Compositional nonblocking verification with always enabled events and selfloop-only events

This paper proposes to improve compositional nonblocking verification through the use of always enabled and selfloop-only events. Compositional verification involves abstraction to simplify parts of a system during verification. Normally, this abstraction is based on the set of events not used in the remainder of the system, i.e., in the part of the system not being simplified. Here, it is proposed to exploit more knowledge about the system and abstract events even though they are used in the remainder of the system. Abstraction rules from previous work are generalised, and experimental results demonstrate the applicability of the resulting algorithm to verify several industrial-scale discrete event system models, while achieving better state-space reduction than before

Natural archives of long-range transported contamination at the remote lake Letšeng-la Letsie, Maloti Mountains, Lesotho

Naturally accumulating archives, such as lake sediments and wetland peats, in remote areas may be used to identify the scale and rates of atmospherically deposited pollutant inputs to natural ecosystems. Co-located lake sediment and wetland cores were collected from Letšeng-la Letsie, a remote lake in the Maloti Mountains of southern Lesotho. The cores were radiometrically dated and analysed for a suite of contaminants including trace metals and metalloids (Hg, Pb, Cu, Ni, Zn, As), fly-ash particles, stable nitrogen isotopes, polycyclic aromatic hydrocarbons (PAHs) and persistent organic pollutants such as polychlorinated biphenyls (PCBs), polybrominated flame retardants (PBDEs) and hexachlorobenzene (HCB). While most trace metals showed no recent enrichment, mercury, fly-ash particles, high molecular weight PAHs and total PCBs showed low but increasing levels of contamination since c.1970, likely the result of long-range transport from coal combustion and other industrial sources in the Highveld region of South Africa. However, back-trajectory analysis revealed that atmospheric transport from this region to southern Lesotho is infrequent and the scale of contamination is low. To our knowledge, these data represent the first palaeolimnological records and the first trace contaminant data for Lesotho, and one of the first multi-pollutant historical records for southern Africa. They therefore provide a baseline for future regional assessments in the context of continued coal combustion in South Africa through to the mid-21st century

Distributed Synthesis in Continuous Time

We introduce a formalism modelling communication of distributed agents strictly in continuous-time. Within this framework, we study the problem of synthesising local strategies for individual agents such that a specified set of goal states is reached, or reached with at least a given probability. The flow of time is modelled explicitly based on continuous-time randomness, with two natural implications: First, the non-determinism stemming from interleaving disappears. Second, when we restrict to a subclass of non-urgent models, the quantitative value problem for two players can be solved in EXPTIME. Indeed, the explicit continuous time enables players to communicate their states by delaying synchronisation (which is unrestricted for non-urgent models). In general, the problems are undecidable already for two players in the quantitative case and three players in the qualitative case. The qualitative undecidability is shown by a reduction to decentralized POMDPs for which we provide the strongest (and rather surprising) undecidability result so far

Applications of Fair Testing

In this paper we present the application of the fair testing pre-order, introduced in a previous paper, to the specification and analysis of distributed systems. This pre-order combines some features of the standard testing pre-orders, viz. the possibility to refine a specification by the resolution of nondeterminism, with a powerful feature of standard observation congruence, viz. the fair abstraction from divergences. Moreover, it is a pre-congruence with respect to all standard process-algebraic combinators, thus allowing for the standard algebraic proof techniques by substitution and rewriting. In this paper we will demonstrate advantages of the fair testing pre-order by the application to a number of examples, including a scheduling problem, a version of the Alternating Bit-protocol, and fair communication channels

Accelerating Discovery for Complex Neurological and Behavioral Disorders Through Systems Genetics and Integrative Genomics in the Laboratory Mouse

Recent advances in systems genetics and integrative functional genomics have greatly improved the study of complex neurological and behavioral traits. The methods developed for the integrated characterization of new, high-resolution mouse genetic reference populations and systems genetics enable behavioral geneticists an unprecedented opportunity to address questions of the molecular basis of neurological and psychiatric disorders and their comorbidities. Integrative genomics augment these strategies by enabling rapid informatics-assisted candidate gene prioritization, cross-species translation, and mechanistic comparison across related disorders from a wealth of existing data in mouse and other model organisms. Ultimately, through these complementary approaches, finding the mechanisms and sources of genetic variation underlying complex neurobehavioral disease related traits is becoming tractable. Furthermore, these methods enable categorization of neurobehavioral disorders through their underlying biological basis. Together, these model organism-based approaches can lead to a refinement of diagnostic categories and targeted treatment of neurological and psychiatric disease

How functional programming mattered

In 1989 when functional programming was still considered a niche topic, Hughes wrote a visionary paper arguing convincingly ‘why functional programming matters’. More than two decades have passed. Has functional programming really mattered? Our answer is a resounding ‘Yes!’. Functional programming is now at the forefront of a new generation of programming technologies, and enjoying increasing popularity and influence. In this paper, we review the impact of functional programming, focusing on how it has changed the way we may construct programs, the way we may verify programs, and fundamentally the way we may think about programs

