Feed-forward observer-based intermittent fault detection

This paper provided an approach to design feed-forward observer for nonlinear systems with Lipchitz nonlinearity and bounded unknown inputs (disturbances/uncertainties) to ensure the sensitivity against intermittent faults. The proposed observer design guarantees the system error stability. Some variables and scalars are also introduced to design observer's parameters, which bring more degrees of flexibility available to the designer. The designed observer is used to propose a precision fault detection scheme including adaptive threshold design to detect intermittent faults. The efficiency of the considered approach is examined by the intermittent failure case in the suspension system of a vehicle. Simulation results show that the accurate state estimation and fault detection are achieved successfully

Feed-forward observer-based intermittent fault detection

This paper provided an approach to design feed-forward observer for nonlinear systems with Lipchitz nonlinearity and bounded unknown inputs (disturbances/uncertainties) to ensure the sensitivity against intermittent faults. The proposed observer design guarantees the system error stability. Some variables and scalars are also introduced to design observer's parameters, which bring more degrees of flexibility available to the designer. The designed observer is used to propose a precision fault detection scheme including adaptive threshold design to detect intermittent faults. The efficiency of the considered approach is examined by the intermittent failure case in the suspension system of a vehicle. Simulation results show that the accurate state estimation and fault detection are achieved successfully

Research of stress strain state of power structural elements with functional holes under uniaxial cyclic loading

Методом скінченних елементів обчислено одновісне пружно-пластичне деформування пластини з центральним деформаційно зміцненим отвором діаметром 8 мм, 10 мм після дорнування з натягом із алюмінієвого сплаву Д16чТ 1%, 2%, 3%. Побудовано розподіл розмаху локальних напружень, максимальних та мінімальних напружень та в околі отвору залежно від кількості циклів навантаження та відносного натягу дорнування. У середній ділянці циліндричної поверхні отвору ( ) розрахункові локальні коефіцієнти асиметрії циклу у другому півциклі навантаження знижуються зі збільшенням відстані від краю отвору та зі збільшенням відносного натягу дорнування. Найменші локальні коефіцієнти асиметрії циклу навантаження R=-4…-5 для натягу дорнування 3% і сталі по товщині зразка ( мм).Using finite element method taking advantage of the software module ANSYS Explicit Dynamics elastic-plastic deformation of the plate with 8 mm, 10 mm central strain hardened hole diameter with burnishing tension 1%, 2%, 3% have been calculated. To calculate the stress strain state in the threshold of the functional hole after burnishing with different tension and cyclic loading finite-element models of a quarter of the sample with a central hole were built. The load was applied to one surface of the edge of sample model and the other surface was fixed and limited by vertical movement (along the direction of application of force). The cyclic elastic-plastic deformation of aluminum D16chT alloy plate under of soft load at and has been studied. Characteristics of mechanical properties are and . Scale distribution of local stresses , maximum and minimum local stress and in the threshold of the hole depending on the number of loading cycles and burnishing tension has been built. Local stresses and , while calculating taking advantage of the finite element method has been stabilized already for two load half-cycles. The largest range of local stresses occur in the middle part of the hole thickness without burnishing (i = 0%, ) and on the edge of the mandrel entrance after burnishing with the tension (1% ... 3%, ). For burnished holes initiation and propagation of crack from the edge of the mandrel entrance are the characteristics. It is caused by the fact, that the compressive residual stresses caused by burnishing and the range of local strains for study of tightened burnishing (i = 1% ... 3%) on the hole edge are much smaller than in the middle part. Distribution of local coefficients of asymmetry of loading cycles for burnishing tension 1%, 2%, 3% and without burnishing obtained by finite element calculation has been built. In the middle section of the cylindrical surface of the hole ( ) calculation local coefficients of asymmetry in the second half cycle load decrease with the increase of distance from the edge of the hole and with the increase of burnishing tension. Local load cycle asymmetry coefficients decrease with the threshold of depth of the cylindrical surface of the hole along the X axis for the average in depth section along the axis Z ( ) The smallest local load cycles of asymmetry coefficients R = -4 ... -5 are for burnishing tension 3% and are stable for all thickness of the sample ( mm)

