The Spatial Association of Gene Expression Evolves from Synchrony to Asynchrony and Stochasticity with Age

For multicellular organisms, different tissues coordinate to integrate physiological functions, although this systematically and gradually declines in the aging process. Therefore, an association exists between tissue coordination and aging, and investigating the evolution of tissue coordination with age is of interest. In the past decade, both common and heterogeneous aging processes among tissues were extensively investigated. The results on spatial association of gene changes that determine lifespan appear complex and paradoxical. To reconcile observed commonality and heterogeneity of gene changes among tissues and to address evolution feature of tissue coordination with age, we introduced a new analytical strategy to systematically analyze genome-wide spatio-temporal gene expression profiles. We first applied the approach to natural aging process in three species (Rat, Mouse and Drosophila) and then to anti-aging process in Mouse. The results demonstrated that temporal gene expression alteration in different tissues experiences a progressive association evolution from spatial synchrony to asynchrony and stochasticity with age. This implies that tissue coordination gradually declines with age. Male mice showed earlier spatial asynchrony in gene expression than females, suggesting that male animals are more prone to aging than females. The confirmed anti-aging interventions (resveratrol and caloric restriction) enhanced tissue coordination, indicating their underlying anti-aging mechanism on multiple tissue levels. Further, functional analysis suggested asynchronous DNA/protein damage accumulation as well as asynchronous repair, modification and degradation of DNA/protein in tissues possibly contributes to asynchronous and stochastic changes of tissue microenvironment. This increased risk for a variety of age-related diseases such as neurodegeneration and cancer that eventually accelerate organismal aging and death. Our study suggests a novel molecular event occurring in aging process of multicellular species that may represent an intrinsic molecular mechanism of aging

On the effects of firing memory in the dynamics of conjunctive networks

Boolean networks are one of the most studied discrete models in the context of the study of gene expression. In order to define the dynamics associated to a Boolean network, there are several \emph{update schemes} that range from parallel or \emph{synchronous} to \emph{asynchronous.} However, studying each possible dynamics defined by different update schemes might not be efficient. In this context, considering some type of temporal delay in the dynamics of Boolean networks emerges as an alternative approach. In this paper, we focus in studying the effect of a particular type of delay called \emph{firing memory} in the dynamics of Boolean networks. Particularly, we focus in symmetric (non-directed) conjunctive networks and we show that there exist examples that exhibit attractors of non-polynomial period. In addition, we study the prediction problem consisting in determinate if some vertex will eventually change its state, given an initial condition. We prove that this problem is {\bf PSPACE}-complete

CAMILA: formal software engineering supported by functional programming

This paper describes two experiences in teaching a formal approach to software engineering at undergraduate level supported by Camila a functional programming based tool Carried on in diferent institutions each of them addresses a particular topic in the area requirement analysis and generic systems design in the first case specification and implementation development in the second Camila the common framework to both experiences animates a set based language extended with a mild use of category theory which can be reasoned upon for program calculation and classification purpose. The project afiliates itself to but is not restricted to the research in exploring Functional Programming as a rapid prototyping environment for formal software model. Its kernel is fully connectable to external applications and equipped with a component repository and distribution facilities. The paper explains how Camila is being used in the educational practice as a tool to think with providing a kind of cross fertilization between students under standing of diferent parts of the curriculum. Furthermore it helps in developinga number of engineering skills namely the ability to analyze and classify information problems and models and to resort to the combined use of diferent programming frameworks in approaching them

A Survey of Desynchronization in a Polychronous Model of Computation

AbstractThe synchronous hypothesis arose in the late Eighties as a conceptual framework for the computer-aided design of embedded systems. Along with this framework, the issue of desynchronization was simultaneously raised as the major topic of mapping the ideal communication and computation model of synchrony on realistic and distributed computer architectures.The aim of the present article is to survey the development of this topics in the particular yet promising model of one of the prominent environments that were build along these principles: Signal and its polychronous (synchronous multi-clocked) model of computation, before to give some hints and ideas about ongoing research addressing this issue

Desynchronization: Synthesis of asynchronous circuits from synchronous specifications

Asynchronous implementation techniques, which measure logic delays at run time and activate registers accordingly, are inherently more robust than their synchronous counterparts, which estimate worst-case delays at design time, and constrain the clock cycle accordingly. De-synchronization is a new paradigm to automate the design of asynchronous circuits from synchronous specifications, thus permitting widespread adoption of asynchronicity, without requiring special design skills or tools. In this paper, we first of all study different protocols for de-synchronization and formally prove their correctness, using techniques originally developed for distributed deployment of synchronous language specifications. We also provide a taxonomy of existing protocols for asynchronous latch controllers, covering in particular the four-phase handshake protocols devised in the literature for micro-pipelines. We then propose a new controller which exhibits provably maximal concurrency, and analyze the performance of desynchronized circuits with respect to the original synchronous optimized implementation. We finally prove the feasibility and effectiveness of our approach, by showing its application to a set of real designs, including a complete implementation of the DLX microprocessor architectur

CAMILA formal software engineering supported by functional programming

This paper describes two experiences in teaching a formal approach to software engineering at undergraduate level supported by Camila a functional programming based tool Carried on in di erent institutions each of them addresses a particular topic in the area requirement analysis and generic systems design in the rst case speci cation and implementation development in the second Camila the common framework to both experiences animates a set based language extended with a mild use of category theory which can be reasoned upon for program calculation and classi cation purposes The project a liates itself to but is not restricted to the research in exploring Functional Programming as a rapid prototyping environment for formal software models Its kernel is fully connectable to external applications and equipped with a component repository and distribution facilities The paper explains how Camila is being used in the educational practice as a tool to think with providing a kind of cross fertilization between students under standing of di erent parts of the curriculum Furthermore it helps in developing a number of engineering skills namely the ability to analyze and classify infor mation problems and models and to resort to the combined use of di erent programming frameworks in approaching them.Eje: Conferencia latinoamericana de programación funcionalRed de Universidades con Carreras en Informática (RedUNCI