4,667 research outputs found

    Lorenzo Riccardi, Corpus della pittura monumentale bizantina in Italia, II, Calabria, Soveria Mannelli: Rubbettino 2021

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    Recensione del volume di Lorenzo Riccardi Corpus della pittura monumentale bizantina in Italia, II, Calabria (Soveria Mannelli: Rubbettino 2021

    Vectores e ratos

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    La spettrometria di massa nel drug discovery

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    Since the introduction of the electrospray ion source the role of Mass Spectrometry in the drug discovery has become crucial involving all the key steps of the process. In fact this ionization technique permits the coupling of mass analyzers with high pressure liquid chromatography (HPLC) opening the way for the development of many different applications. This presentation will give an overview of the analytical activities that support discovery projects including the analytical characterization of New Chemical Entities (Identity and Purity) and the quality control of active hits. The second part of the presentation will concern the development and validation of an ESI-MS screening method for the identification of new molecules able to recognize TG mismatched base pairs in DNA. This would help in the synthesis of new chemotherapeutic agents particularly effective on MMR deficient cell lines. In fact TG mismatched base pairs in DNA are responsible for most of the common mutations leading to formation of tumors in humans. TG mismatches are particularly abundant in cells lacking mismatch repair mechanism (MMR). MMR deficiency increases 50-1000-fold spontaneous mutation rates (microsatellite instability MSI). An increase of MSI is observed in hereditary nonpolyposis colon cancer (HNPCC) and in a series of sporadic tumor types. In addition, MMR deficiency can lead to resistance to several chemotherapeutic agents (DNA damaging agent).Different papers confirm that the duplex DNA structure is maintained in the gas phase and the Watson-Crick base pairing is preserved [1,2]. In our study the formation of duplexes was confirmed by ESI-MS and dissociation curves were obtained for the different oligonucleotides confirming a decreasing stability of the duplexes when TG mismatches are present. This hairpin DNA was used to set up the method for studying the complexes formed with minor groove binders and intercalators (doxorubicin). The association constants (Kas) were directly determined from the MS spectrum following a procedure developed by Rosu et all. [3]. Different standard compounds were tested against the three DNA targets at 5 uM (HFM; HSM; A5TG). The amount of bound ligand was used to determine the selectivity of a binder among the different DNA sequences [4]. As expected the minor groove binders (Distamycin A, H33258, H33342, DAPI) show an evident selectivity for the polyAT sequence A5TG and a poor affinity for the DNA sequence bearing a single mismatch (HSM). Intercalator doxorubicin did not show any selectivity between the Hairpin Single Mismatch (HSM) and A5TG. Different Lexitropsin derivatives, able to recognize single and double mismatches, were designed, synthesized and tested with this procedure. NMS-077 reveals a significant selectivity for the Hairpin Single mismatch and the ligand binds with positive cooperativity Ka1<4Ka2.[1] Schnier, PD; Klassen, JS; Strittmatter, EF; Williams, ER; J. Am. Chem. Soc. 120 (1998) 9605[2] Gabelica, V; De Pauw, E; Int. J. Mass Spectrom 219 (2002) 151[3] Rosu, F; Gabelica, V; Hossier, C; De Pauw, E; Nucleic Acid Res 30/16 (2002) e82[4] Rosu, F; De Pauw , E; Gabelica, V; Biochimie 90(7) (2008) 107

    Erratum: Functional analysis of OCTN2 and ATB0,+ in normal human airway epithelial cells (PLoS ONE (2020) 15:2 (e0228568) DOI: 10.1371/journal.pone.0228568)

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    There is an error in reference 12. The correct reference is: Ingoglia F, Visigalli R, Rotoli BM, Barilli A, Riccardi B, Puccini P, et al. (2016) Functional activity of L-carnitine transporters in human airway epithelial cells. Biochim Biophys Acta. 1858(2):210–9. 10.1016/j.bbamem.2015. 11.013

    A review of the concept of circulatory bioassist focused on the "new" demand dynamic cardiomyoplasty: the renewal of dynamic cardiomyoplasty?

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    Angiology. 2003 May-Jun;54(3):301-6. A review of the concept of circulatory bioassist focused on the "new" demand dynamic cardiomyoplasty: the renewal of dynamic cardiomyoplasty? Rigatelli G, Carraro U, Barbiero M, Riccardi R, Cobelli F, Gemelli M, Rigatelli G. Source Cardiomyoplasty Project Unit, Legnago General Hospital, Verona, Italy. [email protected] Abstract After the initial enthusiasm, the dynamic cardiomyoplasty lost its reputation owing to the poor long-term results, caused by the muscular degeneration subsequent to chronic continuous electrical stimulation of the latissimus dorsi. An activity-rest stimulation protocol that avoids full transformation of the skeletal muscle, maintaining muscular properties over time, has been successfully tried. This "demand" stimulation protocol showed in humans good results improving NYHA class, ejection fraction value, and survival. The discussion about the capability of this and a unique kind of cardiocirculatory bioassist is due to be reopened. In fact, heart transplant, percutaneous circulatory-supporting device, multisites stimulation therapy, and total artificial heart have some drawbacks, one of which is the economic cost. In developing countries the more economic demand dynamic cardiomyoplasty may still play a role. PMID: 12785022 [PubMed - indexed for MEDLINE

    When Criminals Invest in Businesses: Are We Looking in the Right Direction? An Exploratory Analysis of Companies Controlled by Mafias

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    The chapter carries out an analysis of approximatively 2,000 firms confiscated from mafia organised crime in Italy. It studies the drivers behind the infiltration, the territories and sectors in which they were active. It eventually tests the correelation between the distribution of 'mafia firms' across territories and sectors, and a variety of contextual variables , including trade openness, levels of R&amp;D activity and the presence of mafia members. Finally, it discusses future lines of research
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