105 research outputs found
FUNCTIONAL CHARACTERIZATION OF A NOVEL GENETIC VARIANT PREDISPOSING TO ADVANCED FIBROSIS AND HEPATOCELLULAR CARCINOMA DEVELOPMENT IN NONALCOHOLIC FATTY LIVER DISEASE
No full textFunctional characterization of a novel genetic variant predisposing to advanced fibrosis and hepatocellular carcinoma development in nonalcoholic fatty liver disease
Introduzione
La steatosi epatica non alcoolica (NAFLD) rappresenta la più comune tra le malattie epatiche croniche nei paesi occidentali e rappresenta una causa emergente di cirrosi epatica e carcinoma epatocellulare (HCC). Numerosi studi hanno sottolineato l'importanza di vari tratti ereditari nel modificare la suscettibilità e il decorso di questa malattia. Tuttavia, la componente ereditabile di NAFLD resta in larga misura sconosciuta.
Scopo dello studio
Nell’ipotesi che una componente dell’ereditarietà della NFLD sia rappresentata da varianti genetiche rare con un forte impatto sull’attività proteica, il primo obiettivo di questo studio è stato quello di identificare, mediante Whole Exome Sequencing (WES), nuove varianti genetiche rare che determinassero un'alterazione dell'attività proteica e si associassero agli stadi avanzati della NAFLD. Abbiamo rilevato un'associazione tra una variante nel gene interferon regulatory factor 3 (IRF3) e lo sviluppo di carcinoma epatocellulare (HCC) correlato alla NAFLD. Abbiamo successivamente esaminato la regolazione specifica delle isoforme di IRF3 nei pazienti a rischio di NAFLD in relazione al danno epatico, abbiamo cercato di comprendere il ruolo di IRF3 nella biologia dell’epatocita e, infine, di mimare l'impatto della perdita di funzione dei trascritti alternativi di IRF3 sfruttando l'approccio di CRISPR/Cas9 genome editing in modelli in vitro. Infine, abbiamo testato l'impatto dell'inibizione della via di IRF3 sul tasso di proliferazione di cellule epatiche (HepG2) da parte dell'amlexanox. Quest’ultimo è un inibitore dell'asse TBK1-IRF3 in studio per il trattamento delle complicanze legate all'obesità.
Metodi e Pazienti
• Abbiamo effettuato il sequenziamento dell'intero esoma (WES) di 72 pazienti NAFLD-HCC italiani e 50 individui sani. I pazienti HCC sono stati confrontati con la popolazione europea (Europei non finlandesi inclusi nell’ Exome Aggregation Consortium, N = 33,370).
• Le associazioni sono state validate in un altro gruppo di pazienti con HCC correlato a NAFLD (N = 105), in 211 pazienti con fibrosi avanzata (N = 211) e altri 270 individui Italiani sani. Inoltre, è stato utilizzato un database più ampio per valutare la popolazione europea (genome aggreagation consortium, N = 64.603).
• Sono state eseguite analisi trascrittomiche su 125 soggetti gravemente obesi (coorte trascrittomica) sottoposti a biopsia epatica percutanea eseguita durante un intervento chirurgico bariatrico. L'RNA-Seq è stato eseguito su RNA estratto da biopsie epatiche congelate rapidamente.
• Per valutare l'effetto di IRF3-CL è stata introdotta una variante somatica nell'accettore di splicing dell’esone 7 specifico di IRF3-CL. In breve, abbiamo generato una linea di cellule HepG2 esprimente Cas9 sotto il controllo di un promotore inducibile da dxiciclina usando vettori lentivirali (Dharmacon, Lafayette, U.S.A.). L’RNA guida specifico è stato disegnato utilizzando il CRISPR design tool (http://crispr.mit.edu/) e clonato in un vettore di espressione (Addgene # 51133). Infine, le cellule trattate con doxiciclina sono state trasfettate con il vettore di espressione. Popolazioni clonali derivate da singole cellule sono state ottenute con il metodo della diluizione limite. In seguito, la presenza di mutazioni nel locus specificato è stata studiata mediante test nucleasi T7 (New England Biolabs, Ipswich, USA) e ulteriormente confermata con sequenziamento diretto (metodo di Sanger).
