Force Percolation Transition of Jammed Granular Systems

The mechanical and transport properties of jammed materials originate from an underlying per- colating network of contact forces between the grains. Using extensive simulations we investigate the force-percolation transition of this network, where two particles are considered as linked if their interparticle force overcomes a threshold. We show that this transition belongs to the random percolation universality class, thus ruling out the existence of long-range correlations between the forces. Through a combined size and pressure scaling for the percolative quantities, we show that the continuous force percolation transition evolves into the discontinuous jamming transition in the zero pressure limit, as the size of the critical region scales with the pressure.Comment: 5 pages, 5 figure

Effects of non-pharmacological or pharmacological interventions on cognition and brain plasticity of aging individuals.

Brain aging and aging-related neurodegenerative disorders are major health challenges faced by modern societies. Brain aging is associated with cognitive and functional decline and represents the favourable background for the onset and development of dementia. Brain aging is associated with early and subtle anatomo-functional physiological changes that often precede the appearance of clinical signs of cognitive decline. Neuroimaging approaches unveiled the functional correlates of these alterations and helped in the identification of therapeutic targets that can be potentially useful in counteracting age-dependent cognitive decline. A growing body of evidence supports the notion that cognitive stimulation and aerobic training can preserve and enhance operational skills in elderly individuals as well as reduce the incidence of dementia. This review aims at providing an extensive and critical overview of the most recent data that support the efficacy of non-pharmacological and pharmacological interventions aimed at enhancing cognition and brain plasticity in healthy elderly individuals as well as delaying the cognitive decline associated with dementia

Involvement of sperm acetylated histones and the nuclear isoform of Glutathione peroxidase 4 in fertilization

We previously demonstrated that the nuclear form of Glutathione peroxidase 4 (nGPx4) has a peculiar distribution in sperm head, being localized to nuclear matrix and acrosome and that sperm lacking nGPx4 are more prone to decondensation in vitro. In this study we have hypothesized that sperm retained acetylated histones and nGPx4 are implicated in paternal chromatin decondensation and male pronucleus formation at fertilization. Indeed, significant higher amounts of acetylated histone H4 and acetylated histone H3 were observed by both immunofluorescence and western blotting in nGPx4-KO sperm vs WT ones. In vitro fertilization of zona pellucida- deprived oocytes by WT sperm in the presence of trichostatin (TSA) also demonstrated that paternal histone acetylation was inversely related to the timing of sperm nucleus decondensation at fertilization. In contrast, TSA had no effect on nGPx4-KO sperm, indicating they had a maximal level of histone acetylation. Moreover the paternally imprinted gene Igf2/H19 was hypomethylated in KO sperm compared to WT ones. The lack of nGPx4 negatively affected male fertility, causing a marked decrease in total pups and pregnancies with delivery, a significant reduction in pronuclei (PN) embryos in in vitro fertilization assays and an approximately 2 h delay in egg fertilization in vivo. Because the zona pellucida binding and fusion to oolemma of nGPx4-KO and WT sperm were similar, the subfertility of nGPx4 sperm reflected a decreased sperm progression through egg cumulus/zona pellucida, pinpointing a defective acrosome in line with acrosomal nGPx4 localization. We conclude that paternal acetylated histones and acrosomal nGPx4 are directly involved in fertilization

The role of randomness in avalanche statistics and synchronization of spring-block models

