Classical osteogenesis imperfecta (OI) is a bone disease caused by type I collagen mutations and characterized by bone fragility, frequent fractures in absence of trauma and growth deficiency. No definitive cure is available for OI and to develop novel drug therapies, taking advantage of a repositioning strategy, the small teleost zebrafish (Danio rerio) is a particularly appealing model. Its small size, high proliferative rate, embryo transparency and small amount of drug required make zebrafish the model of choice for drug screening studies, when a valid disease model is available. We performed a deep characterization of the zebrafish mutant Chihuahua, that carries a G574D (p.G736D) substitution in the α1 chain of type I collagen. We successfully validated it as a model for classical OI. Growth of mutants was delayed compared with WT. X-ray, µCT, alizarin red/alcian blue and calcein staining revealed severe skeletal deformity, presence of fractures and delayed mineralization. Type I collagen extracted from different tissues showed abnormal electrophoretic migration and low melting temperature. The presence of endoplasmic reticulum (ER) enlargement due to mutant collagen retention in osteoblasts and fibroblasts of mutant fish was shown by electron and confocal microscopy. Two chemical chaperones, 4PBA and TUDCA, were used to ameliorate the cellular stress and indeed 4PBA ameliorated bone mineralization in larvae and skeletal deformities in adult, mainly acting on reducing ER cisternae size and favoring collagen secretion. In conclusion, our data demonstrated that ER stress is a novel target to ameliorate OI phenotype; chemical chaperones such as 4PBA may be, alone or in combination, a new class of molecules to be further investigated for OI treatment.

This paper proposes a theoretical model of evaluation of environmental externalities based on the analysis of real estate prices. This issue is included in regional planning policies which include activities and interventions that produce economic and non-economic effects. The monetary assessment of economic and non-economic effects can be expressed as a forecast (ex ante) and/or following (ex post) such activities and interventions. The assessment of the economic impact, with particular reference to interventions and infrastructure work, is widely based on procedures which make use of market prices. The proposed model was applied to an actual case, considering the effects of noise pollution, produced by traffic from the Naples Beltway, on residential property.

Abstract:The main aim of this paper is the interpretation of the existing relationship between real estate rental prices and geographical location of housing units in a central urban area of Naples (Santa Lucia and Riviera of Chiaia neighborhoods). Genetic algorithms (GA) are used for this purpose. Also, to verify the reliability of genetic algorithms for real estate appraisals and, at the same time, to show the forecasting potentialities of these techniques in the analysis of housing markets, a multiple regression analysis (MRA) was applied comparing results of GA and MRA.

Abstract:This paper experiments an artificial neural networks model with Bayesian approach on a small real estate sample. The output distribution has been calculated operating a numerical integration on the weights space with the Markov Chain Hybrid Monte Carlo Method (MCHMCM). On the same real estate sample, MCHMCM has been compared with a neural networks model (NNs), traditional multiple regression analysis (MRA) and the Penalized Spline Semiparametric Method (PSSM). All four methods have been developed for testing the forecasting capacity and reliability of MCHMCM in the real estate field. The Markov Chain Hybrid Monte Carlo Method has proved to be the best model with an absolute average percentage error of 6.61%.

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