Formänderungsgrößenverfahren mittig gedrückter dünnwandiger Stäbe mit einfach‐ und doppeltsymmetrischen offenen Querschnitten

Deformation method for centrically compressed thin‐walled bars with mono‐ and bisymmetrical open cross‐sections. In correspondence with the classic deformation method of warping torsion for thin‐walled bars [1], that method has been moved into the field of column stability. For the single cross‐sectional symmetry, the general solution of the fundamental system of equations has been found and its particular shapes for three basic kinds of column support presented. Thereby, the formulas or the boundary simplified for analysis of the bimoments have been settled. These relations have been simplified for the double cross‐sectional symmetry. An analysis of a bisymmetrical cross‐section has lead to the determination of the necessary boundary forces for the three kinds of column support considered. It has been shown that all the relations for torsion are similar to those for bending. A proposal for the calculations of the critical loads of torsional buckling in continuous columns has been formulated and a relevant numerical example given. The paper calls special attention to the related merits of Professor Kurt Klöppel , a graduate of the former Technischen Hochschule Danzig. Actually, already 100 years have passed since the foundation of TH Danzig. It is also the predecessor of the contemporary Politechnika Gdańska, with which the author is being connected since 1949.     

A Process for Cf/SiC Composites Using Liquid Polymer Infiltration

A continuous carbon fiber/silicon carbide matrix composite material has been produced by a low-cost process. In this process the space in a two-dimensional carbon fiber preform is filled with a SiC powder by a pressure infiltration method. High particle packing densities are achieved within the fiber preform in this way. The compact body is heat-treated at 400°C to form a porous framework, which is then infiltrated with a liquid preceramic polymer, Ceraset^TM SN. Subsequently the infiltrated polymer is pyrolyzed in argon at 1300°C. The microstructure of the final composite is characterized, and mechanical properties of these composites are discussed.     

Influence of Injection, Packaging, and Storage Conditions on the Quality of Beef and Bison Steaks

The combined effects of injection, packaging (modified atmosphere packaging [MAP] with 70% O₂/ 30% CO₂ and vacuum packaging [VP]), storage temperature (‐1 °C and +4 °C), and storage time on the color, microbial and oxidative stability of beef and bison longissimus lumborum (LL) steaks were investigated. Beef LL steaks in MAP retained their bright red color longer than bison steaks. Bison steaks developed higher 2‐Thiobarbituric acid reactive substances (TBARS) during storage, and this might have influenced the resulting rapid loss of redness from the bloomed meat. Storage at ‐1 °C in MAP provided greater color stability and a longer storage life for both meat species studied. Injection of salt/phosphate had a beneficial effect on the color stability of steaks during retail display; however, this positive effect was more pronounced for bison steaks compared with those of beef. Steaks stored overnight under MAP before retail display maintained the highest a* values for up to 5 d compared with those stored under vacuum. MAP‐OV steaks generally maintained the highest OMB content for up to 5 d during retail display compared with those stored under vacuum. Nevertheless, OMB levels were significantly (P < 0.05) lower in bison steaks compared with those of beef irrespective of packaging treatments. Injected steaks and those stored at ‐1 °C had significantly (P < 0.05) higher OMB levels compared with non‐injected counterparts and those stored at +4 °C, respectively. MAP is an excellent option for short‐term storage due to its positive effects on meat color, but for longer storage, VP may be necessary. Storing meat under vacuum and then placing it under MAP just before retail display might be another option to increase shelf life.     

Photopharmacology of Antimitotic Agents

Antimitotic agents such as the clinically approved vinca alkaloids, taxanes and epothilone can arrest cell growth during interphase and are therefore among the most important drugs available for treating cancer. These agents suppress microtubule dynamics and thus interfere with intracellular transport, inhibit cell proliferation and promote cell death. Because these drugs target biological processes that are essential to all cells, they face an additional challenge when compared to most other drug classes. General toxicity can limit the applicable dose and therefore reduce therapeutic benefits. Photopharmacology aims to avoid these side-effects by introducing compounds that can be applied globally to cells in their inactive form, then be selectively induced to bioactivity in targeted cells or tissue during a defined time window. This review discusses photoswitchable analogues of antimitotic agents that have been developed by combining different photoswitchable motifs with microtubule-stabilizing or microtubule-destabilizing agents.     

