Do I need to fix a failed component now, or can I wait until tomorrow?

We investigate how predictive event-based modelling can inform operational decision making in complex systems with component failures. By relating the status of components to service availability, and using stochastic temporal logic reasoning, we quantify the risk of service failure now, and in the future, after a given elapsed time. Decisions can then be taken according to those risks. We demonstrate the approach through application to an industrial case study system in which component failures are sensed and monitored. The system has been deployed for some time. A novel aspect is we calibrate the model(s) according to inferences over historical field data, thus the results of our reasoning can inform decision making in the actual deployed system

Stochastic model checking for predicting component failures and service availability

When a component fails in a critical communications service, how urgent is a repair? If we repair within 1 hour, 2 hours, or n hours, how does this affect the likelihood of service failure? Can a formal model support assessing the impact, prioritisation, and scheduling of repairs in the event of component failures, and forecasting of maintenance costs? These are some of the questions posed to us by a large organisation and here we report on our experience of developing a stochastic framework based on a discrete space model and temporal logic to answer them. We define and explore both standard steady-state and transient temporal logic properties concerning the likelihood of service failure within certain time bounds, forecasting maintenance costs, and we introduce a new concept of envelopes of behaviour that quantify the effect of the status of lower level components on service availability. The resulting model is highly parameterised and user interaction for experimentation is supported by a lightweight, web-based interface

Bigraphs with sharing

Bigraphical Reactive Systems (BRS) were designed by Milner as a universal formalism for modelling systems that evolve in time, locality, co-locality and connectivity. But the underlying model of location (the place graph) is a forest, which means there is no straightforward representation of locations that can overlap or intersect. This occurs in many domains, for example in wireless signalling, social interactions and audio communications. Here, we define bigraphs with sharing, which solves this problem by an extension of the basic formalism: we define the place graph as a directed acyclic graph, thus allowing a natural representation of overlapping or intersecting locations. We give a complete presentation of the theory of bigraphs with sharing, including a categorical semantics, algebraic properties, and several essential procedures for computation: bigraph with sharing matching, a SAT encoding of matching, and checking a fragment of the logic BiLog. We show that matching is an instance of the NP-complete sub-graph isomorphism problem and our approach based on a SAT encoding is also efficient for standard bigraphs. We give an overview of BigraphER (Bigraph Evaluator & Rewriting), an efficient implementation of bigraphs with sharing that provides manipulation, simulation and visualisation. The matching engine is based on the SAT encoding of the matching algorithm. Examples from the 802.11 CSMA/CA RTS/CTS protocol and a network management support system illustrate the applicability of the new theory

Modelling IEEE 802.11 CSMA/CA RTS/CTS with stochastic bigraphs with sharing

Stochastic bigraphical reactive systems (SBRS) is a recent formalism for modelling systems that evolve in time and space. However, the underlying spatial model is based on sets of trees and thus cannot represent spatial locations that are shared among several entities in a simple or intuitive way. We adopt an extension of the formalism, SBRS with sharing, in which the topology is modelled by a directed acyclic graph structure. We give an overview of SBRS with sharing, we extend it with rule priorities, and then use it to develop a model of the 802.11 CSMA/CA RTS/CTS protocol with exponential backoff, for an arbitrary network topology with possibly overlapping signals. The model uses sharing to model overlapping connectedness areas, instantaneous prioritised rules for deterministic computations, and stochastic rules with exponential reaction rates to model constant and uniformly distributed timeouts and constant transmission times. Equivalence classes of model states modulo instantaneous reactions yield states in a CTMC that can be analysed using the model checker PRISM. We illustrate the model on a simple example wireless network with three overlapping signals and we present some example quantitative properties

Responsiveness of bovine cumulus-oocyte-complexes (COC) to porcine and recombinant human FSH, and the effect of COC quality on gonadotropin receptor and Cx43 marker gene mRNAs during maturation in vitro

