27 research outputs found
Enabling Model Testing of Cyber-Physical Systems
Applying traditional testing techniques to Cyber-Physical Systems (CPS) is challenging due to the deep intertwining of software and hardware, and the complex, continuous interactions between the system and its environment. To alleviate these challenges we propose to conduct testing at early stages and over executable models of the system and its environment. Model testing of CPSs is however not without difficulties. The complexity and heterogeneity of CPSs renders necessary the combination of different modeling formalisms to build faithful models of their different components. The execution of CPS models thus requires an execution framework supporting the co-simulation of different types of models, including models of the software (e.g., SysML), hardware (e.g., SysML or Simulink), and physical environment (e.g., Simulink). Furthermore, to enable testing in realistic conditions, the co-simulation process must be (1) fast, so that thousands of simulations can be conducted in practical time, (2) controllable, to precisely emulate the expected runtime behavior of the system and, (3) observable, by producing simulation data enabling the detection of failures. To tackle these challenges, we propose a SysML-based modeling methodology for model testing of CPSs, and an efficient SysML-Simulink co-simulation framework. Our approach was validated on a case study from the satellite domain
N-Acetylcysteine and Allopurinol Synergistically Enhance Cardiac Adiponectin Content and Reduce Myocardial Reperfusion Injury in Diabetic Rats
Background: Hyperglycemia-induced oxidative stress plays a central role in the development of diabetic myocardial complications. Adiponectin (APN), an adipokine with anti-diabetic and anti-ischemic effects, is decreased in diabetes. It is unknown whether or not antioxidant treatment with N-acetylcysteine (NAC) and/or allopurinol (ALP) can attenuate APN deficiency and myocardial ischemia reperfusion (MI/R) injury in the early stage of diabetes. Methodology/Principal Findings: Control or streptozotocin (STZ)-induced diabetic rats were either untreated (C, D) or treated with NAC (1.5 g/kg/day) or ALP (100 mg/kg/day) or their combination for four weeks starting one week after STZ injection. Plasma and cardiac biochemical parameters were measured after the completion of treatment, and the rats were subjected to MI/R by occluding the left anterior descending artery for 30 min followed by 2 h reperfusion. Plasma and cardiac APN levels were decreased in diabetic rats accompanied by decreased cardiac APN receptor 2 (AdipoR2), reduced phosphorylation of Akt, signal transducer and activator of transcription 3 (STAT3) and endothelial nitric oxide synthase (eNOS) but increased IL-6 and TNF-α (all P<0.05 vs. C). NAC but not ALP increased cardiac APN concentrations and AdipoR2 expression in diabetic rats. ALP enhanced the effects of NAC in restoring cardiac AdipoR2 and phosphorylation of Akt, STAT3 and eNOS in diabetic rats. Further, NAC and ALP, respectively, decreased postischemic myocardial infarct size and creatinine kinase-MB (CK-MB) release in diabetic rats, while their combination conferred synergistic protective effects. In addition, exposure of cultured rat cardiomyocytes to high glucose resulted in significant reduction of cardiomyocyte APN concentration and AdipoR2 protein expression. APN supplementation restored high glucose induced AdipoR2 reduction in cardiomyocytes. Conclusions/Significance: NAC and ALP synergistically restore myocardial APN and AdipoR2 mediated eNOS activation. This may represent the mechanism through which NAC and ALP combination greatly reduces MI/R injury in early diabetic rats. © 2011 Wang et al.published_or_final_versio
Adult rat liver cells transdifferentiated with lentiviral IPF1 vectors reverse diabetes in mice: an ex vivo gene therapy approach
Therapeutic Potential of HDL in Cardioprotection and Tissue Repair
Epidemiological studies support a strong association between high-density lipoprotein (HDL) cholesterol levels and heart failure incidence. Experimental evidence from different angles supports the view that low HDL is unlikely an innocent bystander in the development of heart failure. HDL exerts direct cardioprotective effects, which are mediated via its interactions with the myocardium and more specifically with cardiomyocytes. HDL may improve cardiac function in several ways. Firstly, HDL may protect the heart against ischaemia/reperfusion injury resulting in a reduction of infarct size and thus in myocardial salvage. Secondly, HDL can improve cardiac function in the absence of ischaemic heart disease as illustrated by beneficial effects conferred by these lipoproteins in diabetic cardiomyopathy. Thirdly, HDL may improve cardiac function by reducing infarct expansion and by attenuating ventricular remodelling post-myocardial infarction. These different mechanisms are substantiated by in vitro, ex vivo, and in vivo intervention studies that applied treatment with native HDL, treatment with reconstituted HDL, or human apo A-I gene transfer. The effect of human apo A-I gene transfer on infarct expansion and ventricular remodelling post-myocardial infarction illustrates the beneficial effects of HDL on tissue repair. The role of HDL in tissue repair is further underpinned by the potent effects of these lipoproteins on endothelial progenitor cell number, function, and incorporation, which may in particular be relevant under conditions of high endothelial cell turnover. Furthermore, topical HDL therapy enhances cutaneous wound healing in different models. In conclusion, the development of HDL-targeted interventions in these strategically chosen therapeutic areas is supported by a strong clinical rationale and significant preclinical data.status: publishe
