Graph Transformation for Domain-Specific Discrete Event Time Simulation

Proceedings of: Fifth International Conference on Graph Transformation (ICGT 2010). Enschede, The Netherlands, September 27–October 2, 2010.Graph transformation is being increasingly used to express the semantics of domain specific visual languages since its graphical nature makes rules intuitive. However, many application domains require an explicit handling of time in order to represent accurately the behaviour of the real system and to obtain useful simulation metrics. Inspired by the vast knowledge and experience accumulated by the discrete event simulation community, we propose a novel way of adding explicit time to graph transformation rules. In particular, we take the event scheduling discrete simulation world view and incorporate to the rules the ability of scheduling the occurrence of other rules in the future. Hence, our work combines standard, efficient techniques for discrete event simulation (based on the handling of a future event set) and the intuitive, visual nature of graph transformation. Moreover, we show how our formalism can be used to give semantics to other timed approaches.Work partially sponsored by the Spanish Ministry of Science and Innovation, under project “METEORIC” (TIN2008-02081) and mobility grants JC2009-00015 and PR2009-0019, as well as by the R&D programme of the Community of Madrid, project “e-Madrid” (S2009/TIC-1650).Publicad

A systematic approach to bowing and its application in violin playing

The aim of this research was to formulate systematic studies for the right-arm to achieve finer outcomes in violin performance. As modern violin practice involves the marking of numerical symbols on the score to indicate left-hand ‘fingerings’ it is necessary to question why no equivalent system is utilised for the training of the right-arm. Although a system for the notation of bow divisions was formulated by French violinist Lucien Capet over one hundred years ago, its use is virtually unidentified in modern violin playing and teaching. The research method adopted in this project was performance-oriented and focused on incorporating Capet’s eight-part bow division notation system into daily analytical practise allowing for core movements of the right-arm and the distribution of the bow to be documented and made habitual for the performance situation. Critical reflections on the process and specifically the application into key performance repertoire are provided in this exegesis, which contextualises the research conducted. The exegesis and folio of performances are equally weighted (50/50) for examination. The associated performance folio contains recordings of various solo and chamber works by composers Bach, Mozart, Ysaÿe, Brahms, Handel, Debussy, Franck, Strauss, Gragnani, Weber, Charlton and De Falla. The findings of this study were that setting parameters for bow distribution generated a higher level of response to address combinations of colour, timbre, mood and articulation. Notation of bow distribution is not to be understood as a rigid barrier or impediment to personal expression. On the contrary, once habitualised, it provides full awareness and control of the right arm, resulting in a refined, and highly nuanced regulation of sound to convey the desired musical expression

Non-functional properties in the model-driven development of service-oriented systems

Systems based on the service-oriented architecture (SOA) principles have become an important cornerstone of the development of enterprise-scale software applications. They are characterized by separating functions into distinct software units, called services, which can be published, requested and dynamically combined in the production of business applications. Service-oriented systems (SOSs) promise high flexibility, improved maintainability, and simple re-use of functionality. Achieving these properties requires an understanding not only of the individual artifacts of the system but also their integration. In this context, non-functional aspects play an important role and should be analyzed and modeled as early as possible in the development cycle. In this paper, we discuss modeling of non-functional aspects of service-oriented systems, and the use of these models for analysis and deployment. Our contribution in this paper is threefold. First, we show how services and service compositions may be modeled in UML by using a profile for SOA (UML4SOA) and how non-functional properties of service-oriented systems can be represented using the non-functional extension of UML4SOA (UML4SOA-NFP) and the MARTE profile. This enables modeling of performance, security and reliable messaging. Second, we discuss formal analysis of models which respect this design, in particular we consider performance estimates and reliability analysis using the stochastically timed process algebra PEPA as the underlying analytical engine. Last but not least, our models are the source for the application of deployment mechanisms which comprise model-to-model and model-to-text transformations implemented in the framework VIATRA. All techniques presented in this work are illustrated by a running example from an eUniversity case study

Tissue- and sex-specific small RNAomes reveal sex differences in response to the environment.

RNA interference (RNAi) related pathways are essential for germline development and fertility in metazoa and can contribute to inter- and trans-generational inheritance. In the nematode Caenorhabditis elegans, environmental double-stranded RNA provided by feeding can lead to heritable changes in phenotype and gene expression. Notably, transmission efficiency differs between the male and female germline, yet the underlying mechanisms remain elusive. Here we use high-throughput sequencing of dissected gonads to quantify sex-specific endogenous piRNAs, miRNAs and siRNAs in the C. elegans germline and the somatic gonad. We identify genes with exceptionally high levels of secondary 22G RNAs that are associated with low mRNA expression, a signature compatible with silencing. We further demonstrate that contrary to the hermaphrodite germline, the male germline, but not male soma, is resistant to environmental RNAi triggers provided by feeding, in line with previous work. This sex-difference in silencing efficacy is associated with lower levels of gonadal RNAi amplification products. Moreover, this tissue- and sex-specific RNAi resistance is regulated by the germline, since mutant males with a feminized germline are RNAi sensitive. This study provides important sex- and tissue-specific expression data of miRNA, piRNA and siRNA as well as mechanistic insights into sex-differences of gene regulation in response to environmental cues

