La gestione dei token nelle API e nel client di firma digitale sviluppati nell\u27ambito della collaborazione IIT-SECETI

Abstract in italianCon l\u27emanazione della legge n? 59 nel 1997 e la promulgazione del DPR n? 513 dello stesso anno, sostituito successivamente dal testo unico del DPR n? 445 del 2000, ha inizio in Italia una vera e propria rivoluzione che a partire dai rapporti dei cittadini con la pubblica amministrazione, molto presto cambier? le abitudini delle aziende e presumibilmente entro un prossimo futuro delle singole persone in molti aspetti della propria vita quotidiana. Infatti, questa legislazione attribuisce valore legale al documento informatico che pu? sostituire completamente il documento cartaceo sia negli atti amministrativi sia in quelli che attestano le transazioni tra privati. Tuttavia, secondo il DPR n? 445 del 2000, affinch? il documento informatico abbia valore legale ? necessario che abbia determinati requisiti che garantiscano l\u27autenticit?, l\u27integrit? ed il non ripudio e ci? ? possibile grazie alla firma digitale. La legislazione citata indica quali requisiti il documento informatico e la firma digitale su di esso apposta debbano avere, e pi? dettagliatamente le regole tecniche che l\u27AIPA (l\u27Autorit? Italiana per la Pubblica Amministrazione) ha avuto cura di stilare con la partecipazione di esperti nel settore, mostrano le tecnologie e gli standard da utilizzare e le politiche di sicurezza da seguire. Il DPR n? 445 del 2000 ? stato superato dall\u27approvazione del D.L.vo 10 del gennaio del 2002, che recepisce la direttiva quadro europea in materia di firma digitale. Signo ? un\u27applicazione di firma digitale che ? stata sviluppata nell\u27ambito di una accordo di collaborazione scientifica tra IIT e SECETI S.p.A.; essa ? stata progettata quando era in vigore il DPR 513 e le sue modificazioni successive e quindi ottempera ai requisiti di quella legge per permettere all\u27utente, in tutta semplicit?, di apporre la "propria" firma su un documento informatico. Tuttavia, Signo risulta ancora conforme ai requisiti della legge attuale, che impone vincoli meno severi per l\u27apposizione di una firma digitale su un documento informatico. Per questa ragione, nella descrizione tecnica dello strumento si far? riferimento al DPR 513 o al DPR 445 gi? citati, considerando che, soddisfacendo vincoli imposti da queste leggi, automaticamente lo strumento di firma risulta adeguato alla vigente normativa

An Implementation of Role-Base Trust Management Extended with Weights on Mobile Devices

AbstractThis paper describes the implementation of a library for the management and evaluation of Role-based Trust Management (RT) credentials and policies written in RTML, also extended with weights, in mobile devices. In particular, it describes the implementation of the library in J2ME. It is worth noticing, that RTML credentials are XML-like documents and thus the capability of porting these features on mobile devices makes the overall framework very interoperable with other RT frameworks (as for GRID systems). As policy language, we use actually a variant of RTML, whose policies are added with weights and are able to express quantitative experience-based notions of trust. It allow also to encode certain reputation and recommendation models. The obtained results show how the implementation on mobile devices is feasible and the running time acceptable for several applications

Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt

Cancer metabolism is characterized by an accelerated glycolytic rate facing reduced activity of oxidative phosphorylation. This "Warburg effect" represents a standard to diagnose and monitor tumor aggressiveness with (18)F-fluorodeoxyglucose whose uptake is currently regarded as an accurate index of total glucose consumption. Studying cancer metabolic response to respiratory chain inhibition by metformin, we repeatedly observed a reduction of tracer uptake facing a marked increase in glucose consumption. This puzzling discordance brought us to discover that (18)F-fluorodeoxyglucose preferentially accumulates within endoplasmic reticulum by exploiting the catalytic function of hexose-6-phosphate-dehydrogenase. Silencing enzyme expression and activity decreased both tracer uptake and glucose consumption, caused severe energy depletion and decreased NADPH content without altering mitochondrial function. These data document the existence of an unknown glucose metabolism triggered by hexose-6-phosphate-dehydrogenase within endoplasmic reticulum of cancer cells. Besides its basic relevance, this finding can improve clinical cancer diagnosis and might represent potential target for therapy