Risultati
La variante IRF3 rs141490768 è risultata più frequente nel gruppo di pazienti con HCC rispetto alla popolazione europea (OR = 37,1, p = 4,5 * 10-7) e, allo stesso modo, era più frequente nei pazienti con fibrosi avanzata (N = 211, p = 0,049; OR = 5,8; IC al 95% = 0,7-21). Considerando tutti i pazienti con epatopatia avanzata (N = 388), l'associazione è rimasta fortemente significativa (OR = 11; IC 95% = 4-24; p = 6,16 * 10-6). rs141490768 codifica una variante loss-of-function (A418T) nell'isoforma regolatoria IRF3-CL, suggerendo che una maggiore attività dell'IRF3 può predisporre al NAFLD-HCC. Inoltre, anche due trascritti non codificanti a funzione sconosciuta (rispettivamente IRF3-NC1 e IRF3-NC2) si sovrappongono al locus rs141490768. Mediante Burden test abbiamo riscontrato che vi era un arricchimento in varianti rare che alterano specificamente IRF3-CL sia nei pazienti con HCC (p = 5,69 * 10-7; OR = 35,5; IC al 95% = 11-90) che in quelli con fibrosi avanzata (OR = 6,4; IC al 95% = 0,8-24; p = 0,04). Le analisi di trascrittomica hanno rivelato livelli elevati di espressione di IRF3, IRF3-CL e IRF3-NC1. Inoltre, i livelli di mRNA di IRF3-CL erano direttamente correlati con lo stadio della malattia, mentre quelli di IRF3-NC1 erano inversamente correlati (β = 1,3 e -0,77, rispettivamente; p <0,05, entrambi). Mediante analisi immunoistochimica abbiamo evidenziato un’overespressione e iperattivazione di IRF3 in base alla severità del danno epatico. Inoltre, IRF3 è risultato overespresso nel tessuto tumorale rispetto al tessuto sano in una coorte di 20 pazienti del database TCGA e in campioni istologici. Sfruttando modelli in vitro abbiamo visto come l'esposizione ad acidi grassi liberi riesca attivare IRF3 in cellule HepG2, supportando il suo coinvolgimento nella patogenesi NAFLD. Allo stesso modo, anche stimoli proliferativi erano in grado di attivare questo fattore trascrizionale. Per mimare l'impatto della perdita di funzione di IRF3-CL e valutarne l’effetto sulla biologia degli epatociti, abbiamo sviluppato una linea di HepG2 parzialmente difettiva per IRF3-CL. Come previsto, le cellule IRF3-CL +/- presentavano un’attivazione di IRF3 più sostenuta in risposta al siero. Inoltre l'esposizione delle HepG2 all'amlexanox, da solo in combinazione con sorafenib, risultava in grado di ridurre il tasso di crescita cellulare. Questo effetto risultava più evidente nelle cellule IRF3-CL+/-.
Conclusioni
In conclusione, la variante IRF3 rs141490768 è associata ad un aumentato rischio di sviluppare stadi avanzati di NAFLD. Inoltre, l'overespressione di IRF3 è stata associata alla gravità della malattia epatica, in parallelo con l'induzione della risposta infiammatoria, l’alterazione del metabolismo lipidico e la proliferazione cellulare. Anche se saranno necessari ulteriori studi meccanicistici per chiarire la complessa rete di interazioni tra le varie isoforme di IRF3, i nostri esperimenti in vitro confermano che IRF3-CL esercita un effetto inibitorio sull'attivazione dell'isoforma principale, che induce la proliferazione cellulare. Complessivamente, i dati suggeriscono che il meccanismo alla base dell'associazione della variante rs141490768 con la progressione NAFLD a fibrosi grave e HCC è correlato a un’attivazione aberrante della via di IRF3. Infine, i risultati supportano la necessità di ulteriori studi per esaminare il possibile ruolo dell'amlexanox (o altri inibitori Ikk-epsilon) nel trattamento della NAFLD e indicano questa classe di farmaci come buoni candidati da valutare ulteriormente per il trattamento di NAFLD HCC in combinazione con sorafenib.Functional characterization of a novel genetic variant predisposing to advanced fibrosis and hepatocellular carcinoma development in nonalcoholic fatty liver disease
Introduction
Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in the Western countries and represent an emerging cause of liver cirrhosis and hepatocellular carcinoma (HCC). Several studies underlined the importance of heritability in modifying the susceptibility and progression of NAFLD. However, the specific determinants of NAFLD heritability remain largely unkonwn.
