The problem of programming language concurrency semantics

Despite decades of research, we do not have a satisfactory concurrency semantics for any general-purpose programming language that aims to support concurrent systems code. The Java Memory Model has been shown to be unsound with respect to standard compiler optimisations, while the C/C++11 model is too weak, admitting undesirable thin-air executions. Our goal in this paper is to articulate this major open problem as clearly as is currently possible, showing how it arises from the combination of multiprocessor relaxed-memory behaviour and the desire to accommodate current compiler optimisations. We make several novel contributions that each shed some light on the problem, constraining the possible solutions and identifying new difficulties. First we give a positive result, proving in HOL4 that the existing axiomatic model for C/C++11 guarantees sequentially consistent semantics for simple race-free programs that do not use low-level atomics (DRF-SC, one of the core design goals). We then describe the thin-air problem and show that it cannot be solved, without restricting current compiler optimisations, using any per-candidate-execution condition in the style of the C/C++11 model. Thin-air executions were thought to be confined to programs using relaxed atomics, but we further show that they recur when one attempts to integrate the concurrency model with more of C, mixing atomic and nonatomic accesses, and that also breaks the DRF-SC result. We then describe a semantics based on an explicit operational construction of out-of-order execution, giving the desired behaviour for thin-air examples but exposing further difficulties with accommodating existing compiler optimisations. Finally, we show that there are major difficulties integrating concurrency semantics with the C/C++ notion of undefined behaviour. We hope thereby to stimulate and enable research on this key issue

Approximate reasoning for real-time probabilistic processes

We develop a pseudo-metric analogue of bisimulation for generalized semi-Markov processes. The kernel of this pseudo-metric corresponds to bisimulation; thus we have extended bisimulation for continuous-time probabilistic processes to a much broader class of distributions than exponential distributions. This pseudo-metric gives a useful handle on approximate reasoning in the presence of numerical information -- such as probabilities and time -- in the model. We give a fixed point characterization of the pseudo-metric. This makes available coinductive reasoning principles for reasoning about distances. We demonstrate that our approach is insensitive to potentially ad hoc articulations of distance by showing that it is intrinsic to an underlying uniformity. We provide a logical characterization of this uniformity using a real-valued modal logic. We show that several quantitative properties of interest are continuous with respect to the pseudo-metric. Thus, if two processes are metrically close, then observable quantitative properties of interest are indeed close.Comment: Preliminary version appeared in QEST 0

Specification of Dynamic Reconfiguration in the Context of Input/Output Relations

Abstract: Recent advances in telecommunication and software technology have mo-tivated the study of components with dynamically changing syntactic interfaces. Formal development methods are traditionally directed towards components with static inter-faces. We investigate this short-coming of formal development methods and outline how it can be overcome. We start by presenting a semantic model for interactive components communicating asynchronously by message passing. On the top of this model we build a simple specifi-cation language directed towards components with static interfaces. Then we generalise this language to handle components with dynamic interfaces. We introduce operators fo

The genetic organisation of prokaryotic two-component system signalling pathways

<p>Abstract</p> <p>Background</p> <p>Two-component systems (TCSs) are modular and diverse signalling pathways, involving a stimulus-responsive transfer of phosphoryl groups from transmitter to partner receiver domains. TCS gene and domain organisation are both potentially informative regarding biological function, interaction partnerships and molecular mechanisms. However, there is currently little understanding of the relationships between domain architecture, gene organisation and TCS pathway structure.</p> <p>Results</p> <p>Here we classify the gene and domain organisation of TCS gene loci from 1405 prokaryotic replicons (>40,000 TCS proteins). We find that 200 bp is the most appropriate distance cut-off for defining whether two TCS genes are functionally linked. More than 90% of all TCS gene loci encode just one or two transmitter and/or receiver domains, however numerous other geometries exist, often with large numbers of encoded TCS domains. Such information provides insights into the distribution of TCS domains between genes, and within genes. As expected, the organisation of TCS genes and domains is affected by phylogeny, and plasmid-encoded TCS exhibit differences in organisation from their chromosomally-encoded counterparts.</p> <p>Conclusions</p> <p>We provide here an overview of the genomic and genetic organisation of TCS domains, as a resource for further research. We also propose novel metrics that build upon TCS gene/domain organisation data and allow comparisons between genomic complements of TCSs. In particular, '<it>percentage orphaned TCS genes</it>' (or 'Dissemination') and '<it>percentage of complex loci</it>' (or 'Sophistication') appear to be useful discriminators, and to reflect mechanistic aspects of TCS organisation not captured by existing metrics.</p

