Protein Abundance of Drug Metabolizing Enzymes in Human Hepatitis C Livers.

Hepatic drug metabolizing enzymes (DMEs), whose activity may be affected by liver diseases, are major determinants of drug pharmacokinetics. Hepatitis C liver samples in different functional states, i.e., the Child-Pugh class A (n = 30), B (n = 21) and C (n = 7) were analyzed for protein abundances (LC-MS/MS) and mRNA levels (qRT-PCR) of 9 CYPs and 4 UGTs enzymes. The protein levels of CYP1A1, CYP2B6, CYP2C8, CYP2C9, and CYP2D6 were not affected by the disease. In the Child-Pugh class A livers, a significant up-regulation of UGT1A1 (to 163% of the controls) was observed. The Child-Pugh class B was associated with down-regulation of the protein abundance of CYP2C19 (to 38% of the controls), CYP2E1 (to 54%), CYP3A4 (to 33%), UGT1A3 (to 69%), and UGT2B7 (to 56%). In the Child-Pugh class C livers, CYP1A2 was found to be reduced (to 52%). A significant trend in down-regulation of the protein abundance was documented for CYP1A2, CYP2C9, CYP3A4, CYP2E1, UGT2B7, and UGT2B15. The results of the study demonstrate that DMEs protein abundances in the liver are affected by hepatitis C virus infection and depend on the severity of the disease.

Adjusting the Stiffness of Supports during Milling of a Large-Size Workpiece Using the Salp Swarm Algorithm.

This paper concerns the problem of vibration reduction during milling. For this purpose, it is proposed that the standard supports of the workpiece be replaced with adjustable stiffness supports. This affects the modal parameters of the whole system, i.e., object and its supports, which is essential from the point of view of the relative tool-workpiece vibrations. To reduce the vibration level during milling, it is necessary to appropriately set the support stiffness coefficients, which are obtained from numerous milling process simulations. The simulations utilize the model of the workpiece with adjustable supports in the convention of a Finite Element Model (FEM) and a dynamic model of the milling process. The FEM parameters are tuned based on modal tests of the actual workpiece. For assessing simulation results, the proper indicator of vibration level must be selected, which is also discussed in the paper. However, simulating the milling process is time consuming and the total number of simulations needed to search the entire available range of support stiffness coefficients is large. To overcome this issue, the artificial intelligence salp swarm algorithm is used. Finally, for the best combination of stiffness coefficients, the vibration reduction is obtained and a significant reduction in search time for determining the support settings makes the approach proposed in the paper attractive from the point of view of practical applications.

Vibration Suppression with Use of Input Shaping Control in Machining.

This article discusses the problem of vibrations during machining. The manufacturing process of generator turbine blades is highly complex. Machining using Computerized Numerical Control (CNC) requires low cutting parameters in order to avoid vibration problems. However, even under these conditions, the surface quality and accuracy of the manufactured objects suffer from high levels of vibrations. Hence, the aim of this research is to counteract this phenomenon. Basic issues related to vibration problems will also be also discussed and a short review of currently available solutions for both active and passive vibration monitoring during machining will be presented. The authors developed a method which does not require any additional equipment other than modified CNC code. The proposed method can be applied to any CNC machine, and is especially suitable for lathes. The method seeks to eradicate the phenomenon of vibrations by providing enhanced control through Input Shaping Control (ISC). For this purpose, the authors present a method for modeling the machining process and design an ISC filter; the model is then implemented in the Matlab and Simulink environment. The last part of the article presents the results, together with a discussion, and includes a brief summary.

Experimental Studies of an Asymmetric Multi-Bolted Connection under Monotonic Loads.

This article describes the experimental studies of a preloaded asymmetric multi-bolted connection in the exploitation state. The construction of two stands were introduced: for bolt calibration and for evaluating the bolt forces in a multi-bolted connection. The bolts were tightened in a specific optimal sequence, in three passes, monitoring the force values in the bolts using a calibrated strain gauge measuring system. The studies were conducted for the selected multi-bolted connection on an Instron 8850 testing machine. The measurement data were saved in MATLAB R2018b Simulink. The measurement results were analysed statistically and are presented via charts showing the distributions of the normalised values of the bolt forces as a function of the linearly increasing and decreasing exploitation loads. We show that the forces in individual bolts, after unloading the multi-bolted connection, change in relation to the initial values of their preload.

Performance Analysis of Cost-Effective Miniature Microphone Sound Intensity 2D Probe.

This article presents the functional properties of modified versions of the 2D pressure-pressure intensity probe allowing us to determine the vector of sound intensity on a plane using a mechatronic system with one or two miniature electret microphones. The introduction contains basic information about the application areas of the sound intensity and its measurement problems. Next, the principle of operation of the probes and the construction of the prototype measurement system are described. It was subjected to comparative analysis for the stability of obtained results and accuracy of directional characteristics in free field conditions. For this purpose, experiments were conducted to analyze the flow of acoustic power in an anechoic chamber using both (one- and two-microphone) probes. The results were used for a comparative metrological analysis of the described methods and to indicate the advantages and disadvantages of both constructions. The next part of the article presents an experiment concerning the measurement of the sound intensity impulse response of a room, which is an example of practical use of the probe to analyze reflections in the room, which can be used in sound engineering and architectural acoustics.