Aims
In the hypothesis that rare genetic variants with a strong impact on protein activity account for a fraction of NAFLD missing heritability, the first aim of the current study was to identify by Whole Exome Sequencing (WES) novel rare genetic variants determining an alteration of protein activity associated with advanced stage NAFLD. As we detected an association with a variant in Interferon regulatory protein 3 (IRF3) and hepatocellular carcinoma (HCC) related to NAFLD, we next examined the specific regulation of IRF3 isoforms in patients at risk of NAFLD in relation to liver damage, and tried to understand IRF3 regulation and to model the impact of IRF3 alternative transcripts downregulation by exploiting CRISPR/Cas9 gene editing approach in in vitro models. Finally, we tested the impact of IRF3 pathway inhibition by amlexanox, a TBK1-IRF3 axis inhibitor under study for the treatment of obesity related complications, on the proliferation of hepatoma cells (HepG2).
Patients and methods
• Variants discovery was performed by WES in 72 Italian NAFLD-HCC patients and 50 healthy individuals. HCC patients were compared to those in the European population (Exome Aggregation Consortium Non-Finnish Europeans, N=33,370).
• Validation was performed in NAFLD HCC patients (N=105) and in 211 patients with Advanced fibrosis (N=211), further 270 Italian healthy individuals. Furthermore, a larger database was used to evaluate the European population (genome aggregation consortium, N=64,603).
• Transcriptomic analyses were performed on 125 severely obese individuals (Transcriptomic cohort) who underwent to percutaneous liver biopsy performed during bariatric surgery. Bulk RNA-Seq was performed on RNA extracted from flash-frozen liver biopsies.
• To evaluate the effect of IRF3-CL a somatic variant in the IRF3-CL specific exon 7 splicing acceptor was introduced. Briefly, a Doxycycline (Therm-Fisher, Waltham, US) inducible Cas9 expressing HepG2 cell line was produced by lentiviral infection exploiting was produced exploiting Edit-R Inducible Lentiviral Cas9 Nuclease vectors (Dharmacon, Lafayette, U.S.A.). Specific guide RNA was designed using CRISPR design tool (http://crispr.mit.edu/) and cloned into an sgRNA expression vector (Addgene #51133) and doxycycline treated cells were transfected with the expression vector. Single cell derived populations were obtained by limiting diluition method and presence of mutations in the specified locus was investigated by T7 nuclease assay (New England Biolabs, Ipswich, US) and further confirmed by Sanger sequencing.
Results
The rs141490768 SNP in IRF3 resulted enriched in HCCs compared with European population (OR=37.1, p=4.5*10-7). We validated this association in the replication cohort (N=211, p=0.049; OR=5.8; 95% CI = 0.7-21). In the overall series of patients with advanced NAFLD (N=388), the association remained significant (OR=11; 95% CI= 4-24; p=6.16*10-6). The rs141490768 encodes a loss-of-function variant (A418T) in the IRF3 inhibitory isoform IRF3-CL, suggesting that increased IRF3 activity may predispose to NAFLD-HCC. Furthermore, two non-coding transcripts of unknown function (referred as IRF3-NC1 and IRF3-NC2, respectively) also overlap with the rs141490768 locus. Burden test analysis revealed enrichment in rare variants altering specifically IRF3-CL in both our HCC discovery (p=5.69*10-7; OR= 35.5; 95% CI = 11-90) and the patients of our advanced fibrosis cohort with available WES data (OR=6.4; 95% CI= 0.8-24; p=0.04). Transcriptomic analyses revealed high expression levels of IRF3, IRF3-CL, and IRF3-NC1. Moreover, the IRF3-CL mRNA levels were directly correlated with the disease stage, whereas those of IRF3-NC1 were inversely correlated (β=1.3 and -0,77, respectively; p<0.05, both). Immunohistochemical analysis revealed overexpression and hyperactivation of IRF3 according to NAFLD transition to fibrogenic steatohepatitis and HCC. Furthermore, IRF3 was overexpressed in tumor tissue compared with healthy tissue in a cohort of 20 patients of the TCGA database, and in histological samples. In HepG2 hepatoma cells, exposure to free fatty acids triggered IRF3 activation, supporting its involvement in NAFLD pathogenesis. Furthermore, IRF3 was also responsive to proliferation stimuli. To model the impact of IRF3-CL loss of function effect on hepatocyte biology, we developed IRF3-CL+/- HepG2 by CRISPR-Cas9 genome editing. As expected, IRF3-CL+/- HepG2 more sustained IRF3 activation in response to serum. Exposure of HepG2 to amlexanox, alone in combination with sorafenib, was able to impair cell growth rate, but more so in IRF3-CL+/- cells.