ТЕОРЕТИЧНІ ЗАСАДИ ТА ЗАДАЧІ РОЗПІЗНАВАННЯ ГАРМОНІЧНИХ СИГНАЛІВ ТА ОБРАЗІВ НА ОСНОВІ ОЦІНКИ ХЕММІНГОВОЇ ВІДДАЛІ

Special transitional modes and the possibility of damage to the equipment of electric and transformer substations may occur during the operation of high-voltage transmission lines. This leads to mechanical failure of the technological equipment by short circuit currents or arc that occurs at the site of the damage. Special devices for the recognition of harmonic signals and images based on the Hamming distance are successfully used to solve such problems. They are used in the case of perturbations in high-voltage transmission lines such as charges, short to ground and the launch of powerful electrical appliances. The block diagram of the device for identification of charges, short to ground and the launch of powerful electric drives in the transmission lines is proposed in the paper. Time charts of straightened values of phase voltage, current and phase difference at charges, short circuits and the launch of powerful electrical appliances in high voltage transmission lines, are calculated. The structure of the pulse special processor on the basis of the threshold integral quadrant is characterized. The structural scheme of a special processor for determining the Hamming distance in the Rademacher theoretic-numerical basis is developed. An example of the structure of a correlation special processor for recognizing and determining the distance to the source of an acoustic signal, which is given at the polygon of a two-dimensional Hamming space in Cartesian coordinates, is shown. The structural scheme of the device for determining the Hamming distance between two signals in the number-theoretic basis of Rademacher and Haar is developed. The development of a special processor for determining the Hamming distance in the number-theoretic basis of Haar-Kresterson is a promising direction for the development of devices for the recognition of harmonic signals and images based on the estimation of the Hamming distance in the case of perturbations in high-voltage transmission lines such as charges, short to ground and the launch of powerful electrical appliances. Such a special processor is characterized by significantly faster performance compared with existing analogues.Розв'язано задачу розпізнавання гармонічних сигналів та образів на основі оцінки Хеммінгової віддалі, що виникає під час виникнення збурень у високовольтних лініях електропересилень типу накидів, замикань на землю та запусків потужних електроприладів. Проаналізовано основні переваги та недоліки виробників мікроконтролерних засобів релейного захисту. Розроблено теоретичні засади диференціально-різницевого алгоритму розпізнавання накидів і коротких замикань у лініях електропересилань. Розроблено структуру та функціональну схему спецпроцесора розпізнавання збурень у високовольтних лініях електропересилань на основі кореляційної оцінки Хеммінгової віддалі. Проведено дослідження часової складності спецпроцесора визначення Хеммінгової віддалі у теоретико-числовому базисі Радемахера. Виконано постановку задачі динамічного опрацювання цифрових сигналів на основі визначення Хеммінгової віддалі до джерела акустичних сигналів. Розроблено принципи структурної побудови та структурних рішень спецпроцесора кореляційного опрацювання акустичних сигналів. Розроблено структурні рішення спецпристрою визначення Хеммінгової віддалі у базисах Радемахера та Хаара, його структуру та базові компоненти. Сформовано принципи роботи спецпроцесора визначення Хеммінгової віддалі у теоретико-числових базисах Радемахера та Хаара

Simultaneous Induction of Glycolysis and Oxidative Phosphorylation during Activation of Hepatic Stellate Cells Reveals Novel Mitochondrial Targets to Treat Liver Fibrosis

