Membrane computing: traces, neural inspired models, controls

Membrane Computing:Traces, Neural Inspired Models, ControlsAutor: Armand-Mihai IonescuDirectores: Dr. Victor Mitrana (URV)Dr. Takashi Yokomori (Universidad Waseda, Japón)Resumen Castellano:El presente trabajo está dedicado a una área muy activa del cálculo natural (que intenta descubrir la odalidad en la cual la naturaleza calcula, especialmente al nivel biológico), es decir el cálculo con membranas, y más preciso, a los modelos de membranas inspirados de la funcionalidad biológica de la neurona.La disertación contribuye al área de cálculo con membranas en tres direcciones principales. Primero, introducimos una nueva manera de definir el resultado de una computación siguiendo los rastros de un objeto especificado dentro de una estructura celular o de una estructura neuronal. A continuación, nos acercamos al ámbito de la biología del cerebro, con el objetivo de obtener varias maneras de controlar la computación por medio de procesos que inhiben/de-inhiben. Tercero, introducimos e investigamos en detallo - aunque en una fase preliminar porque muchos aspectos tienen que ser clarificados - una clase de sistemas inspirados de la manera en la cual las neuronas cooperan por medio de spikes, pulsos eléctricos de formas idénticas.English summary:The present work is dedicated to a very active branch of natural computing (which tries to discover the way nature computes, especially at a biological level), namely membrane computing, more precisely, to those models of membrane systems mainly inspired from the functioning of the neural cell.The present dissertation contributes to membrane computing in three main directions. First, we introduce a new way of defining the result of a computation by means of following the traces of a specified object within a cell structure or a neural structure. Then, we get closer to the biology of the brain, considering various ways to control the computation by means of inhibiting/de-inhibiting processes. Third, we introduce and investigate in a great - though preliminary, as many issues remain to be clarified - detail a class of P systems inspired from the way neurons cooperate by means of spikes, electrical pulses of identical shapes

Toward a Self-replicating Metabolic P System

This work concerns the synthesis of a "minimal cell' by means of a P system, which is a distributed rewriting system inspired by the structure and the functioning of the biological cell. Specifically, we aim to define a dynamical system which exhibits a steady metabolic evolution, resulting in self-maintenance and self-reproduction. Metabolic P systems represent a class of P systems particularly promising to model a minimal cell in discrete terms, since they have already successfully modeled several metabolisms. The main further step is thus to find a simple way to obtain Metabolic P system self-replication. This paper deals with ideas presented at the BWMC11 (held in Seville, Feb 2011) and opens a new trend in membrane computing, based on computational synthetic biology oriented applications of P systems modeling. The framework is here outlined, and some problems to tackle the synthesis of a minimal cell are discussed. Moreover, an overview of literature and a list of appealing research directions is given, along with several references

Structured Modeling with Hyperdag P Systems: Part A

P systems provide a computational model based on the structure and interaction of living cells. A P system consists of a hierarchical nesting of cell-like membranes, which can be visualized as a rooted tree. Although the P systems are computationally complete, many real world models, e.g., from socio-economic systems, databases, operating systems, distributed systems, seem to require more expressive power than provided by tree structures. Many such systems have a primary tree-like structure completed with shared or secondary communication channels. Modeling these as tree-based systems, while theoretically possible, is not very appealing, because it typically needs artificial extensions that introduce additional complexities, nonexistent in the originals. In this paper we propose and define a new model that combines structure and flexibility, called hyperdag P systems, in short, hP systems, which extend the definition of conventional P systems, by allowing dags, interpreted as hypergraphs, instead of trees, as models for the membrane structure. We investigate the relation between our hP systems and neural P systems. Despite using an apparently less powerful structure, i.e., a dag instead of a general graph, we argue that hP systems have essentially the same computational power as tissue and neural P systems. We argue that hP systems offer a structured approach to membrane-based modeling that is often closer to the behavior and underlying structure of the modeled objects. Additionally, we enable dynamical changes of the rewriting modes (e.g., to alternate between determinism and parallelism) and of the transfer modes (e.g., the switch between unicast or broadcast). In contrast, classical P systems, both tree and graph based P systems, seem to focus on a statical approach. We support our view with a simple but realistic example, inspired from computer networking, modeled as a hP system with a shared communication line (broadcast channel). In Part B of this paper we will explore this model further and support it with a more extensive set of examples