Conclusion
In conclusion, the rs141490768 IRF3 variant was associated with an increased risk to develop advanced NAFLD. Moreover, IRF3 upregulation was associated liver disease severity, in parallel with induction of the inflammatory response, altered lipid metabolism and cell proliferation. Even if further mechanistic studies are required to clarify the complex network of interactions among alternative IRF3 transcripts, our in vitro experiments confirm that IRF3-CL exerts an inhibitory effect on the activation of the main IRF3 isoform, which promotes cell proliferation. Altogether, data suggest that the mechanism underpinning the association of the rs141490768 variant with NAFLD progression to severe fibrosis and HCC is related to facilitation of IRF3 pathway activation. Finally, results support the necessity of further studies to examine the possible role of amlexanox (or other Ikk-epsilon inhibitors) in NAFLD treatment and points out this class of chemicals as good candidates to be further evaluated for the treatment of NAFLD HCC in combination with Sorafenib
Programmed cell death 1 ligand 1 (PD-L1) expression is associated with poor prognosis of malignant pleural mesothelioma patients with good performance status
No full textMalignant pleural mesothelioma (MPM) is often associated with a poor prognosis and options for the treatment of this disease are few. To date, the important role of the immune microenvironment in modifying the disease natural history is well established. The programmed cell death pathway (PD-1/PD-L1) limits the T lymphocyte activation in peripheral tissues when an inflammatory response occurs, and controls the tumour immune escape. PD-L1 is broadly expressed in several malignant tumours and associated with poor clinical outcomes. Thus, the aim of our study is to investigate the potential role of PD-L1 expression in MPM prognosis. Biopsy samples from 198 patients diagnosed with MPM were examined by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) to evaluate PD-L1 protein and gene expression. For PD-L1 protein expression we consider at least 5% membranous staining as positive. Gene expression levels were calculated with ΔΔCt method. Positive expression of PD-L1 by IHC was correlated with worse overall survival (OS; p=0.0225) in MPM patients. PD-L1 positive status was correlated with worse OS in the subgroup of patients with ECOG score <2 (p=0.0004, n=129) and these data were confirmed by multivariate analysis. No significant correlation was found between PD-L1 gene expression and OS. Our results show that PD-L1 evaluated by IHC assay may be a prognostic biomarker for MPM patients with good performance status
Caisson Foundations for Competitive Offshore wind Farms in ITALY
No full textAbstractThe research presented in the paper moves from the results of a feasibility study recently carried out for the development of an offshore wind farm off the cost of Rimini, in the Northern Adriatic Sea. The work, based on in-situ measurements of the environmental conditions, assessed the suitability of the considered area for the development of a relatively large wind farm, although at the profitability limit. The study has considered 60 offshore wind turbines installed on monopiles, as they are, at present, the most common solution and a quantification of the investment costs could be reliably completed. With reference to such case, the paper addresses the use of caisson foundations, a convenient alternative to monopiles in water of shallow to intermediate depth, with the final aim of improving the overall cost-effectiveness of the investment
PNPLA3 I148M gene variant and chronic kidney disease in Type 2 diabetic patients with NAFLD: Clinical and experimental findings
No full textBackground and Aims: Emerging evidence suggests an association between patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 (I148M protein variant) and risk of chronic kidney disease (CKD), but the mechanisms underpinning this association are poorly understood. Methods: We studied 157 patients with type 2 diabetes (T2DM) who underwent ultrasonography and vibration-controlled transient elastography for diagnosing nonalcoholic fatty liver disease (NAFLD). CKD was defined as estimated glomerular filtration rate (e-GFR) '60 mL/min/1.73 m
2 and/or abnormal albuminuria. We surveyed PNPLA3 mRNA expression in human tissues, using the liver as a positive control, and also measured PNPLA3 mRNA and protein expression levels in human cell lines represented in the kidney and the liver. Results: In all, 112 patients had NAFLD and 43 had CKD. Patients homozygous for the I148M variant (n = 11) had lower e-GFR levels (60.6 ± 11.7 vs 77.8 ± 15.9 vs 83.5 ± 16.5 mL/min/1.73 m
2, P =.0001) and higher prevalence of CKD (63.6% vs 24.2% vs 25.0%, P =.028), compared to those with I/M (n = 66) and I/I (n = 80) PNPLA3 genotype. The association of I148M homozygosity with lower e-GFR levels (P '.0001) and higher risk of CKD (adjusted-odds ratio 6.65; 95% CI 1.65-26.8, P =.008) was independent of liver disease severity (as detected by liver stiffness ≥7kPa) and other risk factors. PNPLA3 mRNA expression was greatest in liver and renal cortex, and podocytes showed high PNPLA3 mRNA and protein levels, comparable to that of hepatocytes and hepatic stellate cells respectively. Conclusions: The PNPLA3 I148M variant was associated with CKD, independently of common renal risk factors and severity of NAFLD PNPLA3 expression levels were particularly high in renal podocytes.
