The Learning Tourism Destination: The potential of a learning organisation approach for improving the sustainability of tourism destinations

Globalisation, increasing complexity, and the need to address triple-bottom line sustainability has seen the proliferation of Learning Organisations (LO) who, by definition, have the capacity to anticipate environmental changes and economic opportunities and adapt accordingly. Such organisations use system dynamics modelling (SDM) for both strategic planning and the promotion of organisational learning. Although SDM has been applied in the context of tourism destination management for predictive reasons, the current literature does not analyse or recognise how this could be used as a foundation for an LO. This study introduces the concept of the Learning Tourism Destinations (LTD) and discusses, on the basis of a review of 6 case studies, the potential of SDM as a tool for the implementation and enhancement of collective learning processes. The results reveal that SDM is capable of promoting communication between stakeholders and stimulating organisational learning. It is suggested that the LTD approach be further utilised and explored

Molecular characterization and analysis of the acrB gene of Aspergillus nidulans: A gene identified by genetic interaction as a component of the regulatory network that includes the CreB deubiquitination enzyme

Copyright © 2003 by the Genetics Society of AmericaMutations in the acrB gene, which were originally selected through their resistance to acriflavine, also result in reduced growth on a range of sole carbon sources, including fructose, cellobiose, raffinose, and starch, and reduced utilization of ω-amino acids, including GABA and ß-alanine, as sole carbon and nitrogen sources. The acrB2 mutation suppresses the phenotypic effects of mutations in the creB gene that encodes a regulatory deubiquitinating enzyme, and in the creC gene that encodes a WD40-repeat-containing protein. Thus AcrB interacts with a regulatory network controlling carbon source utilization that involves ubiquitination and deubiquitination. The acrB gene was cloned and physically analyzed, and it encodes a novel protein that contains three putative transmembrane domains and a coiled-coil region. AcrB may play a role in the ubiquitination aspect of this regulatory network.Natasha A. Boase, Robin A. Lockington, Julian R. J. Adams, Louise Rodbourn and Joan M. Kell

Estimating groundwater evapotranspiration by a subtropical pine plantation using diurnal water table fluctuations: implications from night-time water use

Exotic pine plantations have replaced large areas of the native forests for timber production in the subtropical coastal Australia. To evaluate potential impacts of changes in vegetation on local groundwater discharge, we estimated groundwater evapotranspiration (ET) by the pine plantation using diurnal water table fluctuations for the dry season of 2012 from August 1st to December 31st. The modified White method was used to estimate the ET, considering the night-time water use by pine trees (T). Depth-dependent specific yields were also determined both experimentally and numerically for estimation of ET. Night-time water use by pine trees was comprehensively investigated using a combination of groundwater level, sap flow, tree growth, specific yield, soil matric potential and climatic variables measurements. Results reveal a constant average transpiration flux of 0.02 mm h at the plot scale from 23:00 to 05:00 during the study period, which verified the presence of night-time water use. The total ET for the period investigated was 259.0 mm with an accumulated T of 64.5 mm, resulting in an error of 25% on accumulated evapotranspiration from the groundwater if night-time water use was neglected. The results indicate that the development of commercial pine plantations may result in groundwater losses in these areas. It is also recommended that any future application of diurnal water table fluctuation based methods investigate the validity of the zero night-time water use assumption prior to use

Spreading of a density front in the K\"untz-Lavall\'ee model of porous media

We analyze spreading of a density front in the K\"untz-Lavall\'ee model of porous media. In contrast to previous studies, where unusual properties of the front were attributed to anomalous diffusion, we find that the front evolution is controlled by normal diffusion and hydrodynamic flow, the latter being responsible for apparent enhancement of the front propagation speed. Our finding suggests that results of several recent experiments on porous media, where anomalous diffusion was reported based on the density front propagation analysis, should be reconsidered to verify the role of a fluid flow