CDK-1 inhibits meiotic spindle shortening and dynein-dependent spindle rotation in C. elegans

Before chromosome expulsion into polar bodies during female meiosis, the APC inhibits CDK-1 to allow dynein-driven spindle rotation

Stage-Specific Expression Profiling of Drosophila Spermatogenesis Suggests that Meiotic Sex Chromosome Inactivation Drives Genomic Relocation of Testis-Expressed Genes

In Drosophila, genes expressed in males tend to accumulate on autosomes and are underrepresented on the X chromosome. In particular, genes expressed in testis have been observed to frequently relocate from the X chromosome to the autosomes. The inactivation of X-linked genes during male meiosis (i.e., meiotic sex chromosome inactivation—MSCI) was first proposed to explain male sterility caused by X-autosomal translocation in Drosophila, and more recently it was suggested that MSCI might provide the conditions under which selection would favor the accumulation of testis-expressed genes on autosomes. In order to investigate the impact of MSCI on Drosophila testis-expressed genes, we performed a global gene expression analysis of the three major phases of D. melanogaster spermatogenesis: mitosis, meiosis, and post-meiosis. First, we found evidence supporting the existence of MSCI by comparing the expression levels of X- and autosome-linked genes, finding the former to be significantly reduced in meiosis. Second, we observed that the paucity of X-linked testis-expressed genes was restricted to those genes highly expressed in meiosis. Third, we found that autosomal genes relocated through retroposition from the X chromosome were more often highly expressed in meiosis in contrast to their X-linked parents. These results suggest MSCI as a general mechanism affecting the evolution of some testis-expressed genes

LEM-3 – A LEM Domain Containing Nuclease Involved in the DNA Damage Response in C. elegans

The small nematode Caenorhabditis elegans displays a spectrum of DNA damage responses similar to humans. In order to identify new DNA damage response genes, we isolated in a forward genetic screen 14 new mutations conferring hypersensitivity to ionizing radiation. We present here our characterization of lem-3, one of the genes identified in this screen. LEM-3 contains a LEM domain and a GIY nuclease domain. We confirm that LEM-3 has DNase activity in vitro. lem-3(lf) mutants are hypersensitive to various types of DNA damage, including ionizing radiation, UV-C light and crosslinking agents. Embryos from irradiated lem-3 hermaphrodites displayed severe defects during cell division, including chromosome mis-segregation and anaphase bridges. The mitotic defects observed in irradiated lem-3 mutant embryos are similar to those found in baf-1 (barrier-to-autointegration factor) mutants. The baf-1 gene codes for an essential and highly conserved protein known to interact with the other two C. elegans LEM domain proteins, LEM-2 and EMR-1. We show that baf-1, lem-2, and emr-1 mutants are also hypersensitive to DNA damage and that loss of lem-3 sensitizes baf-1 mutants even in the absence of DNA damage. Our data suggest that BAF-1, together with the LEM domain proteins, plays an important role following DNA damage – possibly by promoting the reorganization of damaged chromatin

Membrane Invaginations Reveal Cortical Sites that Pull on Mitotic Spindles in One-Cell C. elegans Embryos

Asymmetric positioning of the mitotic spindle in C. elegans embryos is mediated by force-generating complexes that are anchored at the plasma membrane and that pull on microtubules growing out from the spindle poles. Although asymmetric distribution of the force generators is thought to underlie asymmetric positioning of the spindle, the number and location of the force generators has not been well defined. In particular, it has not been possible to visualize individual force generating events at the cortex. We discovered that perturbation of the acto-myosin cortex leads to the formation of long membrane invaginations that are pulled from the plasma membrane toward the spindle poles. Several lines of evidence show that the invaginations, which also occur in unperturbed embryos though at lower frequency, are pulled by the same force generators responsible for spindle positioning. Thus, the invaginations serve as a tool to localize the sites of force generation at the cortex and allow us to estimate a lower limit on the number of cortical force generators within the cell

E4 ligase–specific ubiquitination hubs coordinate DNA double-strand-break repair and apoptosis

Multiple protein ubiquitination events at DNA double-strand breaks (DSBs) regulate damage recognition, signaling and repair. It has remained poorly understood how the repair process of DSBs is coordinated with the apoptotic response. Here, we identified the E4 ubiquitin ligase UFD-2 as a mediator of DNA-damage-induced apoptosis in a genetic screen in Caenorhabditis elegans. We found that, after initiation of homologous recombination by RAD-51, UFD-2 forms foci that contain substrate-processivity factors including the ubiquitin-selective segregase CDC-48 (p97), the deubiquitination enzyme ATX-3 (Ataxin-3) and the proteasome. In the absence of UFD-2, RAD-51 foci persist, and DNA damage-induced apoptosis is prevented. In contrast, UFD-2 foci are retained until recombination intermediates are removed by the Holliday-junction-processing enzymes GEN-1, MUS-81 or XPF-1. Formation of UFD-2 foci also requires proapoptotic CEP-1 (p53) signaling. Our findings establish a central role of UFD-2 in the coordination between the DNA-repair process and the apoptotic response