Numerical model of a planar jet wiping system for continuous strip lines

Journal of Mechanical Science and Technology - The present study focuses on the numerical modelling of gas-jet wiping process. Many processes involving liquids are necessary during steel...     

Colloidal thiophosphorus calcium salt as antiwear additive

This paper describes the synthesis of an oil-soluble colloidal calcium thiophosphate by a direct route. It consists of the reaction of calcium oxide or hydroxide with tetraphosphorus decasulphide and water in the presence of a surfactant such as a calcium alkylaryl sulphonate in an organic medium. Reaction and micellisation occurred simultaneously according to a one-step process. The product is characterised by a high calcium, phosphorus and sulphur content. The colloidal nature of the product has been confirmed by dialysis. The ³¹P-NMR spectrum showed signals characteristic of a blend of different calcium thiophosphates, plus calcium phosphate. The product could be defined as a core of different calcium (thio)phosphates surrounded by a calcium alkylaryl sulphonate shell, according to a reverse micelle type association in oil. This compound was evaluated as an antiwear additive in a 130 Neutral Solvent mineral oil by anti-wear and extreme-pressure four-ball tests. The extreme-pressure characteristics depend on the concentration of mineral colloidal core in oil. The antiwear properties are a function not only of the concentration, but also of the colloidal core/surfactant shell ratio. Thermogravimetric analysis of these colloidal species shows a weight loss in the 350°C to 450°C range, due to surfactant degradation. The further evolution of weight loss up to 900°C demonstrates the high thermal stability of the colloidal calcium (thio)phosphate core.     

Glial Modulation of Energy Balance: The Dorsal Vagal Complex Is No Exception

The avoidance of being overweight or obese is a daily challenge for a growing number of people. The growing proportion of people suffering from a nutritional imbalance in many parts of the world exemplifies this challenge and emphasizes the need for a better understanding of the mechanisms that regulate nutritional balance. Until recently, research on the central regulation of food intake primarily focused on neuronal signaling, with little attention paid to the role of glial cells. Over the last few decades, our understanding of glial cells has changed dramatically. These cells are increasingly regarded as important neuronal partners, contributing not just to cerebral homeostasis, but also to cerebral signaling. Our understanding of the central regulation of energy balance is part of this (r)evolution. Evidence is accumulating that glial cells play a dynamic role in the modulation of energy balance. In the present review, we summarize recent data indicating that the multifaceted glial compartment of the brainstem dorsal vagal complex (DVC) should be considered in research aimed at identifying feeding-related processes operating at this level.     

Structural and Functional Characterization of 4-Hydroxyphenylacetate 3-Hydroxylase from Escherichia coli

The hydroxylation of phenols into polyphenols, which are valuable chemicals and pharmaceutical products, is a challenging reaction. The search for green synthetic processes has led to considering microorganisms and pure hydroxylases as catalysts for phenol hydroxylation. Herein, we report the structural and functional characterization of the flavin adenine dinucleotide (FAD)-dependent 4-hydroxyphenylacetate 3-monooxygenase from Escherichia coli, named HpaB. It is shown that this enzyme enjoys a relatively broad substrate specificity, which allows the conversion of a number of non-natural phenolic compounds, such as tyrosol, hydroxymandelic acid, coumaric acid, hydroxybenzoic acid and its methyl ester, and phenol, into the corresponding catechols. The reaction can be performed by using a simple chemical assay based on formate as the electron donor and the organometallic complex [Rh(bpy)Cp*(H₂O)]²⁺ (Cp*: 1,2,3,4,5-pentamethylcyclopentadiene, bpy: 2,2′-bipyridyl) as the catalyst for FAD reduction. The availability of a crystal structure of HpaB in complex with FAD at 1.8 Å resolution opens up the possibility of the rational tuning of the substrate specificity and activity of this interesting class of phenol hydroxylases.     

Prolonged display or rapid internalization of the IgG-binding protein ZZ anchored to the surface of cells using the diphtheria toxin T domain

We have shown previously that the diphtheria toxin transmembranedomain (T) may function as a membrane anchor for soluble proteinsfused at its C-terminus. Binding to membranes is triggered byacidic pH. Here, we further characterized this anchoring device.Soluble proteins may be fused at the N-terminus of the T domainor at both extremities, without modifying its membrane bindingproperties. This allows one to choose the orientation of theprotein to be attached to the membrane. Maximum binding to thecell surface is reached within 1 h. Anchoring occurs on cellspreviously treated with proteinase K, suggesting that T interactswith the lipid phase of the membrane without the help of cellsurface proteins. Binding does not permeabilize cells or affectcell viability, despite the fact that it permeabilizes liposomesand alters their structure. When attached to L929 fibroblasts,the proteins are not internalized and remain displayed at theirsurface for more than 24 h. When bound to K562 myeloid cells,the molecules are internalized and degraded. Thus, dependingon the cell type, soluble proteins may be anchored to the surfaceof cells by the T domain for an extended time or directed towardsan internalization pathway.     

