150 research outputs found
Attilio Hortis e Boccaccio. Appunti dal 'Carteggio' inedito (con tre lettere di Oscar Hecker)
C2-Symmetric Val-Val Dipeptide Isosteres via Diethylaluminium Azide Ring Opening of Epoxyalcohols
Diethylaluminium azide has been used as a highly regio- and stereo-selective reagent for the ring opening of valine-derived, sterically hindered epoxyalcohols. This reagent has enabled extending a previously described synthesis of diaminodiol dipeptide isosteres (P1-Ψ[CH(OH)-CH(OH)]-P1\u27) also to isosteres with branched residues in position P1\u27. The new methodology is compatible with Boe and Cbz proteetion of the starting aminoacid and has been applied to the synthesis of a C2-symmetric diaminodiol Val-Val dipeptide isostere 11, starting from the methyl ester of L-valine, in 25% over-all yield over seven (for Boe proteetion) or six (for Cbz proteetion) passages. A C2-symmetric di-MEM proteeted diaminodiol 17 and a mono-Boc proteeted, desymmetrized derivative 10 have also been obtained by the same approach. Compounds 10, 11 and 17 can be used as core units of C2-symmetric and non-symmetric peptido-mimetic inhibitors of aspartic proteases and as intermediates for the synthesis of cyclic urea inhibitors of HIV-protease
TANKI RT (PUNTA SOTTILE) I MILJSKO PRIOBALJE OD RTA RONKO (PUNTA RONCO) (RT OLMI-PUNTA OLMI) DO LAZARETA (LAZZARETTO)
L’articolo prende in esame il tratto di litorale che dal centro urbano di Muggia si
sviluppa in direzione ovest tra Punta Ronco (Olmi) e l’ex stabilimento contumaciale
– Lazzaretto – di San Bartolomeo nel lasso di tempo tra la seconda metà del XIX e
la prima metà del XX secolo, con particolare riguardo l’area di Punta Sottile.Pokretanjem djelatnosti brodogradilišta San Rocco čija je izgradnja započela
1858. godine te izgradnjom kopnene prometnice između brodogradilišta i
urbanog središta Milje postavljaju se temelji za širenje cestovne infrastrukture
koja će desetak godina kasnije stići do sanitarne ustanove Lazareta Svetog
Bartola (Lazzaretto di San Bartolomeo) čija djelatnost započinje 1. listopada
1868. Zahvaljujući posebnim morfološkim obilježjima, najzanimljiviji dio svakako
je onaj na trasi oko Tankog rta (Punta Sottile) gdje je krajem 1960-ih podignut
svjetionik sa stanom za svjetioničara i njegovu obitelj. Početkom 20. stoljeća
javile su se određene inicijative za izgradnju kupališta s prigrađenim pristaništima
za lakši iskrcaj i ukrcaj kupača koji su mogli koristiti redovne i posebne pomorske
linije. Godine 1913. inaugurirano je kupalište Punta Sottile koje će s vremenom
mijenjati ime, no i dalje zadržati izvornu lokaciju i namjenu, i to do današnjih
dana. U godinama nakon Drugoga svjetskog rata, na susjednom je području
počela djelovati pomorska kolonija humanitarne organizacije “Opera Figli del
Popolo di Trieste”. Velik dio dokumentarne građe pronađen je u fondovima koji se
čuvaju u Državnom arhivu u Trstu (l’Archivio di Stato di Trieste), kao i kartografija
Franciskanskog katastra (Catasto Franceschino), neophodna za praćenje razvoja
urbanizacije specifičnog područja Tankog rta (Punta Sottile) u promatranom
razdoblju. Ostali podaci dobiveni su iz novina tog razdoblja, posebice Il Piccolo,
te iz raznih monografskih publikacija
TANKI RT (PUNTA SOTTILE) I MILJSKO PRIOBALJE OD RTA RONKO (PUNTA RONCO) (RT OLMI-PUNTA OLMI) DO LAZARETA (LAZZARETTO)
L’articolo prende in esame il tratto di litorale che dal centro urbano di Muggia si
sviluppa in direzione ovest tra Punta Ronco (Olmi) e l’ex stabilimento contumaciale
– Lazzaretto – di San Bartolomeo nel lasso di tempo tra la seconda metà del XIX e
la prima metà del XX secolo, con particolare riguardo l’area di Punta Sottile.Pokretanjem djelatnosti brodogradilišta San Rocco čija je izgradnja započela
1858. godine te izgradnjom kopnene prometnice između brodogradilišta i
urbanog središta Milje postavljaju se temelji za širenje cestovne infrastrukture
koja će desetak godina kasnije stići do sanitarne ustanove Lazareta Svetog
Bartola (Lazzaretto di San Bartolomeo) čija djelatnost započinje 1. listopada
1868. Zahvaljujući posebnim morfološkim obilježjima, najzanimljiviji dio svakako
je onaj na trasi oko Tankog rta (Punta Sottile) gdje je krajem 1960-ih podignut
svjetionik sa stanom za svjetioničara i njegovu obitelj. Početkom 20. stoljeća
javile su se određene inicijative za izgradnju kupališta s prigrađenim pristaništima
za lakši iskrcaj i ukrcaj kupača koji su mogli koristiti redovne i posebne pomorske
linije. Godine 1913. inaugurirano je kupalište Punta Sottile koje će s vremenom
