77 research outputs found

    L’azienda agro-alimentare: aspetti definitori

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    L’azienda agraria, pur essendo una delle prime manifestazioni produttive organizzate dall’uomo, è stata studiata dalle discipline economico-aziendali in misura meno diffusa, ad eccezione di illustri contributi (Cassandro,Giannessi,Coda), rispetto a quanto avvenuto per altre tipologie di aziende. Tuttavia, a partire dagli anni 80, è possibile registrare un rinnovato interesse delle discipline aziendalistiche per le attività produttive agrarie, soprattutto in seguito all’affermazione di nuovi modelli produttivi che, nell’agricoltura come nel manifatturiero e nei servizi, hanno determinato fenomeni sempre più rilevanti di innovazione tecnologica, di mercato ed organizzativa. In particolare, l’applicazione della logica industriale alla produzione agricola, da un lato, e, lo sviluppo di nuove relazioni interorganizzative nei processi di acquisizione, produzione e distribuzione, dall’altro, hanno generato un intenso dibattito sulle caratteristiche strutturali e gestionali di tali realtà aziendali, giungendo anche a posizioni diverse, ma complementari, rispetto agli studi di matrice economica. Tra le realtà agricole innovative, in tempi più recenti, soprattutto le aziende agro-alimentari sono al centro di un particolare interesse scientifico e operativo, per la spiccata afferenza con il mercato e per l’elevata capacità innovativa ed imprenditoriale che le differenzia dalle altre aziende agricole. L’obiettivo di questo capitolo è rivolto alla verifica di particolari aspetti o connotati che caratterizzano, condizionano e qualificano l’effettiva natura dal punto di vista economico-aziendale delle realtà produttive agricole e, in particolare, di quelle agro-alimentari

    Protein metalation by metal-based drugs: reactions of cytotoxic gold compounds with cytochrome c and lysozyme

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    Protein metalation processes are crucial for the mechanism of action of several anticancer metallodrugs and warrant deeper characterisation. We have explored the reactions of three cytotoxic gold(III) compounds—namely [(bipy2Me)2Au2(l-O)2][PF6]2 (where bipy2Me is 6,60-dimethyl- 2,20-bipyridine) (Auoxo6), [(phen2Me)2Au2(l-O)2] [PF6]2 (where phen2Me is 2,9-dimethyl-1,10-phenanthroline) (Au2phen) and [(bipydmb-H)Au(OH)][PF6] [where bipydmb-H is deprotonated 6-(1,1-dimethylbenzyl)-2,20- bipyridine] (Aubipyc)—with two representative model proteins, i.e. horse heart cytochrome c and hen egg whitelysozyme, through UV–visible absorption spectroscopy and electrospray ionisation mass spectrometry (ESI MS) to characterise the inherent protein metalation processes. Notably, Auoxo6 and Au2phen produced stable protein adducts where one or more ‘‘naked’’ gold(I) ions are protein- coordinated; very characteristic is the case of cytochrome c, which upon reaction with Auoxo6 or Au2phen preferentially forms ‘‘tetragold’’ adducts with four proteinbound gold(I) ions. In turn, Aubipyc afforded monometalated protein adducts where the structural core of the gold(III) centre and its ?3 oxidation state are conserved. Auranofin yielded protein derivatives containing the intact auranofin molecule. Additional studies were performed to assess the role played by a reducing environment in protein metalation. Overall, the approach adopted provides detailed insight into the formation of metallodrug–protein derivatives and permits trends, peculiarities and mechanistic details of the underlying processes to be highlighted. In this respect, electrospray ionisation mass spectrometry is a very straightforward and informative research tool. The protein metalation processes investigated critically depend on the nature of both the metal compound and the interacting protein and also on the solution conditions used; thus, predicting with accuracy the nature and the amounts of the adducts formed for a given metallodrug–protein pair is currently extremely difficult

    Chemistry and biology of three representative gold(III) compounds as prospective anticancer agents

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    Aubipyc, i.e.[(bipydmb-H)Au(OH)][PF6] (where bipydmb-H = deprotonated 6-(1,1-dimethylbenzyl)-2,20- bipyridine), Auoxo6, i.e. [(bipy2Me)2Au2(l-O)2][PF6]2 (where bipy2Me = 6,60-dimethyl-2,20-bipyridine) and Au2phen i.e. [(phen2Me)2Au2(l-O)2][PF6]2 (where phen2Me = 2,9-dimethyl-1,10-phenanthroline), are three representative gold(III) compounds prepared and characterised in our laboratories during the last few years that manifested remarkable anticancer properties in vitro. Herein, the main chemical features of these compounds are summarised. Aubipyc is a mononuclear organogold(III) compound while Auoxo6 and Au2phen are binuclear gold(III) complexes. These compounds manifest a reasonable stability of their gold(III) chromophore in aqueous solutions at physiological pH; yet, a rather different redox behaviour was highlighted as Aubipyc displays high stability toward reduction while both Auoxo6 and Au2phen are rapidly reduced by ascorbic acid and glutathione. The antiproliferative properties of these gold(III) compounds were analysed in detail against a wide panel of human tumour cell lines. Remarkably, Auoxo6 and Au2phen revealed potent and rather similar patterns of antiproliferative actions while Aubipyc turned out to be less effective. For Auoxo6 and Au2phen more detailed biochemical studies are available documenting their effects on the proteome of treated cancer cells. Recent studies described the reactions of these gold compounds with various proteins at the molecular level; adduct formation was clearly documented in a few cases and their nature determined. Preliminary results suggest that these gold compounds may act as strong inhibitors of the selenoenzyme thioredoxin reductase and cause mitochondrial dysfunction. Based on the available in vitro data, these gold compounds look quite promising as prospective anticancer agents. Studies will soon be extended to assess their safety and efficacy in relevant animal models of cancer

