Insulin signaling in insulin resistance states and cancer: A modeling analysis

Insulin resistance is the common denominator of several diseases including type 2 diabetes and cancer, and investigating the mechanisms responsible for insulin signaling impairment is of primary importance. A mathematical model of the insulin signaling network (ISN) is proposed and used to investigate the dose-response curves of components of this network. Experimental data of C2C12 myoblasts with phosphatase and tensin homologue (PTEN) suppressed and data of L6 myotubes with induced insulin resistance have been analyzed by the model. We focused particularly on single and double Akt phosphorylation and pointed out insulin signaling changes related to insulin resistance. Moreover, a new characterization of the upstream signaling of the mammalian target of rapamycin complex 2 (mTORC2) is presented. As it is widely recognized that ISN proteins have a crucial role also in cell proliferation and death, the ISN model was linked to a cell population model and applied to data of a cell line of acute myeloid leukemia treated with a mammalian target of rapamycin inhibitor with antitumor activity. The analysis revealed simple relationships among the concentrations of ISN proteins and the parameters of the cell population model that characterize cell cycle progression and cell death

A Clientelistic Perspective of Managing Municipal Solid Waste System: An Analysis of the Social Impact of clientelism on the Municipality of Palermo

This thesis aims to analyse the impact that clientelistic political pressures produces on the performance of Amia S.p.A., namely the public utility responsible of managing the solid waste management system of the municipality of Palermo, by making particular reference to the phenomenon of overstaffing. Synthetically, clientelism consists in a series of reciprocal convenience-based relationships between politicians and citizens, commanding unequal resources and involving mutually beneficial transactions in terms of economic, social and political consequences. The motivation of this research arise from the conviction that a deep analysis of this phenomenon, on one hand, could offer a greater contribution to improve the quality of electoral strategies and the consequential public policies and, on the other hand, to facilitate public managers in managing the performance of public organizations according to a perspective of sustainability. Therefore, the major issues of this research can be synthesized into three key questions: which are the main causes that led to the failure of the company Amia SpA? Which are the most remarkable managerial and organizational consequences that clientelistic political interferences have produced in respect of the performance of Amia S.p.A? Which policies could be implemented in order to mitigate the negative effects of clientelism thus maintaining a satisfying standard in the provision of the public service considered herein? Is clientelism a sustainable mechanism to expand significantly the electoral base of a given political party? Due to the high level of dynamic complexity that characterizes the system under observation the author believe that the combination between a dynamic performance management approach based on the so-called instrumental view and the system dynamic methodology may represent a powerful instrument in the hand of policy makers to frame a complex system and understand its development over time. Therefore in order to answer the above questions, firstly, a qualitative model showing which are the key variables of the system and the dynamic produced from their interactions will be elaborated and, secondly, will be identified the performance drivers on which public managers can leverage in order to drive the performance of Amia S.p.A. according to a perspective of sustainability. To conclude, the innovative aspect of this work is the attempt to apply the dynamic performance management approach, combined with the System Dynamics methodology, to assess the impact that clientelistic political interferences produces on the performance of a public utility. Therefore, the usefulness of this study is precisely to provide decision makers with a conceptual map that can enable them to promptly perceive and evaluate the causes and consequences of this phenomenon and, in addition, which policies can be implemented to mitigate the distortive effects that clientelistic political interferences may produces on the performance of a given public utility

The fixed point action for the Schwinger model: a perturbative approach

We compute the fixed point action of a properly defined renormalization group transformation for the Schwinger model through an expansion in the gauge field. It is local, with couplings exponentially suppressed with the distance. We check its perfection by computing the 1-loop mass gap at finite spatial volume, finding only exponentially vanishing cut off effects, in contrast with the standard action, which is affected by large power-like cut off effects. We point out that the 1-loop mass gap calculation provides a check of the classical perfection of the fixed point action, and not of the 1-loop perfection, as could be naively expected.Comment: 34 pages, LaTeX, 8 figures, uses style [epsfig

Antimicrobial and antibiofilm activity and machine learning classification analysis of essential oils from different mediterranean plants against pseudomonas aeruginosa

Pseudomonas aeruginosa is a ubiquitous organism and opportunistic pathogen that can cause persistent infections due to its peculiar antibiotic resistance mechanisms and to its ability to adhere and form biofilm. The interest in the development of new approaches for the prevention and treatment of biofilm formation has recently increased. The aim of this study was to seek new non-biocidal agents able to inhibit biofilm formation, in order to counteract virulence rather than bacterial growth and avoid the selection of escape mutants. Herein, different essential oils extracted from Mediterranean plants were analyzed for their activity againstP. aeruginosa. Results show that they were able to destabilize biofilm at very low concentration without impairing bacterial viability. Since the action is not related to a bacteriostatic/bactericidal activity onP. aeruginosa, the biofilm change of growth in presence of the essential oils was possibly due to a modulation of the phenotype. To this aim, application of machine learning algorithms led to the development of quantitative activity-composition relationships classification models that allowed to direct point out those essential oil chemical components more involved in the inhibition of biofilm production. The action of selected essential oils on sessile phenotype make them particularly interesting for possible applications such as prevention of bacterial contamination in the community and in healthcare environments in order to prevent human infections. We assayed 89 samples of different essential oils asP. aeruginosaanti-biofilm. Many samples inhibitedP. aeruginosabiofilm at concentrations as low as 48.8 µg/mL. Classification of the models was developed through machine learning algorithms

