Stability of Dirac cone in artificial graphene

Trabajo presentado al 18th ETSF Workshop celebrado en Luxemburgo del 1 al 4 de Octubre de 2013.ETSF - European Theoretical Spectroscopy Facility I3 (211956).Peer Reviewe

Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from CaRe, a multicentric, observational study

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available. Methods: We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years. Results: Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles. Conclusion: The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning effectiveness, and strongly invite further research

Studio dei danni indotti da radiazioni non ionizzanti, UV e luminosa ad alta frequenza, a livello delle cellule staminali limbari

Il danno oculare da radiazioni luminose riguarda normalmente la cornea, ma può coinvolgere la retina. La cornea è la porzione anteriore dell'occhio e riceve il suo nutrimento dalle anse vascolari del limbus o giunzione sclero-corneale da cui provengo anche le cellule in grado di sostituire le cellule della cornea danneggiate. L’oftalmia da irradiazione luminosa è una lesione causata dalle radiazioni solari, conosciuto anche come "danno da luce blu", e/o da UV; la patologia è in grado di procurare dolore e arrossamento degli occhi e danni cicatriziali talvolta irreversibili. Per tali danni è stato suggerita una eziologia apoptotica mitocondriale oltre a normali eventi necrotici. Un elevato contenuto di ROS accelera la comparsa e la gravità dei danni da fotocheratite. Risulta importante proteggere e/o trattare farmacologicamente chi fosse stato esposto accidentalmente o continuativamente a rilevante irraggiamento, quali per esempio piloti di aereo, oppure particolari popolazioni. Per limitare tali danni utilizzare lenti filtranti non sembra essere in grado di risolvere il problema, soprattutto in soggetti già esposti. Diviene necessario studiare presidi farmacologici atti ad eliminare o ridurre eventuali rischi di danno irreversibile. Per ottimizzare tale studio si propone la valutazione delle risposte su sistemi in vitro che utilizzino colture cellulari quali: epiteliali; cheratociti e cellule staminali da espianti di limbus Su tali cellule si può indurre citoprotezione al fine di ridurne il danno da radiazioni, somministrando farmaci in grado di interferire con i meccanismi degenerativi, in particolare per prevenire danni al livello del DNA indotti da UVa/b

Development of novel phenoxyalkylpiperidines as high-affinity Sigma-1 (σ1) receptor ligands with potent anti-amnesic effect

International audienceThe sigma-1 (σ1) receptor plays a significant role in many normal physiological functions and pathological disease states, and as such represents an attractive therapeutic target for both agonists and antagonists. Here, we describe a novel series of phenoxyalkylpiperidines based on the lead compound 1-[ω-(4-chlorophenoxy)ethyl]-4-methylpiperidine (1a) in which the degree of methylation at the carbon atoms alpha to the piperidine nitrogen was systematically varied. The affinity at σ1 and σ2 receptors and at Δ8-Δ7 sterol isomerase (SI) ranged from subnanomolar to micromolar Ki values. While the highest-affinity was displayed at the σ1, the increase of the degree of methylation in the piperidine ring progressively decreased the affinity. The subnanomolar affinity 1a and 1-[ω-(4-methoxyphenoxy)ethyl]-4-methylpiperidine (1b) displayed potent anti-amnesic effects associated with σ1 receptor agonism, in two memory tests. Automated receptor-small-molecule ligand docking provided a molecular structure-based rationale for the agonistic effects of 1a and 1b. Overall, the class of the phenoxyalkylpiperidines holds potential for the development of high affinity σ1 receptor agonists, and compound 1a, that appears as the best in class (exceeding by far the activity of the reference compound PRE-084) deserves further investigation

DEVELOPMENT OF PHENOXYALKYLPIPERIDINES AS HIGH-AFFINITY SIGMA-1 (s1) RECEPTOR LIGANDS WITH POTENT ANTI-AMNESIC ACTIVITY

The sigma-1 (σ1) receptor plays a significant role in many physiological functions and pathological disease states, and, as such, it represents an attractive therapeutic target for both agonists and antagonists. Here, we describe a novel series of phenoxyalkylpiperidines (Figure 1) that were prepared and tested at σ1, σ2, and sterol Δ8- Δ7 isomerase (SI) sites by in vitro radioligand binding assays. These new compounds are derivatives of the σ ligand 1-[3-(4-chlorophenoxy)propyl]-4-methylpiperidine (L1), which has been claimed as a therapeutic agent for CNS disorders and neuropathies. In order to explore the structure-affinity relationships (SAFIRs) of this class of compounds, we modified the aryloxyl and piperidine moieties and the linker that connects them. In particular, we evaluated the influence of the stereochemistry on σ receptors affinity and selectivity through the introduction of methyl groups either on the chain or on the piperidine ring. The affinity at σ1 and σ2 receptors and at Δ8-Δ7 sterol isomerase (SI) ranged from subnanomolar to micromolar Ki values. While the highest affinity was displayed at the σ1 receptor (Ki = 0.34 nM), the chirality introduced by a methyl substitution in the linker resulted only in slight differences. The higher was the degree of methylation on the piperidine ring the lower was the ligand affinity, in agreement with other classes of σ1 receptor ligands. Nevertheless, the shorter oxyethylenic chain was beneficial for the σ1 selectivity. Importantly, these shorter-chain compounds displayed potent antiamnesic effects associated with σ1 receptor agonism, in two different memory tests. Overall, phenoxyalkylpiperidines hold potential for the development of high affinity σ1 receptor agonists

Stability of the Dirac cone in artificial graphene formed in quantum wells: a computational many-electron study

We carry out a comprehensive computational study on the stability of the Dirac cone in artificial graphene realized in nanopatterned quantum wells. Our real-space approach allows us to vary the size, shape, and positioning of the quantum dots in the hexagonal lattice. We compare the (noninteracting) single-particle calculations to density-functional studies within both local-density approximation and meta-generalized-gradient approximation. Furthermore, the density-functional results are compared against numerically precise path-integral quantum Monte Carlo calculations. As a whole, our results indicate high stability of the Dirac bands against external parameters, which is reassuring for further experimental investigations