Completeness for a First-order Abstract Separation Logic

Existing work on theorem proving for the assertion language of separation logic (SL) either focuses on abstract semantics which are not readily available in most applications of program verification, or on concrete models for which completeness is not possible. An important element in concrete SL is the points-to predicate which denotes a singleton heap. SL with the points-to predicate has been shown to be non-recursively enumerable. In this paper, we develop a first-order SL, called FOASL, with an abstracted version of the points-to predicate. We prove that FOASL is sound and complete with respect to an abstract semantics, of which the standard SL semantics is an instance. We also show that some reasoning principles involving the points-to predicate can be approximated as FOASL theories, thus allowing our logic to be used for reasoning about concrete program verification problems. We give some example theories that are sound with respect to different variants of separation logics from the literature, including those that are incompatible with Reynolds's semantics. In the experiment we demonstrate our FOASL based theorem prover which is able to handle a large fragment of separation logic with heap semantics as well as non-standard semantics.Comment: This is an extended version of the APLAS 2016 paper with the same titl

Classical BI: Its Semantics and Proof Theory

We present Classical BI (CBI), a new addition to the family of bunched logics which originates in O'Hearn and Pym's logic of bunched implications BI. CBI differs from existing bunched logics in that its multiplicative connectives behave classically rather than intuitionistically (including in particular a multiplicative version of classical negation). At the semantic level, CBI-formulas have the normal bunched logic reading as declarative statements about resources, but its resource models necessarily feature more structure than those for other bunched logics; principally, they satisfy the requirement that every resource has a unique dual. At the proof-theoretic level, a very natural formalism for CBI is provided by a display calculus \`a la Belnap, which can be seen as a generalisation of the bunched sequent calculus for BI. In this paper we formulate the aforementioned model theory and proof theory for CBI, and prove some fundamental results about the logic, most notably completeness of the proof theory with respect to the semantics.Comment: 42 pages, 8 figure

A Substructural Epistemic Resource Logic: Theory and Modelling Applications

We present a substructural epistemic logic, based on Boolean BI, in which the epistemic modalities are parametrized on agents’ local resources. The new modalities can be seen as generalizations of the usual epistemic modalities. The logic combines Boolean BI’s resource semantics—we introduce BI and its resource semantics at some length—with epistemic agency. We illustrate the use of the logic in systems modelling by discussing some examples about access control, including semaphores, using resource tokens. We also give a labelled tableaux calculus and establish soundness and completeness with respect to the resource semantics

Selective involvement of serum response factor in pressure-induced myogenic tone in resistance arteries

OBJECTIVE: In resistance arteries, diameter adjustment in response to pressure changes depends on the vascular cytoskeleton integrity. Serum response factor (SRF) is a dispensable transcription factor for cellular growth, but its role remains unknown in resistance arteries. We hypothesized that SRF is required for appropriate microvascular contraction. METHODS AND RESULTS: We used mice in which SRF was specifically deleted in smooth muscle or endothelial cells, and their control. Myogenic tone and pharmacological contraction was determined in resistance arteries. mRNA and protein expression were assessed by quantitative real-time PCR (qRT-PCR) and Western blot. Actin polymerization was determined by confocal microscopy. Stress-activated channel activity was measured by patch clamp. Myogenic tone developing in response to pressure was dramatically decreased by SRF deletion (5.9+/-2.3%) compared with control (16.3+/-3.2%). This defect was accompanied by decreases in actin polymerization, filamin A, myosin light chain kinase and myosin light chain expression level, and stress-activated channel activity and sensitivity in response to pressure. Contractions induced by phenylephrine or U46619 were not modified, despite a higher sensitivity to p38 blockade; this highlights a compensatory pathway, allowing normal receptor-dependent contraction. CONCLUSIONS: This study shows for the first time that SRF has a major part to play in the control of local blood flow via its central role in pressure-induced myogenic tone in resistance arteries

Human bone marrow mesenchymal stem cells : a systematic reappraisal via the genostem experience

Genostem (acronym for “Adult mesenchymal stem cells engineering for connective tissue disorders. From the bench to the bed side”) has been an European consortium of 30 teams working together on human bone marrow Mesenchymal Stem Cell (MSC) biological properties and repair capacity. Part of Genostem activity has been dedicated to the study of basic issues on undifferentiated MSCs properties and on signalling pathways leading to the differentiation into 3 of the connective tissue lineages, osteoblastic, chondrocytic and tenocytic. We have evidenced that native bone marrow MSCs and stromal cells, forming the niche of hematopoietic stem cells, were the same cellular entity located abluminally from marrow sinus endothelial cells. We have also shown that culture-amplified, clonogenic and highly-proliferative MSCs were bona fide stem cells, sharing with other stem cell types the major attributes of self-renewal and of multipotential priming to the lineages to which they can differentiate (osteoblasts, chondrocytes, adipocytes and vascular smooth muscle cells/pericytes). Extensive transcription profiling and in vitro and in vivo assays were applied to identify genes involved in differentiation. Thus we have described novel factors implicated in osteogenesis (FHL2, ITGA5, Fgf18), chondrogenesis (FOXO1A) and tenogenesis (Smad8). Another part of Genostem activity has been devoted to studies of the repair capacity of MSCs in animal models, a prerequisite for future clinical trials. We have developed novel scaffolds (chitosan, pharmacologically active microcarriers) useful for the repair of both bone and cartilage. Finally and most importantly, we have shown that locally implanted MSCs effectively repair bone, cartilage and tendonWork supported by the European Community (Key action 1.2.4-3 Integrated Project Genostem, contract No 503161)

