SVtL: System Verification through Logic: tool support for verifying sliced hierarchical statecharts

SVtL is the core of a slicing-based verification environment for UML statechart models. We present an overview of the SVtL software architecture. Special attention is paid to the slicing approach. Slicing reduces the complexity of the verification approach, based on removing pieces of the model that are not of interest during verification. In [18] a slicing algorithm has been proposed for statecharts, but it was not able to handle orthogonal regions efficiently. We optimize this algorithm by removing false dependencies, relying on the broadcasting mechanism between different parts of the statechart model

Circulating beta cell-specific CD8(+) T cells restricted by high-risk HLA class I molecules show antigen experience in children with and at risk of type 1 diabetes

In type 1 diabetes (T1D), autoreactive cytotoxic CD8(+) T cells are implicated in the destruction of insulin-producing beta cells. The HLA-B*3906 and HLA-A*2402 class I genes confer increased risk and promote early disease onset, suggesting that CD8(+) T cells that recognize peptides presented by these class I molecules on pancreatic beta cells play a pivotal role in the autoimmune response. We examined the frequency and phenotype of circulating preproinsulin (PPI)-specific and insulin B (InsB)-specific CD8(+) T cells in HLA-B*3906(+) children newly diagnosed with T1D and in high-risk HLA-A*2402(+) children before the appearance of disease-specific autoantibodies and before diagnosis of T1D. Antigen-specific CD8(+) T cells were detected using human leucocyte antigen (HLA) class I tetramers and flow cytometry was used to assess memory status. In HLA-B*3906(+) children with T1D, we observed an increase in PPI5-12-specific transitional memory CD8(+) T cells compared to non-diabetic, age- and HLA-matched subjects. Furthermore, PPI5-12-specific CD8(+) T cells in HLA-B*3906(+) children with T1D showed a significantly more antigen-experienced phenotype compared to polyclonal CD8(+) T cells. In longitudinal samples from high-risk HLA-A*2402(+) children, the percentage of terminal effector cells within the InsB(15-24)-specific CD8(+) T cells was increased before diagnosis relative to samples taken before the appearance of autoantibodies. This is the first study, to our knowledge, to report HLA-B*3906-restricted autoreactive CD8(+) T cells in T1D. Collectively, our results provide evidence that beta cell-reactive CD8(+) T cells restricted by disease-associated HLA class I molecules display an antigen-experienced phenotype and acquire enhanced effector function during the period leading to clinical diagnosis, implicating these cells in driving disease.Peer reviewe

Forest canopy mitigates soil N2O emission during hot moments

Funding Information: This study was supported by the Ministry of Education and Science of Estonia (SF0180127s08 grant), the Estonian Research Council (IUT2-16, PRG-352, and MOBERC20), the Czech Science Foundation (17-18112Y) and project SustES— Adaptation strategies for sustainable ecosystem services and food security under adverse environmental conditions (CZ.02.1.01/0.0/0.0/16_019/0000797), the EU through the European Regional Development Fund (Centres of Excellence ENVIRON, grant number TK-107, EcolChange, grant number TK-131, and the MOBTP101 returning researcher grant by the Mobilitas Pluss program) and the European Social Fund (Doctoral School of Earth Sciences and Ecology). This work was also supported by the Academy of Finland (294088, 288494), and from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program under grant agreement No [757695]. We would like to thank Marek Jakubík for his technical support. Publisher Copyright: © 2021, The Author(s).Peer reviewedPublisher PD

Long-term dynamics of soil, tree stem and ecosystem methane fluxes in a riparian forest