Biological Effects of Cyclin-Dependent Kinase Inhibitors Ribociclib,Palbociclib and Abemaciclib on Breast Cancer Bone Microenvironment

The CDK4/6 inhibitors (CDKi) palbociclib, ribociclib, and abemaciclib are currently approved in combination with anti-estrogen therapy for the treatment of advanced and/or metastatic hormone receptor-positive/HER2-neu-negative breast cancer patients. Given the high incidence of bone metastases in this population, we investigated and compared the potential effects of palbociclib, ribociclib, and abemaciclib on the breast cancer bone microenvironment. Primary osteoclasts (OCs) and osteoblasts (OBs) were obtained from human monocyte and mesenchymal stem cells, respectively. OC function was evaluated by tartrate-resistant acid phosphatase assay and real-time PCR; OB activity was assessed by an alizarin red assay. OB/breast cancer co-culture models were generated via the seeding of MCF-7 cells on a layer of OBs, and tumor cell proliferation was analyzed using flow cytometry. Here, we showed that ribociclib, palbociclib, and abemaciclib exerted similar inhibitory effects on the OC differentiation and expression of bone resorption markers without affecting OC viability. On the other hand, the three CDKi did not affect the ability of OB to produce bone matrix, even if the higher doses of palbociclib and abemaciclib reduced the OB viability. In OB/MCF-7 co-culture models, palbociclib demonstrated a lower anti-tumor effect than ribociclib and abemaciclib. Overall, our results revealed the direct effects of CDKi on the tumor bone microenvironment, highlighting differences potentially relevant for clinical practice.     

Ni3(PO4)2-coated Li[Ni0.8Co0.15Al0.05]O2 lithium battery electrode with improved cycling performance at 55 °C

To improve the cycling performance of LiNi_0.8Co_0.15Al_0.05O₂ at 55 °C, a thin Ni₃(PO₄) layer was homogeneously coated onto the cathode particle via simple ball milling. The morphology of the Ni₃(PO₄)₂-coated LiNi_0.8Co_0.15Al_0.05O₂ particle was characterized using SEM and TEM analysis, and the coating thickness was found to be approximately 10-20 nm. The Ni₃(PO₄)₂-coated LiNi_0.8Co_0.15Al_0.05O₂ cell showed improved lithium intercalation stability and rate capability especially at high C rates. This improved cycling performance was ascribed to the presence of Ni₃(PO₄)₂ on the LiNi_0.8Co_0.15Al_0.05O₂ particle, which protected the cathode from chemical attack by HF and thus suppressed an increase in charge transfer resistance. Transmission electron microscopy of extensively cycled particles confirmed that the particle surface of the Ni₃(PO₄)₂-coated LiNi_0.8Co_0.15Al_0.05O₂ remained almost undamaged, whereas pristine particles were severely serrated. The stabilization of the host structure by Ni₃(PO₄)₂ coating was also verified using X-ray diffraction.     

Defective Thyroglobulin: Cell Biology of Disease

The primary functional units of the thyroid gland are follicles of various sizes comprised of a monolayer of epithelial cells (thyrocytes) surrounding an apical extracellular cavity known as the follicle lumen. In the normal thyroid gland, the follicle lumen is filled with secreted protein (referred to as colloid), comprised nearly exclusively of thyroglobulin with a half-life ranging from days to weeks. At the cellular boundary of the follicle lumen, secreted thyroglobulin becomes iodinated, resulting from the coordinated activities of enzymes localized to the thyrocyte apical plasma membrane. Thyroglobulin appearance in evolution is essentially synchronous with the appearance of the follicular architecture of the vertebrate thyroid gland. Thyroglobulin is the most highly expressed thyroid gene and represents the most abundantly expressed thyroid protein. Wildtype thyroglobulin protein is a large and complex glycoprotein that folds in the endoplasmic reticulum, leading to homodimerization and export via the classical secretory pathway to the follicle lumen. However, of the hundreds of human thyroglobulin genetic variants, most exhibit increased susceptibility to misfolding with defective export from the endoplasmic reticulum, triggering hypothyroidism as well as thyroidal endoplasmic reticulum stress. The human disease of hypothyroidism with defective thyroglobulin (either homozygous, or compound heterozygous) can be experimentally modeled in thyrocyte cell culture, or in whole animals, such as mice that are readily amenable to genetic manipulation. From a combination of approaches, it can be demonstrated that in the setting of thyroglobulin misfolding, thyrocytes under chronic continuous ER stress exhibit increased susceptibility to cell death, with interesting cell biological and pathophysiological consequences.     

Structural Plasticity Is a Feature of Rheostat Positions in the Human Na+/Taurocholate Cotransporting Polypeptide (NTCP)

In the Na⁺/taurocholate cotransporting polypeptide (NTCP), the clinically relevant S267F polymorphism occurs at a “rheostat position”. That is, amino acid substitutions at this position (“S267X”) lead to a wide range of functional outcomes. This result was particularly striking because molecular models predicted the S267X side chains are buried, and thus, usually expected to be less tolerant of substitutions. To assess whether structural tolerance to buried substitutions is widespread in NTCP, here we used Rosetta to model all 19 potential substitutions at another 13 buried positions. Again, only subtle changes in the calculated stabilities and structures were predicted. Calculations were experimentally validated for 19 variants at codon 271 (“N271X”). Results showed near wildtype expression and rheostatic modulation of substrate transport, implicating N271 as a rheostat position. Notably, each N271X substitution showed a similar effect on the transport of three different substrates and thus did not alter substrate specificity. This differs from S267X, which altered both transport kinetics and specificity. As both transport and specificity may change during protein evolution, the recognition of such rheostat positions may be important for evolutionary studies. We further propose that the presence of rheostat positions is facilitated by local plasticity within the protein structure. Finally, we note that identifying rheostat positions may advance efforts to predict new biomedically relevant missense variants in NTCP and other membrane transport proteins.