Deciding the Consistency of Branching Time Interval Networks

Allen’s Interval Algebra (IA) is one of the most prominent formalisms in the area of qualitative temporal reasoning; however, its applications are naturally restricted to linear flows of time. When dealing with nonlinear time, Allen’s algebra can be extended in several ways, and, as suggested by Ragni and Wölfl, a possible solution consists in defining the Branching Algebra (BA) as a set of 19 basic relations (13 basic linear relations plus 6 new basic nonlinear ones) in such a way that each basic relation between two intervals is completely defined by the relative position of the endpoints on a tree-like partial order. While the problem of deciding the consistency of a network of IA-constraints is well-studied, and every subset of the IA has been classified with respect to the tractability of its consistency problem, the fragments of the BA have received less attention. In this paper, we first define the notion of convex BA-relation, and, then, we prove that the consistency of a network of convex BA-relations can be decided via path consistency, and is therefore a polynomial problem. This is the first non-trivial tractable fragment of the BA; given the clear parallel with the linear case, our contribution poses the bases for a deeper study of fragments of BA towards their complete classification

Superfici complesse di tipo generale e applicazioni pluricanoniche

In questa tesi, dopo una breve esposizione sulle superfici di Riemann, si introducono le basi dell'approccio moderno alla classificazione delle superfici complesse (secondo la classificazione di Enriques-Kodaira). Successivamente ci si concentra sull'argomento principale della tesi, e cioè lo studio della classe delle superfici di tipo generale, descrivendone vari aspetti legati ai numeri di Chern (tra cui i principali vincoli e il problema correlato della loro "geografia"), per poi porre l'attenzione sull'applicazione canonica e pluricanonica per questa classe di superfici. Qui si riprendono due lavori storici sull'argomento: il primo, dovuto a Bombieri, mostra che l'n-esima applicazione pluricanonica è un isomorfismo per n>4 e dà alcune condizioni affinché lo stesso valga per valori di n inferiori (condizioni successivamente rese più precise grazie al contributo di altri matematici), mentre il secondo, dovuto a Beauville, si concentra sulle proprietà dell'applicazione canonica (n=1)

The Horn Fragment of Branching Algebra

Branching Algebra is the natural branching-time generalization of Allen's Interval Algebra. As in the linear case, the consistency problem for Branching Algebra is NP-hard. Being relatively new, however, not much is known about the computational behaviour of the consistency problem of its sub-algebras, except in the case of the recently found subset of convex branching relations, for which the consistency of a network can be tested via path consistency and it is therefore deterministic polynomial. In this paper, following Nebel and Bürckert, we define the Horn fragment of Branching Algebra, and prove that it is a sub-algebra of the latter, being closed under inverse, intersection, and composition, that it strictly contains both the convex fragment of Branching Algebra and the Horn fragment of Interval Algebra, and that its consistency problem can be decided via path consistency. Finally, we experimentally prove that the Horn fragment of Branching Algebra can be used as an heuristic for checking the consistency of a generic network with a considerable improvement over the convex subset

Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease

Fabry disease (FD) is a lysosomal storage disorder (LSD) characterized by lysosomal accumulation of glycosphingolipids in a wide variety of cytotypes, including endothelial cells (ECs). FD patients experience a significantly reduced life expectancy compared to the general population; therefore, the association with a premature aging process would be plausible. To assess this hypothesis, miR-126-3p, a senescence-associated microRNA (SA-miRNAs), was considered as an aging biomarker. The levels of miR-126-3p contained in small extracellular vesicles (sEVs), with about 130 nm of diameter, were measured in FD patients and healthy subjects divided into age classes, in vitro, in human umbilical vein endothelial cells (HUVECs) "young" and undergoing replicative senescence, through a quantitative polymerase chain reaction (qPCR) approach. We confirmed that, in vivo, circulating miR-126 levels physiologically increase with age. In vitro, miR-126 augments in HUVECs underwent replicative senescence. We observed that FD patients are characterized by higher miR-126-3p levels in sEVs, compared to age-matched healthy subjects. We also explored, in vitro, the effect on ECs of glycosphingolipids that are typically accumulated in FD patients. We observed that FD storage substances induced in HUVECs premature senescence and increased of miR-126-3p levels. This study reinforces the hypothesis that FD may aggravate the normal aging process

IN "POLPO ... SITION" E ALTRI BREVI RACCONTI

Assalito dalla felicità corsi al mare, guardai l’acqua e fui preso da una forza, non mia, non umana che mi trascinò in acqua. Lì venni rapito da fantastiche sensazioni, l’adrenalina salì a mille, vidi un enorme creatura che suscitò in me delle emozioni mai provate prima, si era avvicinata talmente tanto che stava per toccarmi e, appena lo fece, il mio corpo si illuminò magicamente, le mie mani iniziarono pian piano ad assottigliarsi, il mio petto diventava sempre più piccolo e tondo e da lì a poco, ero diventato un polpo

