A robust semantics hides fewer errors

In this paper we explore how formal models are interpreted and to what degree meaning is captured in the formal semantics and to what degree it remains in the informal interpretation of the semantics. By applying a robust approach to the definition of refinement and semantics, favoured by the event-based community, to state-based theory we are able to move some aspects from the informal interpretation into the formal semantics

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Towards an Operational Semantics for Alloy

Abstract. The Alloy modeling language has a mathematically rigorous denotational semantics based on relational algebra. Alloy specifications often represent operations on a state, suggesting a transition-system semantics. Because Alloy does not intrinsically provide a notion of state, however, this interpretation is only implicit in the relational-algebra semantics underlying the Alloy Analyzer. In this paper we demonstrate the subtlety of representing state in Alloy specifications. We formalize a natural notion of transition semantics for state-based specifications and show examples of specifications in this class for which analysis based on relational algebra can induce false confidence in designs. We characterize the class of facts that guarantees that Alloy’s analysis is sound for statetransition systems, and offer a sufficient syntactic condition for membership in this class. We offer some practical evaluation of the utility of this syntactic discipline and show how it provides a foundation for program synthesis from Alloy.

A beginner’s course on reasoning about imperative programs

Abstract. Formal Methods teaching at undergraduate level has been going on at Manchester for a good number of years. We have introduced various courses based on different approaches. We have experienced the usual problems. To combat these problems, our approaches and our course contents have evolved accordingly over the years. In this paper we briefly trace this evolution, and describe the latest course, on reasoning about simple imperative programs, for first-year students who are half-way through our introductory programming course.