Acute pancreatitis(AP)is a potentially life-threatening inflammatory disease of the pancreas,with clinical management determined by the severity of the disease.Diagnosis,severity prediction,and prognosis assessment of...Acute pancreatitis(AP)is a potentially life-threatening inflammatory disease of the pancreas,with clinical management determined by the severity of the disease.Diagnosis,severity prediction,and prognosis assessment of AP typically involve the use of imaging technologies,such as computed tomography,magnetic resonance imaging,and ultrasound,and scoring systems,including Ranson,Acute Physiology and Chronic Health Evaluation II,and Bedside Index for Severity in AP scores.Computed tomography is considered the gold standard imaging modality for AP due to its high sensitivity and specificity,while magnetic resonance imaging and ultrasound can provide additional information on biliary obstruction and vascular complications.Scoring systems utilize clinical and laboratory parameters to classify AP patients into mild,moderate,or severe categories,guiding treatment decisions,such as intensive care unit admission,early enteral feeding,and antibiotic use.Despite the central role of imaging technologies and scoring systems in AP management,these methods have limitations in terms of accuracy,reproducibility,practicality and economics.Recent advancements of artificial intelligence(AI)provide new opportunities to enhance their performance by analyzing vast amounts of clinical and imaging data.AI algorithms can analyze large amounts of clinical and imaging data,identify scoring system patterns,and predict the clinical course of disease.AI-based models have shown promising results in predicting the severity and mortality of AP,but further validation and standardization are required before widespread clinical application.In addition,understanding the correlation between these three technologies will aid in developing new methods that can accurately,sensitively,and specifically be used in the diagnosis,severity prediction,and prognosis assessment of AP through complementary advantages.展开更多
BACKGROUND Oxaliplatin(Oxa)is the first-line chemotherapy drug for colorectal cancer(CRC),and Oxa resistance is crucial for treatment failure.Prostaglandin F_(2α)synthase(PGF 2α)(PGFS),an enzyme that catalyzes the p...BACKGROUND Oxaliplatin(Oxa)is the first-line chemotherapy drug for colorectal cancer(CRC),and Oxa resistance is crucial for treatment failure.Prostaglandin F_(2α)synthase(PGF 2α)(PGFS),an enzyme that catalyzes the production of PGF_(2α),is involved in the proliferation and growth of a variety of tumors.However,the role of PGFS in Oxa resistance in CRC remains unclear.AIM To explore the role and related mechanisms of PGFS in mediating Oxa resistance in CRC.METHODS The PGFS expression level was examined in 37 pairs of CRC tissues and paracancerous tissues at both the mRNA and protein levels.Overexpression or knockdown of PGFS was performed in CRC cell lines with acquired Oxa resistance(HCT116-OxR and HCT8-OxR)and their parental cell lines(HCT116 and HCT8)to assess its influence on cell proliferation,chemoresistance,apoptosis,and DNA damage.For determination of the underlying mechanisms,CRC cells were examined for platinum-DNA adducts and reactive oxygen species(ROS)levels in the presence of a PGFS inhibitor or its products.RESULTS Both the protein and mRNA levels of PGFS were increased in the 37 examined CRC tissues compared to the adjacent normal tissues.Oxa induced PGFS expression in the parental HCT116 and HCT8 cells in a dosedependent manner.Furthermore,overexpression of PGFS in parental CRC cells significantly attenuated Oxainduced proliferative suppression,apoptosis,and DNA damage.In contrast,knockdown of PGFS in Oxa-resistant HCT116 and HCT8 cells(HCT116-OxR and HCT8-OxR)accentuated the effect of Oxa treatment in vitro and in vivo.The addition of the PGFS inhibitor indomethacin enhanced the cytotoxicity caused by Oxa.Treatment with the PGFS-catalyzed product PGF_(2α)reversed the effect of PGFS knockdown on Oxa sensitivity.Interestingly,PGFS inhibited the formation of platinum-DNA adducts in a PGF_(2α)-independent manner.PGF_(2α)exerts its protective effect against DNA damage by reducing ROS levels.CONCLUSION PGFS promotes resistance to Oxa in CRC via both PGF_(2α)-dependent and PGF_(2α)-independent mechanisms.展开更多
