Information Routing Driven by Background Chatter in a Signaling Network

Living systems are capable of processing multiple sources of information simultaneously. This is true even at the cellular level, where not only coexisting signals stimulate the cell, but also the presence of fluctuating conditions is significant. When information is received by a cell signaling network via one specific input, the existence of other stimuli can provide a background activity –or chatter– that may affect signal transmission through the network and, therefore, the response of the cell. Here we study the modulation of information processing by chatter in the signaling network of a human cell, specifically, in a Boolean model of the signal transduction network of a fibroblast. We observe that the level of external chatter shapes the response of the system to information carrying signals in a nontrivial manner, modulates the activity levels of the network outputs, and effectively determines the paths of information flow. Our results show that the interactions and node dynamics, far from being random, confer versatility to the signaling network and allow transitions between different information-processing scenarios

Transient and stochastic dynamics in cellular processes

This Thesis studies different cellular and cell population processes driven by non-linear and stochastic dynamics. The problems addressed here gravitate around the concepts of transient dynamics and relaxation from a perturbed to a steady state. In this regard, in all processes studied, stochastic fluctuations, either intrinsically present in or externally applied to these systems play an important and constructive role, by either driving the systems out of equilibrium, interfering with the underlying deterministic laws, or establishing suitable levels of heterogeneity. The first part of the Thesis is committed the analysis of genetically regulated transient cellular processes. Here, we analyse, from a theoretical standpoint, three genetic circuits with pulsed excitable dynamics. We show that all circuits can work in two different excitable regimes, in contrast to what was previously speculated. We also study how, in the presence of molecular noise, these excitable circuits can generate periodic polymodal pulses due to the combination of two noise induced phenomena: stabilisation of an unstable spiral point and coherence resonance. We also studied an excitable genetic mechanism for the regulation of the transcriptional fluctuations observed in some pluripotency factors in Embryonic Stem cells. In the embryo, pluripotency is a transient cellular state and the exit of cells from it seems to be associated with transcriptional fluctuations. In regard to pluripotency control, we also propose a novel mechanism based on the post-translational regulation of a small set of four pluripotency factors. We have validated the theoretical model, based on the formation of binary complexes among these factors, with quantitative experimental data at the single-cell level. The model suggests that the pluripotency state does not depend on the cellular levels of a single factor, but rather on the equilibrium of correlations between the different proteins. In addition, the model is able to anticipate the phenotype of several mutant cell types and suggests that the regulatory function of the protein interactions is to buffer the transcriptional activity of Oc4, a key pluripotency factor. In the second part of the Thesis we studied the behaviour of a computational cell signalling network of the human fibroblast in the presence of external fluctuations and signals. The results obtained here indicate that the network responds in a nontrivial manner to background chatter, both intrinsically and in the presence of external periodic signals. We show that these responses are consequence of the rerouting of the signal to different network information-transmission paths that emerge as noise is modulated. Finally, we also study the cell population dynamics during the formation of microbial biofilms, wrinkled pellicles of bacteria glued by an extracellular matrix that are one of the simplest cases of self-organised multicellular structures. In this Thesis we develop a spatiotemporal model of cellular growth and death that accounts for the experimentally observed patterns of massive bacterial death that precede wrinkle formation in biofilms. These localised patterns focus mechanical forces during biofilm expansion and trigger the formation of the characteristic ridges. In this sense, the proposed model suggests that the death patterns emerge from the mobility changes in bacteria due to the production of extracellular matrix and the spatially inhomogeneous cellular growth. An important prediction of the model is that matrix productions is crucial for the appearance of the patterns and, therefore for winkle formation. We have also experimentally validated validated this prediction with matrix deficient bacterial strains, which show neither death patterns nor wrinkles.En aquesta Tesi s’estudien diferents processos intracel·lulars i de poblacions cel·lulars regits per dinàmica estocàstica i no lineal. El problemes biològics tractats graviten al voltant el concepte de dinàmica transitòria i de relaxació d’un estat dinàmic pertorbat a l’estat estacionari. En aquest sentit, en tots els processos estudiats, les fluctuacions estocàstiques, presents intrínsecament o aplicades de forma externa, hi tenen un paper constructiu, ja sigui empenyent els sistemes fora de l’equilibri, interferint amb les lleis deterministes subjacents, o establint els nivells d’heterogeneïtat necessaris. La primera part de la Tesi es dedica a l’estudi de processos cel·lulars transitoris regulats genèticament. En ella analitzem des d’un punt de vista teòric tres circuits genètics de control de polsos excitables i, contràriament al que s’havia especulat anteriorment, establim que tots ells poden treballar en dos tipus de règim excitable. Analitzem també com, en presència de soroll molecular, aquests circuits excitables poden generar polsos periòdics i multimodals degut a la combinació de dos fenòmens induïts per soroll: l’estabilització estocàstica d’estats inestables i la ressonància de coherència. D’altra banda, estudiem com un mecanisme genètic excitable pot ser el responsable de regular a nivell transcripcional les fluctuacions que s’observen experimentalment en alguns factors de pluripotència en cèl·lules mare embrionàries. En l’embrió, la pluripotència és un estat cel·lular transitori i la sortida de les cèl·lules d’aquest sembla que està associada a fluctuacions transcripcionals. En relació al control de la pluripotència, presentem també un nou mecanisme basat en la regulació post-traduccional d’un petit conjunt de 4 factors de pluripotència. El model teòric proposat, basat en la formació de complexos entre els diferents factors de pluripotència, l’hem validat mitjançant experiments quantitatius en cèl·lules individuals. El model postula que l’estat de pluripotència no depèn dels nivells cel·lulars d’un únic factor, sinó d’un equilibri de correlacions entre diverses proteïnes. A més, prediu el fenotip de cèl·lules mutants i suggereix que la funció reguladora de les interaccions entre les quatre proteïnes és la d’esmorteir l’activitat transcripcional d’Oct4, un dels principals factors de pluripotència. En el segon apartat de la Tesi estudiem el comportament d’una xarxa computacional de senyalització cel·lular de fibroblast humà en presència de senyals externs fluctuants i cíclics. Els resultats obtinguts mostren que la xarxa respon de forma no trivial a les fluctuacions ambientals, fins i tot en presència d’una senyal externa. Diferents nivells de soroll permeten modular la resposta de la xarxa, mitjançant la selecció de rutes alternatives de transmissió de la informació. Finalment, estudiem la dinàmica de poblacions cel·lulars durant la formació de biofilms, pel·lícules arrugades d’aglomerats de bacteris que conformen un dels exemples més simples d’estructures multicel·lulars autoorganitzades. En aquesta Tesi presentem un model espai-temporal de creixement i mort cel·lular motivat per l’evidència experimental sobre l’aparició de patrons de mort massiva de bacteris previs a la formació de les arrugues dels biofilms. Aquests patrons localitzats concentren les forces mecàniques durant l’expansió del biofilm i inicien la formació de les arrugues característiques. En aquest sentit, el model proposat explica com es formen els patrons de mort a partir dels canvis de mobilitat dels bacteris deguts a la producció de matriu extracel·lular combinats amb un creixement espacialment heterogeni. Una important predicció del model és que la producció de matriu és un procés clau per a l’aparició dels patrons i, per tant de les arrugues. En aquest aspecte, els nostres resultats experimentals en bacteris mutants que no produeixen components essencials de la matriu, confirmen les prediccions