Upon liver injury, hepatic stellate cells (HSCs) transdifferentiate to migratory, proliferative and extracellular matrix-producing myofibroblasts (e.g., activated HSCs; aHSCs) causing liver fibrosis. HSC activation is associated with increased glycolysis and glutaminolysis. Here, we compared the contribution of glycolysis, glutaminolysis and mitochondrial oxidative phosphorylation (OXPHOS) in rat and human HSC activation. Basal levels of glycolysis (extracellular acidification rate similar to 3-fold higher) and particularly mitochondrial respiration (oxygen consumption rate similar to 5-fold higher) were significantly increased in rat aHSCs, when compared to quiescent rat HSC. This was accompanied by extensive mitochondrial fusion in rat and human aHSCs, which occurred without increasing mitochondrial DNA content and electron transport chain (ETC) components. Inhibition of glycolysis (by 2-deoxy-D-glucose) and glutaminolysis (by CB-839) did not inhibit rat aHSC proliferation, but did reduce Acta2 (encoding alpha-SMA) expression slightly. In contrast, inhibiting mitochondrial OXPHOS (by rotenone) significantly suppressed rat aHSC proliferation, as well as Col1a1 and Acta2 expression. Other than that observed for rat aHSCs, human aHSC proliferation and expression of fibrosis markers were significantly suppressed by inhibiting either glycolysis, glutaminolysis or mitochondrial OXPHOS (by metformin). Activation of HSCs is marked by simultaneous induction of glycolysis and mitochondrial metabolism, extending the possibilities to suppress hepatic fibrogenesis by interfering with HSC metabolism

Oxidative stress is associated with suspected non-alcoholic fatty liver disease and all-cause mortality in the general population

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation, inflammation and an imbalanced redox homeostasis. We hypothesized that systemic free thiol levels, as a proxy of systemic oxidative stress, are associated with NAFLD. Methods: Protein-adjusted serum free thiol concentrations were determined in participants from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort study (n = 5562). Suspected NAFLD was defined by the Fatty Liver Index (FLI ≥ 60) and Hepatic Steatosis Index (HSI > 36). Results: Protein-adjusted serum free thiols were significantly reduced in subjects with FLI ≥ 60 (n = 1651). In multivariable logistic regression analyses, protein-adjusted serum free thiols were associated with NAFLD (FLI ≥ 60) (OR per doubling of concentration: 0.78 [95% CI 0.64-0.96], P =.016) even when adjusted for potential confounding factors, including systolic blood pressure, diabetes, current smoking, use of alcohol and total cholesterol (OR 0.80 [95% CI 0.65-0.99], P =.04). This association lost its significance (OR 0.94 [95% CI 0.73-1.21], P =.65) after additional adjustment for high-sensitive C-reactive protein. Stratified analyses showed significantly differential associations of protein-adjusted serum free thiol concentrations with suspected NAFLD for gender (P <.02), hypertension (P <.001) and hypercholesterolemia (P <.003). Longitudinally, protein-adjusted serum free thiols were significantly associated with the risk of all-cause mortality in subjects with NAFLD (FLI ≥ 60) (HR 0.27 [95% CI 0.17-0.45], P <.001). Conclusion: Protein-adjusted serum free thiol levels are reduced and significantly associated with all-cause mortality in subjects with suspected NAFLD. Quantification of free thiols may be a promising, minimally invasive strategy to improve detection of NAFLD and associated risk of all-cause mortality in the general population

Mitochondrial DNA methylation in metabolic associated fatty liver disease

INTRODUCTION: Hepatic lipid accumulation and mitochondrial dysfunction are hallmarks of metabolic associated fatty liver disease (MAFLD), yet molecular parameters underlying MAFLD progression are not well understood. Differential methylation within the mitochondrial DNA (mtDNA) has been suggested to be associated with dysfunctional mitochondria, also during progression to Metabolic Steatohepatitis (MeSH). This study further investigates whether mtDNA methylation is associated with hepatic lipid accumulation and MAFLD.METHODS: HepG2 cells were constructed to stably express mitochondria-targeted viral and prokaryotic cytosine DNA methyltransferases (mtM.CviPI or mtM.SssI for GpC or CpG methylation, respectively). A catalytically inactive variant (mtM.CviPI-Mut) was constructed as a control. Mouse and human patients' samples were also investigated. mtDNA methylation was assessed by pyro- or nanopore sequencing.RESULTS AND DISCUSSION: Differentially induced mtDNA hypermethylation impaired mitochondrial gene expression and metabolic activity in HepG2-mtM.CviPI and HepG2-mtM.SssI cells and was associated with increased lipid accumulation, when compared to the controls. To test whether lipid accumulation causes mtDNA methylation, HepG2 cells were subjected to 1 or 2 weeks of fatty acid treatment, but no clear differences in mtDNA methylation were detected. In contrast, hepatic Nd6 mitochondrial gene body cytosine methylation and Nd6 gene expression were increased in mice fed a high-fat high cholesterol diet (HFC for 6 or 20 weeks), when compared to controls, while mtDNA content was unchanged. For patients with simple steatosis, a higher ND6 methylation was confirmed using Methylation Specific PCR, but no additional distinctive cytosines could be identified using pyrosequencing. This study warrants further investigation into a role for mtDNA methylation in promoting mitochondrial dysfunction and impaired lipid metabolism in MAFLD.</p