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“I PROMESSI SPOSI” DI GUIDO DA VERONA: APPUNTI SULLA LINGUA E SULLO STILE
No full textNel dare alle stampe la sua parodia dei Promessi Sposi (1930), Guido da Verona non immaginava di compiere delitto di lesa maestà nei confronti del totem manzoniano né che sarebbe stato oscurato dal controllo igienico fascista. Nel saggio si sostiene infatti, anche sulla base di evidenze ricavate dall'analisi del manoscritto, che la sua intenzione non fosse satirica, bensì ludico-parodica. Il cuore del saggio si incentra sull'analisi comparativa tra la versione daveroniana e l'ipotesto manzoniano, con particolare attenzione alle scaturigini del comico. Oltre che mettere in evidenza i tratti caratterizzanti la prosa di da Verona, captante e alluvionata di wits linguistici, il saggio descrive le strategie comiche usate dall'autore, quelle basate sul carattere e sulle situazioni e quelle del discorso vero e proprio. Nel corso dell'analisi si evidenzia come sia il comico del significante sia l'infrazione dei legami logici e di successione cooperino a incrinare la visione ordinata del mondo e della lingua strenuamente voluta e ottenuta da Alessandro Manzoni. When the parody of Promessi Sposi (1930) was sent to press, Guido da Verona did not imagine he was committing the crime of lese-majesty with regard to the Manzonian totem, nor that it would be blacklisted by the Fascist regime. This paper shows that, based on the analysis of the manuscript, the author's intention was not satirical, but a playful parody. It is a comparative analysis between the da Verona version and the Manzonian hypertext, with particular attention placed on the origin of the comic. Besides highlighting the traits that characterize the text brimming with linguistic wit by da Verona, the paper describes the comedic strategies used by the author based on the characters and situations, as well as in the discourse itself. The analysis shows how the comic meaning and the breaking of logical and temporal links crack the orderly vision of the world and the language carefully chosen and utilized by Alessandro Manzoni.</p
Giovan Battista Casti, "Il poema tartaro". Edizione critica e commento.
No full textMy thesis is a critical edition of the Poema tartaro by the libertine abbot Giovan Battista Casti (1724-1803). This work is a long octave poem, which satirizes, in accordance with the rules of the mock-heroic genre, Catherine II’s Russian court, where the author lived for years (1776-1779) as a member of the Hapsburg diplomacy. Although Casti was the Austrian court’s official poet, his work never received the authorization to be printed: the emperor Joseph II, after his 1781 alliance with Russia, forbade in fact the publication of a poem whose theme was explicitly against his new ally. Still, Casti’s text circulated widely in form of both manuscript copies and unauthorised (as well as defective) printed ones. A thorough analysis of these materials led to main findings: the version of the poem that Casti realized for the emperor in 1786, including 84 new stanzas, missing in the nineteenth-century pirate printed editions of the poem.