The Mechanism for RNA Recognition by ANTAR Regulators of Gene Expression

ANTAR proteins are widespread bacterial regulatory proteins that have RNA–binding output domains and utilize antitermination to control gene expression at the post-initiation level. An ANTAR protein, EutV, regulates the ethanolamine-utilization genes (eut) in Enterococcus faecalis. Using this system, we present genetic and biochemical evidence of a general mechanism of antitermination used by ANTARs, including details of the antiterminator structure. The novel antiterminator structure consists of two small hairpins with highly conserved terminal loop residues, both features being essential for successful antitermination. The ANTAR protein dimerizes and associates with its substrate RNA in response to signal-induced phosphorylation. Furthermore, bioinformatic searches using this conserved antiterminator motif identified many new ANTAR target RNAs in phylogenetically diverse bacterial species, some comprising complex regulons. Despite the unrelatedness of the species in which they are found, the majority of the ANTAR–associated genes are thematically related to nitrogen management. These data suggest that the central tenets for gene regulation by ANTAR antitermination occur widely in nature to specifically control nitrogen metabolism

Plasmodium vivax: paroxysm-associated lipids mediate leukocyte aggregation

<p>Abstract</p> <p>Background</p> <p>Paroxysms are recurrent febrile episodes, characteristic of <it>Plasmodium vivax </it>infections, which coincide with the rupture of schizont-infected erythrocytes in the patients' circulation. The present study describes the formation of prominent aggregates of leukocytes <it>in vitro </it>in the presence of parasite and host factors released during paroxysms.</p> <p>Methods</p> <p>Whole blood cells from uninfected malaria-naïve donors were incubated with plasma taken during a paroxysm or normal human plasma as a control and cell smears were observed under the microscope for the presence of leukocyte aggregates. Plasma factors involved in mediating the leukocyte aggregation were identified using immune depletion and reconstitution experiments. Furthermore, biochemical characterization was carried out to determine the chemical nature of the active moieties in plasma present during paroxysms.</p> <p>Results</p> <p>Leukocyte aggregates were seen exclusively when cells were incubated in plasma collected during a paroxysm. Immune depletion and reconstitution experiments revealed that the host cytokines TNF-alpha, GM-CSF, IL-6 and IL-10 and two lipid fractions of paroxysm plasma comprise the necessary and sufficient mediators of this phenomenon. The two lipid components of the paroxysm plasmas speculated to be of putative parasite origin, were a phospholipid-containing fraction and another containing cholesterol and triglycerides. The phospholipid fraction was dependent upon the presence of cytokines for its activity unlike the cholesterol/triglyceride-containing fraction which in the absence of added cytokines was much more active than the phospholipids fraction. The biological activity of the paroxysm plasmas from non-immune patients who presented with acute <it>P. vivax </it>infections was neutralized by immune sera raised against schizont extracts of either <it>P. vivax </it>or <it>Plasmodium falciparum</it>. However, immune sera against <it>P. vivax </it>were more effective than that against <it>P. falciparum </it>indicating that the parasite activity involved may be antigenically at least partially parasite species-specific.</p> <p>Conclusion</p> <p>Leukocyte aggregation was identified as associated with paroxysms in <it>P. vivax </it>infections. This phenomenon is mediated by plasma factors including host-derived cytokines and lipids of putative parasite origin. The characteristics of the phospholipid fraction in paroxysm plasma are congruent with those of the parasite-derived, TNF-inducing GPI moieties described by others. The more active cholesterol/triglyceride(s), however, represent a novel malarial toxin, which is a new class of biologically active lipid associated with the paroxysm of <it>P. vivax </it>malaria.</p