2015 - 2016Self-organized criticality is a collective behaviour whose main feature is that the dynamical system we are considering moves towards its critical point, without any tuning of adjustable external parameters. The most famous example of SOC is the sandpile model, introduced in 1987 by Bak, Tang and Wiesenfeld. Other examples are variants of this first model, like the forest fire model, a model for front propagation, evolution models for species, and so on. SOC raised interest also in geophysics, as a possible explanation for the scale invariant behaviour of earthquakes, whose empirical distributions in magnitude (Gutenberg Richter Law) and in time (Omori Law) are power laws. A classical model of earthquakes is the Burridge-Knopoff spring-block model, where the fault between two tectonic plates is described as a lattice of rigid blocks elastically connected among them and to one surface of the fault. Due to the relative movement of the tectonic plates, the stresses on all the blocks increase until the stress of some block reaches an upper threshold and relaxes, causing the slipping of the block and a rearrangement of the constraints on the neighboring blocks. This can possibly push other blocks to relax and trigger an avalanche of slippings, i.e., an earthquake. Springblock models are the most simple description of a seismic fault reproducing at qualitative level experimental observations as the Gutenberg-Richter law. In the cellular automata version, the so-called OFC model, randomness is present only in the initial condition and avalanche sizes follow a power law distribution with an exponent depending on the dissipation parameter. It has been proposed that the critical behavior of this model is related to the tendency to synchronization in such systems (Middleton, Tang). In fact, this model presents critical behavior when disomogeneities from the boundaries (open boundary conditions) propagates into the bulk of the system, leading to a partially but non tototally synchronized state. Temporal and spatial correlation of real earthquakes, though, are not correctly described by this model in its original form. The OFC model can be mapped in the evolution of a driven elastic inter 2 face in a disordered medium after adding randomness in the level of friction instability. In this case the avalanche size distribution is still a power law but with a stable exponent independent of the dissipation parameter. A very good agreement with GR law exponent and with spatial correlations of the aftershocks was obtained in a recent work (Jagla, Rosso, Landes) on the depinning of viscoelastic interfaces. The introduction of a relaxation mechanism, in a time scale in between the small one of the avalanches and the big one of the drive, leads to a periodic stick-slip dynamics of the big avalanches, and that time scale is the one involved in the aftershocks phenomenon. In the Thesis I study the mechanism responsible for the observed differences between the pure and the random OFC model, focusing on the role of synchronization leading to quasi-periodic behavior. In order to achieve a better understanding of synchronization and dissipation in the system we also study simplified models including mean-field models up to two-block systems. The role of relaxation is also discussed in these simplified systems. [edited by author]La criticit´a auto-organizzata ´e un comportamento collettivo la cui caratteristica principale ´e che il sistema dinamico in esame si muove verso uno stato critico senza nessuna opportuna calibrazione di parametri esterni. Il piu´ famoso esempio di criticita´ auto-organizzata ´e il modello della pila di grani di sabbia, introdotto nel 1987 da Bak, Tang e Wiesenfeld. Altri esempi sono varianti di questo primo modello, come il modello di incendio delle foreste, di propagazione di un fronte, modelli evolutivi per le specie, e cos´ı via. La criticita´ auto-organizzata ha riscosso interesse anche in geofisica, come possibile spiegazione per l’invarianza di scala presente nei terremoti, le cui distribuzioni empiriche in magnitudo (legge di Gutenberg Richter) e nel tempo (legge di Omori) sono delle leggi a potenza. Un modello classico per i terremoti ´e il modello a blocchi con accoppiamento elastico di Burridge-Knopoff, dove la faglia tra due placche tettoniche ´e descritta come un reticolo di blocchi rigidi connessi tramite molle e tra di loro e ad un piatto che si muove a velocita´ costante (drive). A causa del movimento relativo delle placche, la forza su tutti i blocchi aumenta fino a quando la forza su di un generico blocco raggiunge una soglia massima e rilassa, provocando lo spostamento del blocco e una redistribuzione della forza perduta sui blocchi vicini. Questo puo´ indurre lo spostamento di altri blocchi ed innescare una valanga di spostamenti, e cio´e il terremoto. I modelli a blocchi con accoppiamento elastico sono la descrizione piu´ semplice di una faglia sismica in grado di riprodurre, qualitativamente, le osservazioni sperimentali come la legge di Gutenberg Richter. Nella sua versione automa cellulare, il modello OFC, il disordine ´e presente solo nella condizione iniziale e le taglie delle valanghe seguono una distribuzione a legge di potenza con un esponente che dipende dalla dissipazione. Middleton e Tang hanno introdotto l’ipotesi che il comportamento critico di questo modello sia collegato alla tendenza alla sincronizzazione in sistemi di questo tipo. Infatti, questo modello presenta un comportamento critico quando le disomogenita´ dai bordi (condizioni al bordo aperta) si propagano verso il centro del sistema, portandolo in uno stato parzialmente sincronizza 2 to. Tuttavia le correlazioni spaziali e temporali dei veri terremoti non sono correttamente descritti da questo modello nella sua forma originale. Il modello OFC puo´ essere mappato su di un altro modello, l’evoluzione di un’interfaccia elastica guidata in un mezzo disordinato, dopo aver aggiunto del disordine nelle soglie d’attrito. In questo caso la distribuzione delle taglie delle valanghe ´e ancora una legge a potenza, ma con un esponente stabile che non dipende dalla dissipazione. Un accordo molto buono con l’esponente della Gutenberg Richter, nonch´e con la correlazione spaziale degli aftershock, ´e stato ottenuto in un modello recente di interfacce visco-elastiche (Jagla, Rosso, Landes). L’introduzione di un meccanismo di rilassamento, in una scala temporale che si colloca tra quella del drive e quella delle valanghe, istantanea rispetto alla prima, comporta una dinamica stick-slip periodica delle valanghe grandi, e questa nuova scala temporale ´e responsabile del fenomeno degli aftershocks. In questo lavoro di Tesi abbiamo studiato il meccanismo responsabile delle differenze osservate tra il modello standard OFC e il modello OFC con disordine, focalizzandoci sul ruolo della sincronizzazione che conduce ad un comportamento quasi periodico. Per avere una migliore comprensione della sincronizzazione e della dissipazione nel sistema abbiamo studiato modelli semplificati, come modelli in campo medio e modelli a due blocchi. In quest’ultimo caso ´e stato discusso anche il ruolo del rilassamento. [a cura dell'autore]XXIX n.s