Gene Variants Related to Cardiovascular and Pulmonary Diseases May Correlate with Severe Outcome of COVID-19

Background: Severe outcomes of COVID-19 account for up to 15% of all cases. The study aims to check if any gene variants related to cardiovascular (CVD) and pulmonary diseases (PD) are correlated with a severe outcome of COVID-19 in a Polish cohort of COVID-19 patients. Methods: In this study, a subset of 747 samples from unrelated individuals collected across Poland in 2020 and 2021 was used and whole-genome sequencing was performed. Results: The GWAS analysis of SNPs and short indels located in genes related to CVD identified one variant significant in COVID-19 severe outcome in the HADHA gene, while for the PD gene panel, we found two significant variants in the DRC1 gene. In this study, both potentially protective and risk variants were identified, of which variants in the HADHA gene deserve the most attention. Conclusions: This is the first study reporting the association between the HADHA and DRC1 genetic variants and COVID-19 severe outcome based on the cohort WGS analysis. Although all the identified variants are localised in introns, they may be correlated and therefore inherited along with other risk variants, potentially causative to severe outcome of COVID-19 but not discovered yet.     

Model of Environmental Membrane Field for Transmembrane Proteins

The water environment determines the activity of biological processes. The role of such an environment interpreted in the form of an external field expressed by the 3D Gaussian distribution in the fuzzy oil drop model directs the folding process towards the generation of a centrally located hydrophobic core with the simultaneous exposure of polar residues on the surface. In addition to proteins soluble in the water environment, there is a significant group of membrane proteins that act as receptors or channels, including ion channels in particular. The change of the polar (water) environment into a highly hydrophobic (membrane) environment is quite radical, resulting in a different hydrophobicity distribution within the membrane protein. Modification of the notation of the force field expressing the presence of the hydrophobic environment has been proposed in this work. A modified fuzzy oil drop model with its adaptation to membrane proteins was used to interpret the structure of membrane proteins–mechanosensitive channel. The modified model was also used to describe the so-called negative cases—i.e., for water-soluble proteins with a clear distribution consistent with the fuzzy oil drop model.     

Advanced Spectroscopy and APBS Modeling for Determination of the Role of His190 and Trp103 in Mouse Thymidylate Synthase Interaction with Selected dUMP Analogues

A homo-dimeric enzyme, thymidylate synthase (TS), has been a long-standing molecular target in chemotherapy. To further elucidate properties and interactions with ligands of wild-type mouse thymidylate synthase (mTS) and its two single mutants, H190A and W103G, spectroscopic and theoretical investigations have been employed. In these mutants, histidine at position 190 and tryptophan at position 103 are substituted with alanine and glycine, respectively. Several emission-based spectroscopy methods used in the paper demonstrate an especially important role for Trp 103 in TS ligands binding. In addition, the Advanced Poisson–Boltzmann Solver (APBS) results show considerable differences in the distribution of electrostatic potential around Trp 103, as compared to distributions observed for all remaining Trp residues in the mTS family of structures. Together, spectroscopic and APBS results reveal a possible interplay between Trp 103 and His190, which contributes to a reduction in enzymatic activity in the case of H190A mutation. Comparison of electrostatic potential for mTS complexes, and their mutants, with the substrate, dUMP, and inhibitors, FdUMP and N4-OH-dCMP, suggests its weaker influence on the enzyme–ligand interactions in N4OH-dCMP-mTS compared to dUMP-mTS and FdUMP-mTS complexes. This difference may be crucial for the explanation of the ”abortive reaction” inhibitory mechanism of N4OH-dCMP towards TS. In addition, based on structural analyses and the H190A mutant capacity to form a denaturation-resistant complex with N4-OH-dCMP in the mTHF-dependent reaction, His190 is apparently responsible for a strong preference of the enzyme active center for the anti rotamer of the imino inhibitor form.     

Foam Cells as Therapeutic Targets in Atherosclerosis with a Focus on the Regulatory Roles of Non-Coding RNAs

Atherosclerosis is a major cause of human cardiovascular disease, which is the leading cause of mortality around the world. Various physiological and pathological processes are involved, including chronic inflammation, dysregulation of lipid metabolism, development of an environment characterized by oxidative stress and improper immune responses. Accordingly, the expansion of novel targets for the treatment of atherosclerosis is necessary. In this study, we focus on the role of foam cells in the development of atherosclerosis. The specific therapeutic goals associated with each stage in the formation of foam cells and the development of atherosclerosis will be considered. Processing and metabolism of cholesterol in the macrophage is one of the main steps in foam cell formation. Cholesterol processing involves lipid uptake, cholesterol esterification and cholesterol efflux, which ultimately leads to cholesterol equilibrium in the macrophage. Recently, many preclinical studies have appeared concerning the role of non-encoding RNAs in the formation of atherosclerotic lesions. Non-encoding RNAs, especially microRNAs, are considered regulators of lipid metabolism by affecting the expression of genes involved in the uptake (e.g., CD36 and LOX1) esterification (ACAT1) and efflux (ABCA1, ABCG1) of cholesterol. They are also able to regulate inflammatory pathways, produce cytokines and mediate foam cell apoptosis. We have reviewed important preclinical evidence of their therapeutic targeting in atherosclerosis, with a special focus on foam cell formation.