Acumen : an open-source testbed for cyber-physical systems research

Developing Cyber-Physical Systems requires methods and tools to support simulation and verification of hybrid (both continuous and discrete) models. The Acumen modeling and simulation language is an open source testbed for exploring the design space of what rigorousbut- practical next-generation tools can deliver to developers of Cyber- Physical Systems. Like verification tools, a design goal for Acumen is to provide rigorous results. Like simulation tools, it aims to be intuitive, practical, and scalable. However, it is far from evident whether these two goals can be achieved simultaneously. This paper explains the primary design goals for Acumen, the core challenges that must be addressed in order to achieve these goals, the “agile research method” taken by the project, the steps taken to realize these goals, the key lessons learned, and the emerging language design

Lightweight Three-Dimensional Visualization For Hybrid Systems Simulation

Simulation plays a key role in the computer-aided design of systems, primarily because it helps in catching design bugs at an early stage and in quickly ruling out many unreasonable options in the design space. There is a wealth of tools and languages that have been proposed over the years for the design and verification of hybrid systems and most of them provide 3D visualization utility for facilitating design process. However, their visualization systems often rely on some external configuration files written in naive 3D APIs like VRML or Java3D and complicated connections have to be established between the simulation data and the visualization. Numerous efforts have to be invested in visualization related modeling and certain level of understanding of the low level 3D libraries are needed. Thus it is not an easy job for non-professions to build a 3D visualization. In this thesis we explore the idea that in a hybrid system model, almost all the information need for visualization is already in place. This means that very few annotation should be enough to fully specify a useful 3D visualization. Based on this idea, we propose a lightweight 3D visualization framework which allows the user to expresses the three-dimensional object in a high level and abstract way and to take advantage of the data already in the simulation. We evaluate our approaching by building a prototype extension of modeling language called Acumen. The result of this thesis work is included in Acumen's official release version that can be download at www.acumen-language.org. To build a 3D visualization in Acumen, only very few annotations need to be added to the simulation model and are included inside one reserved variable. Non-professions like students who are studying Cyber-physical systems can easily use this tool to visualize their models in Acumen without any prerequisite knowledge regarding 3D visualization technology. We also developed a number of benchmarks to test the correctness and functionality of Acumen3D. Besides, as a lager case study into the expressivity of Acumen and its visualizaiton efficiency, we developed a simplified model of a Ping Pong game. We gained experience about how to model complex hybrid system in Acumen. Moreover by comparing modeling such a hybrid system in Java3D and in Acumen3D, we find concrete evidence that modelling it in Acumen3D is easier in that of less code and less prerequisite knowledge and more supporting built in functions.

The occurrence of immune-related adverse events is an independent risk factor both for serum HBsAg increase and HBV reactivation in HBsAg-positive cancer patients receiving PD-1 inhibitor combinational therapy

BackgroundPrevious studies have suggested the potential of PD-1/PD-L1 inhibitors in the treatment of chronic HBV infection. However, since phase III clinical trials have not yet been announced, additional clinical insights may be obtained by observing changes in serum hepatitis B surface antigen (HBsAg) and HBV-DNA levels in cancer patients undergoing PD-1 inhibitor therapy.ObjectiveTo explore the effects of PD-1 inhibitor combinational therapy on serum HBsAg and HBV-DNA levels, investigate the incidence of HBsAg loss, HBV reactivation (HBVr), and immune-related adverse events (irAEs), and identify the risk factors associated with significant HBsAg fluctuations and HBVr. MethodsA retrospective study including 1195 HBsAg-positive cancer patients who received PD-1 inhibitors between July 2019 and June 2023 was conducted, and 180 patients were enrolled in this study. Serum HBsAg levels before and after PD-1 inhibitor administration were compared across different subgroups. The Pearson χ2 or Fisher exact test was performed to investigate the relationships between categorical variables. Univariable and multivariable analysis were performed to identify the risk factors associated with significant HBsAg fluctuations and HBVr. ResultsWith the concurrent use of antiviral agents, serum HBsAg levels decreased (Z=-3.966, P < 0.0001) in 129 patients and increased (t=-2.047, P=0.043) in 51 patients. Additionally, 7 patients (3.89%) achieved serum HBsAg loss. Virus replication was suppressed in most of the enrolled patients. When divided patients into different subgroups, significant HBsAg decreases after PD-1 inhibitor administration were discovered in lower baseline HBsAg group (Z=-2.277, P=0.023), HBeAg-seronegative group (Z=-2.200, P=0.028), non-irAEs occurrence group (Z=-2.007, P=0.045) and liver cancer group (Z=-1.987, P=0.047). Of note, 11 patients and 36 patients experienced HBVr (6.11%) and irAEs (20%), respectively, which could lead to discontinuation or delayed use of PD-1 inhibitors. After multivariable analysis, HBeAg-seropositive (OR, 7.236 [95% CI, 1.757-29.793], P=0.01) and the occurrence of irAEs (OR, 4.077 [95% CI, 1.252-13.273], P=0.02) were identified as the independent risk factors for significant HBsAg increase, the occurrence of irAEs (OR, 5.560 [95% CI, 1.252-13.273], P=0.01) was identified as the only independent risk factor for HBVr. ConclusionPD-1 inhibitors combined with nucleos(t)ide analogues (NAs) may exert therapeutic potential for chronic HBV infection in cancer patients. However, attention also should be paid to the risk of significant elevation in HBsAg levels, HBVr, and irAEs associated with PD-1 inhibitor combinational therapy

Comparison of the efficacy and safety of TAF, TDF, and LdT to prevent the transmission of hepatitis B in pregnant women: A retrospective study