Recombinant mussel protein Pvfp-5β: a potential tissue bioadhesive

During their lifecycle, many marine organisms rely on natural adhesives to attach to wet surfaces for movement and self-defence in aqueous tidal environments. Adhesive proteins from mussels are biocompatible and elicit only minimal immune responses in humans. Therefore these proteins have received increased attention for their potential applications in medicine, biomaterials and biotechnology. The Asian green mussel Perna viridis secretes several byssal plaque proteins, molecules that help anchor the mussel to surfaces. Among these proteins, protein-5β (Pvfp-5β) initiates interactions with the substrate, displacing interfacial water molecules before binding to the surface. Here, we established the first recombinant expression in Escherichia coli of Pvfp-5β. We characterized recombinant Pvfp-5β, finding that despite displaying a CD spectrum consistent with features of a random coil, the protein is correctly folded as indicated by MS and NMR analyses. Pvfp-5β folds as a β-sheet-rich protein as expected for an epidermal growth factor (EGF)-like module. We examined the effects of Pvfp-5β on cell viability and adhesion capacity in NIH-3T3 and HeLa cell lines, revealing that Pvfp-5β has no cytotoxic effects at the protein concentrations used and provides good cell-adhesion strength on both glass and plastic plates. Our findings suggest that the adhesive properties of recombinant Pvfp-5β make it an efficient surface coating material, potentially suitable for biomedical applications including regeneration of damaged tissues

miR-126-3p and miR-21-5p as Hallmarks of Bio-Positive Ageing; Correlation Analysis and Machine Learning Prediction in Young to Ultra-Centenarian Sicilian Population.

Human ageing can be characterized by a profile of circulating microRNAs (miRNAs), which are potentially predictors of biological age. They can be used as a biomarker of risk for age-related inflammatory outcomes, and senescent endothelial cells (ECs) have emerged as a possible source of circulating miRNAs. In this paper, a panel of four circulating miRNAs including miR-146a-5p, miR-126-3p, miR-21-5p, and miR-181a-5p, involved in several pathways related to inflammation, and ECs senescence that seem to be characteristic of the healthy ageing phenotype. The circulating levels of these miRNAs were determined in 78 healthy subjects aged between 22 to 111 years. Contextually, extracellular miR-146a-5p, miR-126-3p, miR-21-5p, and miR-181a-5p levels were measured in human ECs in vitro model, undergoing senescence. We found that the levels of the four miRNAs, using ex vivo and in vitro models, progressively increase with age, apart from ultra-centenarians that showed levels comparable to those measured in young individuals. Our results contribute to the development of knowledge regarding the identification of miRNAs as biomarkers of successful and unsuccessful ageing. Indeed, they might have diagnostic/prognostic relevance for age-related diseases

Renal function and peak exercise oxygen consumption in chronic heart failure with reduced left ventricular ejection fraction

Background: Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V˙O2) in heart failure (HF) patients. Methods and Results: We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV˙O2 (P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, Btype natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakVO2 <12 ml ・ kg−1 ・ min−1 was 1.75 (95% confidence interval (CI): 1.06–2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87–3.61; P=0.1141) in those with eGFR of 45–59, and 2.72 (1.01– 7.37; P=0.0489) in those with eGFR <45 ml ・ min−1 ・ 1.73 m−2. The area under the receiver-operating characteristic curve for peakV˙O2 <12 ml ・ kg−1 ・ min−1 was 0.63 (95% CI: 0.54–0.71), 0.67 (0.56–0.78), and 0.57 (0.47–0.69), respectively. Testing for interaction was not significant. Conclusions: Renal dysfunction is correlated with peakV O2. A peakV O2 cutoff of 12 ml ・ kg–1 ・ min–1 offers limited prognostic information in HF patients with more severely impaired renal function

Exploring the Prognostic Performance of MECKI Score in Heart Failure Patients with Non-Valvular Atrial Fibrillation Treated with Edoxaban

Introduction: Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF. Materials and Methods: This study included consecutive outpatients with HF and NVAF treated with edoxaban (n = 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry (n = 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation. Results: Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively, p = 0.452). The two populations' survival appeared non-significantly different at the 2-year follow-up. Conclusions: this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients

Metabolic exercise test data combined with cardiac and kidney indexes, the MECKI score: A multiparametric approach to heart failure prognosis

Objectives: We built and validated a new heart failure (HF) prognostic model which integrates cardiopulmonary exercise test (CPET) parameters with easy-to-obtain clinical, laboratory, and echocardiographic variables. Background: HF prognostication is a challenging medical judgment, constrained by a magnitude of uncertainty. Methods: Our risk model was derived from a cohort of 2716 systolic HF patients followed in 13 Italian centers. Median follow up was 1041 days (range 4-5185). Cox proportional hazard regression analysis with stepwise selection of variables was used, followed by cross-validation procedure. The study end-point was a composite of cardiovascular death and urgent heart transplant. Results: Six variables (hemoglobin, Na+, kidney function by means of MDRD, left ventricle ejection fraction [echocardiography], peak oxygen consumption [% pred] and VE/VCO2 slope) out of the several evaluated resulted independently related to prognosis. A score was built from Metabolic Exercise Cardiac Kidney Indexes, the MECKI score, which identified the risk of study end-point with AUC values of 0.804 (0.754-0.852) at 1 year, 0.789 (0.750-0.828) at 2 years, 0.762 (0.726-0.799) at 3 years and 0.760 (0.724-0.796) at 4 years. Conclusions: This is the first large-scale multicenter study where a prognostic score, the MECKI score, has been built for systolic HF patients considering CPET data combined with clinical, laboratory and echocardiographic measurements. In the present population, the MECKI score has been successfully validated, performing very high AUC. © 2012 Elsevier Ireland Ltd