Along with the critical edition of the text, my thesis provides a broad commentary on the poem. The commentary is essential in order to illustrate the different perspectives from which the text can be approached. Sure enough, one of the components peculiar to the Poema Tartaro is the continuous overlap of elements that draw on different historical moments: even if the main scenery of the plot is the thirteenth-century Mongolian Empire, ruled by Genghis Khan, there are in fact several references to the nineteenth-century Russia of Catherine II. This strategy aims to present Russia allegorically as a country of perennial savagery. Depicting Petersburg as if it were the lost city of Karakorum and the czarina Catherine as a despotic and “oriental” sovereign, Casti contrasts the French Illuminists’ vision (in particular Voltaire’s) of nineteenth-century Russia as a model for the European Enlightenment. The thesis is completed by an index of the different historical transvestisms used by Casti to assign to every character in Catherine’s court a counterpart in the Mongolian scenery. Furthermore, the index is conceived as a tool to analyse the correlated controversies that inform the whole poem
Charge transfer in organic materials with potential applications in electronics
No full text2017 - 2018Search for low cost electronic materials has led towards the synthesis and
the employment of organic semiconductors (OSCs), a class of materials
that combine the electronic advantages of semiconducting materials with
the chemical and mechanical benefits of organic compounds. Despite the
intense research effort, new OSCs have usually been discovered by trial and
error and, even retrospectively, it was not always possible to explain why
some materials exhibit better performances than others. A more efficient
approach is now required and, in this respect, the use of computer-aided
materials discovery can be highly beneficial. Increasing numbers of new
OSCs have already been designed and improved through computational
modeling, which requires the efficient simulation of charge transport (CT)
processes taking place in OSC-based devices.
In this thesis we study and compare the relative performances of differ-
ent models in the simulations of charge transport in OSCs.
In the first part we focus on the different properties of organic semicon-
ductors with respect to their inorganic counterpart, their benefits and their
drawbacks, restricting our analysis to organic crystalline semiconductors,
which show the highest mobilities among all OSCs. Then we describe some
of the most widely studied classes of OSC materials, showing some cases
in which theory-guided material design has already been applied leading
towards new materials with improved electronic performances.
2
In the second part of this thesis we dwell on the unique physical prop-
erties of organic semiconductors and on the reasons that animates the still
topical debate about the most appropriate theoretical model for the CT de-
scription in these materials. Then, we briefly analyze strengths and draw-
backs of five theoretical models: the Marcus theory, the Fermi Golden Rule
(FGR), the Second Order Cumulant expansion of the density matrix (SOC),
the quantum dynamics, and a recently developed approach, the Transient
Localization Theory (TLT). In particular we describe some approximated
strategies that significantly speed up the computations still ensuring accu-
rate results.
In the third part we apply the abovementioned models to the description
of charge transport in some of the most studied OSCs, comparing their
predictions with experimental data and discussing the relative performances
of each method. Our results show that SOC and TLT predictions are
in good agreement with experimental data, the latter being the method
of choice because of its low computational cost and physically well-sound
assumptions.
In the last part of this thesis we focus on the simulation of CT in
DNA oligomers, a topical issue since long range charge migration makes
DNA a potentially well-suited material for nanoelectronics. Our analysis
reproduces in a quantitative way published experimental data and allows
us to reconcile experimental results disagreeing about the role of thymine
bridges in CT across DNA oligomers. [edited by Author]XXXI cicl
Problemi di attribuzione conflittuale nella musica strumentale veneta del Settecento
No full textThis thesis takes into consideration conflicting attributions, an issue occurring when a composition is ascribed to different authors in different sources. The aim of the research has been to investigate in depth this phenomenon in order to highlight its causes, considering in particular case studies from the repertory of instrumental music of Eighteenth century Veneto, analysed both from the historical-musicological and conceptual standpoint.
Three cases of study were carefully selected as representative of the wider repertory: the Concert for oboe in D minor attributed to Alessandro and Benedetto Marcello, Antonio Vivaldi and Johann Sebastian Bach; the collection of trio sonatas attributed to Domenico Gallo and Giovanni Battista Pergolesi; the collection of Concerti a cinque op.1 libro terzo, attributed to Giuseppe Tartini and Gasparo Visconti.
The investigation has in the first place allowed locating new sources and fresh information relative to the persons involved in the attributions. The detailed reconstruction of the history of the attributions and the examination of sources made it possible to advance different hypotheses on the originating factors of the conflicting attributions.