Unexpected effects of biphosphonates in in vitro models of activated CLL cells

Recent studies suggest that the commonly prescribed anti-osteoporosis drugs bisphosphonates (BPs) might also exhibit antitumor activity. We investigated a possible anticancer effect of BPs on B-chronic lymphocytic leukemia (CLL) cells obtained from peripheral blood of 26 CLL patients. Zoledronate, etidronate and clodronate were administered in vitro simultaneously to following activation stimuli: i) CD40L-expressing fibroblasts, ii) soluble recombinant CD40L produced in our laboratory +IL-4, iii) CpG ODN 2006+IL-15 with or without bone marrow stromal cells (BMSC). CLL cell viability, activation/proliferation were monitored by flow cytometry. We unexpectedly observed that BPs generated a protective effect from spontaneous apoptosis in 11/26 (42%) patients (viability + 18%-392%) and an augmentation in CLL cell activation/proliferation in 61% of the samples (S+G2M phase: +100%±25). Interestingly, protection from spontaneous apoptosis or increment of cell activation, required the presence of either fibroblasts, BMSC or autologous Nurse Like Cells (NLC). We thus hypothesized that supportive cells are involved in the BPs effects either through cell-cell interactions with leukemic cells or T cells, or through soluble factors release in the medium. Functional experiments with transwells suggest that stromal cells, in presence of Clodronate, release soluble factors in the medium that may probably concur to the unexpected Clodronate-mediated enhancement of CLL cell activation/proliferation. This work is in progress and several critical questions on the mechanisms are still unanswered. Nevertheless, the phenomenological data argue that caution should be taken when administering BPs against osteoporosis in elderly persons, who could have Monoclonal B Lymphocytosis or CLL

Nanovesicles from Organic Agriculture-Derived Fruits and Vegetables: Characterization and Functional Antioxidant Content

Dietary consumption of fruits and vegetables is related to a risk reduction in a series of leading human diseases, probably due to the plants’ antioxidant content. Plant-derived nanovesicles (PDNVs) have been recently receiving great attention regarding their natural ability to deliver several active biomolecules and antioxidants. To investigate the presence of active antioxidants in fruits, we preliminarily analyzed the differences between nanovesicles from either organic or conventional agriculture-derived fruits, at equal volumes, showing a higher yield of nanovesicles with a smaller size from organic agriculture-derived fruits as compared to conventional ones. PDNVs from organic agriculture also showed a higher antioxidant level compared to nanovesicles from conventional agriculture. Using the PDNVs from fruit mixes, we found comparable levels of Total Antioxidant Capacity, Ascorbic Acid, Catalase, Glutathione and Superoxide Dismutase 1. Finally, we exposed the nanovesicle mixes to either chemical or physical lytic treatments, with no evidence of effects on the number, size and antioxidant capacity of the treated nanovesicles, thus showing a marked resistance of PDNVs to external stimuli and a high capability to preserve their content. Our study provides for the first time a series of data supporting the use of plant-derived nanovesicles in human beings’ daily supplementation, for both prevention and treatment of human diseases

The Potentiality of Plant-Derived Nanovesicles in Human Health—A Comparison with Human Exosomes and Artificial Nanoparticles

Research in science and medicine is witnessing a massive increases in literature concerning extracellular vesicles (EVs). From a morphological point of view, EVs include extracellular vesicles of a micro and nano sizes. However, this simplistic classification does not consider both the source of EVs, including the cells and the species from which Evs are obtained, and the microenvironmental condition during EV production. These two factors are of crucial importance for the potential use of Evs as therapeutic agents. In fact, the choice of the most suitable Evs for drug delivery remains an open debate, inasmuch as the use of Evs of human origin may have at least two major problems: (i) autologous Evs from a patient may deliver dangerous molecules; and (ii) the production of EVs is also limited to cell factory conditions for large-scale industrial use. Recent literature, while limited to only a few papers, when compared to the papers on the use of human EVs, suggests that plant-derived nanovesicles (PDNV) may represent a valuable tool for extensive use in health care