Fluorescent Liquid Tetrazines

Tetrazines with branched alkoxy substituents are liquids at ambient temperature that despite the high chromophore density retain the bright orange fluorescence that is characteristic of this exceptional fluorophore. Here, we study the photophysical properties of a series of alkoxy-tetrazines in solution and as neat liquids. We also correlate the size of the alkoxy substituents with the viscosity of the liquids. We show using time-resolved spectroscopy that intersystem crossing is an important decay pathway competing with fluorescence, and that its rate is higher for 3,6-dialkoxy derivatives than for 3-chloro-6-alkoxytetrazines, explaining the higher fluorescence quantum yields for the latter. Quantum chemical calculations suggest that the difference in rate is due to the activation energy required to distort the tetrazine core such that the [Formula: see text] [Formula: see text] and the higher-lying [Formula: see text] [Formula: see text] states cross, at which point the spin-orbit coupling exceeding 10 cm [Formula: see text] allows for efficient intersystem crossing to occur. Femtosecond time-resolved anisotropy studies in solution allow us to measure a positive relationship between the alkoxy chain lengths and their rotational correlation times, and studies in the neat liquids show a fast decay of the anisotropy consistent with fast exciton migration in the neat liquid films

Towards Scientific Incident Response

A scientific incident analysis is one with a methodical, justifiable approach to the human decision-making process. Incident analysis is a good target for additional rigor because it is the most human-intensive part of incident response. Our goal is to provide the tools necessary for specifying precisely the reasoning process in incident analysis. Such tools are lacking, and are a necessary (though not sufficient) component of a more scientific analysis process. To reach this goal, we adapt tools from program verification that can capture and test abductive reasoning. As Charles Peirce coined the term in 1900, “Abduction is the process of forming an explanatory hypothesis. It is the only logical operation which introduces any new idea.” We reference canonical examples as paradigms of decision-making during analysis. With these examples in mind, we design a logic capable of expressing decision-making during incident analysis. The result is that we can express, in machine-readable and precise language, the abductive hypotheses than an analyst makes, and the results of evaluating them. This result is beneficial because it opens up the opportunity of genuinely comparing analyst processes without revealing sensitive system details, as well as opening an opportunity towards improved decision-support via limited automation

Large oesophageal varice screening by a sequential algorithm using a cirrhosis blood test and optionally capsule endoscopy

BACKGROUND & AIMS: Large oesophageal varice (LEV) screening is recommended in cirrhosis. We performed a prospective study to improve non-invasive LEV screening. DESIGN: 287 patients with cirrhosis had upper gastrointestinal endoscopy (LEV reference), oesophageal capsule endoscopy (ECE), liver elastography and blood marker analyses. CirrhoMeter (cirrhosis blood test), the most accurate non-invasive LEV test, was segmented for cirrhosis (reference comparator) or LEV. VariScreen, a sequential and partially minimally invasive diagnostic algorithm, was developed by multivariate analysis. It uses CirrhoMeter first, then ECE if CirrhoMeter cannot rule LEV out or in, and finally endoscopy if CirrhoMeter+ECE combination remains uninformative. RESULTS: Diagnostic effectiveness rates for LEV were: cirrhosis-segmented CirrhoMeter: 14.6%, LEV-segmented CirrhoMeter: 34.6%, ECE: 60.6% and VariScreen: 66.4% (P ≤ .001 for overall or pair comparison). The respective missed LEV rates were: 2.8%, 5.6%, 8.3% and 5.6% (P = .789). Spared endoscopy rates were, respectively: 15.6%, 36.0%, 70.6% and 69%, (P < .001 for overall or paired comparison except ECE vs VariScreen: P = .743). VariScreen spared 38% of ECE and reduced missed LEV by 87% compared to classical ECE performed in all patients. Excepting cirrhosis-segmented CirrhoMeter, these spared endoscopy rates were significantly higher than that of the Baveno VI recommendation (using platelets and Fibroscan): 18.4% (P < .001). Ascites and Child-Pugh class independently predicted endoscopy sparing by VariScreen: from 86.0% in compensated Child Pugh class A to 24.1% in Child-Pugh class C with ascites. CONCLUSION: VariScreen algorithm significantly reduced the missed LEV rate with ECE by 87%, ECE use by 38% and endoscopy requirement by 69%, and even 86% in compensated cirrhosis