Computer-aided development of a real-time program

The refinement calculus is a well-established theory for formal development of imperative program code and is supported by a number of automated tools. Via a detailed case study, this article shows how refinement theory and tool support can be extended for a program with real-time constraints. The approach adapts a timed variant of the refinement calculus and makes corresponding enhancements to a theorem-prover based refinement tool.     

Data and process requirements for product recall coordination

When an organisation becomes aware that one of its products may pose a safety risk to customers, it must take appropriate action as soon as possible or it can be held liable. The ability to automatically trace potentially dangerous goods through the supply chain would thus help organisations fulfil their legal obligations in a timely and effective manner. Furthermore, product recall legislation requires manufacturers to separately notify various government agencies, the health department and the public about recall incidents. This duplication of effort and paperwork can introduce errors and data inconsistencies. In this paper, we examine traceability and notification requirements in the product recall domain from two perspectives: the activities carried out during the manufacturing and recall processes and the data collected during the enactment of these processes. We then propose a workflow-based coordination framework to support these data and process requirements.     

The Variety of Variables in Computer-Aided Real-Time Programming

The refinement calculus is a well-established theory for translating specifications to program code. Recent research has extended the calculus to handle real-time requirements and we have developed an interactive support tool based on these extensions. Via a case study, this paper shows how the tool helps the programmer by supporting the many forms of variables used in the theory. These include simple state variables as in the untimed calculus, timed-trace variables that model the evolution of properties over time, and auxiliary variables that exist to support formal reasoning only.     

Structural and functional properties of full-length and truncated human proapolipoprotein AI expressed in escherichia coli

Utilizing the Escherichia coli/pGex vector expression system incorporating a thrombin cleavage site, full-length (residues -6-243) and truncated forms of proapolipoprotein AI (proapoAI), terminating at amino acid residues 222, 210, 150, and 135, were purified to levels of at least 5 mg/L, after thrombin cleavage. Assessed by circular dichroism, the helical contents of L-alpha-dimyristoylphosphatidylcholine-associated forms of human plasma-derived apolipoprotein AI (apoAI) and recombinant proapoAI were comparable, being 69% and 65%, respectively. Circular dichroism measurements of the lipid-associated complexes of the truncated forms showed that between the sequence of residues 150-222 no additional helicity was gained until the carboxyl-terminal sequence was present in the molecule, indicating that the carboxyl terminus of the protein is required for the formation of helix within this central region. While tryptophan residues were more than 86% accessible, as assessed by iodide quenching, in the two truncated forms, proapoAI-6-135 and proapoAI-6-150, for both free and complexed protein, this figure fell to about 50% for full-length recombinant proapoAI, further indicating the influence of the carboxyl terminus on the structure of the whole protein. While cross-linking human plasma apoAI in solution with dithiobis-(succinimidyl propionate) revealed high molecular weight oligomers by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, recombinant proapoAI did not strongly form complexes larger than trimers. None of the truncated proapoAI molecules formed oligomers larger than trimers. The shortest form, proapoAI-6-135, only dimerized. Initial results from lecithin:cholesterol acyltransferase activation (apoAI peptide concentration 0.2 microM) indicated that truncation of the 21 carboxy-terminal amino acids resulted in a drop of approximately 53% in activation and 33 residues a drop of 67% relative to the full-length protein. Overall these results indicate the important influence of the carboxyl terminus on the structure of apoAI.     

Efflux of intracellular versus plasma membrane cholesterol in HepG2 cells: different availability and regulation by apolipoprotein A-I

We have compared the efflux of cholesterol from different cellular pools of human hepatoma cells HepG2 using intact cells or isolated membrane fractions. To label different pools, cells were incubated with either unesterified [14C]cholesterol that had been incorporated into high density lipoproteins ([14C]FC-HDL), low density lipoproteins ([14C]FC-LDL), or phosphatidylcholine liposomes ([14C]FC-PC), or with [14C]acetate. Cell fractionation revealed that labeling of cells with [14C]FC-PC resulted in the incorporation of [14C]cholesterol almost exclusively into the plasma membrane (PM), while incubation with [14C]FC-HDL resulted in the majority of [14C]cholesterol incorporation into the PM, but with a smaller component associated with lysosomes. Labeling with [14C]FC-LDL or [14C]acetate led to an accumulation of [14C]cholesterol predominantly in lysosomes or the endoplasmic reticulum (ER), respectively. When the kinetics of [14C]cholesterol efflux was analyzed after pulse-labeling of different cellular pools, half-times of cholesterol efflux from lysosomes and ER were significantly longer than that from PM. In another set of experiments, when both labeling and efflux times varied, efflux of [14C]cholesterol from the PM to human serum after 1.5 h pulse and chase incubations was double that from lysosomes and 8-fold that from ER. Extension of the incubation times from 1.5 to 3 h diminished the difference in cholesterol efflux from different membranes. Further incubation to 6 h almost abolished the different responses. Cell-free preparations of membranes, obtained from cells labeled with [14C]cholesterol, showed no differences in cholesterol efflux. No differences in the distribution of [14C]cholesterol released into serum among lipoprotein subfractions was observed. Pretreatment of the serum with Fab fragments of polyclonal rabbit anti-human apolipoprotein A-I antibodies reduced its ability to promote efflux of cholesterol from the ER by 77%, but had no effect on cholesterol efflux from the PM. Fab fragments of non-immune IgG had no effect on the efflux of both ER and PM cholesterol. We conclude that the availability of cellular cholesterol for efflux from HepG2 cells is strongly influenced by its subcellular location, and is regulated by apolipoprotein A-I.     