A Role of Tumor-Released Exosomes in Paracrine Dissemination and Metastasis

Metastatic diffusion is thought to be a multi-step phenomenon involving the release of cells from the primary tumor and their diffusion through the body. Currently, several hypotheses have been put forward in order to explain the origin of cancer metastasis, including epithelial⁻mesenchymal transition, mutagenesis of stem cells, and a facilitating role of macrophages, involving, for example, transformation or fusion hybridization with neoplastic cells. In this paradigm, tumor-secreted extracellular vesicles (EVs), such as exosomes, play a pivotal role in cell communications, delivering a plethora of biomolecules including proteins, lipids, and nucleic acids. For their natural role in shuttling molecules, EVs have been newly considered a part of the metastatic cascade. They have a prominent role in preparing the so-called “tumor niches„ in target organs. However, recent evidence has pointed out an even more interesting role of tumor EVs, consisting in their ability to induce malignant transformation in resident mesenchymal stem cells. All in all, in this review, we discuss the multiple involvements of EVs in the metastatic cascade, and how we can exploit and manipulate EVs in order to reduce the metastatic spread of malignant tumors

Oral Administration of Fermented Papaya (FPP^®) Controls the Growth of a Murine Melanoma through the In Vivo Induction of a Natural Antioxidant Response

Prolonged oxidative stress may play a key role in tumor development. Antioxidant molecules are contained in many foods and seem to have a potential role in future anti-tumor strategies. Among the natural antioxidants the beneficial effect of Fermented Papaya (FPP®) is well known. The aim of this study was to investigate the effects of orally administered FPP® in either the prevention or treatment of a murine model of melanoma. The tumor growth was analyzed together with the blood levels of both oxidants (ROS) and anti-oxidants (SOD-1 and GSH). The results showed that FPP® controlled tumor growth, reducing the tumor mass of about three to seven times vs. untreated mice. The most significant effect was obtained with sublingual administration of FPP® close to the inoculation of melanoma. At the time of the sacrifice none of mice treated with FPP® had metastases and the subcutaneous tumors were significantly smaller and amelanotic, compared to untreated mice. Moreover, the FPP® anti-tumor effect was consistent with the decrease of total ROS levels and the increase in the blood levels of GSH and SOD-1. This study shows that a potent anti-oxidant treatment through FPP® may contribute to both preventing and inhibiting tumors growth

Oral Treatment with Plant-Derived Exosomes Restores Redox Balance in H₂O₂-Treated Mice

Plant-derived exosomes (PDEs) are receiving much attention as a natural source of antioxidants. Previous research has shown that PDEs contain a series of bioactives and that their content varies depending on the fruit or vegetable source. It has also been shown that fruits and vegetables derived from organic agriculture produce more exosomes, are safer, free of toxic substances, and contain more bioactives. The aim of this study was to investigate the ability of orally administered mixes of PDE (Exocomplex®) to restore the physiological conditions of mice treated for two weeks with hydrogen peroxide (H2O2), compared with mice left untreated after the period of H2O2 administration and mice that received only water during the experimental period. The results showed that Exocomplex® had a high antioxidant capacity and contained a series of bioactives, including Catalase, Glutathione (GSH), Superoxide Dismutase (SOD), Ascorbic Acid, Melatonin, Phenolic compounds, and ATP. The oral administration of Exocomplex® to the H2O2-treated mice re-established redox balance with reduced serum levels of both reactive oxygen species (ROS) and malondialdehyde (MDA), but also a general recovery of the homeostatic condition at the organ level, supporting the future use of PDE for health care