The microstructure of liquid immiscible Fe–Cu-based in situ formed amorphous/crystalline composite

In the microstructures of slowly and rapidly cooled liquid of the immiscible alloy Fe₃₀Cu₃₂Ni₁₀Si₁₃Sn₄B₉Y₂ two distinct regions were observed following arc melting and slow cooling, confirming that liquid/liquid phase separation had occurred. Rapid cooling from a temperature within the liquid immiscibility gap, melt spinning, resulted in an amorphous/crystalline composite, formed from the previously melted Fe- and Cu-rich regions, respectively. Transmission electron microscopic studies of this melt-spun ribbon revealed the glassy nature of the Fe-rich matrix, as well as of the Fe-rich spheres formed within the previously existing Cu-rich liquid.     

Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists

The incidence of type 2 diabetes (T2D) has been increasing worldwide, and diabetic kidney disease (DKD) remains one of the leading long-term complications of T2D. Several lines of evidence indicate that glucose-lowering agents prevent the onset and progression of DKD in its early stages but are of limited efficacy in later stages of DKD. However, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor (GLP-1R) agonists were shown to exert nephroprotective effects in patients with established DKD, i.e., those who had a reduced glomerular filtration rate. These effects cannot be solely attributed to the improved metabolic control of diabetes. In our review, we attempted to discuss the interactions of both groups of agents with inflammation and oxidative stress—the key pathways contributing to organ damage in the course of diabetes. SGLT2i and GLP-1R agonists attenuate inflammation and oxidative stress in experimental in vitro and in vivo models of DKD in several ways. In addition, we have described experiments showing the same protective mechanisms as found in DKD in non-diabetic kidney injury models as well as in some tissues and organs other than the kidney. The interaction between both drug groups, inflammation and oxidative stress appears to have a universal mechanism of organ protection in diabetes and other diseases.     

Modelling of the spring-in phenomenon in curved parts made of a thermosetting composite

In this study, a simple two step finite element model is developed to predict the spring-in of C-sections parts made of AS4/8552 composite. The development of resin properties throughout the MRCC were derived using Group Interaction Modelling and the mechanical properties of the composite predicted by using micromechanical models. Important mechanisms during manufacturing that are effective in the formation of residual stresses and shape distortions are defined. The finite element method implemented is composed of two steps before and after the vitrification of the resin. Vitrification is treated as a point at which the material suddenly changes from the rubbery to glassy state with constant properties in each state. The spring-in angles predicted by the finite element analysis are compared to the angles measured on C-section specimens of various lay-ups and thicknesses. The correlation is good showing the validity of the assumptions adopted.     

Simplified modeling strategies for surrogate validation with multivariate failure-time data

The linear mixed effects model has become a standard tool for the analysis of continuous hierarchical data such as, for example, repeated measures or data from meta-analyses. However, in certain situations the model does pose unavoidable computational problems. In the context of surrogate markers, this problem has appeared when using an estimation and prediction-based approach for the evaluation of surrogate endpoints. Convergence problems can occur mainly due to small between-trial variability or small number of trials. A number of alternative strategies has been proposed and studied for normally distributed data, but not such study has been conducted for other types of endpoints. The idea is to study if such simplified strategies, which always ignore individual level surrogacy, can also be applied when both surrogate and true endpoints are of failure-time types. It is shown via simulations that the 3 simplified strategies produced biased estimates, especially for the cases in which the strength of individual level association is different from the strength of trial level association. For this reason, it is recommended not to use simplified strategies when dealing with failure-time data, in contrast to the case of normally distributed data, for which simplified strategies are recommended. Possible reasons for this discrepancy might be that, in this case, ignoring the individual level association influences estimates of the mean structure parameters, what results in distorted estimates of the trial level association.     

