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The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities of liver lipid metabolism. On the contrary, a diet enriched with n-3 polyunsaturated fatty acids (n-3-PUFAs) has been reported to ameliorate the progression of NAFLD. The aim of our study was to investigate the impact of dietary n-3-PUFA enrichment on the development of NAFLD and liver lipidome. Mice were fed for 6 weeks either a high-fat methionine choline-deficient diet (MCD) or standard chow with or without n-3-PUFAs. Liver histology, serum biochemistry, detailed plasma and liver lipidomic analyses, and genome-wide transcriptome analysis were performed. Mice fed an MCD developed histopathological changes characteristic of NAFLD, and these changes were ameliorated with n-3-PUFAs. Simultaneously, n-3-PUFAs decreased serum triacylglycerol and cholesterol concentrations as well as ALT and AST activities. N-3-PUFAs decreased serum concentrations of saturated and monounsaturated free fatty acids (FAs), while increasing serum concentrations of long-chain PUFAs. Furthermore, in the liver, the MCD significantly increased the hepatic triacylglycerol content, while the administration of n-3-PUFAs eliminated this effect. Administration of n-3-PUFAs led to significant beneficial differences in gene expression within biosynthetic pathways of cholesterol, FAs, and pro-inflammatory cytokines (IL-1 and TNF-α). To conclude, n-3-PUFA supplementation appears to represent a promising nutraceutical approach for the restoration of abnormalities in liver lipid metabolism and the prevention and treatment of NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. n‐3 polyunsaturated fatty acids (n‐3‐PUFAs) have been reported to ameliorate the progression of NAFLD in experimental studies; however, clinical trials have yielded contradictory results. The aim of our study was to assess the effects of n‐3‐PUFA administration on lipid metabolism and the progression of NAFLD in patients with metabolic syndrome. Sixty patients with metabolic syndrome and NAFLD were randomized in a double‐blind placebo‐controlled trial (3.6 g/day n‐3‐PUFA vs. placebo). During the 1‐year follow‐up, the patients underwent periodic clinical and laboratory examinations, liver stiffness measurements, magnetic resonance spectroscopy of the liver, and plasma lipidomic analyses. After 12 months of n‐3‐PUFA administration, a significant decrease in serum GGT activity was recorded compared with the placebo group (2.03 ± 2.8 vs. 1.43 ± 1.6; P < 0.05). Although no significant changes in anthropometric parameters were recorded, a significant correlation between the reduction of liver fat after 12 months of treatment—and weight reduction—was observed; furthermore, this effect was clearly potentiated by n‐3‐PUFA treatment (P < 0.005). In addition, n‐3‐PUFA treatment resulted in substantial changes in the plasma lipidome, with n‐3‐PUFA‐enriched triacylglycerols and phospholipids being the most expressed lipid signatures. Conclusion: Twelve months of n‐3‐PUFA treatment of patients with NAFLD patients was associated with a significant decrease in GGT activity, the liver fat reduction in those who reduced their weight, and beneficial changes in the plasma lipid profile.

Abstract The patatin-like phospholipase domain containing 3 (PNPLA3) gene (viz. its I148M variant) is one of the key players in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We have identified a novel insertion/deletion variant of 1114 bp, localized in the second intron of the PNPLA3 gene, which corresponds to the 3′ terminal sequence of the long-interspersed element (LINE-1). DNA analysis of 122 NAFLD patients and 167 control subjects as well as RNA analysis of 19 liver biopsies revealed that the novel variant is very common (frequency = 0.41), fully linked to the clinically important I148M variant, and clinically silent. Although the LINE-1 insertion does not seem to have any biological effect, it can impede genotyping of the I148M variant. If insertion prevents the attachment of the diagnostic primer, then the non-insertion allele will be selectively amplified; and thus the frequency of the 148M "risk" allele will be significantly overestimated due to the complete linkage of the LINE-1 insertion and the 148I allele of the PNPLA3 gene. Therefore, our findings underline the importance of careful design and consistent documentation of the methodology, including primer sequences. Critical revisions of the results of some studies that have already been reported may therefore be needed.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder worldwide. The aim of our study was to assess the role of bilirubin, and the heme oxygenase 1 (HMOX1) and bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variants, which are involved in bilirubin homeostasis, in the NAFLD development in adult patients. The study was performed on 84 patients with NAFLD and 103 age/sex-matched controls. Routine biochemistry, inflammatory markers, adipokines, and the fibrosis/steatohepatitis stage were determined in the NAFLD patients. The (GT)n/(TA)n dinucleotide variations in HMOX1/UGT1A1 gene promoters, respectively, were analyzed by fragment analysis. Compared to controls, serum bilirubin concentrations in NAFLD patients tended to be decreased, while the prevalence of phenotypic Gilbert syndrome was significantly low. Genetic variations in HMOX1 and UGT1A1 gene promoters did not differ between NAFLD patients and controls, and no relationship was found in the NAFLD patients between these gene variants and any of the laboratory or histological parameters. In conclusion, metabolism of bilirubin is dysregulated in NAFLD patients, most likely due to increased oxidative stress, since frequencies of the major functional variants in the HMOX1 or UGT1A1 gene promoters did not have any effect on development of NAFLD in adult patients.

