Sfogliando per Titolo

  • Pubblicazione
    027.1 Biblioteche private e di famiglia
    (Bibliografica, 2007)
    NUOVO ANGELA
      38
  • Pubblicazione
    03-DPACS: an open source solution for critical PACS systems integratedin the 03 Consortium project.
    (Università degli studi di Trieste, 2008-03-18)
    Beltrame, Marco
    ABSTRACT The student started his work towards the PhD. in 2005, joining the Bioengineering and ICT group of the University of Trieste, whose core research was in the e-health area. The personal research project conducted by the PhD student was inserted in the O3 Consortium research project, which had the aim to propose a complete solution for the adoption of open technology in the healthcare environment. The solution should become a whole new model for e-health application and include new products integrated with a development, support and business model. The PhD student contributed to the project in thinking and designing all the aspects of the complete solution presented in this thesis, in the development and business models, as well as in developing the products and in writing and publishing the results of the steps of this work. He personally contributed proposing the original idea of the support model and designing and implementing a product to test the proposed model. The student had an intermediate step in his personal project: he built a state of the art server for the management of DICOM data and of imaging objects (PACS – Picture and Archiving Communication System), with the aim to ease the adoption of e-health technology and to develop a product on which the model would have been tested. The research was conducted in the following way: first, based on the analysis of real world needs, literature and past experience, the definition of the O3 Consortium project software design guidelines (called “requirements” in the thesis) was performed. Then the product was designed and a new release of the PACS system was developed, implementing original solutions to best achieve all those “requirements”. The technological choices and the original aspects against the state of the art have been discussed and underlined throughout the entire thesis, such as the compliance to all the requirements and the choices for portability, project organization, standard implementation and performance. The idea of O3-DPACS being an integrated project, system plus support model has been also presented and discussed in the thesis.. It should be remarked again that the O3 Consortium means not only software development but also new procedures in both technology and service delivering. Moreover, the PhD student performed the validation of the software and the model, which needed to verify the assumption and to obtain the first results in the O3 Consortium research on e-health adoption. Should be noted the originality of the O3 Consortium project proposal of a whole complete application model to the healthcare real world based on open source software. No other solution for open source software application makes a complete proposal for all the topics of development, design, software architecture, support and business opportunity. Thus, a real research interest exists in testing and validating the model. ABSTRACT Il dottorato comincia il suo corso di studi nel 2005, unendosi al gruppo di Bioengineering and ICT dell’Università di Trieste. Il principale filone di ricerca del gruppo è nell’area dell’e-health. Il progetto di ricerca condotto personalmente dal dottorando s’inserisce nel progetto O3-Consortium, che ha come obiettivo la realizzazione di una soluzione completa per l’adozione e la diffusione dell’e-health in sanità. Tale soluzione ha l’ambizione di diventare un nuovo modello di riferimento per l’utilizzo di tecnologie aperte in sanità, e per l’adozione di nuove tecnologie software in generale, includendo un insieme di prodotti all’avanguardia con nuovi modelli di sviluppo, produzione e assistenza. Il dottorando ha contribuito al lavoro di gruppo che ha portato all’ideazione e definizione di tutti gli aspetti della