mijenjati ime, no i dalje zadržati izvornu lokaciju i namjenu, i to do današnjih
dana. U godinama nakon Drugoga svjetskog rata, na susjednom je području
počela djelovati pomorska kolonija humanitarne organizacije “Opera Figli del
Popolo di Trieste”. Velik dio dokumentarne građe pronađen je u fondovima koji se
čuvaju u Državnom arhivu u Trstu (l’Archivio di Stato di Trieste), kao i kartografija
Franciskanskog katastra (Catasto Franceschino), neophodna za praćenje razvoja
urbanizacije specifičnog područja Tankog rta (Punta Sottile) u promatranom
razdoblju. Ostali podaci dobiveni su iz novina tog razdoblja, posebice Il Piccolo,
te iz raznih monografskih publikacija
C2-Symmetric Val-Val Dipeptide Isosteres via Diethylaluminium Azide Ring Opening of Epoxyalcohols
Diethylaluminium azide has been used as a highly regio- and stereo-selective reagent for the ring opening of valine-derived, sterically hindered epoxyalcohols. This reagent has enabled extending a previously described synthesis of diaminodiol dipeptide isosteres (P1-Ψ[CH(OH)-CH(OH)]-P1\u27) also to isosteres with branched residues in position P1\u27. The new methodology is compatible with Boe and Cbz proteetion of the starting aminoacid and has been applied to the synthesis of a C2-symmetric diaminodiol Val-Val dipeptide isostere 11, starting from the methyl ester of L-valine, in 25% over-all yield over seven (for Boe proteetion) or six (for Cbz proteetion) passages. A C2-symmetric di-MEM proteeted diaminodiol 17 and a mono-Boc proteeted, desymmetrized derivative 10 have also been obtained by the same approach. Compounds 10, 11 and 17 can be used as core units of C2-symmetric and non-symmetric peptido-mimetic inhibitors of aspartic proteases and as intermediates for the synthesis of cyclic urea inhibitors of HIV-protease
PACSIN2 modifies miRNAs in extracellular vesicles, modulating thiopurine response
Thiopurines, such as mercaptopurine, are antimetabolites, used in the treatment of acute
lymphoblastic leukemia (ALL) and inflammatory bowel disease (IBD). PACSIN2 rs2413739
is associated with gastrointestinal toxicity in children with ALL and with drug-efficacy
in IBD pediatric patients. PACSIN2 is involved in vesicular trafficking and may affect the
release and content of extracellular vesicles (EVs), which mediate cell communication
and whose cargo modifies phenotypes of target cells. This study evaluates mechanisms
associating PACSIN2 polymorphism with interindividual variability in efficacy of thiopurines,
by considering the role of PACSIN2 in sorting specific miRNA in EVs.
Effects of stable PACSIN2 knock-down (KD) were evaluated in intestinal LS180 cells.
MTT cytotoxicity assay was used to verify mercaptopurine-sensitivity. EVs, released by
LS180 KD and MOCK control cells were isolated by ultracentrifuge and characterized by
nanoparticle tracking analysis (NTA). EVs miRNA-sequencing was performed by Illumina
Hi-seq 2000. EVs may alter drug cytotoxicity, therefore LS180 MOCK and KD cells were
co-treated with mercaptopurine and EVs. Statistical analysis was performed using t-test
and ANOVA.
Mercaptopurine was more cytotoxicity in LS180 KD cells (IC50 MOCK 3.23; IC50 KD 2.18
μM). No differences were observed by NTA in release of EVs between MOCK and KD cells
(t-test, p = 0.13). PACSIN2 KD altered intracellular and EVs expression of 6 and 24 miRNAs
respectively. EVs released by reduced mercaptopurine cytotoxicity (about 10%) and Rac1
protein expression in KD cells (ANOVA, p < 0.001), probably because they transport
different miRNAs.
In conclusion, PACSIN2 KD increase mercaptopurine cytotoxicity, probably, by deregulation
of miRNA expression in cells and EVs. These results will be further investigated to better
explain the link between PACSIN2 and EVs, whose miRNAs could provide a new scenario
in personalizing thiopurine treatment.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202
La falsificazione epigrafica. Questioni di metodo e casi di studio
This paper aims to reconsider the manuscript by Jacopo Valvasone (1499-1570), formerly owned by the Earl of Leicester (now British Library, Additional MS 49369), which Theodor Mommsen borrowed and inspected in 1876, just before the publication of the second part of CIL V. In the letter that he wrote to thank the Vicar and Librarian of Halkham Hall, Mommsen declared that Valvasone joined \u201cthe the long list of forgers\u201d. The analysis of forgeries in Valvasone\u2019s manuscript could show whether Mommsen was right in his opinion
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