Lean requirements traceability automation enabled by model-driven engineering.

BACKGROUND: The benefits of requirements traceability, such as improvements in software product and process quality, early testing, and software maintenance, are widely described in the literature. Requirements traceability is a critical, widely accepted practice. However, very often it is not applied for fear of the additional costs associated with manual efforts or the use of additional tools. METHODS: This article presents a "low-cost" mechanism for automating requirements traceability based on the model-driven paradigm and formalized by a metamodel for the creation and monitoring of traces and an integration process for traceability management. This approach can also be useful for information fusion in industry insofar that it facilitates data traceability. RESULTS: This article extends an existing model-driven development methodology to incorporate traceability as part of its development tool. The tool has been used successfully by several companies in real software development projects, helping developers to manage ongoing changes in functional requirements. One of those projects is cited as an example in the paper. The authors' current work leads them to conclude that a model-driven engineering approach, traditionally used only for the automatic generation of code in a software development process, can also be used to successfully automate and integrate traceability management without additional costs. The systematic evaluation of traceability management in industrial projects constitutes a promising area for future work.

Opposing Roles of S1P3 Receptors in Myocardial Function.

Sphingosine-1-phosphate (S1P) is a lysophospholipid mediator with diverse biological function mediated by S1P1-5 receptors. Whereas S1P was shown to protect the heart against ischemia/reperfusion (I/R) injury, other studies highlighted its vasoconstrictor effects. We aimed to separate the beneficial and potentially deleterious cardiac effects of S1P during I/R and identify the signaling pathways involved. Wild type (WT), S1P2-KO and S1P3-KO Langendorff-perfused murine hearts were exposed to intravascular S1P, I/R, or both. S1P induced a 45% decrease of coronary flow (CF) in WT-hearts. The presence of S1P-chaperon albumin did not modify this effect. CF reduction diminished in S1P3-KO but not in S1P2-KO hearts, indicating that in our model S1P3 mediates coronary vasoconstriction. In I/R experiments, S1P3 deficiency had no influence on postischemic CF but diminished functional recovery and increased infarct size, indicating a cardioprotective effect of S1P3. Preischemic S1P exposure resulted in a substantial reduction of postischemic CF and cardiac performance and increased the infarcted area. Although S1P3 deficiency increased postischemic CF, this failed to improve cardiac performance. These results indicate a dual role of S1P3 involving a direct protective action on the myocardium and a cardiosuppressive effect due to coronary vasoconstriction. In acute coronary syndrome when S1P may be released abundantly, intravascular and myocardial S1P production might have competing influences on myocardial function via activation of S1P3 receptors.

Increased Frequency of CD49b/LAG-3(+) Type 1 Regulatory T Cells in HIV-Infected Individuals.

In HIV-1 infection elevated serum levels of interferon-α (IFN-α) and interleukin-10 (IL-10) are associated with immune hyperactivation and disease progression. Recently, coexpression of CD49b and LAG-3 was shown to identify Type 1 regulatory T (Tr1) cells, which secrete large amounts of the immunosuppressive cytokine IL-10. We analyzed the frequency of CD49b/LAG-3(+) Tr1 cells in the peripheral blood of HIV-infected individuals at different stages of the disease. We found increased levels of CD49b/LAG-3(+) Tr1 cells as well as IL-10 in HIV patients. With disease progression, Tr1 cells negatively correlate with frequency of plasmacytoid dendritic cells (pDCs), the main producers of IFN-α. However, elevated IL-10 levels could not be ascribed to the CD49b/LAG-3(+)Tr1 cell population. Moreover, we showed in vitro that IFN-α leads to an upregulation of IL-10 as well as CD49b/LAG-3(+) Tr1 cell counts in healthy controls, recapitulating effects observed in vivo during HIV infection. Our results suggest that overexpression of IFN-α during HIV infection drives the generation of CD49b/LAG-3(+) Tr1 cells and the immunosuppressive cytokine IL-10. Furthermore, it remains unclear whether elevated IL-10 levels are beneficial or detrimental in regard to disease progression.

Longitudinal analysis of distribution and function of plasmacytoid dendritic cells in peripheral blood and gut mucosa of HIV infected patients.

Aberrant activation of plasmacytoid dendritic cells (pDCs) with excessive production of interferon alpha (IFNα) represents one of the hallmarks of immune activation during chronic phase of human immunodeficiency virus (HIV) infection. A number of studies have shown that disruption of mucosal integrity in the gut is a cause of persistent immune activation. However, little is known about the role that pDCs play in this process, and our current understanding comes from the simian immunodeficiency virus macaque model. Thus, in the present study we sought to investigate the frequency and function of pDCs in peripheral blood and gut samples from HIV-infected individuals before and 6 months after initiation of antiretroviral therapy (ART). We show that circulating pDCs were depleted in ART-naive HIV+ patients, and upregulated the gut-homing receptor CD103 compared with uninfected controls. By converse, pDCs accumulated in the terminal ileum of ART-naive HIV individuals compared with controls. Baseline levels of IFNα production and markers of immune activation in gut samples of ART-naive HIV subjects were elevated. All these parameters declined after 6 months of ART. Our results suggest that in chronic HIV infection, pDCs migrate from peripheral blood to the gut-associated lymphatic tissue, where they may contribute to immune activation.