Abstract Objective To compare the efficacy and safety of telbivudine (LdT), tenofovir alafenamide fumarate (TAF), and tenofovir disoproxil fumarate (TDF) for preventing hepatitis B transmission in immune‐tolerant pregnant women with HBV infection. Methods We conducted a retrospective cohort study involving women who had hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 2 × 105 IU/mL and initiated LdT, TDF, or TAF to prevent mother‐to‐child transmission (MTCT). The primary endpoint was the safety of mothers and infants. The secondary endpoints were maternal HBV DNA reduction at delivery and MTCT rate. Results A total of 96 patients were enrolled in the study (LdT group, n = 36; TDF group, n = 35; TAF group, n = 25). All infants received hepatitis B virus immunoprophylaxis. The MTCT rate was 0%([0 of 25] vs. [0 of 35] vs. [0 of 36], p > .05). No severe liver function damage occurred in any of the mothers. Babies delivered in all groups had prenatal ultrasound screening abnormalities, but abnormality rates were not statistically significant between groups. Conclusion The application of TDF, TAF, or LdT to immune‐tolerant HBV‐infected pregnant women in middle–late pregnancy can successfully interrupt MTCT of the HBV virus. However, for all three groups of pregnant women who delivered babies with abnormal prenatal ultrasound screening, an expanded sample size may be needed for further observation

Chattering-Free Simulation for Hybrid Dynamical Systems: Semantics and Prototype Implementation

International audienceChattering is a fundamental phenomenon that is unique to hybrid systems, due to the complex interaction between discrete dynamics (in the form of discrete transitions) and continuous dynamics (in the form of time). In practice, simulating chattering hybrid systems is challenging in that simulation effectively halts near the chattering time point, as an infinite number of discrete transitions would need to be simulated. In this paper, formal conditions are provided for when the simulated models of hybrid systems display chattering behavior, and methods are proposed for avoiding chattering “on the fly” in runtime. We utilize dynamical behavior analysis to derive conditions for detecting chattering without enumeration of modes. We also present a new iterative algorithm to allow for solutions to be carried past the chattering point, and we show by a prototypical implementation how to generate the equivalent chattering-free dynamics internally by the simulator in the main simulation loop. The concepts are illustrated with examples throughout the paper

Using Rigorous Simulation to Support ISO 26262 Hazard Analysis and Risk Assessment

Rigorous simulation is a new technology that can play a key role in managing uncertainty in the design of safety-critical cyber-physical systems. One of its important applications is the analysis and evaluation of functional safety for road vehicles according to international standards such as ISO 26262. Previous work  presented preliminary evidence to support the feasibility of using rigorous simulation for this purpose. Here we report on advances in our implementation of rigorous simulation and show how they enable the rigorous simulation of more refined and more complete models. A larger case study highlights the benefits of these advances and helps us identify new challenges that should be addressed by future work. © 2015 IEEE.This work was supported by US National Science Foundation award CPS-1136099, the Swedish Knowledge Foundation (KK), The Center for Research on Embedded Systems (CERES), and VINNOVA (Dnr. 2011-01819).</p

A Core Language for Executable Models of Cyber-Physical Systems (Preliminary Report)

Recently we showed that an expressive class of mathematical equations can be automatically translated into simulation codes. By focusing on the expressivity of equations formed from continuous functions, this work did not accommodate a wide range of discrete behaviors or a dynamic collection of components. However, the interaction between continuous and hybrid components in many cyber-physical domains is highly coupled, and such systems are often highly dynamic in both respects. This paper gives an overview of a proposed core language for capturing executable hybrid models of highly dynamic cyber-physical systems

A Core Language for Executable Models of Cyber-Physical Systems (Preliminary Report)

International audienceRecently we showed that an expressive class of mathematical equations can be automatically translated into simulation codes. By focusing on the expressivity of equations formed from continuous functions, this work did not accommodate a wide range of discrete behaviors or a dynamic collection of components. However, the interaction between continuous and hybrid components in many cyber-physical domains is highly coupled, and such systems are often highly dynamic in both respects. This paper gives an overview of a proposed core language for capturing executable hybrid models of highly dynamic cyber-physical systems

Analysis of Monocytic and Granulocytic Myeloid-Derived Suppressor Cells Subsets in Patients with Hepatitis C Virus Infection and Their Clinical Significance

Myeloid-derived suppressor cells (MDSCs) have been shown to inhibit T-cell responses in many diseases, but, in hepatitis C virus (HCV) infected patients, MDSCs are still poorly studied. In this assay, we investigated the phenotype and frequency of two new populations of MDSCs denoted as monocytic and granulocytic MDSCs (M-MDSCs and G-MDSCs) in HCV infected patients and analyzed their clinical significance in these patients respectively. We found that the frequency of CD14+HLA-DR-/low cells (M-MDSCs) from HCV infected patients (mean ± SE, 3.134% ± 0.340%) was significantly increased when compared to healthy controls (mean ± SE, 1.764% ± 0.461%) (Z = −2.438, P = 0.015), while there was no statistical difference between the frequency of HLA-DR-/lowCD33+CD11b+CD15+ (G-MDSCs) of HCV infected patients and healthy donors (0.201% ± 0.038% versus 0.096% ± 0.026%, P > 0.05), which suggested that HCV infection could cause the proliferation of M-MDSCs instead of G-MDSCs. Besides, we found that the frequency of M-MDSCs in HCV infected patients had certain relevance with age (r = 0.358, P = 0.003); patients older than 40 years old group (mean ± SE, 3.673% ± 0.456%) had a significantly higher frequency of M-MDSCs than that of age less than 40 years old group (mean ± SE, 2.363% ± 0.482%) (Z = −2.685, P = 0.007). The frequency of M-MDSCs, however, had no correlation with HCV RNA loads, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the level of liver inflammation degree