A model for reactive porous transport during re-wetting of hardened concrete

A mathematical model is developed that captures the transport of liquid water in hardened concrete, as well as the chemical reactions that occur between the imbibed water and the residual calcium silicate compounds residing in the porous concrete matrix. The main hypothesis in this model is that the reaction product -- calcium silicate hydrate gel -- clogs the pores within the concrete thereby hindering water transport. Numerical simulations are employed to determine the sensitivity of the model solution to changes in various physical parameters, and compare to experimental results available in the literature.Comment: 30 page

Wicking and evaporation of liquids in porous wicks: a simple analytical approach to optimization of wick design

Wicking and evaporation of volatile liquids in porous, cylindrical wicks is investigated where the goal is to model, using simple analytical expressions, the effects of variation in geometrical parameters of a wick, such as porosity, height and bead-size, on the wicking and evaporation processes, and find optimum design conditions. An analytical sharp-front flow model involving the single-phase Darcy’s law is combined with analytical expressions for the capillary suction pressure and wick permeability to yield a novel analytical approach for optimizing wick parameters. First, the optimum beadradius and porosity maximizing the wicking flow-rate are estimated. Later, after combining the wicking model with evaporation from the wick-top, the allowable ranges of bead-radius, height and porosity for ensuring full saturation of the wick are calculated. The analytical results are demonstrated using some highly volatile alkanes in a polycarbonate sintered wick

The molecular basis of atypicality in antipsychotic drug action

Dopamine D2 receptor (D2R) antagonism is thought to be the pharmacological mechanism behind the clinical efficacy of antipsychotic drugs (APDs) in treating the positive symptoms of schizophrenia. Unfortunately, D2R antagonism is also associated with extrapyramidal symptoms (EPS) that encompass a range of motor side effects. More recently developed APDs are termed ‘atypical’ based on their low propensity to cause EPS. Despite several suggested hypotheses, no single mechanism has yet to account for all cases of atypicality in clinically prescribed APDs. This thesis explored two promising molecular mechanisms recently proposed to account for APD atypicality: (1) the reduced rebinding of atypical APDs to D2R resulting in surmountable D2R antagonism and (2) the low efficacy of atypical APDs as pharmacological chaperones of D2R, resulting in reduced D2R upregulation to the cell surface. First, in-solution reads of fluorescent APDs with differing binding kinetics at D2R, spiperone-d2 and clozapine-Cy5, were optimised using the advanced spectroscopy technique, fluorescence correlation spectroscopy (FCS). In addition, the variable expression of SNAP-D2R in a CHO tetracycline-inducible SNAP-D2R cell line was characterised using confocal imaging and FCS. FCS was also used to investigate the membrane dynamics of SNAP-D2R within CHO tetracycline-inducible SNAP-D2R cells which revealed that a small percentage of receptors may form clusters on the plasma membrane. Subsequently, the rebinding effects of these fluorescent APDs at D2R were investigated by measuring their concentration above cells with a range of SNAP-D2R expression levels. A high concentration of spiperone-d2 was found near the upper membrane of D2R-expressing cells which decreased further away from cells into the bulk aqueous solution. Interestingly, spiperone-d2 formed concentration gradients above cells that were dependent on the level of SNAP-D2R expression at the plasma membrane. These concentration gradients were indicative of spiperone-d2 rebinding to D2R and provided evidence of drug rebinding in vitro. In contrast, clozapine-Cy5, which has a slower association rate, showed negligible concentrating effects above D2R-expressing cells. When an added concentration of 0.2 x Kd of each fluorescent APD was used, the concentrating effect at 3 μm above the membrane of high D2R- expressing cells was 95-fold greater for spiperone-d2 in comparison to clozapine-Cy5. This is consistent with the association rate of APDs at D2R being the driver for APD rebinding, resulting in sustained D2R antagonism leading to higher EPS risks. The APD-induced trafficking of D2R to various cellular compartments was next investigated using a bystander BRET-based D2R trafficking assay and confocal imaging. Most notably, APDs showed differing efficacies as pharmacological chaperones of D2R by increasing D2R trafficking from the endoplasmic reticulum to the plasma membrane. Interestingly, APDs that showed high efficacy for D2R chaperoning were also associated with high EPS risks. However, the APD-induced upregulation of D2R at the plasma membrane was also shown to be acutely reversible in vitro. Finally, the optimisation of the primary culture of striatal neurones from SNAP-D2R mice was carried out with the aim of extending studies into more therapeutically relevant cells. Determining the molecular basis behind the atypicality of APDs would enable better prediction of the EPS risks of future APDs, ultimately leading to the improved treatment of schizophrenia and other psychiatric disorders where psychosis is a primary symptom