BACKGROUND Artificial intelligence in colonoscopy is an emerging field,and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas.Several deep learning-bas...BACKGROUND Artificial intelligence in colonoscopy is an emerging field,and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas.Several deep learning-based computer-assisted detection(CADe)techniques were established from small single-center datasets,and unrepresentative learning materials might confine their application and generalization in wide practice.Although CADes have been reported to identify polyps in colonoscopic images and videos in real time,their diagnostic performance deserves to be further validated in clinical practice.AIM To train and test a CADe based on multicenter high-quality images of polyps and preliminarily validate it in clinical colonoscopies.METHODS With high-quality screening and labeling from 55 qualified colonoscopists,a dataset consisting of over 71000 images from 20 centers was used to train and test a deep learning-based CADe.In addition,the real-time diagnostic performance of CADe was tested frame by frame in 47 unaltered full-ranged videos that contained 86 histologically confirmed polyps.Finally,we conducted a selfcontrolled observational study to validate the diagnostic performance of CADe in real-world colonoscopy with the main outcome measure of polyps per colonoscopy in Changhai Hospital.RESULTS The CADe was able to identify polyps in the test dataset with 95.0%sensitivity and 99.1%specificity.For colonoscopy videos,all 86 polyps were detected with 92.2%sensitivity and 93.6%specificity in frame-by-frame analysis.In the prospective validation,the sensitivity of CAD in identifying polyps was 98.4%(185/188).Folds,reflections of light and fecal fluid were the main causes of false positives in both the test dataset and clinical colonoscopies.Colonoscopists can detect more polyps(0.90 vs 0.82,P<0.001)and adenomas(0.32 vs 0.30,P=0.045)with the aid of CADe,particularly polyps<5 mm and flat polyps(0.65 vs 0.57,P<0.001;0.74 vs 0.67,P=0.001,respectively).However,high efficacy is not realized in colonoscopies with inadequate bowel preparation and withdrawal time(P=0.32;P=0.16,respectively).CONCLUSION CADe is feasible in the clinical setting and might help endoscopists detect more polyps and adenomas,and further confirmation is warranted.展开更多
BACKGROUND Sorafenib is the first-line treatment for patients with advanced hepatocellular carcinoma(HCC).Y-box binding protein 1(YB-1)is closely correlated with tumors and drug resistance.However,the relationship bet...BACKGROUND Sorafenib is the first-line treatment for patients with advanced hepatocellular carcinoma(HCC).Y-box binding protein 1(YB-1)is closely correlated with tumors and drug resistance.However,the relationship between YB-1 and sorafenib resistance and the underlying mechanism in HCC remain unknown.AIM To explore the role and related mechanisms of YB-1 in mediating sorafenib resistance in HCC.METHODS The protein expression levels of YB-1 were assessed in human HCC tissues and adjacent nontumor tissues.Next,we constructed YB-1 overexpression and knockdown hepatocarcinoma cell lines with lentiviruses and stimulated these cell lines with different concentrations of sorafenib.Then,we detected the proliferation and apoptosis in these cells by terminal deoxynucleotidyl transferase dUTP nick end labeling,flow cytometry and Western blotting assays.We also constructed a xenograft tumor model to explore the effect of YB-1 on the efficacy of sorafenib in vivo.Moreover,we studied and verified the specific molecular mechanism of YB-1 mediating sorafenib resistance in hepatoma cells by digital gene expression sequencing(DGE-seq).RESULTS YB-1 protein levels were found to be higher in HCC tissues than in corresponding nontumor tissues.YB-1 suppressed the effect of sorafenib on cell proliferation and apoptosis.Consistently,the efficacy of sorafenib in vivo was enhanced after YB-1 was knocked down.Furthermore,KEGG pathway enrichment analysis of DGEseq demonstrated that the phosphoinositide-3-kinase(PI3K)/protein kinase B(Akt)signaling pathway was essential for the sorafenib resistance induced by YB-1.Subsequently,YB-1 interacted with two key proteins of the PI3K/Akt signaling pathway(Akt1 and PIK3R1)as shown by searching the BioGRID and HitPredict websites.Finally,YB-1 suppressed the inactivation of the PI3K/Akt signaling pathway induced by sorafenib,and the blockade of the PI3K/Akt signaling pathway by LY294002 mitigated YB-1-induced sorafenib resistance.CONCLUSION Overall,we concluded that YB-1 augments sorafenib resistance through the PI3K/Akt signaling pathway in HCC and suggest that YB-1 is a key drug resistance-related gene,which is of great significance for the application of sorafenib in advanced-stage HCC.展开更多