Substantially less development to the blastocyst stage occurs in vitro than in vivo and this may be due to deficiencies in oocyte competence. Although a large proportion of bovine oocytes undergo spontaneous nuclear maturation, less is known about requirements for proper cytoplasmic maturation. Commonly, supraphysiological concentrations of FSH and LH are added to maturation media to improve cumulus expansion, fertilization and embryonic development. Therefore, various concentrations of porcine FSH (pFSH) and recombinant human FSH (rhFSH) were investigated for their effect on bovine cumulus expansion in vitro. Expression of FSHr, LHr and Cx43 mRNAs was determined in cumulus-oocyte complexes to determine whether they would be useful markers of oocyte competence. In serum-free media, only 1000 ng/ml pFSH induced marked cumulus expansion, but the effect of 100 ng/ml pFSH was amplified in the presence of 10% serum. In contrast, cumulus expansion occurred with 1 ng/ml rhFSH in the absence of serum. FSHr mRNA was highest at 0–6 h of maturation, then abundance decreased. Similarly, Cx43 mRNA expression was highest from 0–6 h but decreased by 24 h of maturation. However, the relative abundance of LHr mRNA did not change from 6–24 h of maturation. Decreased levels of FSHr, LHr and Cx43 mRNAs were detected in COCs of poorer quality. In conclusion, expansion of bovine cumulus occurred at low doses of rhFSH in serum-free media. In summary, FSHr, LHr and Cx43 mRNA abundance reflects COC quality and FSHr and Cx43 mRNA expression changes during in vitro maturation; these genes may be useful markers of oocyte developmental competence

Mitogen-activated protein kinase (MAPK) blockade of bovine preimplantation embryogenesis requires inhibition of both p38 and extracellular signal-regulated kinase (ERK) pathways.

Blastocyst formation, as a critical period during development, is an effective indicator of embryonic health and reproductive efficiency. Out of a number of mechanisms underlying blastocyst formation, highly conserved mitogen-activated protein kinase (MAPK) signaling has emerged as a major mechanism involved in regulating murine preimplantation embryo development. The objective of our study was to ascertain the role of MAPK signaling in regulating bovine development to the blastocyst stage. Using reverse transcriptase PCR and immunohistochemical staining procedures we have demonstrated that mRNA transcripts and polypeptides encoding p38 MAPK pathway constituents are detectable in preimplantation bovine embryos from the one-cell to the blastocyst stage. Further, the effects on bovine embryo development following inhibition of p38 alpha/beta and extracellular signal-regulated kinase (ERK) signaling by treatment with SB220025 and U0126, respectively, were investigated. Eight-cell bovine embryos (50 per group; three replicates) were placed into treatments consisting of synthetic oviductal fluid (SOF) medium: SOF + SB202474 (inactive analogue), SOF + SB220025, SOF + U0124 (inactive analogue), SOF + U0126, and SOF + SB220025 + U0126. Inhibition of p38 MAPK or ERK signaling individually did not affect development to the blastocyst stage. However, when both pathways were blocked simultaneously there was a significant reduction (P \u3c 0.05) in blastocyst formation, cell number and immunofluorescence of phosphorylated downstream pathway constituents. We have determined that, in variance to what was observed during murine preimplantation development, bovine early embryos progress at normal frequencies to the blastocyst stage in the presence of p38 MAPK inhibitors

Modelling and Verification of Large-Scale Sensor Network Infrastructures

Large-scale wireless sensor networks (WSN) are increasingly deployed and an open question is how they can support multiple applications. Networks and sensing devices are typically heterogeneous and evolving: topologies change, nodes drop in and out of the network, and devices are reconfigured. The key question we address is how to verify that application requirements are met, individually and collectively, and can continue to be met, in the context of large-scale, evolving network and device configurations. We define a modelling and verification framework based on Bigraphical Reactive Systems (BRS) for modelling, with bigraph patterns and temporal logic properties for specifying application requirements. The bigraph diagrammatic notation provides an intuitive representation of concepts such as hierarchies, communication, events and spatial relationships, which are fundamental to WSNs. We demonstrate modelling and verification through a real-life urban environmental monitoring case-study. A novel contribution is automated online verification using BigraphER and replay of real-life sensed data streams and network events by the Cooja network simulator. Performance results for verification of two application properties running on a WSN with up to 200 nodes indicate our framework is capable of handling WSNs of that scale

Genomic RNA profiling and the programme controlling preimplantation mammalian development.