The molecular basis of atypicality in antipsychotic drug action

Dopamine D2 receptor (D2R) antagonism is thought to be the pharmacological mechanism behind the clinical efficacy of antipsychotic drugs (APDs) in treating the positive symptoms of schizophrenia. Unfortunately, D2R antagonism is also associated with extrapyramidal symptoms (EPS) that encompass a range of motor side effects. More recently developed APDs are termed ‘atypical’ based on their low propensity to cause EPS. Despite several suggested hypotheses, no single mechanism has yet to account for all cases of atypicality in clinically prescribed APDs. This thesis explored two promising molecular mechanisms recently proposed to account for APD atypicality: (1) the reduced rebinding of atypical APDs to D2R resulting in surmountable D2R antagonism and (2) the low efficacy of atypical APDs as pharmacological chaperones of D2R, resulting in reduced D2R upregulation to the cell surface. First, in-solution reads of fluorescent APDs with differing binding kinetics at D2R, spiperone-d2 and clozapine-Cy5, were optimised using the advanced spectroscopy technique, fluorescence correlation spectroscopy (FCS). In addition, the variable expression of SNAP-D2R in a CHO tetracycline-inducible SNAP-D2R cell line was characterised using confocal imaging and FCS. FCS was also used to investigate the membrane dynamics of SNAP-D2R within CHO tetracycline-inducible SNAP-D2R cells which revealed that a small percentage of receptors may form clusters on the plasma membrane. Subsequently, the rebinding effects of these fluorescent APDs at D2R were investigated by measuring their concentration above cells with a range of SNAP-D2R expression levels. A high concentration of spiperone-d2 was found near the upper membrane of D2R-expressing cells which decreased further away from cells into the bulk aqueous solution. Interestingly, spiperone-d2 formed concentration gradients above cells that were dependent on the level of SNAP-D2R expression at the plasma membrane. These concentration gradients were indicative of spiperone-d2 rebinding to D2R and provided evidence of drug rebinding in vitro. In contrast, clozapine-Cy5, which has a slower association rate, showed negligible concentrating effects above D2R-expressing cells. When an added concentration of 0.2 x Kd of each fluorescent APD was used, the concentrating effect at 3 μm above the membrane of high D2R- expressing cells was 95-fold greater for spiperone-d2 in comparison to clozapine-Cy5. This is consistent with the association rate of APDs at D2R being the driver for APD rebinding, resulting in sustained D2R antagonism leading to higher EPS risks. The APD-induced trafficking of D2R to various cellular compartments was next investigated using a bystander BRET-based D2R trafficking assay and confocal imaging. Most notably, APDs showed differing efficacies as pharmacological chaperones of D2R by increasing D2R trafficking from the endoplasmic reticulum to the plasma membrane. Interestingly, APDs that showed high efficacy for D2R chaperoning were also associated with high EPS risks. However, the APD-induced upregulation of D2R at the plasma membrane was also shown to be acutely reversible in vitro. Finally, the optimisation of the primary culture of striatal neurones from SNAP-D2R mice was carried out with the aim of extending studies into more therapeutically relevant cells. Determining the molecular basis behind the atypicality of APDs would enable better prediction of the EPS risks of future APDs, ultimately leading to the improved treatment of schizophrenia and other psychiatric disorders where psychosis is a primary symptom