内镜逆行胰胆管造影术(endoscopic retrograde chola ngiopancreatography,ERCP)是一项有着潜在治疗风险的内镜操作.随着内镜技术的不断发展,现如今ERCP的开展率越来越高,这也意味着出现ERCP相关并发症的概率也在不断上升.但是目前,相...内镜逆行胰胆管造影术(endoscopic retrograde chola ngiopancreatography,ERCP)是一项有着潜在治疗风险的内镜操作.随着内镜技术的不断发展,现如今ERCP的开展率越来越高,这也意味着出现ERCP相关并发症的概率也在不断上升.但是目前,相当一部分患者对ERCP过程及ERCP相关并发症鲜有了解.本文就ERCP术前知情同意研究进展进行简要综述.展开更多
Objective: To study the effect of adjuvant levocarnitine therapy on EPO resistance, oxidative stress response and inflammatory response in patients with hemodialysis. Methods: A total of 78 patients who received maint...Objective: To study the effect of adjuvant levocarnitine therapy on EPO resistance, oxidative stress response and inflammatory response in patients with hemodialysis. Methods: A total of 78 patients who received maintenance hemodialysis in Beijing Chaoyang District Shuangqiao Hospital between May 2015 and October 2016 were selected and randomly divided into two groups, the levocarnitine group received levocarnitine combined with conventional anemia correction therapy, and the control group accepted routine anemia correction therapy. The extent of EPO resistance, oxidative stress response and inflammatory response in two groups of patients were assessed before treatment as well as 3 months and 6 months after treatment. Results: 3 months and 6 months after treatment, the rhuEPO dosage and ERI, Nrf-2 , ARE, HO-1 and NQO-1 expression in peripheral blood mononuclear cells as well as AOPP, 8-OHdG, MDA, MCP-1, sICAM-1, PTX3, IL-4 and IL-10 levels in serum of levocarnitine group had been gradually decreasing while the rhuEPO dosage and ERI, Nrf-2, ARE, HO-1 and NQO-1 expression in peripheral blood mononuclear cells as well as AOPP, 8-OHdG, MDA, MCP-1, sICAM-1, PTX3, IL-4 and IL-10 levels in serum of control group were without significant change. Conclusion: Adjuvant levocarnitine therapy can significantly improve the EPO resistance, oxidative stress response and inflammatory response in patients with hemodialysis.展开更多
The control design problem plays a fundamental role in the study of logical control networks(LCNs).This paper presents a detailed survey on new developments in control design techniques of LCNs.First,some preliminary ...The control design problem plays a fundamental role in the study of logical control networks(LCNs).This paper presents a detailed survey on new developments in control design techniques of LCNs.First,some preliminary results on the semi-tensor product method and LCNs are reviewed.Then,we move on to some new developments for control design techniques of LCNs,including the reachable set approach,the pinning control technique,the control Lyapunov function approach,the event-triggered control technique,and the sampled-data control technique.Finally,an illustrative example is given to demonstrate the effectiveness of these techniques.展开更多
Real-Time Publish and Subscribe (RTPS) protocol is a protocol for implementing message exchange over an unreliable transport in data distribution service (DDS). Formal modelling and verification of the protocol provid...Real-Time Publish and Subscribe (RTPS) protocol is a protocol for implementing message exchange over an unreliable transport in data distribution service (DDS). Formal modelling and verification of the protocol provide stronger guarantees of its correctness and efficiency than testing alone. In this paper, we build formal models for the RTPS protocol using UPPAAL and Simulink/Stateflow. Modelling using Simulink/Stateflow allows analyzing the protocol through simula-tion, as well as generate executable code. Modelling using UPPAAL allows us to verify properties of the model stated in TCTL (Timed Computation Tree Logic), as well as estimate its performance using statistical model checking. We further describe a procedure for translation from Stateflow to timed automata, where a subset of major features in Stateflow is supported, and prove the soundness statement that the Stateflow model is a refinement of the translated timed automata model. As a consequence, any property in a certain fragment of TCTL that we have verified for the timed automata model in UPPAAL is preserved for the original Stateflow model.展开更多
基金Fujian Provincial Health Technology Project,No.2020GGA079Natural Science Foundation of Fujian Province,No.2021J011380National Natural Science Foundation of China,No.62276146.