Preimplantation development shifts from a maternal to embryonic programme rapidly after fertilization. Although the majority of oogenetic products are lost during the maternal to embryonic transition (MET), several do survive this interval to contribute directly to supporting preimplantation development. Embryonic genome activation (EGA) is characterized by the transient expression of several genes that are necessary for MET, and while EGA represents the first major wave of gene expression, a second mid-preimplantation wave of transcription that supports development to the blastocyst stage has been discovered. The application of genomic approaches has greatly assisted in the discovery of stage specific gene expression patterns and the challenge now is to largely define gene function and regulation during preimplantation development. The basic mechanisms controlling compaction, lineage specification and blastocyst formation are defined. The requirement for embryo culture has revealed plasticity in the developmental programme that may exceed the adaptive capacity of the embryo and has fostered important research directions aimed at alleviating culture-induced changes in embryonic programming. New levels of regulation are emerging and greater insight into the roles played by RNA-binding proteins and miRNAs is required. All of this research is relevant due to the necessity to produce healthy preimplantation embryos for embryo transfer, to ensure that assisted reproductive technologies are applied in the most efficient and safest way possible

Culture medium, gas atmosphere and MAPK inhibition affect regulation of RNA-binding protein targets during mouse preimplantation development.

During oogenesis, mammalian oocytes accumulate maternal mRNAs that support the embryo until embryonic genome activation. RNA-binding proteins (RBP) may regulate the stability and turnover of maternal and embryonic mRNAs. We hypothesised that varying embryo culture conditions, such as culture medium, oxygen tension and MAPK inhibition, affects regulation of RBPs and their targets during preimplantation development. STAU1, ELAVL1, KHSRP and ZFP36 proteins and mRNAs were detected throughout mouse preimplantation development, whereas Elavl2 mRNA decreased after the two-cell stage. Potential target mRNAs of RBP regulation, Gclc, Slc2a1 and Slc7a1 were detected during mouse preimplantation development. Gclc mRNA was significantly elevated in embryos cultured in Whitten\u27s medium compared with embryos cultured in KSOMaa, and Gclc mRNA was elevated under high-oxygen conditions. Inhibition of the p38 MAPK pathway reduced Slc7a1 mRNA expression while inhibition of ERK increased Slc2a1 mRNA expression. The half-lives of the potential RBP mRNA targets are not regulated in parallel; Slc2a1 mRNA displayed the longest half-life. Our results indicate that mRNAs and proteins encoding five RBPs are present during preimplantation development and more importantly, demonstrate that expression of RBP target mRNAs are regulated by culture medium, gas atmosphere and MAPK pathways

Effect of serum and cumulus cell expansion on marker gene transcripts in bovine cumulus-oocyte complexes during maturation in vitro.

OBJECTIVE: To determine the distribution of transcripts encoding the FSH receptor (FSHr), LH receptor (LHr), connexin 43 (Cx43), cyclooxygenase-2 (COX-2), and prostaglandin E(2) receptors 2 and 3 (EP2 and EP3) within bovine cumulus-oocyte complexes (COCs) and denuded oocytes and investigate the influence of gonadotropins, serum, and cumulus cell expansion on the abundance of transcripts encoding these genes. DESIGN: Prospective controlled animal study. SETTING: University research laboratory. PATIENT(S): Animal models for human studies. INTERVENTION(S): Cumulus-oocyte complexes were treated in culture with serum and gonadotropin-supplemented media to examine the effects to mRNA transcript levels. MAIN OUTCOME MEASURE(S): Variation in mRNA transcript levels. RESULT(S): Luteinizing hormone receptor, FSHr, and EP3 mRNAs were detected in intact COCs and not in cumulus cell-denuded oocytes, whereas Cx43, COX-2, and EP2 mRNAs were found in both COCs and oocytes. The relative abundance of marker gene mRNAs did not vary in media containing no additives or FSH alone, independent of whether the media induced cumulus cell expansion. However, the presence of serum in maturation media significantly decreased expression of all mRNAs except LHr. CONCLUSION(S): The relative abundance of COC mRNAs is altered by serum in the maturation medium, which may signify long-term consequences for embryonic development