Relational Concurrent Refinement II: Internal Operations and Outputs

Two styles of description arise naturally in formal specification: state-based and behavioural. In state-based notations, a system is characterised by a collection of variables, and their values determine which actions may occur throughout a system history. Behavioural specifications describe the chronologies of actions -- interactions between a system and its environment. The exact nature of such interactions is captured in a variety of semantic models with corresponding notions of refinement; refinement in state based systems is based on the semantics of sequential programs and is modelled relationally. Acknowledging that these viewpoints are complementary, substantial research has gone into combining the paradigms. The purpose of this paper is to do three things. First, we survey recent results linking the relational model of refinement to the process algebraic models. Specifically, we detail how variations in the relational framework lead to relational data refinement being in correspondence with traces-divergences, singleton failures and failures-divergences refinement in a process semantics. Second, we generalise these results by providing a general flexible scheme for incorporating the two main ''erroneous'' concurrent behaviours: deadlock and divergence, into relational refinement. This is shown to subsume previous characterisations. In doing this we derive relational refinement rules for specifications containing both internal operations and outputs that corresponds to failures-divergences refinement. Third, the theory has been formally specified and verified using the interactive theorem prover KIV

Two new rapid SNP-typing methods for classifying Mycobacterium tuberculosis complex into the main phylogenetic lineages

There is increasing evidence that strain variation in Mycobacterium tuberculosis complex (MTBC) might influence the outcome of tuberculosis infection and disease. To assess genotype-phenotype associations, phylogenetically robust molecular markers and appropriate genotyping tools are required. Most current genotyping methods for MTBC are based on mobile or repetitive DNA elements. Because these elements are prone to convergent evolution, the corresponding genotyping techniques are suboptimal for phylogenetic studies and strain classification. By contrast, single nucleotide polymorphisms (SNP) are ideal markers for classifying MTBC into phylogenetic lineages, as they exhibit very low degrees of homoplasy. In this study, we developed two complementary SNP-based genotyping methods to classify strains into the six main human-associated lineages of MTBC, the 'Beijing' sublineage, and the clade comprising Mycobacterium bovis and Mycobacterium caprae. Phylogenetically informative SNPs were obtained from 22 MTBC whole-genome sequences. The first assay, referred to as MOL-PCR, is a ligation-dependent PCR with signal detection by fluorescent microspheres and a Luminex flow cytometer, which simultaneously interrogates eight SNPs. The second assay is based on six individual TaqMan real-time PCR assays for singleplex SNP-typing. We compared MOL-PCR and TaqMan results in two panels of clinical MTBC isolates. Both methods agreed fully when assigning 36 well-characterized strains into the main phylogenetic lineages. The sensitivity in allele-calling was 98.6% and 98.8% for MOL-PCR and TaqMan, respectively. Typing of an additional panel of 78 unknown clinical isolates revealed 99.2% and 100% sensitivity in allele-calling, respectively, and 100% agreement in lineage assignment between both methods. While MOL-PCR and TaqMan are both highly sensitive and specific, MOL-PCR is ideal for classification of isolates with no previous information, whereas TaqMan is faster for confirmation. Furthermore, both methods are rapid, flexible and comparably inexpensive

Phylogenetic and environmental context of a Tournaisian tetrapod fauna

The end-Devonian to mid-Mississippian time interval has long been known for its depauperate palaeontological record, especially for tetrapods. This interval encapsulates the time of increasing terrestriality among tetrapods, but only two Tournaisian localities previously produced tetrapod fossils. Here we describe five new Tournaisian tetrapods ($\textit{Perittodus apsconditus}$, $\textit{Koilops herma}$, $\textit{Ossirarus kierani}$, $\textit{Diploradus austiumensis}$ and $\textit{Aytonerpeton microps}$) from two localities in their environmental context. A phylogenetic analysis retrieved three taxa as stem tetrapods, interspersed among Devonian and Carboniferous forms, and two as stem amphibians, suggesting a deep split among crown tetrapods. We also illustrate new tetrapod specimens from these and additional localities in the Scottish Borders region. The new taxa and specimens suggest that tetrapod diversification was well established by the Tournaisian. Sedimentary evidence indicates that the tetrapod fossils are usually associated with sandy siltstones overlying wetland palaeosols. Tetrapods were probably living on vegetated surfaces that were subsequently flooded. We show that atmospheric oxygen levels were stable across the Devonian/Carboniferous boundary, and did not inhibit the evolution of terrestriality. This wealth of tetrapods from Tournaisian localities highlights the potential for discoveries elsewhere.NERC consortium grants NE/J022713/1 (Cambridge), NE/J020729/1 (Leicester), NE/J021067/1 (BGS), NE/J020621/1 (NMS) and NE/J021091/1 (Southampton