Hepatocyte KLF6 expression affects FXR signalling and the clinical course of primary sclerosing cholangitis

Background & Aims: Primary sclerosing cholangitis (PSC) is characterized by chronic cholestasis and inflammation, which promotes cirrhosis and an increased risk of cholangiocellular carcinoma (CCA). The transcription factor Krueppel-like-factor-6 (KLF6) is a mediator of liver regeneration, steatosis, and hepatocellular carcinoma (HCC), but no data are yet available on its potential role in cholestasis. Here, we aimed to identify the impact of hepatic KLF6 expression on cholestatic liver injury and PSC and identify potential effects on farnesoid-X-receptor (FXR) signalling. Methods: Hepatocellular KLF6 expression was quantified by immunohistochemistry (IHC) in liver biopsies of PSC patients and correlated with serum parameters and clinical outcome. Liver injury was analysed in hepatocyte-specific Klf6-knockout mice following bile duct ligation (BDL). Chromatin-immunoprecipitation-assays (ChIP) and KLF6-overexpressing HepG2 cells were used to analyse the interaction of KLF6 and FXR target genes such as NR0B2. Results: Based on IHC, PSC patients could be subdivided into two groups showing either low (80%) hepatocellular KLF6 expression. In patients with high KLF6 expression, we observed a superior survival in Kaplan-Meier analysis. Klf6-knockout mice showed reduced hepatic necrosis following BDL when compared to controls. KLF6 suppressed NR0B2 expression in HepG2 cells mediated through binding of KLF6 to the NR0B2 promoter region. Conclusion: Here, we show an association between KLF6 expression and the clinical course and overall survival in PSC patients. Mechanistically, we identified a direct interaction of KLF6 with the FXR target gene NR0B2

Mitochondrial DNA methylation in metabolic associated fatty liver disease

IntroductionHepatic lipid accumulation and mitochondrial dysfunction are hallmarks of metabolic associated fatty liver disease (MAFLD), yet molecular parameters underlying MAFLD progression are not well understood. Differential methylation within the mitochondrial DNA (mtDNA) has been suggested to be associated with dysfunctional mitochondria, also during progression to Metabolic Steatohepatitis (MeSH). This study further investigates whether mtDNA methylation is associated with hepatic lipid accumulation and MAFLD.MethodsHepG2 cells were constructed to stably express mitochondria-targeted viral and prokaryotic cytosine DNA methyltransferases (mtM.CviPI or mtM.SssI for GpC or CpG methylation, respectively). A catalytically inactive variant (mtM.CviPI-Mut) was constructed as a control. Mouse and human patients’ samples were also investigated. mtDNA methylation was assessed by pyro- or nanopore sequencing.Results and discussionDifferentially induced mtDNA hypermethylation impaired mitochondrial gene expression and metabolic activity in HepG2-mtM.CviPI and HepG2-mtM.SssI cells and was associated with increased lipid accumulation, when compared to the controls. To test whether lipid accumulation causes mtDNA methylation, HepG2 cells were subjected to 1 or 2 weeks of fatty acid treatment, but no clear differences in mtDNA methylation were detected. In contrast, hepatic Nd6 mitochondrial gene body cytosine methylation and Nd6 gene expression were increased in mice fed a high-fat high cholesterol diet (HFC for 6 or 20 weeks), when compared to controls, while mtDNA content was unchanged. For patients with simple steatosis, a higher ND6 methylation was confirmed using Methylation Specific PCR, but no additional distinctive cytosines could be identified using pyrosequencing. This study warrants further investigation into a role for mtDNA methylation in promoting mitochondrial dysfunction and impaired lipid metabolism in MAFLD