文摘Acute pancreatitis(AP)is a potentially life-threatening inflammatory disease of the pancreas,with clinical management determined by the severity of the disease.Diagnosis,severity prediction,and prognosis assessment of AP typically involve the use of imaging technologies,such as computed tomography,magnetic resonance imaging,and ultrasound,and scoring systems,including Ranson,Acute Physiology and Chronic Health Evaluation II,and Bedside Index for Severity in AP scores.Computed tomography is considered the gold standard imaging modality for AP due to its high sensitivity and specificity,while magnetic resonance imaging and ultrasound can provide additional information on biliary obstruction and vascular complications.Scoring systems utilize clinical and laboratory parameters to classify AP patients into mild,moderate,or severe categories,guiding treatment decisions,such as intensive care unit admission,early enteral feeding,and antibiotic use.Despite the central role of imaging technologies and scoring systems in AP management,these methods have limitations in terms of accuracy,reproducibility,practicality and economics.Recent advancements of artificial intelligence(AI)provide new opportunities to enhance their performance by analyzing vast amounts of clinical and imaging data.AI algorithms can analyze large amounts of clinical and imaging data,identify scoring system patterns,and predict the clinical course of disease.AI-based models have shown promising results in predicting the severity and mortality of AP,but further validation and standardization are required before widespread clinical application.In addition,understanding the correlation between these three technologies will aid in developing new methods that can accurately,sensitively,and specifically be used in the diagnosis,severity prediction,and prognosis assessment of AP through complementary advantages.
基金the S and T Program of Hebei,No.22377704DMedical Science Research Project of Hebei Province,No.20190510Postgraduate’s Innovation Fund Project of Hebei Province,No.CXZZBS2021077.
文摘BACKGROUND Oxaliplatin(Oxa)is the first-line chemotherapy drug for colorectal cancer(CRC),and Oxa resistance is crucial for treatment failure.Prostaglandin F_(2α)synthase(PGF 2α)(PGFS),an enzyme that catalyzes the production of PGF_(2α),is involved in the proliferation and growth of a variety of tumors.However,the role of PGFS in Oxa resistance in CRC remains unclear.AIM To explore the role and related mechanisms of PGFS in mediating Oxa resistance in CRC.METHODS The PGFS expression level was examined in 37 pairs of CRC tissues and paracancerous tissues at both the mRNA and protein levels.Overexpression or knockdown of PGFS was performed in CRC cell lines with acquired Oxa resistance(HCT116-OxR and HCT8-OxR)and their parental cell lines(HCT116 and HCT8)to assess its influence on cell proliferation,chemoresistance,apoptosis,and DNA damage.For determination of the underlying mechanisms,CRC cells were examined for platinum-DNA adducts and reactive oxygen species(ROS)levels in the presence of a PGFS inhibitor or its products.RESULTS Both the protein and mRNA levels of PGFS were increased in the 37 examined CRC tissues compared to the adjacent normal tissues.Oxa induced PGFS expression in the parental HCT116 and HCT8 cells in a dosedependent manner.Furthermore,overexpression of PGFS in parental CRC cells significantly attenuated Oxainduced proliferative suppression,apoptosis,and DNA damage.In contrast,knockdown of PGFS in Oxa-resistant HCT116 and HCT8 cells(HCT116-OxR and HCT8-OxR)accentuated the effect of Oxa treatment in vitro and in vivo.The addition of the PGFS inhibitor indomethacin enhanced the cytotoxicity caused by Oxa.Treatment with the PGFS-catalyzed product PGF_(2α)reversed the effect of PGFS knockdown on Oxa sensitivity.Interestingly,PGFS inhibited the formation of platinum-DNA adducts in a PGF_(2α)-independent manner.PGF_(2α)exerts its protective effect against DNA damage by reducing ROS levels.CONCLUSION PGFS promotes resistance to Oxa in CRC via both PGF_(2α)-dependent and PGF_(2α)-independent mechanisms.