A Survey of Green Networking Research

Reduction of unnecessary energy consumption is becoming a major concern in wired networking, because of the potential economical benefits and of its expected environmental impact. These issues, usually referred to as "green networking", relate to embedding energy-awareness in the design, in the devices and in the protocols of networks. In this work, we first formulate a more precise definition of the "green" attribute. We furthermore identify a few paradigms that are the key enablers of energy-aware networking research. We then overview the current state of the art and provide a taxonomy of the relevant work, with a special focus on wired networking. At a high level, we identify four branches of green networking research that stem from different observations on the root causes of energy waste, namely (i) Adaptive Link Rate, (ii) Interface proxying, (iii) Energy-aware infrastructures and (iv) Energy-aware applications. In this work, we do not only explore specific proposals pertaining to each of the above branches, but also offer a perspective for research.Comment: Index Terms: Green Networking; Wired Networks; Adaptive Link Rate; Interface Proxying; Energy-aware Infrastructures; Energy-aware Applications. 18 pages, 6 figures, 2 table

SBML qualitative models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools

Background: Qualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing. Results: We present the Systems Biology Markup Language (SBML) Qualitative Models Package (“qual”), an extension of the SBML Level 3 standard designed for computer representation of qualitative models of biological networks. We demonstrate the interoperability of models via SBML qual through the analysis of a specific signalling network by three independent software tools. Furthermore, the collective effort to define the SBML qual format paved the way for the development of LogicalModel, an open-source model library, which will facilitate the adoption of the format as well as the collaborative development of algorithms to analyse qualitative models. Conclusions: SBML qual allows the exchange of qualitative models among a number of complementary software tools. SBML qual has the potential to promote collaborative work on the development of novel computational approaches, as well as on the specification and the analysis of comprehensive qualitative models of regulatory and signalling networks

ACUTA Journal of Telecommunications in Higher Education

In This Issue President\u27s Message From the ACUTA CEO Leg/Reg lssues Facing Higher Education Future Proof? The Coming lP Transition Growing Gigs Air U: Transforming TV White Spaces into lnternet Connectivity Taming the Social Media Beast Technology to Comply with Clery Act Emerging Trends on Campus 0ARnet and Ohio\u27s 100 Gbps Broadband Pipeline Iowa State Moves Voice Communications to the Cloud lnstitutional Excellence Awar

