Hexokinase 2 Inhibition and Biological Effects of BNBZ and Its Derivatives: The Influence of the Number and Arrangement of Hydroxyl Groups

Hexokinase 2 (HK2), an enzyme of the sugar kinase family, plays a dual role in glucose metabolism and mediating cancer cell apoptosis, making it an attractive target for cancer therapy. While positive HK2 expression usually promotes cancer cells survival, silencing or inhibiting this enzyme has been found to improve the effectiveness of anti-cancer drugs and even result in cancer cell death. Previously, benitrobenrazide (BNBZ) was characterized as a potent HK2 inhibitor with good anti-cancer activity in mice, but the effect of its trihydroxy moiety (pyrogallol-like) on inhibitory activity and some cellular functions has not been fully understood. Therefore, the main goal of this study was to obtain the parent BNBZ (2a) and its three dihydroxy derivatives 2b–2d and to conduct additional physicochemical and biological investigations. The research hypothesis assumed that the HK2 inhibitory activity of the tested compounds depends on the number and location of hydroxyl groups in their chemical structure. Among many studies, the binding affinity to HK2 was determined and two human liver cancer cell lines, HepG2 and HUH7, were used and exposed to chemicals at various times: 24 h, 48 h and 72 h. The study showed that the modifications to the structures of the new BNBZ derivatives led to significant changes in their activities. It was also found that these compounds tend to aggregate and exhibit toxic effects. They were found to contribute to: (a) DNA damage, (b) increased ROS production, and (c) disruption of cell cycle progression. It was observed that, HepG2, occurred much more sensitive to the tested chemicals than the HUH7 cells; However, regardless of the used cell line it seems that the increase in the expression of HK2 in cancer cells compared to normal cells which have HK2 at a very low level, is a serious obstacle in anti-cancer therapy and efforts to find the effective inhibitors of this enzyme should be intensified.     

Measurement of mechanical properties in a 316L stainless steel welded joint

The aim of this study was to measure the mechanical properties of weld material taken from a single weld bead laid down on a 316L steel plate. Due to the low available volume of weld material, microsamples with a total length of 5.5 mm were used. The Digital Image Correlation method (DIC), which enables measurement of mechanical properties of very small samples, was employed for the strain measurements in a uniaxial tensile test. Samples were cut out from three different zones of the specimen: plate, weld, and the heat affected zone. The material from heat affected zone showed the highest value of the Ultimate Tensile Strength (UTS) (580 ± 7 MPa) and yield strength (339 ± 6 MPa). Plate material had lower UTS (559 ± 5 MPa) and yield strength (304 ± 7 MPa). The lowest values of UTS (526 ± 6 MPa) and yield strength (291 ± 8 MPa) have been revealed for the weld. The values obtained for UTS, yield strength and elongation to failure for the plate material were compared with data obtained using standard test specimens. No significant differences between results obtained for the microsamples and standard samples have been found.     

Evaluation of the mechanical behavior of W7-X central support connections by means of semi-automated FE analysis

The stellarator Wendelstein 7-X is under construction at the Max-Planck-Institut für Plasmaphysik in Greifswald. Its superconducting coil system is fixed by a massive structure. During machine operation the coils exert high forces and moments against each other and the central support structure (CSS). Therefore, the detailed analysis of the coil to CSS connections, the so-called central support elements (CSE), is a critical item. The major details of the design have been frozen; nevertheless, there is still need for detailed analysis of the CSEs due to assembly issues, and later on for exploring operational limits of the machine. These analyses have to be performed quickly, reliably, and shall provide results in a standardized form to enable timely responses to the assembly team. Special numerical tools – finite element (FE) parametric models of CSEs – have been developed for the purpose of such analyses. In the models, the geometry, material properties, contact conditions, loads as well as results presentation are defined in a parametric way. The use of the developed models for the definition of the final weld parameters, bolt preloads, assessment of acceptable tolerances, and optimal positions of the CSE-wedges before welding is also discussed.     