soluzione completa, contribuendo ai modelli di sviluppo, economici, alla realizzazione dei prodotti e alla scrittura del progetto stesso. Personalmente, ha contribuito proponendo l’idea originale del modello di assistenza, e progettando e sviluppando le parti più importanti del software scelto per la sperimentazione dei modelli. Il dottorando, come step intermedio, si è posto l’obiettivo di progettare un server all’avanguardia per l’archiviazione di dati e immagini cliniche (PACS), con lo scopo di testare e validare le idee e i principi definiti durante la creazione dei modelli. La ricerca è stata condotta in due passi. Inizialmente, sono state definite delle linee guida per la progettazione del software, chiamate “requirements” o requisiti, sia attraverso l’analisi dei bisogni reali che l’analisi della letteratura e dell’esperienza più che decennale del gruppo. Il secondo passo è stato concretizzare nel prodotto PACS la massima aderenza ai requisiti, progettando e realizzando l’archivio. Le scelte tecnologiche, i motivi e gli aspetti originali rispetto allo stato dell’arte, quali i metodi e il livello di soddisfacimento dei requisiti, le soluzioni per la portabilità del software, l’organizzazione del progetto software e le scelte in fatto di standard e performance, verranno discussi ed evidenziati sottodiversi aspetti nella tesi. Analogamente, verrà spiegato ed evidenziato il concetto che definisce O3-DPACS come progetto integrato, ove il prodotto è inscindibile da una politica adeguata di supporto. Occorre, infatti, rilevare che il progetto O3 Consortium non significa meramente produrre software, anche se con caratteristiche originali, quanto associarvi nuove procedure nella fornitura, gestione, manutenzione e supporto delle tecnologie software. Infine, il dottorando ha condotto a conclusione la sperimentazione e validazione del modello O3 applicato al proprio sistema PACS, ottenendo i primi risultati positivi nella ricerca delle migliori soluzioni per l’adozione dell’e-health all’interno del progetto O3 Consortium. A conclusione, va osservato che la peculiarità propria di O3 Consortium di voler proporre una soluzione completa per l’applicazione delle tecnologie aperte in sanità non ha analoghi, poiché alcuna altra proposta copre allo stesso tempo tutti gli aspetti quali lo sviluppo, l’assistenza, la ricerca, la fornitura del servizio. Ne consegue che esiste un reale interesse di ricerca nello sperimentare il modello O3.
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  • Pubblicazione
    1 / Domenico Rossetti
    (Udine: Casa editrice Idea, 1944)
    Farinelli, Arturo
      30
  • Pubblicazione
    1 Body plan genes and human malformation
    ( 1998)
    Boncinelli, E
    ;
    Mallamaci, Antonio
    ;
    Broccoli, V.
    WOS© Citazioni 4  29
  • Pubblicazione
    1 voce del "Tesoro della Lingua Italiana delle Origini": 'anima'
    ( 2001)
    ROMANINI, FABIO
    voci del "Tesoro della Lingua Italiana delle Origini" compilate da Fabio Romanini
      24
  • Pubblicazione
    1 voce del "Tesoro della Lingua italiana delle Origini": 'comprendere'
    ( 2003)
    ROMANINI, FABIO
    voci del "Tesoro della Lingua Italiana delle Origini" compilate da Fabio Romanini
      26
  • Pubblicazione
    (1 × n) reconstruction of the Rh (110) surface with n = 2, 3, 4, 5
    ( 1992)
    V. R. Dhanak
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    COMELLI, GIOVANNI
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    CAUTERO, GIUSEPPE
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    G. Paolucci
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    K. C. Prince
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    M. Kiskinova
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    ROSEI, RENZO
      28WOS© Citazioni 60
  • Pubblicazione
      23
  • Pubblicazione