More generally, the thesis attempts to investigate in depth all the aspects related to the context in which a work was produced and transmitted, the economic interests involved in the circulation of a musical work, the mode of production of mss. and printed sources, the practical and legal tools adopted by composers in order to protect their work and the own authorial condition and, in conclusion the concepts of author and intellectual property in the instrumental music of the mid-eighteenth century are questioned
Correction to: Diffusion, outcomes and implementation of minimally invasive liver surgery: a snapshot from the I Go MILS (Italian Group of Minimally Invasive Liver Surgery) Registry (Updates in Surgery, (2017), 69, 3, (271-283), 10.1007/s13304-017-0489-x)
No full textA technical error led to incorrect rendering of the author group in this article. The correct authorship is as follows: Luca Aldrighetti, Francesca Ratti, Umberto Cillo, Alessandro Ferrero, Giuseppe Maria Ettorre, Alfredo Guglielmi, Felice Giuliante, Fulvio Calise on behalf of the Italian Group of Minimally Invasive Liver Surgery (I GO MILS) The collaborators are: Raffaele Dalla Valle, AOU Parma, Parma; Vincenzo Mazzaferro, Istituto Nazionale Tumori, Milano; Elio Jovine, Ospedale Maggiore, Bologna; Luciano Gregorio De Carlis, Ospedale Niguarda Ca’ Granda, Milano; Ugo Boggi, AOU Pisana, Pisa; Salvatore Gruttadauria, ISMETT, Palermo; Fabrizio Di Benedetto, AOU Policlinico di Modena, Modena; Paolo Reggiani, Ospedale Maggiore Policlinico, Milano; Stefano Berti, Ospedale Civile S.Andrea, La Spezia; Graziano Ceccarelli, Ospedale San Donato, Arezzo; Leonardo Vincenti, AOU Consorziale Policlinico, Bari; Giulio Belli, Ospedale SM Loreto Nuovo, Napoli; Guido Torzilli, Istituto Clinico Humanitas, Rozzano; Fausto Zamboni, Ospedale Brotzu, Cagliari; Andrea Coratti, AOU Careggi, Firenze; Pietro Mezzatesta, Casa di Cura La Maddalena, Palermo; Roberto Santambrogio, AO San Paolo, Milano; Giuseppe Navarra, AOU Policlinico G. Martino, Messina; Antonio Giuliani, AO R.N. Cardarelli, Napoli; Antonio Daniele Pinna, Policlinico Sant’Orsola Malpighi, Bologna; Amilcare Parisi, AO Santa Maria di Terni, Terni; Michele Colledan, AO Papa Giovanni XXIII, Bergamo; Abdallah Slim, AO Desio e Vimercate, Vimercate; Adelmo Antonucci, Policlinico di Monza, Monza; Gian Luca Grazi, Istituto Nazionale Tumori Regina Elena, Roma; Antonio Frena, Ospedale Centrale, Bolzano; Giovanni Sgroi, AO Treviglio-Caravaggio, Treviglio; Alberto Brolese, Ospedale S.Chiara, Trento; Luca Morelli, AOU Pisana, Pisa; Antonio Floridi, AO Ospedale Maggiore, Crema; Alberto Patriti, Ospedale San Matteo degli Infermi, Spoleto; Luigi Veneroni, Ospedale Infermi AUSL Romagna, Rimini; Giorgio Ercolani, Ospedale Morgagni Pierantoni, Forlì; Luigi Boni, AOU Fondazione Macchi, Varese; Pietro Maida, Ospedale Villa Betania, Napoli; Guido Griseri, Ospedale San Paolo, Savona; Andrea Percivale, Ospedale Santa Corona, Pietraligure; Marco Filauro, AO Galliera, Genova; Silvio Guerriero, Ospedale San Martino, Belluno; Giuseppe Tisone, Policlinico Tor Vergata, Roma; Raffaele Romito, AOU Maggiore della Carità, Novara; Umberto Tedeschi, AOU Integrata Verona, Verona; Giuseppe Zimmitti, Fondazione Poliambulanza, Brescia. © 2017, Italian Society of Surgery (SIC)
Three-dimensional relative localization and synchronized movement with wireless ranging
No full textRelative localization is a key capability for autonomous robot swarms, and it is a substan-
tial challenge, especially for small flying robots, as they are extremely restricted in terms of
sensors and processing while other robots may be located anywhere around them in three-
dimensional space. In this article, we generalize wireless ranging-based relative localiza-
tion to three dimensions. In particular, we show that robots can localize others in three
dimensions by ranging to each other and only exchanging body velocities and yaw rates.
We perform a nonlinear observability analysis, investigating the observability of relative
locations for different cases. Furthermore, we show both in simulation and with real-world
experiments that the proposed method can be used for successfully achieving various
swarm behaviours. In order to demonstrate the method’s generality, we demonstrate it both
on tiny quadrotors and lightweight flapping wing robots
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