LDLR gene rearrangements in Czech FH patients likely arise from one mutational event.

BACKGROUND: Large deletions and duplications within the low-density lipoprotein receptor (LDLR) gene make up approximately 10% of LDLR pathogenic variants found in Czech patients with familial hypercholesterolemia. The goal of this study was to test the hypothesis that all probands with each rearrangement share identical breakpoints inherited from a common ancestor and to determine the role of Alu repetitive elements in the generation of these rearrangements. METHODS: The breakpoint sequence was determined by PCR amplification and Sanger sequencing. To confirm the breakpoint position, an NGS analysis was performed. Haplotype analysis of common LDLR variants was performed using PCR and Sanger sequencing. RESULTS: The breakpoints of 8 rearrangements within the LDLR gene were analysed, including the four most common LDLR rearrangements in the Czech population (number of probands ranging from 8 to 28), and four less common rearrangements (1-4 probands). Probands with a specific rearrangement shared identical breakpoint positions and haplotypes associated with the rearrangement, suggesting a shared origin from a common ancestor. All breakpoints except for one were located inside an Alu element. In 6 out of 8 breakpoints, there was high homology (≥ 70%) between the two Alu repeats in which the break occurred. CONCLUSIONS: The most common rearrangements of the LDLR gene in the Czech population likely arose from one mutational event. Alu elements likely played a role in the generation of the majority of rearrangements inside the LDLR gene.

Rheological Characteristics of Fe-C-Cr(Ni) Alloys.

The principal objective of this project was to investigate the rheological properties of Fe-C-Cr and Fe-C-Ni-based low-alloy steels using an Anton Paar high-temperature rotational viscometer up to 1550 °C. The emphasis was placed on determining the liquidus temperatures and evaluating the flow and viscosity curves and the temperature dependence of dynamic viscosity. All were studied depending on the change in the content of chromium (0.010-4.863 wt%), nickel (0.001-4.495 wt%), and carbon (0.043-1.563 wt%). It was shown that the dynamic viscosity decreases with increasing nickel content and increases with increasing carbon and chromium content. The experimental data of the flow curves were fitted using the Herschel-Bulkley model with a good agreement between the measured and calculated values. Characterization of the internal structure was performed by SEM and EDX analyses, confirming non-significant changes in the microstructure of the original and remelted samples. The phase composition of the selected samples was also determined using JMatPro 12.0 simulation software (Sente Software Ltd., Guildford, UK).

The Effect of Trace Oxygen Addition on the Interface Behavior of Low-Alloy Steel.

This work aims to assess the effect of an oxygen content graded in minimal quantities, on the order of hundreds of ppms, on the determination of surface tension of low-alloy FeCOCr and FeCONi steels in contact with a corundum substrate. Oxygen, as a surface-active element, was segregated at the surface where it interacted with the major components of the alloys, leading to a reduction in surface tension. The sessile drop method was used for wetting tests in the temperature range from steel liquidus temperatures to 1600 °C under nonoxidizing conditions. The effect of oxygen on surface tension and wetting angles was verified by statistical analysis using the Kruskal-Wallis test, which supported the results stating that the values of these quantities decreased with increasing oxygen content. Furthermore, liquidus temperatures, which are of practical importance, were determined by the optical and DTA methods and then compared with theoretically calculated temperature values. It turned out that the increased chromium content causes difficulties in determining surface tension up to 1550 °C due to the formation of a thin Cr2O3 layer. In addition, SEM and XRD analyses accompanied by calculations in the FactSage oxide database were performed to better understand the wetting mechanism.

Hot Deformation Behavior of Non-Alloyed Carbon Steels.

The hot deformation behavior of selected non-alloyed carbon steels was investigated by isothermal continuous uniaxial compression tests. Based on the analysis of experimentally determined flow stress curves, material constants suitable for predicting peak flow stress σp, peak strain εp and critical strain εcrDRX necessary to induce dynamic recrystallization and the corresponding critical flow stresses σcrDRX were determined. The validity of the predicted critical strains εcrDRX was then experimentally verified. Fine dynamically recrystallized grains, which formed at the boundaries of the original austenitic grains, were detected in the microstructure of additionally deformed specimens from low-carbon investigated steels. Furthermore, equations describing with perfect accuracy a simple linear dependence of the critical strain εcrDRX on peak strain εp were derived for all investigated steels. The determined hot deformation activation energy Q decreased with increasing carbon content (also with increasing carbon equivalent value) in all investigated steels. A logarithmic equation described this dependency with reasonable accuracy. Individual flow stress curves of the investigated steels were mathematically described using the Cingara and McQueen model, while the predicted flow stresses showed excellent accuracy, especially in the strains ranging from 0 to εp.

Analysis of Welded Joint Properties on an AISI316L Stainless Steel Tube Manufactured by SLM Technology.

This work is focused on the analysis of the influence of welding on the properties and microstructure of the AISI316L stainless steel tube produced by 3D printing, specifically the SLM (Selective Laser Melting) method. Both non-destructive and destructive tests, including metallographic and fractographic analyses, were performed within the experiment. Microstructure analysis shows that the initial texture of the 3D print disappears toward the fuse boundary. It is evident that high temperature during welding has a positive effect on microstructure. Material failure occurred in the base material near the heat affected zone (HAZ). The results obtained show the fundamental influence of SLM technology in terms of material defects, on the properties of welded joints.

Microstructure and Electrochemical Behavior of TiO2 Nanotubes Coated on Titanium-Based Substrate Before and After Thermal Treatment.

The comparative study of the structure and electrochemical properties of TiO2 layers on the surfaces of commercially pure titanium and Ti6Al4V alloy were performed. The TiO2 surface layers produced by anodization in ethylene glycol-based electrolyte solution using Power Supply MCS-3204 MANSON at 20 V or 40 V for 60 minutes were formed on the titanium substrates by simultaneous surface oxidation and controlled dissolving of oxide film due the fluorine ions. The SEM and X-ray diffraction analyses were performed to determine the properties of the anodized layers before and after heat treatment at 500 °C for 120 minutes. The as-anodized TiO2 nanotubes exhibited an amorphous structure. An anatase phase appeared in annealed nanotube layers of both Ti based substrates. The corrosion behavior in simulated physiological solution was compared for not anodized, anodized and anodized heat treated conditions of both titanium surfaces. The results of the electrochemical measurements corresponded to the microstructure and treatment condition. The porous feature of the anodizing layers on Ti6Al4V substrate led to lower corrosion resistance that increased after the heat treatment.