    1) Victor-Laurent Tremblay, «L’ambiguité de Neuf jours de haine : roman de guerre dionysiaque et canadien ?», Studies in Canadian Literature/ Études en littérature canadienne, vol. 27, n. 2, 2002, pp. 88-103 ; Richard Patry, «Éclairage à contre-jour de l’expérience d’un dépossédé: les termes francisés dans La vache morte du canyon de Jacques Ferron», Studies in Canadian Literature/ Études en littérature canadienne, vol. 27, n. 2, 2002, pp. 104-122 ; Kenneth Meadwell, «De la réflexion à l’œuvre : une analyse des dossiers scénarique et scriptique du Passager de Gilbert La Roque», Studies in Canadian Literature/ Études en littérature canadienne, vol. 27, n. 2, 2002, pp. 123- 139 ; Anne Brown, «Le parcours identitaire de Dany Laferrière ou Mon cœur est à Port-au-Prince, mon esprit à Montréal et mon corps à Miami», Studies in Canadian Literature/ Études en littérature canadienne, vol. 28, n. 2, 2003, pp. 39-48, Studies in Canadian Literature/ Études en littérature canadienne, vol. 29, n. 1, 2004, Karin Schwerdtner, Karen Bamford (éd.), « Special Section : Women in Motion/ Dossier spécial : femmes en mouvement »
    ( 2005)
    Alessandra Ferraro
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  • Pubblicazione
    (1)H magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in bipolar disorder patients
    ( 2005)
    BRAMBILLA P
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    STANLEY JA
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    NICOLETTI MA
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    SASSI RB
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    MALLINGER AG
    ;
    FRANK E
    ;
    KUPFER D
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    KESHAVAN MS
    ;
    SOARES JC
    BACKGROUND: Magnetic resonance spectroscopy studies (MRS) reported abnormally low levels of N-acetylaspartate (NAA, a marker of neuronal integrity) in dorsolateral prefrontal cortex (DLPFC) of adult bipolar patients, suggesting possible neuronal dysfunction. Furthermore, recent MRS reports suggested possible lithium-induced increase in NAA levels in bipolar patients. We examined with in vivo (1)H MRS NAA levels in the DLPFC of adult bipolar patients. METHODS: Ten DSM-IV bipolar disorder patients (6 lithium-treated, 4 drug-free) and 32 healthy controls underwent a short echo-time 1H MRS session, which localized an 8 cm3 single-voxel in the left DLPFC using a STEAM sequence. RESULTS: No significant differences between the two groups were found for NAA, choline-containing molecules (GPC+PC), or phosphocreatine plus creatine (PCr+Cr) (Student t-test, p > 0.05). Nonetheless, NAA/PCr+Cr ratios were significantly increased in lithium-treated bipolar subjects compared to unmedicated patients and healthy controls (Mann-Whitney U-test, p < 0.05). LIMITATIONS: Relatively small sample size may have reduced the statistical power of our analyses and the utilization of a single-voxel approach did not allow for the examination of other cortical brain areas. CONCLUSIONS: This study did not find abnormally reduced levels of NAA in left DLPFC of adult bipolar patients, in a sample of patients who were mostly on medications. However, elevated NAA/PCr+Cr ratios were shown in lithium-treated bipolar patients. Longitudinal 1H MRS studies should further examine NAA levels in prefrontal cortex regions in untreated bipolar patients before and after mood stabilizing treatment.
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  • Pubblicazione
    1,2,4-Triazolo[1,5-a]-1,3,5-triazine nucleus: a possible template for adenosine receptor subtypes.
    (Comitato organizzatore del VNPCF, 2011)
    FEDERICO, STEPHANIE
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    Paoletta, Silvia
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    Cheong, Siew Lee
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    Pastorin, Giorgia
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    Cacciari, Barbara
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    Stragliotto, Stefano
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    Klotz, Karl Norbert
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    Siegel, Jeffrey
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    Gao, Zhan Guo
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    Jacobson, Kenneth A.