The degradation of electrical insulating materials has been a subject of interest for decades as they are commonly applied in many fields of electrical engineering. Suitably modeling such a process is important since the known and well-described degradation process reveals the effect of ambient conditions, and this allows us to possibly estimate a material’s remaining useful life. However, not many studies are dealing with the effect of the hygrothermal degradation of impregnating mono-component epoxy resins in the context of electrical engineering. Therefore, this study deals with this issue and discusses both the dielectric response (based on the measurement of relative permittivity, dissipation factor, and dielectric strength) and the mechanical response (based on measurements of tensile strength and Shore D hardness) to a hygrothermal degradation experiment. In addition, the results of thermal analyses are presented for the evaluation of the pristine specimen manufacturing process and possible post-curing processes. Furthermore, this study presents several methodologies for modeling the degradation process, including a novel methodology in this area based on Bayesian experimental design. As an outcome, mechanical parameters are proven to be specific in terms of the actual condition of the material and the Bayesian enhanced degradation model seems to be superior to the conventional evaluation methods in this particular study.

Abstract Capability to deliver maximum power of a converter is essential for increasing power density that is limiting in many applications. Therefore, control algorithm should guarantee operation within converter thermal limits. This requirement can be formalized by a hard constraint in the cost function of model predictive control (MPC). However, the temperatures of the converter elements are not constant in the steady state, which complicates evaluation of the cost on long prediction horizon. Therefore, the evaluation is simplified utilizing the analysis of steady state behaviour of the model and derived current derating laws calculated in off‐line manner. The derating law is used as the terminal set in MPC which allows using one‐step‐ahead evaluation for efficient real‐time implementation. The steady state analysis also provides coefficients for power loss balancing. The proposed approach is applied to control of dual converter, which has high redundancy of switching elements and, thus, wide space for optimization. It is shown in simulation that the proposed approach has better performance than previously published algorithms, at lower computational cost. Experimental evaluation of the algorithm performed on a converter prototype of rated power of 10 kW shows that the proposed controller is able to safely operate the converter near the thermal limit.

Cirrhosis is a primary cause of liver-related mortality and morbidity. The basic process driving chronic liver disease to cirrhosis is accelerated fibrogenesis. Although the pathogenesis of liver cirrhosis is a multifactorial process, the essential step in the evolution of liver fibrosis is the activation of hepatic stellate cells, which are the main source of collagen produced in the extracellular matrix. This activation process is mediated by multiple growth factors, cytokines, and chemokines. One of the hepatic stellate cell-activating signaling molecules (and also one associated with cell injury and fibrosis) is osteopontin (OPN). OPN concentration in the plasma has been found to be predictive of liver fibrosis in various liver diseases. OPN concentrations correlate significantly with the stage of fibrosis, liver insufficiency, portal hypertension, and the presence of hepatocellular cancer. However, due to its versatile signaling functions, OPN not only contributes to the development of liver cirrhosis, but is also implicated in the pathogenesis of other chronic hepatic diseases such as viral hepatitis, both alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and hepatocellular cancer. Thus, the targeting of OPN pathways seems to be a promising approach in the treatment of chronic liver diseases.

We are concerned with the problem of fast and accurate tracking of currents in the general synchronous drive. The problem becomes complicated with decreasing available voltage, which is common in high-speed and field weakening regimes. The existing time-optimal controllers rely on a simplified model, ignoring stator resistance and differences in inductances. We derive a solution for the general model considering all parameters and show how the parameters affect the current trajectory. One simplifying assumption had to be made, but we show in simulation that it has a negligible impact on accuracy. The simplification allowed for the design of a feed-forward controller that has a low computational cost and can be easily implemented in realtime. We provide experimental validation of the controller on the developed IPMSM drive prototype of the rated power of 4.5 kW using conventional industrial DSP. The controller is compared to conventional PI and deadbeat solutions, demonstrating that the time-optimal controller can reach the required setpoint four times faster than the competitors at the field weakening regime of the drive. The proposed feed-forward control can be seen as a universal building block that can be combined with existing feedback controllers and observers and thus incorporated into existing control solutions.

The estimation of the speed of human motion from wearable IMU sensors is required in applications such as pedestrian dead reckoning. In this paper, we test deep learning methods for the prediction of the motion speed from raw readings of a low-cost IMU sensor. Each subject was observed using three sensors at the shoe, shin, and thigh. We show that existing general-purpose architectures outperform classical feature-based approaches and propose a novel architecture tailored for this task. The proposed architecture is based on a semi-supervised variational auto-encoder structure with innovated decoder in the form of a dense layer with a sinusoidal activation function. The proposed architecture achieved the lowest average error on the test data. Analysis of sensor placement reveals that the best location for the sensor is the shoe. Significant accuracy gain was observed when all three sensors were available. All data acquired in this experiment and the code of the estimation methods are available for download.

