Influence of compaction procedure on the mechanical behaviour of an unsaturated compacted clay, Part 1: Wetting and Isotropic Compression

The influence of compaction pressure, compaction water content and type of compaction (static or dynamic) on subsequent soil behaviour during wetting and isotropic loading has been investigated by conducting controlled-suction tests on samples of unsaturated compacted speswhite kaolin. The results are interpreted within the context of an elastoplastic framework for unsaturated soils, to examine which compaction-induced effects can be explained simply by variation in the initial state of the soil and which require that soils produced by different compaction procedures are modelled as fundamentally different materials. The compaction pressure influences initial state, by affecting the initial position of the yield surface, but it also influences, to a limited degree, the positions of the normal compression lines for different values of suction. The compaction water content influences the initial suction, but also has a significant influence (greater than does compaction pressure) on the positions of the normal compression lines. A change from static to dynamic compaction has no significant effect on subsequent behaviour

Influence of compaction procedure on the mechanical behaviour of an unsaturated compacted clay. Part 2: shearing and constitutive modelling

The influence of compaction pressure, compaction water content and type of compaction (static or dynamic) on subsequent soil behaviour was investigated by conducting controlled-suction triaxial tests on samples of unsaturated compacted speswhite kaolin. Compaction pressure influences initial state, by determining the initial position of the yield surface, thus affecting, among other things, the shape of stress–strain curves during shearing. Compaction pressure also influences, to a limited degree, the positions of the normal compression lines for different values of suction, but it has no effect on critical state relationships. The effect of compaction pressure can probably be modelled solely in terms of initial state if an anisotropic elastoplastic model incorporating rotational hardening is employed, whereas the parameters defining the slopes and intercepts of the normal compression lines for different values of suction require adjustment with variation of compaction pressure if a conventional isotropic hardening elastoplastic model is employed. Compaction water content influences the initial suction, but also has a substantial influence on normal compression lines and a noticeable effect on the volumetric behaviour at critical states. It is likely that soil samples compacted at different water contents will have to be modelled as different materials, irrespective of whether an isotropic or anisotropic hardening elastoplastic model is employed. A change from static to dynamic compaction has no significant effect on subsequent behaviour.

Inflammation and Anti-inflammatory strategies for alzheimer disease a mini review

Until recently, the central nervous system (CNS) has been thought to be an immune privileged organ. However, it is now understood that neuroinflammation is linked with the development of several CNS diseases including late-onset Alzheimer's disease (LOAD). The development of inflammation is a complex process involving a wide array of molecular interactions which in the CNS remains to be further characterized. The development of neuroinflammation may represent an important link between the early stages of LOAD and its pathological outcome. It is proposed that risks for LOAD, which include genetic, biological and environmental factors can each contribute to impairment of normal CNS regulation and function. The links between risk factors and the development of neuroinflammation are numerous and involve many complex interactions which contribute to vascular compromise, oxidative stress and ultimately neuroinflammation. Once this cascade of events is initiated, the process of neuroinflammation can become overactivated resulting in further cellular damage and loss of neuronal function. Additionally, neuroinflammation has been associated with the formation of amyloid plaques and neurofibrillary tangles, the pathological hallmarks of LOAD. Increased levels of inflammatory markers have been correlated with an advanced cognitive impairment. Based on this knowledge, new therapies aimed at limiting onset of neuroinflammation could arrest or even reverse the development of the disease.

Antibody Targeting of Cathepsin S Inhibits Angiogenesis and Synergistically Enhances Anti-VEGF

BACKGROUND: Angiogenesis is a key hallmark of tumourigenesis and its inhibition is a proven strategy for the development of novel anti-cancer therapeutics. An important aspect of early angiogenesis is the co-ordinated migration and invasion of endothelial cells through the hypoxic tumour tissue. Cathepsin S has been shown to play an important role in angiogenesis as has vascular endothelial growth factor (VEGF). We sought to assess the anti-angiogenic effect of Fsn0503, a novel cathepsin S inhibitory antibody, when combined with anti-VEGF on vascular development.

METHODOLOGY/PRINCIPAL FINDINGS: Cathepsin S expression and secretion from endothelial cells was characterised using RT-PCR and western blotting. We further show that cathepsin S promotes pericellular hydrolysis of extracellular matrix components in the tumour microenvironment and facilitates endothelial invasion. The cathepsin S inhibitory antibody, Fsn0503, blocks extracellular proteolysis, inhibiting endothelial invasion and tube formation in cell-based assays. The anti-angiogenic effects of Fsn0503 were also shown in vivo where it significantly retarded the development of vasculature in human xenograft models. Furthermore, when Fsn0503 was combined with an anti-VEGF antibody, a synergistic inhibition of microvascular development was observed.

CONCLUSIONS/SIGNIFICANCE: Taken together, this data demonstrates that the antibody-mediated targeting of cathepsin S represents a novel method of inhibiting angiogenesis. Furthermore, when used in combination with anti-VEGF therapies, Fsn0503 has the potential to significantly enhance current treatments of tumour neovascularisation and may also be of use in the treatment of other conditions associated with inappropriate angiogenesis.

Attitudes, norms, identity and environmental behaviour: Using an expanded theory of planned behaviour to predict participation in a kerbside recycling programme

In an effort to contribute to greater understanding of norms and identity in the theory of planned behaviour, an extended model was used to predict residential kerbside recycling, with self-identity, personal norms, neighbourhood identification, and injunctive and descriptive social norms as additional predictors. Data from a field study (N = 527) using questionnaire measures of predictor variables and an observational measure of recycling behaviour supported the theory. Intentions predicted behaviour, while attitudes, perceived control, and the personal norm predicted intention to recycle. The interaction between neighbourhood identification and injunctive social norms in turn predicted personal norms. Self-identity and the descriptive social norm significantly added to the original theory in predicting intentions as well as behaviour directly. A replication survey on the self-reported recycling behaviours of a random residential sample (N = 264) supported the model obtained previously. These findings offer a useful extension of the theory of planned behaviour and some practicable suggestions for pro-recycling interventions. It may be productive to appeal to self-identity by making people feel like recyclers, and to stimulate both injunctive and descriptive norms in the neighbourhood.