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    MORO, STEFANO
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    SPALLUTO, GIAMPIERO
      22
  • Pubblicazione
    [1,2,4]Triazolo[1,5-a][1,3,5]Triazine Derivatives as Antagonists for the Adenosine Receptors: a Preliminary Study on Affinity at the A3 Subtype
    (Divisione di Chimica Farmaceutica della Società Chimica Italiana, 2013)
    FEDERICO, STEPHANIE
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    Ciancetta, Antonella
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    Cacciari, Barbara
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    Klotz, Karl Norbert
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    Moro, Stefano
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    SPALLUTO, GIAMPIERO
    In the last 20 years intense medicinal chemical efforts led to the synthesis of a variety of adenosine receptor (AR) agonists and antagonists for the pharmacological characterization of this family of G protein-coupled receptors.1 Several classes of heterocyclic derivatives have been reported as AR antagonists with high levels of both affinity and selectivity. Recently, the synthesis of more simplified heterocyclic derivatives has been strongly investigated in order to obtain derivatives with a better pharmacokinetic profile. In particular bicyclic systems such as adenine, triazolo-pyrazine, triazolo-pyrimidines and triazolo-triazine could be considered some of the most promising targets.2 One of the most appealing bicyclic core is the triazolo-triazine nucleus, which led in the past to the discovery of potent and selective A2A AR antagonists, such as ZM241385.3 In the past, our group performed a study on this nucleus trying to optimize substitution at the C5 and N7 positions with the aim of improving affinity and selectivity versus the hA2BAR and hA3AR subtypes. In particular, inclusion at the N7 position of arylcarbamoyl (for A3) or arylacetyl (for A2B) moieties, which gave good results in the pyrazolotriazolopyrimidine family, has been investigated.4 Unfortunately, none of these substitutions led to the desired selectivity. Regarding the A3 subtype, lack of affinity was probably observed because only lipophilic moieties were present at the 5 position (phenoxy, dimethylamino, thiomethyl) avoiding the formation of hydrogen bonds with residues inside the binding pocket of the A3 adenosine receptor. Our aim, in this work, was to synthesise new [1,2,4]triazolo[1,5-a][1,3,5]triazines introducing substituents at the 5 position able to form hydrogen bonds, such as monosubstituted amines, in order to verify if it is capable of enhance affinity and selectivity towards the A3 AR. The analogues were docked in a homology model of the hA3 AR, and the per residue electrostatic and hydrophobic contributions to the binding were assessed and stabilizing factors were proposed in order to support the experimental binding data.References (1) Moro, S, et al. Med. Res. Rev. 2006, 26, 131-159. (2) Muller, C, et al. Biochim. Biophys. Acta 2010, 1808, 1290-1308. (3) Poucher, SM, et al. Br. J. Pharmacol. 1995, 115, 1096–1102. (4) Pastorin, G, et al. Bioorg. Med. Chem. 2010, 18, 2524-2536.
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  • Pubblicazione
    [1,2,4]Triazolo[1,5-c]pyrimidine Nucleus as Adenosine Receptor Antagonists: Shift in Selectivity from A2A to A3 Adenosine Receptors.
    (Purine club, 2012)
    FEDERICO, STEPHANIE
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    Ciancetta, Antonella
    ;
    Paoletta, Silvia
    ;
    Cacciari, Barbara
    ;
    Klotz, Karl Norbert
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    Moro, Stefano
    ;
    SPALLUTO, GIAMPIERO
    [1,2,4]Triazolo[1,5-c]pyrimidine derivatives are reported in literature as A2A adenosine receptor (AR) antagonists useful for the treatment of Parkinson’s disease (PD), senile dementia and depression (1).[1] Several classes of heterocyclic derivatives have been reported as AR antagonists.[2] Among them, the Schering compound, preladenant (2), a pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine (PTP) A2A antagonist (which is under phase III clinical trials for the treatment of PD), possesses the same lateral subtituent of compound 1.[2,3] In the [1,2,4]triazolo[1,5-c]pyrimidine compound (1) the pyrazole moiety of preladenant was substituted by a phenyl spacer, leading to a compound which displays the same affinity at the A2A AR. The [1,2,4]-triazolo[1,5-c]pyrimidine nucleus possesses a simpler structure and less nitrogen atoms than PTPs, thus it may be a scaffold with promising pharmacokinetics properties. So, starting from the similar behavior of [1,2,4]triazolo[1,5-c]pyrimidines and PTPs on ARs, and our experience on PTP as A3 AR antagonists, we decided to explore the [1,2,4]triazolo[1,5-c]pyrimidine scaffold as antagonists towards A3 AR. Initially, we introduced on the bicyclic scaffold the same substituents those give affinity and selectivity at the A3 AR in the PTP nucleus. On the basis of obtained results, the optimization of substitutions allow us, after 4 series (147compounds) of [1,2,4]triazolo[1,5-c]pyrimidine derivatives, to discover a potent and selective A3 AR antagonist, with a Ki of 0.47 nM. [1] Kyowa Hakko Kogyo Cp., Ltd., Tokyo (JP). Shimada, J.; Imma, H.; Osakada, N.; Shiozaki, S.; Kanda, T.; Kuwana, Y. [1,2,4]Triazolo[1,5-c]pyrimidine derivatives. 2003, US6545000. [2] Muller, C.E.; Jacobson, K.A. Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim. Biophys. Acta. 2011, 1808, 1290–1308. [3] Neustadt, B.R.; Hao, J., Lindo, N.; Greenlee, W.J.; Stamford, A.W.; Tulshian, D.; Ongini, E.; Hunter, J.; Monopoli, A.; Bertorelli, R.; Foster, C.; Arik, L.; Lachowicz, J.; Nga, K.; Feng, K.I. Potent, selective, and orally active adenosine A2A receptor antagonists: arylpiperazine derivatives of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines. Bioorg. Med. Chem. Lett. 2007, 17, 1376–1380.
