POLYCOMB ROLE IN CELLULAR PROLIFERATION AND TRANSFORMATION

The Polycomb Group proteins (PcGs) are present in cells nuclei as two main repressive complexes named Polycomb Repressive Complex 1 (PRC1) and 2 (PRC2). Both have been involved in several cellular functions among which the ability to promote cellular proliferation is the main PcG feature that links their activity to cancer development. Both complexes are directly involved in repressing the transcription of the Ink4aArf locus that encodes for the tumor suppressive proteins p16 and p19/Arf (p14/Arf in humans), potent inhibitors of cell growth via the positive regulation of pRb and p53 functions. Thus, since the activity of both PRC1 and PRC2 complexes is frequently enhanced in different type of human tumors, inhibition of PcG function has been proposed for many years as a potential strategy for cancer treatment. Yet, the fact that the pro-proliferative role of PcG proteins depends on the repression of the pRb and p53 pathways, of which most if not all tumors are defective, generates a scientific paradox for the effectiveness of PcG inhibition in cancer treatment. In this thesis, with the help of my colleagues, (from now on referred as we) I will present data showing how PcGs genetic depletion dramatically impairs cellular proliferation independently on the expression of the Ink4a/Arf locus or p53 and pRb activities. We also genetically demonstrate, in cell culture and in vivo, that PcGs activity is required for both the transformation and the maintenance of the transformed phenotype obtained by expression of potent oncogenes such as H-RASV12 or c-MYC in cells defective for the pathways of p53 and pRb. Finally we suggest a potential mechanism to explain the reduced proliferation/tumorigenic potential involving DNA replication control by PcG proteins. We show defects both in fork progression and fork symmetry along with increased replication origin numbers in PcGs knockout transformed cells. Collectively these data strongly support PcGs as master regulators of cellular proliferation and transformation independently on the impairment of main tumor suppressive pathways and introduce a novel general mechanism through which PcGs regulate these processes. Overall this work supports PcGs as druggable targets in tumors where oncosuppressive pathways are de-regulated and proliferation, ergo DNA replication, is enhanced

From Manifesta to Krypta: The Relevance of Categories for Trusting Others

In this paper we consider the special abilities needed by agents for assessing trust based on inference and reasoning. We analyze the case in which it is possible to infer trust towards unknown counterparts by reasoning on abstract classes or categories of agents shaped in a concrete application domain. We present a scenario of interacting agents providing a computational model implementing different strategies to assess trust. Assuming a medical domain, categories, including both competencies and dispositions of possible trustees, are exploited to infer trust towards possibly unknown counterparts. The proposed approach for the cognitive assessment of trust relies on agents' abilities to analyze heterogeneous information sources along different dimensions. Trust is inferred based on specific observable properties (Manifesta), namely explicitly readable signals indicating internal features (Krypta) regulating agents' behavior and effectiveness on specific tasks. Simulative experiments evaluate the performance of trusting agents adopting different strategies to delegate tasks to possibly unknown trustees, while experimental results show the relevance of this kind of cognitive ability in the case of open Multi Agent Systems

Facing Openness with Socio Cognitive Trust and Categories.

Typical solutions for agents assessing trust relies on the circulation of information on the individual level, i.e. reputational images, subjective experiences, statistical analysis, etc. This work presents an alternative approach, inspired to the cognitive heuristics enabling humans to reason at a categorial level. The approach is envisaged as a crucial ability for agents in order to: (1) estimate trustworthiness of unknown trustees based on an ascribed membership to categories; (2) learn a series of emergent relations between trustees observable properties and their effective abilities to fulfill tasks in situated conditions. On such a basis, categorization is provided to recognize signs (Manifesta) through which hidden capabilities (Kripta) can be inferred. Learning is provided to refine reasoning attitudes needed to ascribe tasks to categories. A series of architectures combining categorization abilities, individual experiences and context awareness are evaluated and compared in simulated experiments

Reasoning with Categories for Trusting Strangers: a Cognitive Architecture

A crucial issue for agents in open systems is the ability to filter out information sources in order to build an image of their counterparts, upon which a subjective evaluation of trust as a promoter of interactions can be assessed. While typical solutions discern relevant information sources by relying on previous experiences or reputational images, this work presents an alternative approach based on the cognitive ability to: (i) analyze heterogeneous information sources along different dimensions; (ii) ascribe qualities to unknown counterparts based on reasoning over abstract classes or categories; and, (iii) learn a series of emergent relationships between particular properties observable on other agents and their effective abilities to fulfill tasks. A computational architecture is presented allowing cognitive agents to dynamically assess trust based on a limited set of observable properties, namely explicitly readable signals (Manifesta) through which it is possible to infer hidden properties and capabilities (Krypta), which finally regulate agents' behavior in concrete work environments. Experimental evaluation discusses the effectiveness of trustor agents adopting different strategies to delegate tasks based on categorization

Embodied Organizations: a Unifying Perspective in Programming Agents, Organizations and Environments

http://ceur-ws.org/Vol-627/coin_7.pdfInternational audienceMAS research pushes the notion of openness related to systems combining heterogeneous computational entities. Typically, those entities answer to different purposes and functions and their integration is a crucial issue. Starting from a comprehensive approach in developing agents, organizations and environments, this paper devises an integrated approach and describes a unifying programming model. It introduces the notion of embodied organization, which is described first focusing on the main entities as separate concerns; and, second, establishing different interaction styles aimed to seamlessly integrate the various entities in a coherent system. An integration framework, built on top of Jason, CArtAgO and Moise (as programming platforms for agents, environments and organizations resp.) is described as a suitable technology to build embodied organizations in practice

Energy efficiency perspectives of PMR networks

Recently, the concern about energy efficiency in wireless communications has been growing rapidly. Manufacturers and researchers have developed innovative solutions, highlighting the benefits in reducing operational expenditures (OPEX) and carbon footprint. Professional Mobile Radio (PMR) systems, like Terrestrial Trunked Radio (TETRA), have been designed to provide voice and data services to professional users. The energy consumption is one of the critical aspects of PMR broadband solutions and a major constraint for PMR services. The future convergence of PMR to the LTE system introduces a new topic in the research discussion about the energy efficiency of wireless systems. This paper focuses on the feasibility of energy efficient solutions for current and potentially future PMR networks, by providing a mathematical formulation of power consumption in TETRA base stations and assessing possible business models and energy saving solutions for enhanced mission-critical operations. The energy efficiency evaluation has been performed by taking into account the traffic load of a deployed TETRA regional network: in the considered network scenario with 150 base stations, significant OPEX savings up to 70 thousand Euros per year of operation are achieved. Moreover, the proposed solutions allow for saving more than 1 ton of CO 2 per year

AmI Systems as Agent-Based Mirror Worlds: Bridging Humans and Agents through Stigmergy

In this chapter we introduce a vision of agent-oriented AmI systems that is extended to integrate ideas inspired by MirrorWorlds as introduced by Gelernter at the beginning of the eighties. In this view, AmI systems are actually a digital world mirroring but also augmenting the physical world with capabilities, services and functionalities.We then discuss the value of stigmergy as background reference conceptual framework to define and understand interactions occurring between the physical environments and its digital agent-based extension. The digital world augments the physical world so that traces left by humans acting in the physical world are represented in the digital one in order to be perceived by software agents living there and, viceversa, actions taken by software agents in the mirror can have an effect on the connected physical counterpart