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

Alfaviiruse mittestruktuurne proteaas ja tema liitvalgust substraat: täiuslikult korraldatud kooselu reeglid

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Alfaviirused (sugukond Togaviridae) on artriiti ja entsefaliiti põhjustavad RNA genoomsed viirused. Nende paljunemise strateegia aluseks on viiruse replikaasi valkude süntees ühe nn. mittestruktuurse eelvalgu P1234 kujul ning selle ajaliselt reguleeritud lõikamine valmis valkudeks nsP2 proteaasi abil. Käesoleva väitekirja aluseks olevad uurimistööd viisid nsP2 substraat-spetsiifilisust tagavate mehhanismide väljaselgitamiseni; muu hulgas kirjeldati uudset proteolüütiliste lõikamiste regulatsioonimehhanismi, mis põhineb liitvalgu erinevate regioonide vahelisel „suhtlemisel“ viiruse replikatsiooni kompleksi moodustamise käigus. Sellest saab järeldada, et P1234 lõikamise ajaline regulatsioon sõltub otseselt replikatsioonikompleksi konfiguratsioonidest, millised omakorda on määratud selle komponentide vaheliste interaktsioonide poolt. Seega tõuseb viiruse nsP2 proteaas esile kui keerulise signaalvõrgustiku keskne element, mille roll viirus infektsiooni regulatsioonis seisneb replikatsiooniga kaasnevate sündmuste „jälgimises“ ja nendele reageerimises. Viimane põhineb sellel, et kui viiruse paljunemine jõuab kindla vahe-etapini, siis kaasneb sellega lõikamiskohtade ja/või muude oluliste struktuuride „esitlemine“ proteaasile, mis reageerib toimunud muudatustele lokaalse signaalülekande, mis lõppkokkuvõttes viib replikaasi kompleksi struktuuri järjestikulistele muudatustele, käivitamisega. Kokkuvõttes, tõid läbiviidud uurimised välja asjaolu, et lisaks varem teada olnud lõikamisjärjestuste äratundmisele, omab ka makromolekulaarsete struktuuride moodustamine viiruse valkude poolt olulist (ja mitmel juhul isegi määravat) rolli viiruse proteaasi töö reguleerimisel. Veel enam, eeldati, et seesugune mitmetahuline regulatsioon võib olla paljukomponentsete proteolüütiliste süsteemide üldine omadus. Kirjeldatud avastused ja nende lahtimõtestamine omavad olulist rolli uurimistöödele, mille eesmärgiks on alfaviiruste paljunemist takistavate lähenemiste väljatöötamine. Nii võib saadud tulemuste põhjal järeldada, et lisaks proteaasi aktiivsuse otsesele mõjutamisele võib viiruse replikatsiooni takistada ka mõjutades proteolüüsi regulatsiooni tagavaid molekulide vahelised seoseid.Alphaviruses from the Togaviridae family are RNA viruses that may cause arthritic syndroms and encephalitis. The alphavirus replication strategy relies on the production of replicase proteins initially in the form of non-structural (ns) polyprotein precursor P1234, which during the course of replication becomes proteolytically processed by the virus-encoded nsP2 protease in a temporally regulated manner. The studies that constitute the basis of this thesis led to identification of the requirements for substrate specificity of nsP2 protease and revealed novel mechanism for the regulation of processing based on the specific communication between distant parts of the viral polyprotein brought together during assembly of replication complex. It was concluded that the order of alphaviral ns-polyprotein processing is mostly dependent on the configuration of the replication complex imposed by intermolecular interactions meant to guarantee timely cleavages. The alphaviral protease therefore emerges as an integral part of the sophisticated signaling mechanism, in which the regulatory task of the protease consists of monitoring the succession and completion of the events of viral infection. Once the respective replication status-induced conformational changes within replicase allow the presentation of the scissile bond and/or other essential determinants of substrate recognition like exosites, the local protease signaling is initiated, which apparently leads to further reconfiguration of the viral replication complex. Combined, the studies unveiled the decisive role played by the macromolecular assembly-dependent component of substrate recognition in addition to the sequence-dependent component, the combination of which may be expected to constitute the basis of regulation in multi-site proteolytic systems in general. Described findings and their interpretations are expected to provide with essential grounds and directions for further studies on the restriction of alphaviral replication through affecting the center of viral proteolytic activity or via intervention with its regulation by targeting intramolecular interactions