The Characteristics of the Superconducting and Magnetic Phases in the Polycrystalline Samples of Ruthenocuprates of Nominal Compositions RuSr2GdCu2O8, Ru0.98Sr2GdCu2O8 and Ru0.5Sr2GdCu2.5O8−δ

The temperature dependencies of the resistivity for the superconducting ruthenocuprates of nominal compositions RuSr₂GdCu₂O₈, Ru_0.98Sr₂GdCu₂O₈ and Ru_0.5Sr₂GdCu_2.5O_8?δ were examined for the magnetic field dependent characteristics of the superconducting transitions. The effect of the insignificant diminishing of the Ru/Cu ratio in parent RuSr₂GdCu₂O₈ was confirmed as relevant for the stabilisation of the superconducting phase. Noted differences in the compared characteristics are interpreted for possible inhomogeneous nucleation of the superconducting phase in the parent ruthenocuprate. The phase anisotropy in RuSr₂GdCu₂O₈ and Ru_0.98Sr₂GdCu₂O₈, in presence of the compounds Ru magnetism, appears to be a cause of a significant softening of the H _c2(T) phase line. An anomalous lowering of the magnetoresistivity was observed in the approx. 10 K range above the onset of the superconducting transition, which may suggest the presence of enhanced superconducting fluctuations in the samples. The positive magnetic field shift of the temperatures, which limit the magnetoresistivity and the specific heat signatures of the magnetic ordered state of the Ru sublattice, suggests probing the influence of the ferromagnetic Ru interactions in an effective metallic-like conduction channel present in the samples. Superconducting characteristics of the Ru_0.5Sr₂GdCu_2.5O_8?δ reveal a significant contribution of the Gd paramagnetic signal at low temperatures, interpreted for the presence of a significant anisotropy of the superconducting phase. It is concluded that the Ru–Cu substituted phases of ruthenocuprates may present an opportunity to investigate the effectively anisotropic superconducting phase despite its comparatively high T _c in the compounds related to the 123-type cuprate superconductor.     

Design,Synthesis, and Evaluation of ω‐(Isothiocyanato)alkylphosphinates and Phosphine Oxides as Antiproliferative Agents

A series of 21 novel, structurally diverse ω‐(isothiocyanato)alkylphosphinates and phosphine oxides (ITCs) were designed and synthesized in moderate to good yields. The synthesized compounds were evaluated for in vitro antiproliferative activity using LoVo and LoVo/DX cancer cell lines. The biological activity of the synthesized compounds was higher than that of natural isothiocyanates such as benzyl isothiocyanate or sulforaphane. The antiproliferative activity of selected ITCs was also tested on selected cancer cell lines: A549, MESSA and MESSA/DX‐5, HL60 and HL60MX2, BALB/3T3, and 4T1. These compounds were assessed for their mechanism of action as inducers of cell‐cycle arrest and apoptosis. Ethyl (6‐isothiocyanatohexyl)(phenyl)phosphinate ( 71 ) was tested in vivo on the 4T1 cell line and demonstrated moderate antitumor activity, similar to that benzyl isothiocyanate and cyclophosphamide.     

On the Dependence of Prion and Amyloid Structure on the Folding Environment

Currently available analyses of amyloid proteins reveal the necessity of the existence of radical structural changes in amyloid transformation processes. The analysis carried out in this paper based on the model called fuzzy oil drop (FOD) and its modified form (FOD-M) allows quantifying the role of the environment, particularly including the aquatic environment. The starting point and basis for the present presentation is the statement about the presence of two fundamentally different methods of organizing polypeptides into ordered conformations—globular proteins and amyloids. The present study shows the source of the differences between these two paths resulting from the specificity of the external force field coming from the environment, including the aquatic and hydrophobic one. The water environment expressed in the fuzzy oil drop model using the 3D Gauss function directs the folding process towards the construction of a micelle-like system with a hydrophobic core in the central part and the exposure of polarity on the surface. The hydrophobicity distribution of membrane proteins has the opposite characteristic: Exposure of hydrophobicity at the surface of the membrane protein with an often polar center (as in the case of ion channels) is expected. The structure of most proteins is influenced by a more or less modified force field generated by water through the appropriate presence of a non-polar (membrane-like) environment. The determination of the proportion of a factor different from polar water enables the assessment of the protein status by indicating factors favoring the structure it represents.     

Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments

Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world’s population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.