Neurobiological After-Effects of Low Intensity Transcranial Electric Stimulation of the Human Nervous System: From Basic Mechanisms to Metaplasticity

Non-invasive low-intensity transcranial electrical stimulation (tES) of the brain is an evolving field that has brought remarkable attention in the past few decades for its ability to directly modulate specific brain functions. Neurobiological after-effects of tES seems to be related to changes in neuronal and synaptic excitability and plasticity, however mechanisms are still far from being elucidated. We aim to review recent results from in vitro and in vivo studies that highlight molecular and cellular mechanisms of transcranial direct (tDCS) and alternating (tACS) current stimulation. Changes in membrane potential and neural synchronization explain the ongoing and short-lasting effects of tES, while changes induced in existing proteins and new protein synthesis is required for long-lasting plastic changes (LTP/LTD). Glial cells, for decades supporting elements, are now considered constitutive part of the synapse and might contribute to the mechanisms of synaptic plasticity. This review brings into focus the neurobiological mechanisms and after-effects of tDCS and tACS from in vitro and in vivo studies, in both animals and humans, highlighting possible pathways for the development of targeted therapeutic applications

The absence of cut--off effects for the fixed point action in 1--loop perturbation theory

In order to support the formal renormalization group arguments that the fixed point action of an asymptotically free model gives cut--off independent physical predictions in 1--loop perturbation theory, we calculate the finite volume mass--gap $m(L)$ in the non--linear $\sigma$--model. No cut--off effect of the type $g^4\left(a/L\right)^n$ is seen for any $n$. The results are compared with those of the standard and tree level improved Symanzik actions.Comment: 8 pages (latex) + 1 figure (Postscript), uuencode

Delay prediction system for large-scale railway networks based on big data analytics

State-of-the-art train delay prediction systems do not exploit historical train movements data collected by the railway information systems, but they rely on static rules built by expert of the railway infrastructure based on classical univariate statistic. The purpose of this paper is to build a data-driven train delay prediction system for largescale railway networks which exploits the most recent Big Data technologies and learning algorithms. In particular, we propose a fast learning algorithm for predicting train delays based on the Extreme Learning Machine that fully exploits the recent in-memory large-scale data processing technologies. Our system is able to rapidly extract nontrivial information from the large amount of data available in order to make accurate predictions about different future states of the railway network. Results on real world data coming from the Italian railway network show that our proposal is able to improve the current state-of-the-art train delay prediction systems

Instanton classical solutions of SU(3) fixed point actions on open lattices

We construct instanton-like classical solutions of the fixed point action of a suitable renormalization group transformation for the SU(3) lattice gauge theory. The problem of the non-existence of one-instantons on a lattice with periodic boundary conditions is circumvented by working on open lattices. We consider instanton solutions for values of the size (0.6-1.9 in lattice units) which are relevant when studying the SU(3) topology on coarse lattices using fixed point actions. We show how these instanton configurations on open lattices can be taken into account when determining a few-couplings parametrization of the fixed point action.Comment: 23 pages, LaTeX, 4 eps figures, epsfig.sty; some comments adde

Properties of the Fixed Point Lattice Dirac Operator in the Schwinger Model

We present a numerical study of the properties of the Fixed Point lattice Dirac operator in the Schwinger model. We verify the theoretical bounds on the spectrum, the existence of exact zero modes with definite chirality, and the Index Theorem. We show by explicit computation that it is possible to find an accurate approximation to the Fixed Point Dirac operator containing only very local couplings.Comment: 38 pages, LaTeX, 3 figures, uses style [epsfig], a few comments and relevant references adde

Scaling and topology in the 2-d O(3) σ\sigma-model on the lattice with the fixed point action

We study scaling properties and topological aspects of the 2--d O(3) non--linear $\sigma$--model on the lattice with the parametrized fixed point action recently proposed by P.~Hasenfratz and F.~Niedermayer. The behavior of the mass gap confirms the good properties of scaling of the fixed point action. Concerning the topology, lattice classical solutions are proved to be very stable under local minimization of the action; this outcome ensures the reliability of the cooling method for the computation of the topological susceptibility, which indeed reproduces the results of the field theoretical approach. Disagreement is instead observed with a different approach in which the fixed point topological charge operator is used: we argue that the discrepancy is related to the ultraviolet dominated nature of the model.Comment: 24 pages (Latex) + 8 figures (PostScript) in a uuencoded compressed tar fil