Dynamics of Macrosystems; Proceedings of a Workshop, September 3-7, 1984

There is an increasing awareness of the important and persuasive role that instability and random, chaotic motion play in the dynamics of macrosystems. Further research in the field should aim at providing useful tools, and therefore the motivation should come from important questions arising in specific macrosystems. Such systems include biochemical networks, genetic mechanisms, biological communities, neutral networks, cognitive processes and economic structures. This list may seem heterogeneous, but there are similarities between evolution in the different fields. It is not surprising that mathematical methods devised in one field can also be used to describe the dynamics of another. IIASA is attempting to make progress in this direction. With this aim in view this workshop was held at Laxenburg over the period 3-7 September 1984. These Proceedings cover a broad canvas, ranging from specific biological and economic problems to general aspects of dynamical systems and evolutionary theory

Ontology-based representation and analysis of host-Brucella interactions

Abstract Background Biomedical ontologies are representations of classes of entities in the biomedical domain and how these classes are related in computer- and human-interpretable formats. Ontologies support data standardization and exchange and provide a basis for computer-assisted automated reasoning. IDOBRU is an ontology in the domain of Brucella and brucellosis. Brucella is a Gram-negative intracellular bacterium that causes brucellosis, the most common zoonotic disease in the world. In this study, IDOBRU is used as a platform to model and analyze how the hosts, especially host macrophages, interact with virulent Brucella strains or live attenuated Brucella vaccine strains. Such a study allows us to better integrate and understand intricate Brucella pathogenesis and host immunity mechanisms. Results Different levels of host-Brucella interactions based on different host cell types and Brucella strains were first defined ontologically. Three important processes of virulent Brucella interacting with host macrophages were represented: Brucella entry into macrophage, intracellular trafficking, and intracellular replication. Two Brucella pathogenesis mechanisms were ontologically represented: Brucella Type IV secretion system that supports intracellular trafficking and replication, and Brucella erythritol metabolism that participates in Brucella intracellular survival and pathogenesis. The host cell death pathway is critical to the outcome of host-Brucella interactions. For better survival and replication, virulent Brucella prevents macrophage cell death. However, live attenuated B. abortus vaccine strain RB51 induces caspase-2-mediated proinflammatory cell death. Brucella-associated cell death processes are represented in IDOBRU. The gene and protein information of 432 manually annotated Brucella virulence factors were represented using the Ontology of Genes and Genomes (OGG) and Protein Ontology (PRO), respectively. Seven inference rules were defined to capture the knowledge of host-Brucella interactions and implemented in IDOBRU. Current IDOBRU includes 3611 ontology terms. SPARQL queries identified many results that are critical to the host-Brucella interactions. For example, out of 269 protein virulence factors related to macrophage-Brucella interactions, 81 are critical to Brucella intracellular replication inside macrophages. A SPARQL query also identified 11 biological processes important for Brucella virulence. Conclusions To systematically represent and analyze fundamental host-pathogen interaction mechanisms, we provided for the first time comprehensive ontological modeling of host-pathogen interactions using Brucella as the pathogen model. The methods and ontology representations used in our study are generic and can be broadened to study the interactions between hosts and other pathogens.http://deepblue.lib.umich.edu/bitstream/2027.42/113668/1/13326_2015_Article_36.pd