Funding Information: This study was supported by the Ministry of Education and Science of Estonia (SF0180127s08 grant), the Estonian Research Council (IUT2-16, PRG-352, and MOBERC20), the Czech Science Foundation (17-18112Y), SustES - Adaptation strategies for sustainable ecosystem services and food security under adverse environmental conditions (CZ.02.1.01/0.0/0.0/16_019/0000797), the Ministry of Education, Youth and Sports of Czech Republic within the National Sustainability Program I (NPU I, grant number LO1415), the EU through the European Regional Development Fund (ENVIRON and EcolChange Centres of Excellence, Estonia, and MOBTP101 returning researcher grant by the Mobilitas Pluss programme), the European Social Fund (Doctoral School of Earth Sciences and Ecology). This work was also supported by Academy of Finland (294088, 288494), from the European Research Council (ERC) under the European Union?s Horizon 2020 research and innovation programme under grant agreement No [757695], and a Department of Energy (DOE) grant to JPM (DE-SC0008165). Funding Information: This study was supported by the Ministry of Education and Science of Estonia ( SF0180127s08 grant), the Estonian Research Council ( IUT2-16 , PRG-352 , and MOBERC20 ), the Czech Science Foundation ( 17-18112Y ), SustES - Adaptation strategies for sustainable ecosystem services and food security under adverse environmental conditions ( CZ.02.1.01/0.0/0.0/16_019/0000797 ), the Ministry of Education, Youth and Sports of Czech Republic within the National Sustainability Program I (NPU I, grant number LO1415 ), the EU through the European Regional Development Fund (ENVIRON and EcolChange Centres of Excellence, Estonia, and MOBTP101 returning researcher grant by the Mobilitas Pluss programme), the European Social Fund (Doctoral School of Earth Sciences and Ecology). This work was also supported by Academy of Finland ( 294088 , 288494 ), from the European Research Council (ERC) under the European Union‘s Horizon 2020 research and innovation programme under grant agreement No [ 757695 ], and a Department of Energy (DOE) grant to JPM ( DE-SC0008165 ). Publisher Copyright: © 2021 Elsevier B.V.The carbon (C) budgets of riparian forests are sensitive to climatic variability. Therefore, riparian forests are hot spots of C cycling in landscapes. Only a limited number of studies on continuous measurements of methane (CH4) fluxes from riparian forests is available. Here, we report continuous high-frequency soil and ecosystem (eddy-covariance; EC) measurements of CH4 fluxes with a quantum cascade laser absorption spectrometer for a 2.5-year period and measurements of CH4 fluxes from tree stems using manual chambers for a 1.5 year period from a temperate riparian Alnus incana forest. The results demonstrate that the riparian forest is a minor net annual sink of CH4 consuming 0.24 kg CH4-C ha−1 y−1. Soil water content is the most important determinant of soil, stem, and EC fluxes, followed by soil temperature. There were significant differences in CH4 fluxes between the wet and dry periods. During the wet period, 83% of CH4 was emitted from the tree stems while the ecosystem-level emission was equal to the sum of soil and stem emissions. During the dry period, CH4 was substantially consumed in the soil whereas stem emissions were very low. A significant difference between the EC fluxes and the sum of soil and stem fluxes during the dry period is most likely caused by emission from the canopy whereas at the ecosystem level the forest was a clear CH4 sink. Our results together with past measurements of CH4 fluxes in other riparian forests suggest that temperate riparian forests can be long-term CH4 sinks.Peer reviewe

Forest canopy mitigates soil N2O emission during hot moments

Riparian forests are known as hot spots of nitrogen cycling in landscapes. Climate warming speeds up the cycle. Here we present results from a multi-annual high temporal-frequency study of soil, stem, and ecosystem (eddy covariance) fluxes of N2O from a typical riparian forest in Europe. Hot moments (extreme events of N2O emission) lasted a quarter of the study period but contributed more than half of soil fluxes. We demonstrate that high soil emissions of N2O do not escape the ecosystem but are processed in the canopy. Rapid water content change across intermediate soil moisture was a major determinant of elevated soil emissions in spring. The freeze-thaw period is another hot moment. However, according to the eddy covariance measurements, the riparian forest is a modest source of N2O. We propose photochemical reactions and dissolution in canopy-space water as reduction mechanisms.Peer reviewe

Formal verification of safety protocol in train control system

In order to satisfy the safety-critical requirements, the train control system (TCS) often employs a layered safety communication protocol to provide reliable services. However, both description and verification of the safety protocols may be formidable due to the system complexity. In this paper, interface automata (IA) are used to describe the safety service interface behaviors of safety communication protocol. A formal verification method is proposed to describe the safety communication protocols using IA and translate IA model into PROMELA model so that the protocols can be verified by the model checker SPIN. A case study of using this method to describe and verify a safety communication protocol is included. The verification results illustrate that the proposed method is effective to describe the safety protocols and verify deadlocks, livelocks and several mandatory consistency properties. A prototype of safety protocols is also developed based on the presented formally verifying method

Circulating β cell-specific CD8+ T cells restricted by high-risk HLA class I molecules show antigen experience in children with and at risk of type 1 diabetes

In type 1 diabetes (T1D), autoreactive cytotoxic CD8+ T cells are implicated in the destruction of insulin‐producing β cells. The HLA‐B*3906 and HLA‐A*2402 class I genes confer increased risk and promote early disease onset, suggesting that CD8+ T cells that recognize peptides presented by these class I molecules on pancreatic β cells play a pivotal role in the autoimmune response. We examined the frequency and phenotype of circulating preproinsulin (PPI)‐specific and insulin B (InsB)‐specific CD8+ T cells in HLA‐B*3906+ children newly diagnosed with T1D and in high‐risk HLA‐A*2402+ children before the appearance of disease‐specific autoantibodies and before diagnosis of T1D. Antigen‐specific CD8+ T cells were detected using human leucocyte antigen (HLA) class I tetramers and flow cytometry was used to assess memory status. In HLA‐B*3906+ children with T1D, we observed an increase in PPI5–12‐specific transitional memory CD8+ T cells compared to non‐diabetic, age‐ and HLA‐matched subjects. Furthermore, PPI5–12‐specific CD8+ T cells in HLA‐B*3906+ children with T1D showed a significantly more antigen‐experienced phenotype compared to polyclonal CD8+ T cells. In longitudinal samples from high‐risk HLA‐A*2402+ children, the percentage of terminal effector cells within the InsB15–24‐specific CD8+ T cells was increased before diagnosis relative to samples taken before the appearance of autoantibodies. This is the first study, to our knowledge, to report HLA‐B*3906‐restricted autoreactive CD8+ T cells in T1D. Collectively, our results provide evidence that β cell‐reactive CD8+ T cells restricted by disease‐associated HLA class I molecules display an antigen‐experienced phenotype and acquire enhanced effector function during the period leading to clinical diagnosis, implicating these cells in driving disease.</p

