A Colored Petri Net Executable Modeling Approach for a Data Flow Well-Structured BPMN Process Model

BPMN process models have been widely used in software designs. The BPMN process models are characterized by a static graph-oriented modeling language and a lack of analytical capabilities as well as dynamic behavior verification capabilities, which not only leads to inconsistencies in the semantics of the BPMN process models, but also leads to a lack of model error detection capabilities for the BPMN process models, which also hinders the correctness verification and error correction efforts of the models. In this study, we propose an executable modeling approach for CPN-based data flow well-structured BPMN (dw-BPMN) process models, and consider both control-flow and data-flow perspectives. First, we present a formal definition of the dw-BPMN process model, which is formally mapped into a CPN executable model in three steps: splitting, mapping and combining. Then, we discuss four types of data flow errors that can occur in the model: missing, lost, redundant, and inconsistent data error. To detect these four data flow errors, we propose a detection method based on the execution results of the CPN model. Subsequently, we propose correction strategies for these four data flow errors. Finally, a dw-BPMN process model of a robot's temperature detection system for COVID-19 prevention and control in a kindergarten was used as an example to verify the validity of the method.

The Dysregulation of the Renin-Angiotensin System in COVID-19 Studied by Serum Proteomics: Angiotensinogen Increases with Disease Severity.

(1) Background: ACE and CPN serum activity correlated with disease severity in an earlier study of 45 hospitalized COVID-19 patients. The serum protein profile was investigated in the same cohort here to shed more light on the involvement of the renin-angiotensin system (RAS). (2) Methods: High-definition mass spectrometry-based protein expression analysis was performed, followed by multivariate statistical and network analyses. (3) Results: The protein profiles of hospitalized patients (HoP) differed significantly from those of convalescent and healthy probands. Surprisingly, HoP samples separated into six groups according to their protein profiles: group (G) 1 represented the youngest and the least afflicted patients, and G6 the oldest and critically ill patients. At least two major pathophysiological schemes were indicated based on differing involvement of the kallikrein-kinin system (KKS), the RAS and complement activation. The serum angiotensinogen concentration increased with disease severity. (4) Conclusions: The important role of the RAS in the response to COVID-19 infection was substantiated, but other pathways such as the KKS, plasminogen activation and complement activation influence the systemic response to the infection.

High Angiotensin-Converting Enzyme and Low Carboxypeptidase N Serum Activity Correlate with Disease Severity in COVID-19 Patients.

(1) Background: Angiotensin-converting enzyme 2 (ACE2) is a functional receptor of SARS-CoV-2 and counter-balances ACE in the renin-angiotensin system (RAS). An imbalance of the RAS could be associated with severe COVID-19 progression. (2) Methods: Activities of serum proteases angiotensin-converting enzyme (ACE) and carboxypeptidase N (CPN) for 45 hospitalized and 26 convalescent COVID-19 patients were investigated vs. healthy controls using labeled bradykinin (DBK) degradation with and without inhibition by captopril as a read-out. Data were correlated to clinical parameters. (3) Results: DBK degradation and CPN activity were significantly reduced gender-independently in COVID-19 and returned to normal during convalescence. ACE activity was over-active in severe disease progression; product DBK1-5 was significantly increased in critically ill patients and strongly correlated with clinical heart and liver parameters. ACE inhibitors seemed to be protective, as DBK1-5 levels were normal in moderately ill patients in contrast to critically ill patients. (4) Conclusions: CPN and ACE serum activity correlated with disease severity. The RAS is affected in COVID-19, and ACE could be a therapeutic target. Further proof from dedicated studies is needed.