86,586 research outputs found
Ionic Self Assembly in the Design of Fluorinated Ionic Liquid Crystals (ILCs)
No full textIonic liquid crystals are a class of compounds containing anions and cations, that combine the properties of liquid crystals and ionic liquids[1].
In the conventional design of ionic liquid crystalline compounds, an ionic core is connected with mesogenic groups via chemical covalent bonding . Alternatively, in ionic compounds, strong electrostatic interactions between cation and anion can be used to build up liquid crystalline order at supramolecular level. This general approach, called ionic self-assembly (ISA), allows one to create ionic phases and mesophases with highly organized supramolecular order [2].
In this context, a new series of fluorinated ionic liquids (ILs) and ionic liquid crystals (ILCs) was obtained starting from perfluoro-alkylated carboxylic acids and 1,2,4-oxadiazolyl-pyridine units (Figure 1). Their thermotropic properties were investigated by combined differential scanning calorimetry and polarized optical microscopy.
Figure 1.
[1] K.V. Axenov and S. Laschat, Materials, 4, 2011, 206; F. Lo Celso, I. Pibiri, A. Triolo, R. Triolo, A. Pace, S. Buscemi and N. Vivona, J. Mater. Chem., 17, 2007, 1201; V. Causin and G. Saielli, J. Mater. Chem., 19, 2009, 9153.
[2] C.F.J. Faul and M. Antonietti, Adv. Mater., 15, 2003, 673
PTHash: Revisiting FCH Minimal Perfect Hashing
No full textGiven a set S of n distinct keys, a function f that bijectively maps the keys of S into the range (0,...,n-1) is called a minimal perfect hash function for S. Algorithms that find such functions when n is large and retain constant evaluation time are of practical interest; for instance, search engines and databases typically use minimal perfect hash functions to quickly assign identifiers to static sets of variable-length keys such as strings. The challenge is to design an algorithm which is efficient in three different aspects: time to find f (construction time), time to evaluate f on a key of S (lookup time), and space of representation for f. Several algorithms have been proposed to trade-off between these aspects. In 1992, Fox, Chen, and Heath (FCH) presented an algorithm at SIGIR providing very fast lookup evaluation. However, the approach received little attention because of its large construction time and higher space consumption compared to other subsequent techniques. Almost thirty years later we revisit their framework and present an improved algorithm that scales well to large sets and reduces space consumption altogether, without compromising the lookup time. We conduct an extensive experimental assessment and show that the algorithm finds functions that are competitive in space with state-of-the art techniques and provide 2-4x better lookup time
Optimization of a new lead promoting the readthrough of the nonsense mutations for CFTR rescue in human CF cells
No full textOptimization of a new lead promoting the readthrough of the nonsense mutations for CFTR rescue in human CF cells
Laura Lentini, Raffaella Melfi, Sara Baldassano, Marco Tutone, Aldo Di Leonardo, Andrea Pace, Ivana Pibiri
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo
Background and rationale
Cystic Fibrosis patients with nonsense mutations in the CFTR gene have a more severe form of the disease. Nonsense mutations represent about 10% of the mutations that affect the CFTR gene and they are frequently associated to the classical F508 mutation (1). A potential treatment for this genetic alteration is to promote the translational readthrough of premature termination codons (PTCs) by Translational Read-Through-Inducing Drugs (TRIDs) (2-4).
Hypothesis and objectives
Our objective is to evaluate the functionality of the CFTR channel after treatment with a new molecule that we individuated in a precedent FFC project, and the activity of new lead molecules in cells stably expressing a nonsense-CFTR-mRNA (ns CFTR) in CF cellular model systems. We want also to study the supramolecular interactions among TRIDs, CFTR mRNA and the ribosomal A-site to identify the biological target and the mechanism of action.
Essential methods
QSAR, carried out on the basis of our preliminary results, will allow to achieve lead optimization and synthesize then a small library of analogs to be tested and compared to the Lead. We will mutagenize the CFTR cDNA by introducing the most diffuse nonsense mutations. Subsequently, FRT cells engineered with the vector expressing mutagenized nsCFTR, and nonsense-CF-human broncoepithelial cells will be grown in the air-liquid culture system to reproduce in vitro the epithelial organization. CFTR expression after treatments with our molecule will be evaluated by biomolecular techniques. CFTR activity will be revealed by specific CFTR-functionality assays. Finally, in vitro-in vivo (Zebrafish model) analyses of the safety profile for the set of synthesized molecules will complete the study.