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  • Pubblicazione
    [1,2,4]triazolo[1,5-c]pyrimidines as A(3) adenosine receptor antagonists
    ( 2014)
    FEDERICO, STEPHANIE
    ;
    REDENTI, SARA
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    Ciancetta, Antonella
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    Cacciari, Barbara
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    Klotz, Karl Norbert
    ;
    Moro, Stefano
    ;
    SPALLUTO, GIAMPIERO
    Question:[1,2,4]Triazolo[1,5-c]pyrimidine (TP) derivatives are reported in literature as A2A adenosine receptor (AR) antagonists useful for the treatment of Parkinson’s disease, senile dementia and depression (1).1 The Schering compound, preladenant (2), a pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine (PTP) A2A antagonist, possesses a lateral substituent similar to those of the TP compound 1.2,3 Although these two compounds are both potent A2A antagonist, the TP nucleus possesses a simpler structure and less nitrogen atoms than PTPs, thus it may be a scaffold with promising pharmacokinetics properties. So, starting from the structural similarity between TP and PTP A2A AR antagonists, and our experience on PTP nucleus as A3 AR antagonists, we decided to explore the TP scaffold in order to obtain potent antagonists towards A3 AR. Methods: All compounds were synthesized according to literature1 and have been evaluated for potency at all four human ARs. Results: Initially, we introduced at the 5 position of the TP scaffold the same substituents which gave affinity and selectivity at the A3 AR at the 5 position in the PTP nucleus. On the basis of obtained results, the optimization of substitutions at the 5, 8 and 2 positions, which led to 147 [1,2,4]triazolo[1,5-c]pyrimidine derivatives, allowed us to reach subnanomolar Ki values at the A3 AR and good levels of selectivity versus the other adenosine receptor subtypes. Conclusions: A novel promising class of potent and selective A3 adenosine receptor antagonist with a [1,2,4]triazolo[1,5-c]pyrimidine nucleus was discovered. References: [1] Kyowa Hakko Kogyo Cp., Ltd., Tokyo (JP). Shimada, J.; Imma, H.; Osakada, N.; Shiozaki, S.; Kanda, T.; Kuwana, Y. [1,2,4]Triazolo[1,5-c]pyrimidine derivatives. 2003, US6545000. [2] Muller, C.E.; Jacobson, K.A. Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim. Biophys. Acta. 2011, 1808, 1290–1308. [3] Neustadt, B.R.; Hao, J., Lindo, N.; Greenlee, W.J.; Stamford, A.W.; Tulshian, D.; Ongini, E.; Hunter, J.; Monopoli, A.; Bertorelli, R.; Foster, C.; Arik, L.; Lachowicz, J.; Nga, K.; Feng, K.I. Potent, selective, and orally active adenosine A2A receptor antagonists: arylpiperazine derivatives of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines. Bioorg. Med. Chem. Lett. 2007, 17, 1376–1380.