Antibodies against high-density lipoprotein binding proteins enhance high-density lipoprotein uptake but do not affect cholesterol efflux from rat hepatoma cells

High-density lipoprotein plays a key role in the reverse cholesterol transport pathway as well as in the delivery of cholesterol to the liver and steroidogenic tissues. Metabolism of high-density lipoprotein is determined by one of its apolipoproteins, apolipoprotein A-I; however, the identity and function of cellular protein which binds high-density lipoprotein remains unclear. The effect of antibodies against rat high-density lipoprotein binding proteins, HB1 and HB2, on high-density lipoprotein metabolism in a rat hepatoma cell line were studied. Cells were preincubated with the antibodies and 125I-labeled high-density lipoprotein binding and uptake as well as cholesterol biosynthesis and cholesterol efflux to human plasma or isolated high-density lipoprotein were studied. Both antibodies reacted specifically with HB1 and HB2 on the ligand and Western blots, but their binding was not blocked by high-density lipoprotein. Both antibodies inhibited 125I-labeled high-density lipoprotein binding to cells by 20-40%, but stimulated 125I-labeled high-density lipoprotein uptake by up to 2.5-fold. The antibodies had no effect on cholesterol efflux or on cholesterol synthesis. It is concluded that high-density lipoprotein binding proteins, HB1 and HB2, may be involved in high-density lipoprotein uptake in the liver rather than in mediating cholesterol efflux.     

LibVM: an architecture for shared library sandboxing

Many software applications extend their functionality by dynamically loading libraries into their allocated address space. However, shared libraries are also often of unknown provenance and quality and may contain accidental bugs or, in some cases, deliberately malicious code. Most sandboxing techniques that address these issues require recompilation of the libraries using custom tool chains, require significant modifications to the libraries, do not retain the benefits of single address space programming, do not completely isolate guest code, or incur substantial performance overheads. In this paper, we present LibVM, a sandboxing architecture for isolating libraries within a host application without requiring any modifications to the shared libraries themselves, while still retaining the benefits of a single address space and also introducing a system call inter‐positioning layer that allows complete arbitration over a shared library's functionality. We show how to utilize contemporary hardware‐virtualization support towards this end with reasonable performance overheads, and, in the absence of such hardware support, our model can also be implemented using a software‐based mechanism. We ensure that our implementation conforms as closely as possible to existing shared library manipulation functions, minimizing the amount of effort needed to apply such isolation to existing programs. Our experimental results show that it is easy to gain immediate benefits in scenarios where the goal is to guard the host application against unintentional programming errors when using shared libraries, as well as in more complex scenarios, where a shared library is suspected of being actively hostile. In both cases, no changes are required to the shared libraries themselves. Copyright © 2014 John Wiley & Sons, Ltd.     

Real-Time Schedulability Tests for Preemptive Multitasking

When developing multitasking real-time systems, schedulability tests are used to formally prove that a given task set will meet its deadlines. A wide range of such tests have appeared in the literature. This tutorial acts as a guide to the major tests available for preemptive multitasking applications.     

Fundamentals of distributed system observation

It's difficult to determine event order in distributed systems because of the observability problem. The author discusses this problem and evaluates different strategies for determining arrival order. The author analyzed four time stamping methods to determine their effectiveness in contending with observability problems. Although he focuses on distributed systems, the concepts also apply to any system exhibiting concurrency-the appearance of two or more events occurring simultaneously-including multiprocessor machines and uniprocessor multitasking. Events in this context may be the execution of single machine instructions or entire procedures; the level of granularity is unimportant. To define event order, the author uses the idea of causality-the ability of one event to affect another-because it allows us to reason independent of any particular time frame