Preliminary results
We screened the activity of several molecules synthetized by us in a precedent FFC project, identifying some molecules that showed high readthrough activity associated to the expression of the CFTR protein in ns CF immortalized cells.
Expected final results and their significance
We are confident that our findings will provide the validation of molecules with readthrough activity for the recovery of the CFTR function. Moreover, our pre-clinical study will assess the presence of toxic effects caused by the molecules in vivo.
References
1. Sermet-Gaudelus I, Boeck KD, Casimir GJ, Vermeulen F, Leal T, Mogenet A, Roussel D, Fritsch J, Hanssens L, Hirawat S, Miller NL, Constantine S, Reha A, Ajayi T, Elfring GL, Miller LL. Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis., Am J RespirCrit Care Med. 2010 Nov 15;182(10):1262-72.
2. Lentini L, Melfi R, Di Leonardo A, Spinello A, Barone G, Pace A, Palumbo Piccionello A, Pibiri I. Towards a rationale for the PTC124 (Ataluren) promoted read-through of premature stop codons: a computational approach and GFP-reporter cell-based assay. Mol. Pharm. 2014 11, 653-664.
3. Pibiri I, Lentini L, Melfi R, Gallucci G, Pace A, Spinello A, Barone G, Di Leonardo A. Enhancement of premature stop codon readthrough in the CFTR gene by Ataluren (PTC124) derivatives European Journal of Medicinal Chemistry 06/2015; 101.
4. Nagel-Wolfrum K, Möller F, Penner I, Baasov T4, Wolfrum U. Targeting Nonsense Mutations in Diseases with Translational Read-Through-Inducing Drugs (TRIDs), BioDrugs. 2016 Apr;30(2):49-74
Contratti ENEA con la Commissione Europea. Dati riassuntivi 2022
No full textCome ogni anno il rapporto ‘Contratti dell’ENEA con la Commissione Europea’ presenta il quadro delle attività in corso in cui è coinvolta l’Agenzia, finanziate da programmi, di ricerca e non, dell’Unione Europea (UE). L’ENEA, infatti, partecipa da anni con successo a programmi e iniziative dell’UE, in particolare i Programmi Quadro Ricerca e Innovazione e il Programma Quadro Euratom, che costituiscono un’importante fonte di finanziamento esterno per l’Agenzia. Nel presente rapporto sono stati considerati tutti i contratti stipulati dall’Agenzia, in vigore nel corso del 2022 relativi sia a progetti finanziati attraverso la precedente programmazione europea (2014-2020) non ancora conclusi e sia a progetti finanziati attraverso la nuova programmazione europea (2021-2027) i cui primi bandi sono stati pubblicati nel 2021. L’ENEA ha partecipato con numerose proposte ai nuovi bandi, confermando e migliorando gli eccellenti risultati già ottenuti nella programmazione 2014-2020. Il rapporto annuale contiene dati di sintesi aggregati e informazioni di dettaglio su progetti cofinanziati dall’UE e formalizzati attraverso specifici contratti. I dati sono elaborati sulla base dei contenuti della banca dati progetti UE (progettiue.enea.it) dell’ENEA, di recente completamente rinnovata. La banca dati è disponibile su web dal 2009, raccogliendo e rendendo omogenee le informazioni sui contratti stipulati dall’ENEA con la Commissione Europea (CE) e completandole con dati ricavati dai documenti contrattuali. Tale strumento, gestito dalla Direzione Innovazione e Sviluppo dell’Agenzia, ha l’obiettivo di favorire la diffusione di informazioni all’interno e all’esterno dell’Agenzia, costituendo anche uno strumento a supporto della progettualità dei ricercatori. Ad oggi sono presenti nella banca dati più di 1100 contratti e per ciascuno di questi sono disponibili, ad esempio, informazioni dettagliate relative a: programma di finanziamento dell'UE, acronimo, titolo, date di inizio e fine, abstract e attività ENEA, sito web del progetto, coordinatore e partenariato, responsabile ENEA. Ciò rende possibile la realizzazione di report complessi come l'analisi del partenariato nazionale ed internazionale dell'ENEA per tipologia, per area geografica e per progetto. Possono essere prodotte anche elaborazioni ad hoc relative all’esperienza specifica dell’Agenzia in determinate aree geografiche e/o ambiti di ricerca, da utilizzare, ad esempio, come ‘referenze’ dell’ENEA, indispensabili nel caso della partecipazione a tender della CE e a call of proposals di specifici programmi nazionali, europei e internazionali. La banca dati, quindi, oltre ad essere uno strumento per l’analisi e la condivisione