1,458 research outputs found
EXPLORING THE EXTRACELLULAR VESICLE-NANOSTRUCTURED SECRETOME INTERFACE TOWARD CLINICAL TRANSLATION
No full textLe vescicole extracellulari (EVs), in quanto nanoparticelle biogeniche, offrono un grande potenziale diagnostico e terapeutico grazie alla loro biocompatibilità, alla capacità di trasportare molecole bioattive e alla possibilità di fornire un rilascio mirato di farmaci. Tuttavia, la loro traslazione clinica incontra sfide legate alle loro proprietà chimico-fisiche, ai fenomeni interfacciali e alle loro interazioni dinamiche nei fluidi biologici, che alterano la loro identità biologica e funzione. Pertanto, questa tesi di dottorato ha avuto l’obiettivo di studiare le interazioni all’interfaccia tra le EVs e il secretoma nanostrutturato, con l'intento di favorire la traslazione delle EV in medicina di precisione colmando il divario tra i risultati sperimentali e l’applicazione clinica. Questa tesi fornisce nuovi dati ed evidenze sui fenomeni di interfaccia delle EVs e sulle loro applicazioni come sistemi di rilascio di farmaci, introducendo nuovi concetti e tecniche originali.
Nello specifico, il Capitolo 1 offre una panoramica completa delle EVs nella nanomedicina, delineando le loro applicazioni nella diagnostica, nel rilascio di farmaci e nelle terapie, evidenziando al contempo le attuali limitazioni per la loro applicazione clinica. Il Capitolo 2 introduce i fenomeni all'interfaccia tra EVs e secretoma nanostrutturato, concentrandosi sulla formazione della corona biomolecolare (BC) e le sue implicazioni sull'identità, la funzione e la biodistribuzione delle EVs.
Nel Capitolo 3, lo studio indaga l'effetto del fisisorbimento di proteine durante la funzionalizzazione superficiale delle EVs con anticorpi, sottolineando l'importanza di controllare tutte le fasi del processo, poiché questo adsorbimento può andare ad influenzare significativamente l'efficacia del targeting per cui la formulazione di EVs è stata progettata.
Il Capitolo 4 presenta un approccio innovativo basato sulla spettroscopia di correlazione di fluorescenza (FCS) per studiare la dinamica di formazione della BC su due diverse sottopopolazioni di EVs in condizioni fisiologiche, fornendo nuovi dati su come la composizione e le proprietà superficiali delle EVs influenzano il loro comportamento biologico.
Nel Capitolo 5, vengono esaminate le interazioni tra EVs e lipoproteine (HDL, LDL, VLDL) utilizzando la spettroscopia di correlazione incrociata di fluorescenza (FCCS). I risultati rivelano modelli di interazione distinti, potenzialmente rilevanti dal punto di vista biologico a causa del ruolo degli aggregati EV-lipoproteine in condizioni patologiche come, per esempio, la metastasi tumorale.
Infine, il Capitolo 6 descrive lo sviluppo di una piattaforma multimodale per il rilascio di farmaci basata su EVs, mirata al trattamento del carcinoma mammario triplo negativo (TNBC). Ingegnerizzando le EVs per trasportare cetuximab e cisplatino, questo approccio migliora l'efficienza del rilascio dei farmaci, riduce la chemioresistenza e attiva meccanismi di morte cellulare come la ferroptosi, offrendo una promettente soluzione per il trattamento del TNBC.
Complessivamente, questa tesi rappresenta un avanzamento significativo nella comprensione dei fenomeni interfacciali delle EVs e delle loro applicazioni nei sistemi di trasporto di farmaci. I risultati forniscono una solida base per studi futuri che potrebbero portare alla traslazione clinica di terapie basate su EVs, specialmente nel contesto della medicina di precisione, aprendo nuove strade per lo sviluppo di farmaci nanotecnologici specifici per patologie complicate da trattare, come il TNBC.Extracellular Vesicles (EVs), as biogenic nanoparticles, hold great potential for disease diagnosis and treatment due to their biocompatibility, ability to transport bioactive molecules, and capacity for targeted delivery. However, their clinical translation faces challenges related to their physicochemical properties, interfacial phenomena, and dynamic interactions within biological fluids that alter their biological identity and function. Thus, this PhD thesis investigates the interface between EVs and nanostructured secretomes, aiming to advance precision medicine by bridging experimental findings with clinical applications. Furthermore, this thesis provides new insights into EV-interface phenomena and EV applications such as drug delivery systems, advancing state-of-the-art with new original concepts and techniques.