Therapeutic potential of the phosphino Cu(I) complex (HydroCuP) in the treatment of solid tumors

[Cu(thp)4][PF6] (HydroCuP) is a phosphino copper(I) complex highly soluble and stable in physiological media that has been developed as a possible viable alternative to platinum-based drugs for anticancer therapy. HydroCuP potently inhibited the growth of human cancer cells derived from solid tumors by inducing endoplasmatic reticulum (ER) stress thus leading to cell death through paraptosis with a preferential efficacy against cancer rather than non-cancer cells. Aim of the present study was to assess the therapeutic potential of HydroCuP in vivo, in syngenic and xenograft murine models of solid tumors by triggering the Unfolded Protein Response (UPR) pathway. With respect to platinum drugs, HydroCuP induced a markedly higher reduction of tumor growth associated with minimal animal toxicity. In human colorectal cancer xenografts, chemotherapy with HydroCuP was extremely effective in both oxaliplatin-sensitive and resistant models. The favorable in vivo tolerability of HydroCuP was also correlated to an encouraging biodistribution profile. Additionally, no signs of drug-related neurotoxicity and nephrotoxicity were observed. Altogether, these results demonstrate that HydroCuP appears worth of further investigation to evaluate its therapeutic activity towards a broad spectrum of solid malignancies

The use of a positive mood induction video-clip to target eating behaviour in people with bulimia nervosa or binge eating disorder: An experimental study

Recent theoretical models and empirical research have indicated that momentary negative affect increases the likelihood of binge eating episodes for individuals with bulimia nervosa and binge eating disorder. However, relatively little research has explored the potential for positive mood to serve a protective effect in reducing the likelihood of overeating behaviour in bulimia nervosa and binge eating disorder. The current study included 30 women with bulimia nervosa or binge eating disorder in a within-subjects crossover design. Following exposure to a video designed to induce food craving, we found that a positive mood vodcast was associated with significantly lower levels of negative mood and food consumption in a taste test meal, when compared to a neutral vodcast (p = .002). These findings support a role for decreasing negative mood in reducing the likelihood of binge eating behaviour in women with bulimia nervosa and binge eating disorder