delle informazioni sui progetti in corso, rende disponibili elementi utili alla formulazione di strategie e alla definizione di accordi con partner nazionali e internazionali. I dati sono organizzati in quattro diverse sezioni: i risultati di partecipazione dell’ENEA alla programmazione 2021-2027, i contratti stipulati nel 2022, i contratti in corso nel 2022. Infine, una sezione è dedicata alla partecipazione dell’ENEA al Consorzio EUROfusion che, per l’entità del finanziamento e le modalità di aggiudicazione e funzionamento, non è assimilabile agli altri progetti ed è oggetto di approfondimento specifico nella sezione 2; per questi motivi il co-finanziamento riconosciuto a ENEA non è incluso nei dati di sintesi elaborati. La pubblicazione è completata dall’allegato relativo alle schede sintetiche di ciascuno dei 179 progetti in corso
Parallel and External-Memory Construction of Minimal Perfect Hash Functions with PTHash
No full textA function f:U \to {0,...,n−1} is a minimal perfect hash function for a set S \subseteq U of size n , if f bijectively maps S into the first n natural numbers. These functions are important for many practical applications in computing, such as search engines, computer networks, and databases. Several algorithms have been proposed to build minimal perfect hash functions that: scale well to large sets, retain fast evaluation time, and take very little space, e.g., 2 – 3 bits/key. PTHash is one such algorithm, achieving very fast evaluation in compressed space, typically many times faster than other techniques. In this work, we propose a new construction algorithm for PTHash enabling: (1) multi-threading , to either build functions more quickly or more space-efficiently, and (2) external-memory processing , to scale to inputs much larger than the available internal memory. Only few other algorithms in the literature share these features, despite of their practical impact. We conduct an extensive experimental assessment on large real-world string collections and show that, with respect to other techniques, PTHash is competitive in construction time and space consumption, but retains 2 – 6× better lookup time
A review of pharmacology of NCS-382, a putative antagonist of gamma-hydroxybutyric acid (GHB) receptor
No full textgamma-Hydroxybutyric acid (GHB), a naturally occurring metabolite of gamma-aminobutyric acid (GABA), has been postulated to act as a specific agonist of GHB receptors and as well as a weak GABA(B) receptor agonist. To date, 6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (NCS-382), a semirigid compound structurally related to GHB, is the only compound reported to be an antagonist of the GHB receptor sites. In this article we review the in vivo and in vitro pharmacological properties of NCS-382 and its interaction with GHB and GABA(B) receptors. Binding studies have demonstrated that NCS-382 is a stereoselective ligand for GHB-binding sites, with both, the high and the low component of population, showing the same distribution of GHB receptors. Indeed, this compound did not display affinity for GABA(A), GABA(B), or any other known receptors, while conflicting data have been reported as to its selective antagonist action at GHB receptor. Only a few studies have shown that NCS-382 antagonizes GHB-induced effect, but a re-evaluation of all data reported in the literature suggests that the antagonistic effect of this compound could be due to an indirect action at GABA(B) receptors. As revealed by several behavioral studies, NCS-382 fails to antagonize GHB discriminative stimuli, GHB-induced inhibition of locomotor activity and ataxia or suppression of operant responses. Moreover, it is capable of either eliciting qualitatively similar effects to those of GHB or enhancing some actions of GHB. In addition, the NCS-382-sensitive electrophysiological effects of endogenous and exogenous GHB observed in vivo have not been completely replicated in vitro. The only electrophysiological action of GHB antagonized in vitro by NCS-382 required a previous blockade of GABA(B) receptors. We concluded that NCS-382 is a good ligand but not a selective antagonist for GHB recepto
Thyroid hormone receptor ligands induce regression of rat preneoplastic liver lesions causing their reversion to a differentiated phenotype
No full textHepatology. 2009 Apr;49(4):1287-96.
