Agglomeration economies, knowledge spillovers, technological diversity and spatial clustering of innovations.

This paper explores the spatial patterns of innovative activities from an empirical perspective and with reference to the Italian case. Using patent and other economic data at the NUTS 3 level (provinces), it borrows methodology and techniques from spatial statistics in order to analyse the way innovative and economic activities are arranged in space. Results show that innovative activities are considerably more spatially concentrated than production, but that there are also large differences across sectors in the spatial patterns of innovation. In mechanical engineering, industrial equipment and instruments sectors innovative activities tend to cluster around local systems of contiguous provinces, while in most chemical and electronic sectors innovative activities tend to concentrate in few metropolitan provinces surrounded by other non-innovative provinces. Regression analysis is also carried out to evaluate the impact of agglomeration economies, knowledge spillovers and technological diversity on the innovative performance of provinces.

Technological change and international competitiveness: the case of Switzerland.

The paper presents the preliminary results of a research project on the relationship between technological and trade performance with a special focus on Switzerland. The analysis is based on two sources of data: a dataset based on patent applications by firms from major industrialized countries to the European Patent Office (EPO) and a data set on export flows of OECD countries (IMPEX database). For both datasets, the period of time is 1980-1992. The analysis is carried out both for the whole aggregate of manufacturing sectors (WS49) and for a subsample of high-tech sectors (HT49). In the first part of the paper, the relationship between trade and technological variables is analyzed descriptively using indexes of technological (RTA) and trade specialization (RCA). Then, in the second part of the paper, the relationship between trade and technological specialization is analyzed using econometric techniques and exploiting the information contained in the datasets along three dimensions: country, sector, time. Finally, sectoral and geographical patterns of innovative activities are analyzed for the case of Switzerland. The paper broadly confirms the existence of a positive relationship between technological and trade specialization. Such relationship is also stable over time. However, the relationship is not very strong and it holds differently across countries.

Spatial patterns of innovation and trade competitiveness

A renewed concern has been growing recently for the role that the spatial organisation of innovation and production plays in determining trade performances. Purely technological externalities can be seen as a core component of this process, and their degree of influence can be investigated in terms of how factors that shape the structure of the innovative activity are definite in space. In the present paper we explore the relationship between technological and trade performances by focusing on the spatial configuration of different structures of the innovative activity in high technology industries in Italy. The data used in the analysis are based on the European Patent Office data base and on trade statistics from the five digit S.I.T.C. classification, and are spatially referenced to the Italy NUT 3 regional partition. Technological and knowledge externalities are modelled through the use of information associated to the connectivity structure of the geographical system under study. The analysis is ultimately aimed at investigating how technology factors evolve with respect to specific and space related carachteristics of the industrial context giving rise to cumulativeness of technology advantages, and to what extent these factors appear to affect trade competitiveness in specific industries. Keywords: spatial externalities. spatial innovation systems. trade competitiveness

Knowledge spillovers and local innovation systems: a critical survey

The paper re-examines critically the growing literature on localised knowledge spillovers (LKSs), and finds the econometric evidence on the subject still lacking of a firm theoretical background, especially in respect of the more recent developments in the economics of knowledge. Therefore such evidence, and even more the concept itself of LKS, should not be read as supportive of new industrial geographers' work on industrial districts, hi-tech agglomerations and 'milieux innovateur'. On the contrary, it may represent a threat to the necessary efforts for gaining more theoretical rigour and getting more empirical fieldwork done. Key words: knowledge, innovation, spillovers, externalities, regional agglomeration. JEL classification: D62, O30, R12

How urban social networks help to inspire creativity in American cities

Cities are an important driver of economic growth – in the last twenty years 90 percent of new patent applications have come from cities. But what influences how inventive cities are? In new research which examines more than 300 US cities, Stefano Breschi and Camilla Lenzi find that the most inventive cities are those where people are more able to reach, collaborate, and form groups with others with inventive talents both in their city and across cities

Cholinesterase-like organocatalysis by imidazole and imidazole-bearing molecules

Organocatalysis, which is mostly explored for its new potential industrial applications, also represents a chemical event involved in endogenous processes. In the present study, we provide the first evidence that imidazole and imidazole derivatives have cholinesterase-like properties since they can accelerate the hydrolysis of acetylthiocholine and propionylthiocholine in a concentration-dependent manner. The natural imidazole-containing molecules as L-histidine and histamine show a catalytic activity, comparable to that of imidazole itself, whereas synthetic molecules, as cimetidine and clonidine, were less active. In the experimental conditions used, the reaction progress curves were sigmoidal and the rational of such unexpected behavior as well as the mechanism of catalysis is discussed. Although indirectly, findings of the present study suggests that imidazolic compounds may interfere with the homeostasis of the cholinergic system in vivo