Specifically, Chapter 1 provides a comprehensive overview of EVs in nanomedicine, outlining their applications in diagnostics, drug delivery, and therapy, while also discussing current limitations in their clinical application. Chapter 2 explores the EV-nanostructured secretome interface, focusing on the formation of the biomolecular corona (BC) on the EV surface and its implications for EV identity, function, and biodistribution.
In Chapter 3, the study investigates the effect of protein physisorption during EV surface functionalization with targeting antibodies, emphasizing the importance of controlling all steps in the functionalization process, as protein adsorption can significantly affect the efficacy of EV-based therapies.
Chapter 4 presents a novel fluorescence correlation spectroscopy (FCS)-based approach to study BC dynamic formation on two distinct EV subpopulations in physiological conditions, providing insights into how EV composition and surface properties influence their biological behavior.
Chapter 5 examines the interactions between EVs and lipoproteins (HDL, LDL, VLDL) using fluorescence cross-correlation spectroscopy (FCCS). The results reveal distinct interaction patterns, which may be biologically relevant due to the role of EV-lipoprotein aggregates in pathological conditions, such as cancer metastasis.
Finally, Chapter 6 details the development of a multimodal EV-based drug delivery (nano)platform for triple-negative breast cancer (TNBC). By engineering EVs to carry cetuximab and cisplatin, this approach enhances drug delivery efficiency, reduces chemoresistance, and activates cell-death pathways such as ferroptosis, offering a promising solution for TNBC treatment.
Overall, this thesis presents significant advancements in understanding the interfacial phenomena of EVs and their application in therapeutic delivery systems. The results provide a solid foundation for future studies which may finally lead to clinical translation of EV-based therapies, particularly in the context of precision medicine, and open up new avenues for the development of targeted treatments for challenging diseases such as TNBC
The history of the Romano famili and "Angelo, tyran de Padoue" by Victor Hugo.
No full textreservedVictor Hugo, nel dramma Angelo, tyran de Padue, ricama tre diverse epoche storiche: i primi decenni dell’Ottocento, a lui contemporanei; la metà del Cinquecento, prescelta per lo svolgimento dell’azione drammatica; il tardo Medioevo evinto dai personaggi principali che compongono il racconto. Tuttavia, l’interesse storico e prettamente romantico verso il periodo medievale assume in quest’opera una rilevanza primaria. Tra le tante casate del nord Italia nominate dall’autore nell’opera, una su tutte sembra essere davvero simbolica. Particolarmente interessante è stato comprendere come la storia della famiglia da Romano costituisca il fulcro della costruzione drammaturgica. Ezzelino III e Cunizza da Romano sono elevati a emblema della poetica romantica e divengono funzionali al messaggio politico e sociale dell’autore.Victor Hugo, in his play Angelo, tyran de Padue, embroiders three different historical epochs: the first decades of the 19th century, contemporary with him; the middle of the 16th century, chosen for the unfolding of the dramatic action; and the late Middle Ages evoked by the main characters in the story. However, the historical and purely romantic interest in the medieval period takes on primary importance in this work. Of the many northern Italian lineages named by the author in the work, one in particular seems to be truly symbolic. It was particularly interesting to understand how the history of the da Romano family forms the core of the dramaturgical construction. Ezzelino III and Cunizza da Romano are elevated to emblems of romantic poetics and become functional to the author's political and social message
Michael Angelo Caruso, international author, consultant, and speaker on Campus
No full textTollefson, Elizabeth. (2013). Michael Angelo Caruso, international author, consultant, and speaker on Campus. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/223386
Oltre i confini della razionalità
No full text- Il contributo di Angelo Volpe prende in esame fondamentalmen-te due oggetti: primo, la potenzialità indiscussa nella sociologia contemporanea degli approcci individualistici e razionali e, secondo, la necessità di trascendere la gabbia stessa della razionalità e di andare oltre. Ciò che l’autore auspica è la realizzazione di un “modello a spettro intero” per l’analisi dei fatti sociali, un modello che possa espandere il raggio d’azione della comprensione sociologica al di là di ciò che possiamo vedere e misurare razionalmente.