基金the National Key R&D Program of China,No.2018YFC1313103the National Natural Science Foundation of China,No.81670473 and No.81873546+1 种基金the“Shu Guang”Project of Shanghai Municipal Education Commission and Shanghai Education Development Foundation,No.19SG30the Key Area Research and Development Program of Guangdong Province,China,No.2018B010111001.
文摘BACKGROUND Artificial intelligence in colonoscopy is an emerging field,and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas.Several deep learning-based computer-assisted detection(CADe)techniques were established from small single-center datasets,and unrepresentative learning materials might confine their application and generalization in wide practice.Although CADes have been reported to identify polyps in colonoscopic images and videos in real time,their diagnostic performance deserves to be further validated in clinical practice.AIM To train and test a CADe based on multicenter high-quality images of polyps and preliminarily validate it in clinical colonoscopies.METHODS With high-quality screening and labeling from 55 qualified colonoscopists,a dataset consisting of over 71000 images from 20 centers was used to train and test a deep learning-based CADe.In addition,the real-time diagnostic performance of CADe was tested frame by frame in 47 unaltered full-ranged videos that contained 86 histologically confirmed polyps.Finally,we conducted a selfcontrolled observational study to validate the diagnostic performance of CADe in real-world colonoscopy with the main outcome measure of polyps per colonoscopy in Changhai Hospital.RESULTS The CADe was able to identify polyps in the test dataset with 95.0%sensitivity and 99.1%specificity.For colonoscopy videos,all 86 polyps were detected with 92.2%sensitivity and 93.6%specificity in frame-by-frame analysis.In the prospective validation,the sensitivity of CAD in identifying polyps was 98.4%(185/188).Folds,reflections of light and fecal fluid were the main causes of false positives in both the test dataset and clinical colonoscopies.Colonoscopists can detect more polyps(0.90 vs 0.82,P<0.001)and adenomas(0.32 vs 0.30,P=0.045)with the aid of CADe,particularly polyps<5 mm and flat polyps(0.65 vs 0.57,P<0.001;0.74 vs 0.67,P=0.001,respectively).However,high efficacy is not realized in colonoscopies with inadequate bowel preparation and withdrawal time(P=0.32;P=0.16,respectively).CONCLUSION CADe is feasible in the clinical setting and might help endoscopists detect more polyps and adenomas,and further confirmation is warranted.
基金Supported by National Natural Science Foundation of China,No.81770601,No.81702324,and No.81602529Natural Science Foundation of Hebei Province,No.H2018206176 and No.H2017206141Post-graduate’s Innovation Fund Project of Hebei Province,No.CXZZBS2019121.
文摘BACKGROUND Sorafenib is the first-line treatment for patients with advanced hepatocellular carcinoma(HCC).Y-box binding protein 1(YB-1)is closely correlated with tumors and drug resistance.However,the relationship between YB-1 and sorafenib resistance and the underlying mechanism in HCC remain unknown.AIM To explore the role and related mechanisms of YB-1 in mediating sorafenib resistance in HCC.METHODS The protein expression levels of YB-1 were assessed in human HCC tissues and adjacent nontumor tissues.Next,we constructed YB-1 overexpression and knockdown hepatocarcinoma cell lines with lentiviruses and stimulated these cell lines with different concentrations of sorafenib.Then,we detected the proliferation and apoptosis in these cells by terminal deoxynucleotidyl transferase dUTP nick end labeling,flow cytometry and Western blotting assays.We also constructed a xenograft tumor model to explore the effect of YB-1 on the efficacy of sorafenib in vivo.Moreover,we studied and verified the specific molecular mechanism of YB-1 mediating sorafenib resistance in hepatoma cells by digital gene expression sequencing(DGE-seq).RESULTS YB-1 protein levels were found to be higher in HCC tissues than in corresponding nontumor tissues.YB-1 suppressed the effect of sorafenib on cell proliferation and apoptosis.Consistently,the efficacy of sorafenib in vivo was enhanced after YB-1 was knocked down.Furthermore,KEGG pathway enrichment analysis of DGEseq demonstrated that the phosphoinositide-3-kinase(PI3K)/protein kinase B(Akt)signaling pathway was essential for the sorafenib resistance induced by YB-1.Subsequently,YB-1 interacted with two key proteins of the PI3K/Akt signaling pathway(Akt1 and PIK3R1)as shown by searching the BioGRID and HitPredict websites.Finally,YB-1 suppressed the inactivation of the PI3K/Akt signaling pathway induced by sorafenib,and the blockade of the PI3K/Akt signaling pathway by LY294002 mitigated YB-1-induced sorafenib resistance.CONCLUSION Overall,we concluded that YB-1 augments sorafenib resistance through the PI3K/Akt signaling pathway in HCC and suggest that YB-1 is a key drug resistance-related gene,which is of great significance for the application of sorafenib in advanced-stage HCC.
