Associative memory in gene regulation networks

The pattern of gene expression in the phenotype of an organism is determined in part by the dynamical attractors of the organism’s gene regulation network. Changes to the connections in this network over evolutionary time alter the adult gene expression pattern and hence the fitness of the organism. However, the evolution of structure in gene expression networks (potentially reflecting past selective environments) and its affordances and limitations with respect to enhancing evolvability is poorly understood in general. In this paper we model the evolution of a gene regulation network in a controlled scenario. We show that selected changes to connections in the regulation network make the currently selected gene expression pattern more robust to environmental variation. Moreover, such changes to connections are necessarily ‘Hebbian’ – ‘genes that fire together wire together’ – i.e. genes whose expression is selected for in the same selective environments become co-regulated. Accordingly, in a manner formally equivalent to well-understood learning behaviour in artificial neural networks, a gene expression network will therefore develop a generalised associative memory of past selected phenotypes. This theoretical framework helps us to better understand the relationship between homeostasis and evolvability (i.e. selection to reduce variability facilitates structured variability), and shows that, in principle, a gene regulation network has the potential to develop ‘recall’ capabilities normally reserved for cognitive systems

Individual and global adaptation in networks

The structure of complex biological and socio-economic networks affects the selective pressures or behavioural incentives of components in that network, and reflexively, the evolution/behaviour of individuals in those networks changes the structure of such networks over time. Such ‘adaptive networks’ underlie how gene-regulation networks evolve, how ecological networks self-organise, and how networks of strategic agents co-create social organisations. Although such domains are different in the details, they can each be characterised as networks of self-interested agents where agents alter network connections in the direction that increases their individual utility. Recent work shows that such dynamics are equivalent to associative learning, well-understood in the context of neural networks. Associative learning in neural substrates is the result of mandated learning rules (e.g. Hebbian learning), but in networks of autonomous agents ‘associative induction’ occurs as a result of local individual incentives to alter connections. Using results from a number of recent studies, here we review the theoretical principles that can be transferred between disciplines as a result of this isomorphism, and the implications for the organisation of genetic, social and ecological networks

A confidence assessment of WCET estimates for software time randomized caches

Obtaining Worst-Case Execution Time (WCET) estimates is a required step in real-time embedded systems during software verification. Measurement-Based Probabilistic Timing Analysis (MBPTA) aims at obtaining WCET estimates for industrial-size software running upon hardware platforms comprising high-performance features. MBPTA relies on the randomization of timing behavior (functional behavior is left unchanged) of hard-to-predict events like the location of objects in memory — and hence their associated cache behavior — that significantly impact software's WCET estimates. Software time-randomized caches (sTRc) have been recently proposed to enable MBPTA on top of Commercial off-the-shelf (COTS) caches (e.g. modulo placement). However, some random events may challenge MBPTA reliability on top of sTRc. In this paper, for sTRc and programs with homogeneously accessed addresses, we determine whether the number of observations taken at analysis, as part of the normal MBPTA application process, captures the cache events significantly impacting execution time and WCET. If this is not the case, our techniques provide the user with the number of extra runs to perform to guarantee that cache events are captured for a reliable application of MBPTA. Our techniques are evaluated with synthetic benchmarks and an avionics application.The research leading to these results has received funding from the European Community’s Seventh Framework Programme [FP7/2007-2013] under the PROXIMA Project (www.proxima-project.eu), grant agreement no 611085. This work has also been partially supported by the Spanish Ministry of Science and Innovation under grant TIN2015-65316, the HiPEAC Network of Excellence, and COST Action IC1202: Timing Analysis On Code-Level (TACLe). Jaume Abella has been partially supported by the Ministry of Economy and Competitiveness under Ramon y Cajal postdoctoral fellowship number RYC-2013-14717.Peer ReviewedPostprint (author's final draft