Thyroid hormone receptor ligands induce regression of rat preneoplastic liver lesions causing their reversion to a differentiated phenotype.
Perra A, Kowalik MA, Pibiri M, Ledda-Columbano GM, Columbano A.
SourceDepartment of Toxicology, Oncology and Molecular Pathology Unit, University of Cagliari, Cagliari, Italy.
Abstract
Triiodothyronine (T3), through interaction with its intracellular thyroid hormone receptors (TRs), influences various physiological functions, including metabolism, development, and growth. We investigated the effect of T3 and the selective TR-beta agonist GC-1 in two models of hepatocarcinogenesis. Preneoplastic lesions were induced in F-344 rats via a single dose of diethylnitrosamine, followed by a choline-deficient (CD) diet for 10 weeks. Rat subgroups were then fed the CD diet or a CD diet containing either 4 mg/kg T3 or 5 mg/kg GC-1 for another week. Rats fed a CD diet alone showed a large number (65/cm(2)) of preneoplastic lesions positive for the placental form of glutathione S-transferase (GSTP). Coadministration of T3 for the last week caused an almost complete disappearance of the foci (3/cm(2)). A reduction of GSTP-positive foci was also observed in rats fed a CD + GC-1 diet (28/cm(2) versus 75/cm(2) of rats fed a CD diet alone) in the absence of significant differences in labeling or apoptotic index of preneoplastic hepatocytes between the two groups. An antitumoral effect of GC-1 was also observed with the resistant hepatocyte model of hepatocarcinogenesis. Nodule regression was associated with a return to a fully differentiated phenotype, indicated by the loss of the fetal markers GSTP and gamma glutamyl transpeptidase, and reacquisition of the activity of glucose 6-phosphatase and adenosine triphosphatase, two enzymes expressed in normal hepatocytes. CONCLUSION: Our results indicate that activated TRs negatively influence the carcinogenic process through induction of a differentiation program of preneoplastic hepatocytes. The results also suggest that TRs could be a meaningful target in liver cancer therapy.
PMID:19115221[PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, SubstancesPublication TypesResearch Support, Non-U.S. Gov'tMeSH TermsAnimalsApoptosis/drug effectsCell Differentiation/drug effects*Choline Deficiency/complicationsDiethylnitrosamineGlutathione Transferase/metabolismHepatocytes/metabolismLiver Neoplasms, Experimental/drug therapy*MalePrecancerous Conditions/drug therapy*Precancerous Conditions/etiologyRatsRats, Inbred F344Receptors, Thyroid Hormone/metabolismTriiodothyronine/analogs & derivativesTriiodothyronine/pharmacologyTriiodothyronine/therapeutic use*SubstancesReceptors, Thyroid HormoneDiethylnitrosamineTriiodothyronineGlutathione Transferase
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Sensibilità allo stress e memoria spaziale nei figli dei ratti sottoposti a stress cronico
No full textPhotocatalysis in dimethyl carbonate green solvent: degradation and partial oxidation of phenanthrene on supported TiO2
No full textDimethyl carbonate (DMC) is here proposed – for the first time – as a green organic solvent for
photocatalytic synthesis. In this work, the photocatalytic partial oxidation of phenanthrene in dimethyl
carbonate (DMC) by using anatase TiO2 as the photocatalyst is described as paradigmatic example of a
green synthetic process starting from polycyclic aromatic hydrocarbons (PAHs). For comparison, the
same reaction carried out also in ethanol, 1-propanol or 2-propanol is reported. The use of DMC as the
solvent allowed us to achieve 19% and 23% selectivity towards 9-fluorenone and 6H-benzo[c]chromen-
6-one, respectively. The proposed approach may represent both a new green synthetic process and an
environmentally friendly route to degradation of PAHs
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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