Implementing SOS with active objects: A case study of a multicore memory system

This paper describes the development of a parallel simulator of a multicore memory system from a model formalized as a structural operational semantics (SOS). Our implementation uses the Abstract Behavioral Specification (ABS) language, an executable, active object modelling language with a formal semantics, targeting distributed systems. We develop general design patterns in ABS for implementing SOS, and describe their application to the SOS model of multicore memory systems. We show how these patterns allow a formal correctness proof that the implementation simulates the formal operational model and discuss further parallelization and fairness of the simulator

From SOS to Asynchronously Communicating Actors

Structural Operational Semantics (SOS) provides a general format to describe a model as a transition system with very powerful synchronization mechanisms. Actor systems are distributed, asynchronously communicating units of computation with encapsulated state, with much weaker means of synchronizing between actors. In this paper, we discuss an implementation of a SOS model using actors in the object-oriented actor language ABS and how to argue that global properties about the model are inherited from the SOS level to the actor implementation. The work stems from a case study modelling the memory system of a cache-coherent multicore architecture

Inseguendo fagiani selvatici: Partial order reduction for guarded command languages

This paper presents a method for testing whether objects in actor languages and active object languages exhibit locally deterministic behavior. We investigate such a method for a class of guarded command programs, abstracting from object-oriented features like method calls but focusing on cooperative scheduling of dynamically spawned processes executing in parallel. The proposed method can answer questions such as whether all permutations of an execution trace are equivalent, by generating candidate traces for testing which may lead to different final states. To prune the set of candidate traces, we employ partial order reduction. To further reduce the set, we introduce an analysis technique to decide whether a generated trace is schedulable. Schedulability cannot be decided for guarded commands using standard dependence and interference relations because guard enabledness is non-monotonic. To solve this problem, we use concolic execution to produce linearized symbolic traces of the executed program, which allows a weakest precondition computation to decide on the satisfiability of guards

Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

High inborn aerobic capacity does not protect the heart following myocardial infarction

Maximal oxygen uptake (V̇O2max) is a strong prognostic marker for morbidity and mortality, but the cardio-protective effect of high inborn V̇O2max remains unresolved. We aimed to investigate whether rats with high inborn V̇O2max yield cardio-protection after myocardial infarction (MI) compared with rats with low inborn V̇O2max. Rats breed for high capacity of running (HCR) or low capacity of running (LCR) were randomized into HCR-SH (sham), HCR-MI, LCR-SH, and LCR-MI. V̇O2max was lower in HCR-MI and LCR-MI compared with respective sham (P < 0.01), supported by a loss in global cardiac function, assessed by echocardiography. Fura 2-AM loaded cardiomyocyte experiments revealed that HCR-MI and LCR-MI decreased cardiomyocyte shortening (39%, and 34% reduction, respectively, both P < 0.01), lowered Ca2+ transient amplitude (37%, P < 0.01, and 20% reduction, respectively), and reduced sarcoplasmic reticulum (SR) Ca2+ content (both; 20%, P < 0.01) compared with respective sham. Diastolic Ca2+ cycling was impaired in HCR-MI and LCR-MI evidenced by prolonged time to 50% Ca2+ decay that was partly explained by the 47% (P <0.01) and 44% (P < 0.05) decrease in SR Ca2+-ATPase Ca2+ removal, respectively. SR Ca2+ leak increased by 177% in HCR-MI (P < 0.01) and 67% in LCR-MI (P < 0.01), which was abolished by inhibition of Ca2+/calmodulin-dependent protein kinase II. This study demonstrates that the effect of MI in HCR rats was similar or even more pronounced on cardiac- and cardiomyocyte contractile function, as well as on Ca2+ handling properties compared with observations in LCR. Thus our data do not support a cardio-protective effect of higher inborn aerobic capacity