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Abstract Malignant melanoma (MM) is known for its abundance of genetic alterations and a tendency for rapid metastasizing. Identification of novel plasma biomarkers may enhance non-invasive diagnostics and disease monitoring. Initially, we examined copy number variations (CNV) in CDK genes (CDKN2A, CDKN2B, CDK4) using MLPA (gDNA) and ddPCR (ctDNA) analysis. Subsequently, low-coverage whole genome sequencing (lcWGS) was used to identify the most common CNV in plasma samples, followed by ddPCR verification of chosen biomarkers. CNV alterations in CDK genes were identified in 33.3% of FFPE samples (Clark IV, V only). Detection of the same genes in MM plasma showed no significance, neither compared to healthy plasmas nor between pre- versus post-surgery plasma. Sequencing data showed the most common CNV occurring in 6q27, 4p16.1, 10p15.3, 10q22.3, 13q34, 18q23, 20q11.21-q13.12 and 22q13.33. CNV in four chosen genes (KIF25, E2F1, DIP2C and TFG) were verified by ddPCR using 2 models of interpretation. Model 1 was concordant with lcWGS results in 54% of samples, for model 2 it was 46%. Although CDK genes have not been proven to be suitable CNV liquid biopsy biomarkers, lcWGS defined the most frequently affected chromosomal regions by CNV. Among chosen genes, DIP2C demonstrated a potential for further analysis.

Mutations in BRAT1 are associated with neurodevelopmental delay and neurodegeneration. Here, the authors show that BRAT1 is a component of Integrator and is important for processing of specific RNAs. They further demonstrate that BRAT1 mutant patient-derived cells exhibit reduced levels of the Integrator catalytic subunit and increased levels of misprocessed UsnRNAs and impaired RNA processing.

Defects in DNA single-strand break repair are associated with neurodegenerative disease. Here the authors reveal that mutations in ARH3 interfere with the catabolism of mono-(ADP-ribose) and lead to its accumulation on core histones following repair of endogenous or exogenous DNA single-strand breaks.

Wavelet transform (WT) is a commonly used method for noise suppression and feature extraction from biomedical images. The selection of WT system settings significantly affects the efficiency of denoising procedure. This comparative study analyzed the efficacy of the proposed WT system on real 292 ultrasound images from several areas of interest. The study investigates the performance of the system for different scaling functions of two basic wavelet bases, Daubechies and Symlets, and their efficiency on images artificially corrupted by three kinds of noise. To evaluate our extensive analysis, we used objective metrics, namely structural similarity index (SSIM), correlation coefficient, mean squared error (MSE), peak signal-to-noise ratio (PSNR) and universal image quality index (Q-index). Moreover, this study includes clinical insights on selected filtration outcomes provided by clinical experts. The results show that the efficiency of the filtration strongly depends on the specific wavelet system setting, type of ultrasound data, and the noise present. The findings presented may provide a useful guideline for researchers, software developers, and clinical professionals to obtain high quality images.

Fatigue behaviour of nodular cast irons is described in specialized literature quite well but the majority of fatigue tests in high cycle region has been made at symmetrical bending or at symmetrical tension-compression loading. The role of loading cycle asymmetry is very important because the fatigue limit of nodular cast irons is substantially influenced by mean static stress. Unfortunately, the number of papers describing the influence of mean static stress is quite low. The aim of the presented paper consists in presenting the results of long-term research of nodular cast irons at high cycle region at different loading cycle asymmetry. Several heats with various heat treatments leading to various structures of matrix were used for fatigue tests performed mainly at symmetrical tension-compression loading and at repeating tensile loading. From S-N curves the fatigue limits for 107 cycles were determined and then used for the calculation and construction of the Haigh and the Smith diagrams. Nodular cast irons seem to be more sensitive to mean static stress than structural steels. It was found that, in contrast to many papers, the dependence of upper stress on mean stress is not linear but parabolic with the exponent lower than 1 whose value is linear function of UTS.

The presented work deals with a high-strength variant of nodular cast iron, so-called ADI (austempered ductile iron). This material ranks among prospective structural materials and is more and more applied in all important branches of machine industry. Recently it has even been applied to castings for cyclically loaded components, i.e. gears and traversing wheels, crankshafts of motor-cars, vans and trucks, swivel pins, rail brakes, pressure pipes in oil industry etc. The microstructure composition of an ADI matrix consists especially of bainitic ferrite and stabilized austenite. However, in dependence on transformation dwell some amount of martensite can appear as well.In this work the relation between mechanical properties and microstructure composition of the matrix mixture was studied in detail for the case of ADI transformed at 380 °C, with emphasis on fatigue properties.

As a result of excellent both mechanical and technological properties, austempered ductile iron (ADI) is ranked with very perspective structural materials. Recently it has been applied even to castings for dynamically loaded components and a considerable part of ADI production is applied also in military industry. The structure of ADI matrix, mostly created by the mixture of bainite and stabilized austenite, strongly depends on transformation conditions, i.e. temperature and the length of isothermal transformation dwell. An ADI transformed at 380 °C during a temporal range from 2 minutes to 9 hours was studied in details, with emphasis on structural composition and fatigue properties. The highest level of fatigue properties was obtained for the transformation dwell of 60 minutes when the maximum portion of austenite was found in ADI structure.