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See detailEvaluation of intervention strategies for a road link in the Netherlands
Adey, Bryan Tyrone; Lethanh, Nam; Hartmann, Andreas et al

in Built Environment Project and Asset Management (2014), 4(2), 180-198

Purpose – The purpose of this paper is to investigate the use of the impact hierarchy and the optimization model to determine the optimal intervention strategy for a road link composed of multiple objects ... [more ▼]

Purpose – The purpose of this paper is to investigate the use of the impact hierarchy and the optimization model to determine the optimal intervention strategy for a road link composed of multiple objects. The paper focusses on the results of a case study of intervention project on A20 road link in Rotterdam, the Netherlands. Design/methodology/approach – The study was a case study research. It describes briefly the impact hierarchy and its link to the optimization model, and then focussed on analyzing the results obtained from running the model. In order to understand the influence of various factors affecting the results of optimization, sensitivity analysis was performed. Findings – The proposed hierarchy is suitable to be used to support the determination of optimal intervention strategies (OISs) for public road. From the case study, it was also realized that optimal intervention strategy can be changed due to not only intervention costs incurred by the owner, but also due to the setup of traffic configuration during the execution of interventions since the impacts incurred to users, directly affected public, and indirectly affected public are significantly different from one traffic configuration to the others. The optimal intervention strategy also depends greatly on the factors of deterioration during the operation of the infrastructure objects. Research limitations/implications – In the impact hierarchy, some impact factors are difficult to be quantified, e.g., the long-term economic impacts on the region where having intervention projects. The use of only exponential function for impacts could be oversimplified the actual behavior of the impacts. Other functional form should be investigated to be used within the framework of the optimization model. Practical implications – The proposed hierarchy and the optimization model could be used in practical situation for determination of OISs for multiple objects within a road link. Originality/value – This paper contributes to the body of knowledge of stakeholder analysis in the field of infrastructure asset management. It also gives a guideline and tool for infrastructure administrators to select the OISs for their infrastructure network. [less ▲]

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See detailProbenecid potentiates MPTP/MPP+ toxicity by interference with cellular energy metabolism.
Alvarez-Fischer, Daniel; Noelker, Carmen; Grünewald, Anne UL et al

in Journal of neurochemistry (2013), 127(6), 782-92

The uricosuric agent probenecid is co-administered with the dopaminergic neurotoxin MPTP to produce a chronic mouse model of Parkinson's disease. It has been proposed that probenecid serves to elevate ... [more ▼]

The uricosuric agent probenecid is co-administered with the dopaminergic neurotoxin MPTP to produce a chronic mouse model of Parkinson's disease. It has been proposed that probenecid serves to elevate concentrations of MPTP in the brain by reducing renal elimination of the toxin. However, this mechanism has never been formally demonstrated to date and is questioned by our previous data showing that intracerebral concentrations of MPP(+), the active metabolite of MPTP, are not modified by co-injection of probenecid. In this study, we investigated the potentiating effects of probenecid in vivo and in vitro arguing against the possibility of altered metabolism or impaired renal elimination of MPTP. We find that probenecid (i) is toxic in itself to several neuronal populations apart from dopaminergic neurons, and (ii) that it also potentiates the effects of other mitochondrial complex I inhibitors such as rotenone. On a mechanistic level, we show that probenecid is able to lower intracellular ATP concentrations and that its toxic action on neuronal cells can be reversed by extracellular ATP. Probenecid can potentiate the effect of mitochondrial toxins due to its impact on ATP metabolism and could therefore be useful to model atypical parkinsonian syndromes. [less ▲]

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See detailBee venom and its component apamin as neuroprotective agents in a Parkinson disease mouse model.
Alvarez-Fischer, Daniel; Noelker, Carmen; Vulinovic, Franca et al

in PloS one (2013), 8(4), 61700

Bee venom has recently been suggested to possess beneficial effects in the treatment of Parkinson disease (PD). For instance, it has been observed that bilateral acupoint stimulation of lower hind limbs ... [more ▼]

Bee venom has recently been suggested to possess beneficial effects in the treatment of Parkinson disease (PD). For instance, it has been observed that bilateral acupoint stimulation of lower hind limbs with bee venom was protective in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In particular, a specific component of bee venom, apamin, has previously been shown to have protective effects on dopaminergic neurons in vitro. However, no information regarding a potential protective action of apamin in animal models of PD is available to date. The specific goals of the present study were to (i) establish that the protective effect of bee venom for dopaminergic neurons is not restricted to acupoint stimulation, but can also be observed using a more conventional mode of administration and to (ii) demonstrate that apamin can mimic the protective effects of a bee venom treatment on dopaminergic neurons. Using the chronic mouse model of MPTP/probenecid, we show that bee venom provides sustained protection in an animal model that mimics the chronic degenerative process of PD. Apamin, however, reproduced these protective effects only partially, suggesting that other components of bee venom enhance the protective action of the peptide. [less ▲]

Detailed reference viewed: 105 (4 UL)