Milk thistle-based dietary supplements have become increasingly popular. The extract from milk thistle (Silybum marianum) is often used for the treatment of liver diseases because of the presence of its active component, silymarin. However, the co-occurrence of toxic mycotoxins in these preparations is quite frequent as well. The objective of this study was to investigate the changes in composition of liver lipidome and other clinical characteristics of experimental mice fed by a high-fat methionine-choline deficient diet inducing non-alcoholic fatty liver disease. The mice were exposed to (i) silymarin, (ii) mycotoxins (trichothecenes, enniatins, beauvericin, and altertoxins) and (iii) both silymarin and mycotoxins, and results were compared to the controls. The liver tissue extracts were analyzed by ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry. Using tools of univariate and multivariate statistical analysis, we were able to identify 48 lipid species from the classes of diacylglycerols, triacylglycerols, free fatty acids, fatty acid esters of hydroxy fatty acids and phospholipids clearly reflecting the dysregulation of lipid metabolism upon exposure to mycotoxin and/or silymarin.

A new predictor–corrector filter for attitude and heading reference systems (AHRS) using data from an orthogonal sensor combination of three accelerometers, three magnetometers and three gyroscopes is proposed. The filter uses the predictor—corrector structure, with prediction based on gyroscopes and independent correction steps for acceleration and magnetic field sensors. We propose two variants of the filter: (i) one using mathematical operations of special orthogonal group SO(3), that are accurate for nonlinear operations, for highest possible accuracy, and (ii) one using linearization of nonlinear operations for fast evaluation. Both approaches are quaternion-based filter realizations without redundant steps. The filters are compared to state of the art methods in this field on data recorded using low-cost microelectromechanical systems (MEMS) sensors with ground truth measured by the VICON optical system. Both filters achieved better accuracy than conventional methods at lower computational cost. The recorded data with ground truth reference and the source codes of both filters are publicly available.

State-of-the-art methods for determining thermal impedance networks for IGBT (Insulated Gate Bipolar Transistor) modules usually involves the establishment of the relationship between the measured transistor or diode voltage and temperature under homogenous temperature distribution across the IGBT module. The junction temperature is recomputed from the established voltage–temperature relationship and used in determining the thermal impedance network. This method requires accurate measurement of voltage drop across the transistors and diodes under specific designed heating and cooling profiles. Validation of the junction temperature is usually done using infrared camera or sensors placed close to the transistors or diodes (in some cases and open IGBT module) so that the measured temperature is as close to the junction as possible. In this paper, we propose an alternative method for determining the IGBT thermal impedance network using the principles of least squares. This method uses measured temperatures for defined heating and cooling cycles under different cooling conditions to determine the thermal impedance network. The results from the proposed method are compared with those obtained using state-of-the-art methods.

A problem of the switched reluctance drive is its natural torque pulsations, which are partially solved with finite control set model predictive control strategies. However, the continuous control set model predictive control, required for precise torque stabilization and predictable power converter behavior, needs sufficient computation resources, thus limiting its practical implementation. The proposed model predictive control strategy utilizes offline processing of the magnetization surface of the switched reluctance motor. This helps to obtain precalculated current references for each torque command and rotor angular position in the offline mode. In online mode, the model predictive control strategy implements the current commands using the magnetization surface for fast evaluation of the required voltage command for the power converter. The proposed strategy needs only two lookup table operations requiring very small computation time, making instant execution of the whole control system possible and thereby minimizing the control delay. The proposed solution was examined using a simulation model, which showed precise and rapid torque stabilization below rated speed.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of a metabolic syndrome. To date, liver biopsy has been the gold standard used to differentiate between simple steatosis and steatohepatitis/fibrosis. Our aim was to compare the relevance of serum non-invasive parameters and scoring systems in the staging of liver fibrosis and non-alcoholic steatohepatitis (NASH) in patients with NAFLD.A total of 112 consecutive patients diagnosed with NAFLD were included. A liver biopsy was performed on 56 patients. The Kleiner score was used for the staging and grading of the histology. Non-invasive parameters for fibrosis (hyaluronic acid; AST/ALT; fibrosis scoring indexes OELF, ELF, BARD score, APRI, NAFLD fibrosis score); and inflammation (M30 and M65 cytokeratin-18 fragments) were measured and calculated. The same analyses were performed in 56 patients diagnosed with NAFLD, who were not indicated for liver biopsy. Based on the liver histology, NASH was diagnosed in 38 patients; simple steatosis in 18 patients. A cut-off value of 750 U/L of serum M65 discriminated patients with and without NASH with a 80% sensitivity and 82% specificity (95% CI:57-95). Fibrosis stage F0-F2 was present in 39 patients; F3-F4 in 17 patients. Serum concentrations of hyaluronic acid were higher in patients with advanced fibrosis (p