Application of a pharmacokinetic/pharmacogenetic approach to assess the nicotine metabolic profile of smokers in the real-life setting

The nicotine metabolite ratio, i.e., the ratio 3-hydroxycotinine/cotinine, is used to assess the nicotine metabolic status and has been proven to predict the response to smoking cessation treatments in randomized clinical trials. In the current study, a pharmacokinetic-pharmacogenetic integrated approach is described, based on the development of a liquid chromatography–tandem mass spectrometry (LC/MS/MS) method for nicotine metabolite ratio assay in plasma and a real-time PCR analysis for fast genotyping of CYP2A6. The pharmacokinetic-pharmacogenetic approach was validated in 66 subjects with different smoking status. The LC/MS/MS assay was rapid and sensitive enough to detect plasma cotinine levels also in second-hand exposed abstainers. In the cohort of patients of the present study the following results were obtained: (i) the frequencies of CYP2A6 genetic variants were comparable with those from clinical trials carried out in Caucasian populations; (ii) all the subjects carrying the CYP2A6 deficient allele also had a slow metabolizer phenotype; (iii) slow metabolizers had mean nicotine metabolite ratio approximately 50% of that of the normal/fast metabolizers; (iv) women had higher nicotine metabolite ratio than men; and (v) salivary nicotine metabolite ratio measures were comparable to plasma levels. Overall, the findings of the current study demonstrate that the simultaneous assessment of nicotine metabolite ratio and CYP2A6 genotype from human blood samples is feasible and accurate and could be used in a smoking cessation program to optimize treatments and identify those smokers who inherit metabolically deficient CYP2A6 alleles

Immunohistochemical and biochemical assay of versican in human sound predentine/dentine matrix

Aim of this study was to investigate the distribution of versican proteoglycan within the human dentine organic matrix by means of a correlative immunohistochemical analysis with field emission in-lens scanning electron microscope (FEI-SEM), transmission electron microscope (TEM), fluorescence microscope (FM) and biochemical assay. Specimens containing dentine and predentine were obtained from non carious human teeth and divided in three groups: 1) FEI-SEM group: sections were exposed to a pre-embedding immunohistochemical procedure; 2) TEM group: specimens were fixed, demineralised, embedded and submitted to a post-embedding immunohistochemical procedure; 3) FM group: sections mineralised and submitted to a pre-embedding immunohistochemical procedure with fluorescence labelling. Specimens were exposed to two different antibodies to assay distribution of versican fragments and whole versican molecule. Western Blotting analysis of dentine and pulp extracts was also performed. The correlative FEI-SEM,TEM and FM analysis revealed positive immunoreaction for versican fragments both in predentine and dentine, while few gold particles identifying the whole versican molecule were found in predentine only under TEM. No labelling of versican whole molecule was detected by FEI-SEM and FM analysis. The immunoblotting analysis confirmed the morphological findings. This study suggests that in fully developed human teeth versican fragments are significant constituents of the human dentine and predentine organic matrix, while versican whole molecule can be visualised in scarce amount within predentine only. The role of versican fragments within human dentine organic matrix should be further elucidated

AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells

Human cutaneous melanoma is an aggressive and chemotherapy-resistant type of cancer. AM251 is a cannabinoid type 1 (CB1) receptor antagonist/inverse agonist with off-target antitumor activity against pancreatic and colon cancer cells. The current study aimed to characterize the in-vitro antimelanoma activity of AM251. The BRAF V600E mutant melanoma cell line, A375, was used as an in-vitro model system. Characterization tools included a cell viability assay, nuclear morphology assessment, gene expression, western blot, flow cytometry with Annexin V-FITC/7-AAD double staining, cell cycle analyses, and measurements of changes in intracellular cAMP and calcium concentrations. AM251 exerted a marked cytotoxic effect against A375 human melanoma cells with potency comparable with that observed for cisplatin without significant changes in the human dermal fibroblasts viability. AM251, at a concentration that approximates the IC50, downregulated genes encoding antiapoptotic proteins (BCL2 and survivin) and increased transcription levels of proapoptotic BAX, induced alteration of Annexin V reactivity, DNA fragmentation, chromatin condensation in the cell nuclei, and G2/M phase arrest.AM251 also induced a 40% increase in the basal cAMP levels, but it did not affect intracellular calcium concentrations. The involvement of GPR55, TRPA1, and COX-2 in the AM251 mechanism of action was excluded. The combination of AM251 with celecoxib produced a synergistic antitumor activity, although the mechanism underlying this effect remains to be elucidated. This study provides the first evidence of a proapoptotic effect and G2/M cell cycle arrest of AM251 on A375 cells. This compound may be a potential prototype for the development of promising diarylpyrazole derivatives to be evaluated in human cutaneous melanoma