    Bell towers of Lima’s Cathedral: An architectural-engineering combined seismic study

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    This paper focuses on the seismic evaluation of the Bell Towers of Lima’s Cathedral. The church, which dates back to 1535, has been modified and reconstructed several times over the centuries, changing its structural assembly in terms of lightening and strengthening. Focusing on the massive 45 m tall towers, linear kinematic analyses have been performed in order to evaluate their vulnerability. The results show how its actual performance is far below the safety requirements of the Peruvian code. Such code, however, lacks of regulations aimed at increasing structural safety of existing buildings and, thus, it does not provide any reference on the minimum safety level to reach on a monumental construction such as the Cathedral. A simple intervention using steel ties has been proposed in order to increase such performance on nearly all the considered collapse mechanisms, however the reference value of structural safety, due to absence of other prescription, has been set as the ultimate limit state for new constructions

    Water-soluble Ru(II)- and Ru(III)-halide-PTA complexes (PTA=1,3,5-triaza-7-phosphaadamantane): Chemical and biological properties

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    Four structurally related Ru(II)-halide-PTA complexes, of general formula trans- or cis-[Ru(PTA)4X2] (PTA = 1,3,5-triaza-7-phosphaadamantane, X = Cl (1, 2), Br (3, 4), were prepared and characterized. Whereas compounds 1 and 2 are known, the corresponding bromo derivatives 3 and 4 are new. The Ru(III)-PTA compound trans-[RuCl4(PTAH)2]Cl (5, PTAH = PTA protonated at one N atom), structurally similar to the well-known Ru(III) anticancer drug candidates (Na)trans-[RuCl4(ind)2] (NKP-1339, ind = indazole) and (Him)trans-[RuCl4(dmso-S)(im)] (NAMI-A, im = imidazole), was also prepared and similarly investigated. Notably, the presence of PTA confers to all complexes an appreciable solubility in aqueous solutions at physiological pH. The chemical behavior of compounds 1–5 in water and in physiological buffer, their interactions with two model proteins – cytochrome c and ribonuclease A – as well as with a single strand oligonucleotide (5′-CGCGCG-3′), and their in vitro cytotoxicity against a human colon cancer cell line (HCT-116) and a myeloid leukemia (FLG 29.1) were investigated. Upon dissolution in the buffer, sequential halide replacement by water molecules was observed for complexes 1–4, with relatively slow kinetics, whereas the Ru(III) complex 5 is more inert. All tested compounds manifested moderate antiproliferative properties, the cis compounds 2 and 4 being slightly more active than the trans ones (1 and 3). Mass spectrometry experiments evidenced that all complexes exhibit a far higher reactivity towards the reference oligonucleotide than towards model proteins. The chemical and biological profiles of compounds 1–5 are compared to those of established ruthenium drug candidates in clinical development

    Chemistry and biology of three representative gold(III) compounds as prospective anticancer agents

    No full text
    Aubipyc, i.e.[(bipydmb-H)Au(OH)][PF6] (where bipydmb-H = deprotonated 6-(1,1-dimethylbenzyl)-2,2′-bipyridine), Auoxo6, i.e. [(bipy2Me)2Au2(μ-O)2][PF6]2 (where bipy2Me = 6,6′-dimethyl-2,2′-bipyridine) and Au2phen i.e. [(phen2Me)2Au2(μ-O)2][PF6]2 (where phen2Me = 2,9-dimethyl-1,10-phenanthroline), are three representative gold(III) compounds prepared and characterised in our laboratories during the last few years that manifested remarkable anticancer properties in vitro. Herein, the main chemical features of these compounds are summarised. Aubipyc is a mononuclear organogold(III) compound while Auoxo6 and Au2phen are binuclear gold(III) complexes. These compounds manifest a reasonable stability of their gold(III) chromophore in aqueous solutions at physiological pH; yet, a rather different redox behaviour was highlighted as Aubipyc displays high stability toward reduction while both Auoxo6 and Au2phen are rapidly reduced by ascorbic acid and glutathione. The antiproliferative properties of these gold(III) compounds were analysed in detail against a wide panel of human tumour cell lines. Remarkably, Auoxo6 and Au2phen revealed potent and rather similar patterns of antiproliferative actions while Aubipyc turned out to be less effective. For Auoxo6 and Au2phen more detailed biochemical studies are available documenting their effects on the proteome of treated cancer cells. Recent studies described the reactions of these gold compounds with various proteins at the molecular level; adduct formation was clearly documented in a few cases and their nature determined. Preliminary results suggest that these gold compounds may act as strong inhibitors of the selenoenzyme thioredoxin reductase and cause mitochondrial dysfunction. Based on the available in vitro data, these gold compounds look quite promising as prospective anticancer agents. Studies will soon be extended to assess their safety and efficacy in relevant animal models of cancer

    The Mode of action of anticancer gold-based drugs: a structural perspective

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    The interactions between a few representative gold-based drugs and hen egg white lysozyme were studied by X-ray crystallography. High resolution crystal structures solved for three metallodrug–protein adducts provide valuable insight into the molecular mechanism of these promising metal compounds and the inherent protein metalation processes
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