.