Retrenching the Purse: Finite Exception Logs, and Validating the Small

The Mondex Electronic Purse is an outstanding example of industrial scale formal refinement, and was the first verification to achieve ITSEC level E6 certification. A formal abstract model and a formal concrete model were developed, and a formal refinement was hand-proved between them. Nevertheless, certain requirements issues were set beyond the scope of the formal development, or handled in an unnatural manner. The retrenchment Tower Pattern is used to address one such issue in detail: the finiteness of the purse log (which records unsuccessful transactions). A retrenchment is constructed from the lowest level model of the purse system to a model in which logs are finite, and is then lifted to create two refinement developments of the purse, working at different levels of detail, and connected via retrenchments, forming the tower. The tower development is appropriately validated, vindicating the design used

Dynamic aspects of retrenchments through temporal logic

Refinement is used as a way to verify an implementation with respect to a specification. States of related systems are linked through a so called gluing invariant which remains always true during the synchronous execution of both systems. Refinement is a sufficient condition for this property. Retrenchment is a generalization of refinement which relax the constraints between both systems. This paper proposes a temporal logic counterpart for some specific forms of retrenchment

Requirements Validation by Lifting Retrenchments in B

Simple retrenchment is briefly reviewed in the B specification language of J.-R.Abrial (Abrial,1996) as a liberalization of classical refinement, for the formal description of application developments too demanding for refinement. The looser relationships allowed by retrenchment between adjacent models in the development process may capture some of the requirements information of the development. This can make requirements validation more difficult to understand since the locus of requirements should be the models, and not their interrelationships, as far as possible. Hence the universal construction of (Banach,2000), originally proposed for simple transition systems, is reformulated in B, in order to "lift" a given retrenchment conceptually, thus retracting such requirements information back to the level of abstraction of the abstract, ideal model. Examples demonstrate the cognitive value of retracting requirements to the abstract level, articulated in a well-understood formal language. This is also seen to yield a more understandable way of comparing alternative retrenchment designs. Some new B syntax in the pre- and postcondition style is presented to facilitate expression of the lifted requirements

Retrenching the purse: The balance enquiry quandary, and generalised and (1, 1) forward refinements

Some of the success stories of model based refinement are recalled, as well as some of the annoyances that arise when refinement is deployed in the engineering of large systems. The way that retrenchment attempts to alleviate such inconveniences is briefly reviewed. The Mondex Electronic Purse formal development provides a highly credible testbed for examining how real world refinement difficulties can be treated via retrenchment. The contributions of retrenchment to integrating the real implementation with the formal development are surveyed, and the extraction of commonly occurring ‘retrenchment patterns’ is recalled. One of the Mondex difficulties, the ‘Balance Enquiry Quandary’ is treated in detail, and the way that retrenchment is able to account for the system behaviour is explained. The problem is reconsidered using generalised forward refinement, and the simplicity of the resolution of the quandary, both by retrenchment, and by generalised forward refinement, inspires the creation of a genuine (1; 1) forward refinement for Mondex, something long thought impossible. The forward treatment exhibits a similar balance enquiry quandary to the backward refinement, as it must, given that both are refinements of an atomic action to a non-atomic protocol, and the forward quandary is dealt with as easily by retrenchment as is the backward case. The simplicity of the retrenchment treatment foreshadows a general purpose retrenchment Atomicity Pattern for dealing with atomic-versus-finegrained situations

Interleukin-6 Increases Matrix Metalloproteinase-14 (MMP-14) Levels via Down-Regulation of p53 to Drive Cancer Progression

Matrix metalloproteinases (MMPs) play critical roles in cancer invasion and metastasis by digesting basement membrane and extracellular matrix (ECM). Much attention has focused on the enzymatic activities of MMPs; however, the regulatory mechanism of MMP expression remains elusive. By employing bioinformatics analysis, we identified a potential p53 response element within the MMP-14 promoter. Experimentally, we found that p53 can repress MMP-14 promoter activity, whereas deletion of this p53 response element abrogated this effect. Furthermore, we found that p53 expression decreases MMP-14 mRNA and protein levels and attenuates MMP-14-mediated cellular functions. Additional promoter analysis and chromatin immunoprecipitation studies identified a mechanism of regulation of MMP-14 expression by which p53 and transcription factor Sp1 competitively bind to the promoter. As the correlation between inflammation and cancer aggressiveness is well described, we next sought to evaluate if inflammatory cytokines could differentially affect p53 and MMP-14 levels. We demonstrate that interleukin-6 (IL-6) down-regulates p53 protein levels and thus results in a concomitant increase in MMP-14 expression, leading to enhanced cancer cell invasion and metastasis. Our data collectively indicate a novel mechanism of regulation of MMP-14 by a cascade of IL-6 and p53, demonstrating that the tumor microenvironment directly stimulates molecular changes in cancer cells to drive an invasive phenotype

Core Hybrid Event-B I: Single Hybrid Event-B machines

Faced with the increasing need for correctly designed hybrid and cyber-physical systems today, the problem of including provision for continuously varying behaviour as well as the usual discrete changes of state is considered in the context of Event-B. An extension of Event-B called Hybrid Event-B is presented, that accommodates continuous behaviours (called pliant events) in between familiar discrete transitions (called mode events in this context). The continuous state change can be specified by a combination of indirect specification via ordinary differential equations, or direct specification via assignment of variables to values that depend on time, or indirect specification by demanding that behaviour obeys a time dependent predicate. The syntactic elements of the extension are discussed, and the semantics is described in terms of the properties of time dependent valuations of variables. Refinement is examined in detail, with reference to the notion of refinement inherited from discrete Event-B. A full suite of proof obligations is presented, covering all aspects of the new framework. A selection of examples and case studies is presented. A particular challenge - bearing in mind the desirability of conforming to existing intuitions about discrete Event-B, and the impact on tool support (as embodied in tools for discrete Event-B like Rodin) - is to design the whole framework so as to disturb as little as possible the existing structures for handling discrete Event-B

Divergences in the Effective Action for Acausal Spacetimes

The 1--loop effective Lagrangian for a massive scalar field on an arbitrary causality violating spacetime is calculated using the methods of Euclidean quantum field theory in curved spacetime. Fields of spin 1/2, spin 1 and twisted field configurations are also considered. In general, we find that the Lagrangian diverges to minus infinity at each of the nth polarised hypersurfaces of the spacetime with a structure governed by a DeWitt-Schwinger type expansion.Comment: 17 pages, Late

On the bounded cohomology of semi-simple groups, S-arithmetic groups and products

We prove vanishing results for Lie groups and algebraic groups (over any local field) in bounded cohomology. The main result is a vanishing below twice the rank for semi-simple groups. Related rigidity results are established for S-arithmetic groups and groups over global fields. We also establish vanishing and cohomological rigidity results for products of general locally compact groups and their lattices

PCSK9 genetic variants and cognitive abilities:a large-scale Mendelian randomization study

Introduction: PCSK9 inhibitors lower low-density lipoprotein (LDL) cholesterol and are efficacious at reducing vascular disease, however questions remain about potential effects on cognitive function. Methods: We examined the association of genetic variants in PCSK9 with continuous measures of cognitive ability in UK Biobank. Six independent polymorphisms in PCSK9 were used in up to 337,348 individuals. Results: The PCSK9 allele score was associated with a lower risk of CHD, and weakly with worse log reaction time. Conclusions: We are unable to rule out meaningful associations of PCSK9 genetic variants with cognition, emphasising the potential need for continued pharmacovigilance for patients currently treated with PCSK9 inhibitors