Verification of Co-simulation Algorithms Subject to Algebraic Loops and Adaptive Steps
Simulation-based analyses of cyber-physical systems are increasingly vital. Co-simulation is one such technique that enables the coupling of specialized simulation tools through an orchestration algorithm. The orchestrator dictates how each simulation tool should simulate its corresponding subsystem. Obtaining correct simulation results requires an implementation-aware orchestration algorithm tailored to the specific scenario, without the orchestrator knowing each simulation tool's implementation. Such an algorithm should stabilize algebraic loops, perform time step negotiation, and adhere to each simulation tool's implementation. This paper describes an approach and implementation to prove that a given orchestration algorithm respects all contracts related to the simulation units' implementation. The approach has been applied to an industrial case study and other complex scenarios. The tool and results are available online
Verification and synthesis of co-simulation algorithms subject to algebraic loops and adaptive steps
Simulation-based analyses are becoming increasingly vital for the development of cyber-physical systems. Co-simulation is one such technique, enabling the coupling of specialized simulation tools through an orchestration algorithm. The orchestrator describes how to coordinate the simulation of multiple simulation tools. The simulation result depends on the orchestration algorithm that must stabilize algebraic loops, choose the simulation resolution, and adhere to each simulation tool's implementation. This paper describes how to verify that an orchestration algorithm respects all contracts related to the simulation tool's implementation and how to synthesize such tailored orchestration algorithms. The approaches work for complex and adaptive co-simulation scenarios and have been applied to several real-world case studies
In Vivo Imaging of Retinal Oxidative Stress Using a Reactive Oxygen Species–Activated Fluorescent ProbeImaging of Retinal Oxidative Stress Using H-800CW
PurposeIn vivo methods for detecting oxidative stress in the eye would improve screening and monitoring of the leading causes of blindness: diabetic retinopathy, glaucoma, and age-related macular degeneration.MethodsTo develop an in vivo biomarker for oxidative stress in the eye, we tested the efficacy of a reactive oxygen species (ROS)-activated, near-infrared hydrocyanine-800CW (H-800CW) fluorescent probe in light-induced retinal degeneration (LIRD) mouse models. After intravitreal delivery in LIRD rats, fluorescent microscopy was used to confirm that the oxidized H-800CW appeared in the same retinal layers as an established ROS marker (dichlorofluorescein).ResultsDose-response curves of increasing concentrations of intravenously injected H-800CW demonstrated linear increases in both intensity and total area of fundus hyperfluorescence in LIRD mice, as detected by scanning laser ophthalmoscopy. Fundus hyperfluorescence also correlated with the duration of light damage and functional deficits in vision after LIRD. In LIRD rats with intravitreal injections of H-800CW, fluorescent labeling was localized to photoreceptor inner segments, similar to dichlorofluorescein.ConclusionsHydrocyanine-800CW detects retinal ROS in vivo and shows potential as a novel biomarker for ROS levels in ophthalmic diseases
In Vivo Imaging of Retinal Oxidative Stress Using a Reactive Oxygen Species–Activated Fluorescent Probe
PURPOSE: In vivo methods for detecting oxidative stress in the eye would improve screening and monitoring of the leading causes of blindness: diabetic retinopathy, glaucoma, and age-related macular degeneration. METHODS: To develop an in vivo biomarker for oxidative stress in the eye, we tested the efficacy of a reactive oxygen species (ROS)–activated, near-infrared hydrocyanine-800CW (H-800CW) fluorescent probe in light-induced retinal degeneration (LIRD) mouse models. After intravitreal delivery in LIRD rats, fluorescent microscopy was used to confirm that the oxidized H-800CW appeared in the same retinal layers as an established ROS marker (dichlorofluorescein). RESULTS: Dose–response curves of increasing concentrations of intravenously injected H-800CW demonstrated linear increases in both intensity and total area of fundus hyperfluorescence in LIRD mice, as detected by scanning laser ophthalmoscopy. Fundus hyperfluorescence also correlated with the duration of light damage and functional deficits in vision after LIRD. In LIRD rats with intravitreal injections of H-800CW, fluorescent labeling was localized to photoreceptor inner segments, similar to dichlorofluorescein. CONCLUSIONS: Hydrocyanine-800CW detects retinal ROS in vivo and shows potential as a novel biomarker for ROS levels in ophthalmic diseases