It is difficult to determine the cost effectiveness of program analysis tools because we cannot evaluate them in the same environment where we will be using the tool. Tool evaluations are usually run on mature, stable code after it has passed developer testing. However, program analysis tools are usually run on unstable code, and some tools are meant to run right after compilation. Naturally, the results of the evaluation are not comparable to the true contribution of the tool. This leaves program analysis tool evaluations being very subjective and usually dependent on the evaluators intuition. While we could not solve this problem, we suggest techniques to make the evaluations more objective. We started by making enforcement-based customizations of the tool to be evaluated. When we evaluate a tool, we used a comparative evaluation technique to make the ROI analysis more objective. We also show how to use coverage models to select several tools when they each find different kinds of issues. Finally, we suggest that the tool vendors include features that assist us with a continuous evaluation of the tool as it runs in our software process.
CHM is commonly used in Taiwan for the treatment of menopausal symptoms. The efficacy and safety of CHM drugs used for the management of menopausal symptoms require further study.
BackgroundAdrenomedullin (ADM) exerts its biological functions through the receptor-mediated enzymatic mechanisms that involve protein kinase A (PKA), or neuronal nitric oxide synthase (nNOS). We previously demonstrated that the receptor-mediated cAMP/PKA pathway involves in ADM-enhanced baroreceptor reflex (BRR) response. It remains unclear whether ADM may enhance BRR response via activation of nNOS-dependent mechanism in the nucleus tractus solitarii (NTS).MethodsIntravenous injection of phenylephrine was administered to evoke the BRR before and at 10, 30, and 60 min after microinjection of the test agents into NTS of Sprague-Dawley rats. Western blotting analysis was used to measure the level and phosphorylation of proteins that involved in BRR-enhancing effects of ADM (0.2 pmol) in NTS. The colocalization of PKA and nNOS was examined by immunohistochemical staining and observed with a laser confocal microscope.ResultsWe found that ADM-induced enhancement of BRR response was blunted by microinjection of NPLA or Rp-8-Br-cGMP, a selective inhibitor of nNOS or protein kinase G (PKG) respectively, into NTS. Western blot analysis further revealed that ADM induced an increase in the protein level of PKG-I which could be attenuated by co-microinjection with the ADM receptor antagonist ADM22-52 or NPLA. Moreover, we observed an increase in phosphorylation at Ser1416 of nNOS at 10, 30, and 60 min after intra-NTS administration of ADM. As such, nNOS/PKG signaling may also account for the enhancing effect of ADM on BRR response. Interestingly, biochemical evidence further showed that ADM-induced increase of nNOS phosphorylation was prevented by co-microinjection with Rp-8-Br-cAMP, a PKA inhibitor. The possibility of PKA-dependent nNOS activation was substantiated by immunohistochemical demonstration of co-localization of PKA and nNOS in putative NTS neurons.ConclusionsThe novel finding of this study is that the signal transduction cascade that underlies the enhancement of BRR response by ADM in NTS is composed sequentially of cAMP/PKA and nNOS/PKG pathways.
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