Freshness and quality attributes of cold stored Atlantic bonito (Sarda sarda) gravad

Quality and safety parameters of Atlantic bonito gravad during 42 days of storage at 7 ± 1 °C were analysed using monitoring sensory quality, microbial contamination, nucleotide degradation products, biogenic amines (BA), trimethylamine (TMA) and thiobarbituric acid reactive substances (TBARS). The shelf‐life of vacuum packed Atlantic bonito gravad was found to be 28 days. Total viable count (TVC) did not exceed 6 log CFU g^?1. Malonodialdehyde (MDA) content did not surpass 10 mg kg^?1. Nine biogenic amines were detected. Histamine level at the end of the storage was 355.3 mg kg^?1. TMA increased from 53.9 to 619.1 mg kg^?1. Among indicators based on the products of nucleotide degradation, the H value is best correlated with the sensory assessment. It can be concluded that the storage temperature of bonito gravad must be below 7 °C to prevent the threat to safety and quality posed by biogenic amines, especially histamine.     

Finishing works after welding of structures made of rust-resistant,high-alloy steels

In this paper, problems that occur when working with welds formed of high-alloy steels to restore their passive layers, damaged as a result of temperature impact, are discussed. Particular attention was paid to the procedures concerning aggressive etching agents during and after completion of the passivation processes (waste neutralization and utilization).     

Technology of welding and properties of welded joints of new bainitic and martensitic steels with creep-resistant steels

This paper shows the results of welding tests used so far on high-temperature creep resistant steels and new bainitic and martensitic steels. The positive results of this research allowed the elaboration of a welding procedure specification that was ultimately approved by TÜV. This then allowed the SEFAKO Company to attempt welding of the latest generation boiler steels for use under heavy conditions.     

TIG brazing technology for zinc-coated sheet steel for bodywork

We propose a method for the assessment of the state of welded joints in terms of arc voltage signals and feed rate appraisal. The signals were recorded during laboratory tests. For the appraisal of the signals, we applied numerical parameters such as, for instance, kurtosis. On the basis of analysis results, we developed diagnostic rules which were written in the binary diagnostic matrix. The proposed method has been implemented in the form of software, the correctness of which has been verified on experimental data.     

A Lamarckian Hybrid of Differential Evolution and Conjugate Gradients for Neural Network Training

The paper describes two schemes that follow the model of Lamarckian evolution and combine differential evolution (DE), which is a population-based stochastic global search method, with the local optimization algorithm of conjugate gradients (CG). In the first, each offspring is fine-tuned by CG before competing with their parents. In the other CG is used to improve both parents and offspring in a manner that is completely seamless for individuals that survive more than one generation. Experiments involved training weights of feed-forward neural networks to solve three synthetic and four real-life problems. In six out of seven cases the DE–CG hybrid, which preserves and uses information on each solution’s local optimization process, outperformed two recent variants of DE.     

Biochemical,microbiological and sensory changes in shrimp (Panaeus aztecus) dipped in different solutions using face‐centred central composite design

Biochemical, microbiological and sensory changes during shelf‐life at ?1 °C were determined in shrimp (Panaeus aztecus) previously dipped in ascorbic acid, citric acid, potassium sorbate and 4‐hexyl resorcinol solutions using face‐centred central composite design. Microbiological count, trimethylamine and hypoxantine production were measured. The lowest level of the total psychrotrophic bacteria, hypoxantine and trimethylamine were found in samples dipped in all containing chemicals solutions comparing to control treatment. Sensory studies showed that treatment A (ascorbic acid 4.50, citric acid 0.12, potassium sorbate 18.60 and 4‐hexyl resorcinol 0.25, all g L^?1) and B (ascorbic acid 4.37, citric acid 1.26, potassium sorbate 7.03 and 4‐hexyl resorcinol 0.25, all g L^?1) did not alter the typical sensory features of shrimp and were effective at delaying the bitter off‐flavour formation for 26 days. This study constitutes a promising alternative to extent shelf‐life of shrimp kept at ?1 °C without freezing.