- The contribution of Angelo Volpe essentially examines two objects: first, the unquestioned potentiality in contemporary sociology of individualistic and rational approaches, and, second, the need to transcend the very cage of rationality and go further. What the author hopes is the realization of a "full-spectrum model" for the analysis of social events, a model that can expand the scope of sociological understanding beyond what we can see and measure rationally
Michael Angelo Buonarroti,
No full textAppendix: "Three dialogues on painting composed by Francisco d'Ollanda, a Portuguese miniature painter who was in Rome in the year 1538. Tr. ... with the help of Mr. A. J. Clift, by Charles Holroyd. The manuscript was published for the first time in Renasçenca portugueza, no. VII, Porto, 1896.""The works of Michael Angelo": p. 281-283."A list of the principal books consulted by the author": p. 285-286.Mode of access: Internet
La fabbrica illuminata
No full textLa fabbrica illuminata, for voice and four-track magnetic tape, was composed by Luigi Nono in 1964. The music on tape, recorded at the Studio di Fonologia Musicale of the RAI in Milan, was the result of the complex elaboration of audio materials from different sources: parts performed by the RAI choir of Milan, “thematic” improvisations sung by the mezzo-soprano Carla Henius, voices and noises from the Italsider plant in Genoa-Cornigliano, and synthesized sounds.
Original audio sources
Three versions by the author were identified in the RAI archives in Milan:
Milan RAI Q6, 1964, analogue magnetic tape, 1 inch, 38 cm/s, quadraphonic, created by the author for performance with live voice;
Milan RAI Q7, 1965, analogue magnetic tape, 1 inch, 38 cm/s, quadraphonic. With the soloist voice recorded3 ;
Milan RAI E28, 196[5], analogue magnetic tape, 1⁄4 inch, 38 cm/s, monophonic. With the soloist voice recorded;
The copy deposited for copyright is conserved in the Ricordi Archive, Milan:
Milan Ricordi E214, 196[7], analogue magnetic tape, 1 inch, 38 cm/s, quadraphonic.
The tapes are still in good condition and include a set of metadata pertinent to the content of the recordings. The preservative re-recording of the analogue document in digital format was carried out in the Audio laboratory of the RAI in Milan, together with the MIRAGE Laboratory.
This restoration is tied to the basic document CLN 0002 in the Archive of Casa Ricordi in Milan, a digital conservative copy of the magnetic tape Q6 of the Archive of the Studio di Fonologia at the RAI in Milan.
The restoration of the sound tracks of the work has been completed at the Audio Laboratories of the University of Udine (Gorizia campus)under the expert supervision of Angelo Orcalli and edited by Angelo Orcalli. This restored version was based on the original documents and is accompanied with a technical report
Epitope Mapping on Microarrays Highlights a Sequence on the N Protein with Strong Immune Response in SARS-CoV-2 Patients
No full textIn SARS-CoV-2 pandemic scenario, the identification of rapid methods to detect antibodies against coronavirus has been a wide and urgent issue. Epitope mapping on peptide microarrays is a rapid way to identify sequences with a high immunoreactivity. The process begins with a proteome-wide screening, based on immune affinity; the use of a high-density microarray is followed by a validation phase, where a restricted panel of probes is tested using peptide microarrays; peptide sequences are immobilized through a click-based strategy.COVID-19-positive sera are tested and immuno-domains regions are identified on SARS-CoV-2 spike (S), nucleocapsid (N) protein, and Orf1ab polyprotein. An epitope on N protein (region 155-171) provided good diagnostic performance in discriminating COVID-19-positive vs. healthy individuals. Using this sequence, 92% sensitivity and 100% specificity are reached for IgG detection in COVID-19 samples, and no cross-reactivity with common cold coronaviruses is detected. Overall, epitope 155-171 from N protein represents a promising candidate for further development and rapid implementation in serological tests
Anthony Angelo and Law Reform in Mauritius
No full textThe author, former Professor and Dean of Law at Victoria University of Wellington and President of the Court of Appeal, discusses his experience working a law reform project in Mauritius with Professor Tony Angelo. As the author has experience in income tax reform, the article focuses on Professor Angelo's legislative drafting and policy development in relation to income tax law. Professor Angelo is described as a "one man Law Reform Commission" regarding his role in Mauritius, and discusses the importance of rules relating to technical interpretation and accessibility
Mont Pelée, from painting by the author
No full textPhotographie d\u27une peinture de Angelo Heilprin représentant la Montagne Pelée, Martiniqu
Anthony Angelo
No full textThe author, having served as his lecturer, provides a tribute to Professor Angelo of the Law Faculty at Victoria University of Wellington. The article recalls Professor Angelo's instrumental role in bringing Comparative Law to the law school, as well as playing an important part in providing academic hospitality to visiting scholars. The author praises Professor Angelo's encyclopaedic knowledge on Comparative Law, and states that the University owes him a real debt for his commitment to expand and diversify law teaching, research, and writing. 
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