Toward a Formal Semantics for Autonomic Components

Autonomic management can improve the QoS provided by parallel/ distributed applications. Within the CoreGRID Component Model, the autonomic management is tailored to the automatic - monitoring-driven - alteration of the component assembly and, therefore, is defined as the effect of (distributed) management code. This work yields a semantics based on hypergraph rewriting suitable to model the dynamic evolution and non-functional aspects of Service Oriented Architectures and component-based autonomic applications. In this regard, our main goal is to provide a formal description of adaptation operations that are typically only informally specified. We contend that our approach makes easier to raise the level of abstraction of management code in autonomic and adaptive applications.Comment: 11 pages + cover pag

04241 Abstracts Collection -- Graph Transformations and Process Algebras for Modeling Distributed and Mobile Systems

Recently there has been a lot of research, combining concepts of process algebra with those of the theory of graph grammars and graph transformation systems. Both can be viewed as general frameworks in which one can specify and reason about concurrent and distributed systems. There are many areas where both theories overlap and this reaches much further than just using graphs to give a graphic representation to processes. Processes in a communication network can be seen in two different ways: as terms in an algebraic theory, emphasizing their behaviour and their interaction with the environment, and as nodes (or edges) in a graph, emphasizing their topology and their connectedness. Especially topology, mobility and dynamic reconfigurations at runtime can be modelled in a very intuitive way using graph transformation. On the other hand the definition and proof of behavioural equivalences is often easier in the process algebra setting. Also standard techniques of algebraic semantics for universal constructions, refinement and compositionality can take better advantage of the process algebra representation. An important example where the combined theory is more convenient than both alternatives is for defining the concurrent (noninterleaving), abstract semantics of distributed systems. Here graph transformations lack abstraction and process algebras lack expressiveness. Another important example is the work on bigraphical reactive systems with the aim of deriving a labelled transitions system from an unlabelled reactive system such that the resulting bisimilarity is a congruence. Here, graphs seem to be a convenient framework, in which this theory can be stated and developed. So, although it is the central aim of both frameworks to model and reason about concurrent systems, the semantics of processes can have a very different flavour in these theories. Research in this area aims at combining the advantages of both frameworks and translating concepts of one theory into the other. The Dagsuthl Seminar, which took place from 06.06. to 11.06.2004, was aimed at bringing together researchers of the two communities in order to share their ideas and develop new concepts. These proceedings4 of the do not only contain abstracts of the talks given at the seminar, but also summaries of topics of central interest. We would like to thank all participants of the seminar for coming and sharing their ideas and everybody who has contributed to the proceedings

Network and Algebraic Topology of Influenza Evolution

Evolution is a force that has molded human existence since its divergence from chimpanzees about 5.4 million years ago. In that same amount of time, an influenza virus, which replicates every six hours, would have undergone an equivalent number of generations over only a hundred years. The fast replication times of influenza, coupled with its high mutation rate, make the virus a perfect model to study real-time evolution at a mega-Darwin scale, more than a million times faster than human evolution. While recent developments in high-throughput sequencing provide an optimal opportunity to dissect their genetic evolution, a concurrent growth in computational tools is necessary to analyze the large influx of complex genomic data. In my thesis, I present novel computational methods to examine different aspects of influenza evolution. I first focus on seasonal influenza, particularly the problems that hamper public health initiatives to combat the virus. I introduce two new approaches: 1. The q2-coefficient, a method of quantifying pathogen surveillance, and 2. FluGraph, a technique that employs network topology to track the spread of seasonal influenza around the world. The second chapter of my thesis examines how mutations and reassortment combine to alter the course of influenza evolution towards pandemic formation. I highlight inherent deficiencies in the current phylogenetic paradigm for analyzing evolution and offer a novel methodology based on algebraic topology that comprehensively reconstructs both vertical and horizontal evolutionary events. I apply this method to viruses, with emphasis on influenza, but foresee broader application to cancer cells, bacteria, eukaryotes, and other taxa

Hierarchical equilibria of branching populations

The objective of this paper is the study of the equilibrium behavior of a population on the hierarchical group $\Omega_N$ consisting of families of individuals undergoing critical branching random walk and in addition these families also develop according to a critical branching process. Strong transience of the random walk guarantees existence of an equilibrium for this two-level branching system. In the limit $N\to\infty$ (called the hierarchical mean field limit), the equilibrium aggregated populations in a nested sequence of balls $B^{(N)}_\ell$ of hierarchical radius $\ell$ converge to a backward Markov chain on $\mathbb{R_+}$. This limiting Markov chain can be explicitly represented in terms of a cascade of subordinators which in turn makes possible a description of the genealogy of the population.Comment: 62 page