ENERGY AWARE TRAFFIC ENGINEERING IN WIRED COMMUNICATION NETWORKS

The reduction of power consumption in communication networks has become a key issue for both the Internet Service Providers (ISP) and the research community. Ac- cording to different studies, the power consumption of Information and Communication Technologies (ICT) varies from 2% to 10% of the worldwide power consumption [1,2]. Moreover, the expected trends for the future predict a notably increase of the ICT power consumption, doubling its value by 2020 [2] and growing to around 30% of the worldwide electricity demand by 2030 according to business-as-usual evaluation scenarios [15]. It is therefore not surprising that researchers, manufacturers and network providers are spending significant efforts to reduce the power consumption of ICT systems from dif- ferent angles. To this extent, networking devices waste a considerable amount of power. In partic- ular, their power consumption has always been increased in the last years, coupled with the increase of the offered performance [16]. Actually, power consumption of network- ing devices scales with the installed capacity, rather than the current load [17]. Thus, for an ISP the network power consumption is practically constant, unrespectively to traffic fluctuations. However, actual traffic is subject to strong day/night oscillations [3]. Thus, many devices are underutilized, especially during off-peak hours when traffic is low. This represents a clear opportunity for saving energy, since many resources (i.e., routers and links) are powered on without being fully utilized. In this context, resource consolidation is a known paradigm for the reduction of the power consumption. It consists in having a carefully selected subset of network devices entering a low power state, and use the rest to transport the required amount of traffic. This is possible without disrupting the Quality of Service (QoS) offered by the network infrastructure, since communication networks are designed over the peak foreseen traffic request, and with redundancy and over-provisioning in mind. In this thesis work, we present different techniques to perform resource consolida- tion in backbone IP-based networks, ranging from centralized solutions, where a central entity computes a global solution based on an omniscient vision of the network, to dis- tributed solutions, where single nodes take independent decisions on the local power- state, based solely on local knowledge. Moreover, different technological assumptions are made, to account for different possible directions of the network devices evolutions, ranging from the possibility to switch off linecard ports, to whole network nodes, and taking into account different power consumption profiles

A Framework for Cyber Vulnerability Assessments of InfiniBand Networks

InfiniBand is a popular Input/Output interconnect technology used in High Performance Computing clusters. It is employed in over a quarter of the world’s 500 fastest computer systems. Although it was created to provide extremely low network latency with a high Quality of Service, the cybersecurity aspects of InfiniBand have yet to be thoroughly investigated. The InfiniBand Architecture was designed as a data center technology, logically separated from the Internet, so defensive mechanisms such as packet encryption were not implemented. Cyber communities do not appear to have taken an interest in InfiniBand, but that is likely to change as attackers branch out from traditional computing devices. This thesis considers the security implications of InfiniBand features and constructs a framework for conducting Cyber Vulnerability Assessments. Several attack primitives are tested and analyzed. Finally, new cyber tools and security devices for InfiniBand are proposed, and changes to existing products are recommended

The Broadband Debate: A User\u27s Guide

What follows is a basic guide to the policy divisions in the broadband debate that have emerged and some suggested areas of reconciliation. For simplicity sake I divide the argument to a debate between the openists and the deregulationists. The summary is critical. I fault the openists for being too prone to favor regulation without making clear the connection between ends and means. For example, too few openists have asked the degree to which the structural open access remedies pushed by independent service providers actually promote the openists\u27 vision. Meanwhile, I fault the deregulationists two reasons. First, the deregulationists have overlooked the fact that limiting government, as they desire, sometimes requires government action. Remedies like network neutrality, for reasons I suggest, may be as important for control of government as it is of industry. I also fault the deregulationists for an exaggerated faith in industry decision-making. I suggest that some deregulationists have failed to familiarize themselves with the processes of industry decision-making before demanding deference to it. This is a particularly serious problem given an industry with a recent track record of terrible judgment and even outright fraud. One example is the demand by some deregulationists that deference is due to a so-called mart pipe vision, without analysis of whether that vision has any independent merit. The Article, finally, seeks to reconcile the two sides of the broadband debate and defends the network neutrality principle as a starting point. Deregulations and openists, while divided along many lines, share a common faith in innovation as the basis of economic growth. Both sides, in short, worship Joseph Schumpeter and his ideas of competitive, capitalistic innovation. Fidelity to this shared faith should mean mutual surrender of idealized models of either government or powerful private entities, respectively, in exchange for a shared cynicism. We should recognize that both government and the private sector have an unhappy record of blocking the new in favor of the old, and that such tendencies are likely to continue. I argue that neither deregulationists or openists should have reason to oppose Network Neutrality rules that create rights in users to use the applications or equipment of their choice. What both sides should want in an inevitable regulatory framework for broadband are rules that pre-commit both industry and government to open market entry. It must be remembered that rules creating rights in users also guarantee the right of operators to enter the application market, free of government hindrance. For these and other reasons discussed below, limited network neutrality rules should on reflection be attractive to both sides