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  • Pubblicazione
    [1,2,4]Triazolo[1,5-c]pyrimidines as adenosine receptor antagonists: Modifications at the 8 position to reach selectivity towards A3 adenosine receptor subtype
    ( 2018)
    Federico, Stephanie
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    Margiotta, Enrico
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    Salmaso, Veronica
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    Pastorin, Giorgia
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    Kachler, Sonja
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    Klotz, Karl-Norbert
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    Moro, Stefano
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    Spalluto, Giampiero
    [1,2,4]Triazolo[1,5-c]pyrimidine is a promising platform to develop adenosine receptor antagonists. Here, we tried to investigate the effect of the substituent at the 8 position of [1,2,4]triazolo[1,5-c]pyrimidine derivatives on affinity and selectivity at the human A3 adenosine receptor subtype. In particular, we have introduced both esters and amides, principally with a benzylic nature. In addition, a small series of 5-substituted [1,2,4]triazolo[1,5-c]pyrimidines was designed in order to complete the structure-activity relationship analysis. Several of these new compounds showed affinity towards human A3 adenosine receptor in the low nanomolar range, with the most potent derivative of the series bringing a 4-ethylbenzylester at the 8 position (compound 18, hA3AR Ki ¼ 1.21 nM). Docking studies performed on the synthesized compounds inside models of human A1, A2A and A3 adenosine receptors showed similar binding modes, comparable with the typical crystallographic binding mode of the inverse agonist ZM-241,385.
    WOS© Citazioni 8  29
  • Pubblicazione
    1,2,4]Triazolo[1,5-c]pyrimidines as New Potent Human A3 Adenosine Receptor Antagonists.
    (Comitato organizzatore NPCF7, 2013)
    SPALLUTO, GIAMPIERO
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    FEDERICO, STEPHANIE
    ;
    Ciancetta, Antonella
    ;
    Cacciari, Barbara
    ;
    Klotz, Karl Norbert
    ;
    Moro, Stefano .
    [1,2,4]Triazolo[1,5-c]pyrimidine derivatives are reported in literature as A2A adenosine receptor (AR) antagonists useful for the treatment of Parkinson’s disease (PD), senile dementia and depression (1).1 We decided to explore the [1,2,4]triazolo[1,5-c]pyrimidine scaffold in order to obtain antagonists selective towards hA3 AR. Inactivation of the A3 AR is being studied in glaucoma but also in inflammatory diseases such as asthma.2 In a previous work, we have found that, in order to obtain good hA3 AR antagonists, the better substitutions at the 5 and 8 positions are a little alkylamino (methyl or ethylamino) and an ethylester moieties, respectively. Here we report a novel series of [1,2,4]triazolo[1,5-c]pyrimidines where we have introduced different alkyl, cycloalkyl, aryl and heteroaryl moieties at the 2 position (2). Surprisingly, the introduction of substituted-phenyl rings led to subnanomolar affinities at the hA3 AR. The best compound of this series is represented by the ethyl 2-(4-methoxyphenyl)-5-(methylamino)-[1,2,4]triazolo[1,5-c]pyrimidine-8-carboxylate (3) which shows a Ki of 0.47 nM towards hA3 AR and a 4200- and 8400-fold selectivity over hA1 and hA2A ARs, respectively.1. Shimada, J.; Imma, H.; Osakada, N.; Shiozaki, S.; Kanda, T.; Kuwana, Y. [1,2,4]Triazolo[1,5-c]pyrimidine derivatives. 2003, US6545000. 2. Cheong, S.L; Federico, S.; Venkatesan, G.; Mandel, A.L.; Shao, Y.M.; Moro, S.; Spalluto, G.; Pastorin, G. The A3 adenosine receptor as multifaceted therapeutic target: pharmacology, medicinal chemistry and in silico approaches. Med. Res. Rev. 2013, 33, 235-335.
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