Epigenetics and immunometabolism in diabetes and aging

Significance: A strong relationship between hyperglycemia, impaired insulin pathway and cardiovascular disease in type 2 diabetes (T2D) is linked to oxidative stress and inflammation. Immunometabolic pathways link these pathogenic processes and pose important potential therapeutic targets. Recent Advances: The link between immunity and metabolism is bi-directional and includes the role of inflammation in the pathogenesis of metabolic disorders such as T2D, obesity, metabolic syndrome and hypertension as well as the role of metabolic factors in regulation of immune cell functions. Low-grade inflammation, oxidative stress, balance between superoxide and nitric oxide, and the infiltration of macrophages, T cells, B cells in insulin-sensitive tissues, leads to metabolic impairment and accelerated ageing. Critical Issues: Inflammatory infiltrate and altered immune cell phenotype precede development of metabolic disorders. Inflammatory changes are tightly linked to alterations in metabolic status and energy expenditure and are controlled by epigenetic mechanisms. Future directions: A better comprehension of these mechanistic insights is of utmost importance to identify novel molecular targets. Here, we describe a complex scenario of epigenetic changes and immunometabolism linking to diabetes and aging-associated vascular disease

Epigenetics and immunometabolism in diabetes and aging

Significance: A strong relationship between hyperglycemia, impaired insulin pathway, and cardiovascular disease in type 2 diabetes (T2D) is linked to oxidative stress and inflammation. Immunometabolic pathways link these pathogenic processes and pose important potential therapeutic targets. Recent Advances: The link between immunity and metabolism is bidirectional and includes the role of inflammation in the pathogenesis of metabolic disorders such as T2D, obesity, metabolic syndrome, and hypertension and the role of metabolic factors in regulation of immune cell functions. Low-grade inflammation, oxidative stress, balance between superoxide and nitric oxide, and the infiltration of macrophages, T cells, and B cells in insulin-sensitive tissues lead to metabolic impairment and accelerated aging. Critical Issues: Inflammatory infiltrate and altered immune cell phenotype precede development of metabolic disorders. Inflammatory changes are tightly linked to alterations in metabolic status and energy expenditure and are controlled by epigenetic mechanisms. Future Directions: A better comprehension of these mechanistic insights is of utmost importance to identify novel molecular targets. In this study, we describe a complex scenario of epigenetic changes and immunometabolism linking to diabetes and aging-associated vascular disease. © Tomasz J

Case study preparation: the whatsApp acquisition from Facebook

The purpose of this work project is to analyze the acquisition of WhatsApp from Facebook occurred on 19th February 2014. The main research has the aim to understand if the price tag of $19 billion paid by Mark Zuckerberg was fair. Along the reaction of Facebook’s EPS on the keydays after the purchase, a balanced assessment of the acquisition was obtained and discussed. Results suggest that the price tag could be reasonable. However, taking into account the industry in which the two companies operate, where competition is quite intense, Facebook should assess this deal in a longerterm perspective.UNL - NSB

Generalization from correlated sets of patterns in the perceptron

Generalization is a central aspect of learning theory. Here, we propose a framework that explores an auxiliary task-dependent notion of generalization, and attempts to quantitatively answer the following question: given two sets of patterns with a given degree of dissimilarity, how easily will a network be able to "unify" their interpretation? This is quantified by the volume of the configurations of synaptic weights that classify the two sets in a similar manner. To show the applicability of our idea in a concrete setting, we compute this quantity for the perceptron, a simple binary classifier, using the classical statistical physics approach in the replica-symmetric ansatz. In this case, we show how an analytical expression measures the "distance-based capacity", the maximum load of patterns sustainable by the network, at fixed dissimilarity between patterns and fixed allowed number of errors. This curve indicates that generalization is possible at any distance, but with decreasing capacity. We propose that a distance-based definition of generalization may be useful in numerical experiments with real-world neural networks, and to explore computationally sub-dominant sets of synaptic solutions

Processing Narrative Coherence: Towards a top-down model of discourse.

Models of discourse and narration elaborated within the classical compositional framework have been characterized as bottom-up models, according to which discourse analysis proceeds incrementally, from phrase and sentence local meaning to discourse global meaning. In this paper we will argue against these models. Assuming as a case study the issue of discourse coherence, we suggest that the assessment of coherence is a top-down process, in which the construction of a situational interpretation at the global meaning level guides local meaning analysis. In support of our hypothesis, we explore the role of executive functions (brain functions involved in planning and organization of goal-oriented behaviors) in coherence’s establishment, discussing the results of several studies on narrative abilities of patients with brain injuries. We suggest that, compared to other models of discourse processing focused on comprehension, our model is a viable candidate for an integrated account of discourse comprehension and production

Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part II

In part II of this review, we describe the epidemiology and clinical consequences of vascular disease in patients with diabetes, and discuss the efficacy of risk factor modification and antiplatelet treatment. Specifically, evidence-based cardiovascular therapies are discussed through novel clinical insights on management of hyperglycaemia, hypertension, dyslipidaemia as well as platelet dysfunction. Recent trends in the incidence and outcomes of vascular disease in diabetes suggest that timely and effective implementation of therapies is making a favourable impac

Grid-free computation of probabilistic safety with Malliavin Calculus

This work concerns continuous-time, continuous-space stochastic dynamical systems described by stochastic differential equations (SDE). It presents a new approach to compute probabilistic safety regions, namely sets of initial conditions of the SDE associated to trajectories that are safe with a probability larger than a given threshold. The approach introduces a functional that is minimised at the border of the probabilistic safety region, then solves an optimisation problem using techniques from Malliavin Calculus, which computes such region. Unlike existing results in the literature, the new approach allows one to compute probabilistic safety regions without gridding the state space of the SDE