Exploring the function and evolution of proteins using domain families

Proteins are frequently composed of multiple domains which fold independently. These are often evolutionarily distinct units which can be adapted and reused in other proteins. The classification of protein domains into evolutionary families facilitates the study of their evolution and function. In this thesis such classifications are used firstly to examine methods for identifying evolutionary relationships (homology) between protein domains. Secondly a specific approach for predicting their function is developed. Lastly they are used in studying the evolution of protein complexes. Tools for identifying evolutionary relationships between proteins are central to computational biology. They aid in classifying families of proteins, giving clues about the function of proteins and the study of molecular evolution. The first chapter of this thesis concerns the effectiveness of cutting edge methods in identifying evolutionary relationships between protein domains. The identification of evolutionary relationships between proteins can give clues as to their function. The second chapter of this thesis concerns the development of a method to identify proteins involved in the same biological process. This method is based on the concept of domain fusion whereby pairs of proteins from one organism with a concerted function are sometimes found fused into single proteins in a different organism. Using protein domain classifications it is possible to identify these relationships. Most proteins do not act in isolation but carry out their function by binding to other proteins in complexes; little is understood about the evolution of such complexes. In the third chapter of this thesis the evolution of complexes is examined in two representative model organisms using protein domain families. In this work, protein domain superfamilies allow distantly related parts of complexes to be identified in order to determine how homologous units are reused

Novel components of the Toxoplasma inner membrane complex revealed by BioID.

UNLABELLED:The inner membrane complex (IMC) of Toxoplasma gondii is a peripheral membrane system that is composed of flattened alveolar sacs that underlie the plasma membrane, coupled to a supporting cytoskeletal network. The IMC plays important roles in parasite replication, motility, and host cell invasion. Despite these central roles in the biology of the parasite, the proteins that constitute the IMC are largely unknown. In this study, we have adapted a technique named proximity-dependent biotin identification (BioID) for use in T. gondii to identify novel components of the IMC. Using IMC proteins in both the alveoli and the cytoskeletal network as bait, we have uncovered a total of 19 new IMC proteins in both of these suborganellar compartments, two of which we functionally evaluate by gene knockout. Importantly, labeling of IMC proteins using this approach has revealed a group of proteins that localize to the sutures of the alveolar sacs that have been seen in their entirety in Toxoplasma species only by freeze fracture electron microscopy. Collectively, our study greatly expands the repertoire of known proteins in the IMC and experimentally validates BioID as a strategy for discovering novel constituents of specific cellular compartments of T. gondii. IMPORTANCE:The identification of binding partners is critical for determining protein function within cellular compartments. However, discovery of protein-protein interactions within membrane or cytoskeletal compartments is challenging, particularly for transient or unstable interactions that are often disrupted by experimental manipulation of these compartments. To circumvent these problems, we adapted an in vivo biotinylation technique called BioID for Toxoplasma species to identify binding partners and proximal proteins within native cellular environments. We used BioID to identify 19 novel proteins in the parasite IMC, an organelle consisting of fused membrane sacs and an underlying cytoskeleton, whose protein composition is largely unknown. We also demonstrate the power of BioID for targeted discovery of proteins within specific compartments, such as the IMC cytoskeleton. In addition, we uncovered a new group of proteins localizing to the alveolar sutures of the IMC. BioID promises to reveal new insights on protein constituents and interactions within cellular compartments of Toxoplasma

A survey on data integration for multi-omics sample clustering

Due to the current high availability of omics, data-driven biology has greatly expanded, and several papers have reviewed state-of-the-art technologies. Nowadays, two main types of investigation are available for a multi-omics dataset: extraction of relevant features for a meaningful biological interpretation and clustering of the samples. In the latter case, a few reviews refer to some outdated or no longer available methods, whereas others lack the description of relevant clustering metrics to compare the main approaches. This work provides a general overview of the major techniques in this area, divided into four groups: graph, dimensionality reduction, statistical and neural-based. Besides, eight tools have been tested both on a synthetic and a real biological dataset. An extensive performance comparison has been provided using four clustering evaluation scores: Peak Signal-to-Noise Ratio (PSNR), Davies-Bouldin(DB) index, Silhouette value and the harmonic mean of cluster purity and efficiency. The best results were obtained by using the dimensionality reduction, either explicitly or implicitly, as in the neural architecture

Hierarchical equilibria of branching populations

The objective of this paper is the study of the equilibrium behavior of a population on the hierarchical group (Omega)N consisting of families of individuals undergoing critical branching random walk and in addition these families also develop according to a critical branching process. Strong transience of the random walk guarantees existence of an equilibrium for this two-level branching system. In the limit N -> (infinity symbol) (called the hierarchical mean field limit), the equilibrium aggregated populations in a nested sequence of balls (symbole)(N) of hierarchical radius (symbol) converge to a backward Markov chain on R+. This limiting Markov chain can be explicitly represented in terms of a cascade of subordinators which in turn makes possible a description of the genealogy of the population.Multilevel branching, hierarchical mean-field limit, strong transience,genealogy.