The global burden of falls: Global, regional and national estimates of morbidity and mortality from the Global Burden of Disease Study 2017

Background: Falls can lead to severe health loss including death. Past research has shown that falls are an important cause of death and disability worldwide. The Global Burden of Disease Study 2017 (GBD 2017) provides a comprehensive assessment of morbidity and mortality from falls. Methods: Estimates for mortality, years of life lost (YLLs), incidence, prevalence, years lived with disability (YLDs) and disability-adjusted life years (DALYs) were produced for 195 countries and territories from 1990 to 2017 for all ages using the GBD 2017 framework. Distributions of the bodily injury (eg, hip fracture) were estimated using hospital records. Results: Globally, the age-standardised incidence of falls was 2238 (1990-2532) per 100 000 in 2017, representing a decline of 3.7% (7.4 to 0.3) from 1990 to 2017. Age-standardised prevalence w

Future and potential spending on health 2015-40 : development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Background The amount of resources, particularly prepaid resources, available for health can affect access to health care and health outcomes. Although health spending tends to increase with economic development, tremendous variation exists among health financing systems. Estimates of future spending can be beneficial for policy makers and planners, and can identify financing gaps. In this study, we estimate future gross domestic product (GDP), all-sector government spending, and health spending disaggregated by source, and we compare expected future spending to potential future spending. Methods We extracted GDP, government spending in 184 countries from 1980-2015, and health spend data from 1995-2014. We used a series of ensemble models to estimate future GDP, all-sector government spending, development assistance for health, and government, out-of-pocket, and prepaid private health spending through 2040. We used frontier analyses to identify patterns exhibited by the countries that dedicate the most funding to health, and used these frontiers to estimate potential health spending for each low-income or middle-income country. All estimates are inflation and purchasing power adjusted. Findings We estimated that global spending on health will increase from US$9.21 trillion in 2014 to$24.24 trillion (uncertainty interval [UI] 20.47-29.72) in 2040. We expect per capita health spending to increase fastest in upper-middle-income countries, at 5.3% (UI 4.1-6.8) per year. This growth is driven by continued growth in GDP, government spending, and government health spending. Lower-middle income countries are expected to grow at 4.2% (3.8-4.9). High-income countries are expected to grow at 2.1% (UI 1.8-2.4) and low-income countries are expected to grow at 1.8% (1.0-2.8). Despite this growth, health spending per capita in low-income countries is expected to remain low, at $154 (UI 133-181) per capita in 2030 and$195 (157-258) per capita in 2040. Increases in national health spending to reach the level of the countries who spend the most on health, relative to their level of economic development, would mean $321 (157-258) per capita was available for health in 2040 in low-income countries. Interpretation Health spending is associated with economic development but past trends and relationships suggest that spending will remain variable, and low in some low-resource settings. Policy change could lead to increased health spending, although for the poorest countries external support might remain essential.Peer reviewe

Future and potential spending on health 2015-40: Development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Background: The amount of resources, particularly prepaid resources, available for health can affect access to health care and health outcomes. Although health spending tends to increase with economic development, tremendous variation exists among health financing systems. Estimates of future spending can be beneficial for policy makers and planners, and can identify financing gaps. In this study, we estimate future gross domestic product (GDP), all-sector government spending, and health spending disaggregated by source, and we compare expected future spending to potential future spending. Methods: We extracted GDP, government spending in 184 countries from 1980-2015, and health spend data from 1995-2014. We used a series of ensemble models to estimate future GDP, all-sector government spending, development assistance for health, and government, out-of-pocket, and prepaid private health spending through 2040. We used frontier analyses to identify patterns exhibited by the countries that dedicate the most funding to health, and used these frontiers to estimate potential health spending for each low-income or middle-income country. All estimates are inflation and purchasing power adjusted. Findings: We estimated that global spending on health will increase from US$9.21 trillion in 2014 to$24.24 trillion (uncertainty interval [UI] 20.47-29.72) in 2040. We expect per capita health spending to increase fastest in upper-middle-income countries, at 5.3% (UI 4.1-6.8) per year. This growth is driven by continued growth in GDP, government spending, and government health spending. Lower-middle income countries are expected to grow at 4.2% (3.8-4.9). High-income countries are expected to grow at 2.1% (UI 1.8-2.4) and low-income countries are expected to grow at 1.8% (1.0-2.8). Despite this growth, health spending per capita in low-income countries is expected to remain low, at $154 (UI 133-181) per capita in 2030 and$195 (157-258) per capita in 2040. Increases in national health spending to reach the level of the countries who spend the most on health, relative to their level of economic development, would mean $321 (157-258) per capita was available for health in 2040 in low-income countries. Interpretation: Health spending is associated with economic development but past trends and relationships suggest that spending will remain variable, and low in some low-resource settings. Policy change could lead to increased health spending, although for the poorest countries external support might remain essential