文摘内镜逆行胰胆管造影术(endoscopic retrograde chola ngiopancreatography,ERCP)是一项有着潜在治疗风险的内镜操作.随着内镜技术的不断发展,现如今ERCP的开展率越来越高,这也意味着出现ERCP相关并发症的概率也在不断上升.但是目前,相当一部分患者对ERCP过程及ERCP相关并发症鲜有了解.本文就ERCP术前知情同意研究进展进行简要综述.
文摘Objective: To study the effect of adjuvant levocarnitine therapy on EPO resistance, oxidative stress response and inflammatory response in patients with hemodialysis. Methods: A total of 78 patients who received maintenance hemodialysis in Beijing Chaoyang District Shuangqiao Hospital between May 2015 and October 2016 were selected and randomly divided into two groups, the levocarnitine group received levocarnitine combined with conventional anemia correction therapy, and the control group accepted routine anemia correction therapy. The extent of EPO resistance, oxidative stress response and inflammatory response in two groups of patients were assessed before treatment as well as 3 months and 6 months after treatment. Results: 3 months and 6 months after treatment, the rhuEPO dosage and ERI, Nrf-2 , ARE, HO-1 and NQO-1 expression in peripheral blood mononuclear cells as well as AOPP, 8-OHdG, MDA, MCP-1, sICAM-1, PTX3, IL-4 and IL-10 levels in serum of levocarnitine group had been gradually decreasing while the rhuEPO dosage and ERI, Nrf-2, ARE, HO-1 and NQO-1 expression in peripheral blood mononuclear cells as well as AOPP, 8-OHdG, MDA, MCP-1, sICAM-1, PTX3, IL-4 and IL-10 levels in serum of control group were without significant change. Conclusion: Adjuvant levocarnitine therapy can significantly improve the EPO resistance, oxidative stress response and inflammatory response in patients with hemodialysis.
基金Project supported by the National Natural Science Foundation of China(No.61873150)the Natural Science Fund for Distinguished Young Scholars of Shandong Province,China(No.JQ201613)the Young Experts of Taishan Scholar Project,China(No.201909076)。
文摘The control design problem plays a fundamental role in the study of logical control networks(LCNs).This paper presents a detailed survey on new developments in control design techniques of LCNs.First,some preliminary results on the semi-tensor product method and LCNs are reviewed.Then,we move on to some new developments for control design techniques of LCNs,including the reachable set approach,the pinning control technique,the control Lyapunov function approach,the event-triggered control technique,and the sampled-data control technique.Finally,an illustrative example is given to demonstrate the effectiveness of these techniques.
基金This work was partially supported by the National Natural Science Foundation of China under Grant Nos.61625206,61972385 and 61732001the Chinese Academy of Sciences Pioneer 100 Talents Program under Grant No.Y9RC585036.
文摘Real-Time Publish and Subscribe (RTPS) protocol is a protocol for implementing message exchange over an unreliable transport in data distribution service (DDS). Formal modelling and verification of the protocol provide stronger guarantees of its correctness and efficiency than testing alone. In this paper, we build formal models for the RTPS protocol using UPPAAL and Simulink/Stateflow. Modelling using Simulink/Stateflow allows analyzing the protocol through simula-tion, as well as generate executable code. Modelling using UPPAAL allows us to verify properties of the model stated in TCTL (Timed Computation Tree Logic), as well as estimate its performance using statistical model checking. We further describe a procedure for translation from Stateflow to timed automata, where a subset of major features in Stateflow is supported, and prove the soundness statement that the Stateflow model is a refinement of the translated timed automata model. As a consequence, any property in a certain fragment of TCTL that we have verified for the timed automata model in UPPAAL is preserved for the original Stateflow model.
