Effect of Temperature and Strain Rate on the Hot Deformation Behaviour of Ferritic Stainless Steel

Metals and Materials International - The flow behaviour and microstructure characteristics of a ferritic stainless steel were investigated using plain strain compression test on a Gleeble 3500...     

A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Supramolecular Glyco‐nanoparticles Toward Immunological Applications

Glyco‐mimicking nanoparticles (glyco‐NPs) with Förster resonance energy transfer (FRET) donor and acceptor groups formed via dynamic covalent bond of benzoboroxole and sugar from two complementary polymers are prepared. The glyco‐NPs are proved to be quite stable under physiological conditions but sensitive to pH. So the glyco‐NPs can be internalized by dendritic cells with integrity and nontoxicity and then dissociate within the acidic organelles. This particle dissociation is directly observed and visualized in vitro, for the first time via the FRET measurements and fluorescent microscopy. This feature makes controlled release of drug or protein by glyco‐NPs possible, i.e., when model antigen Ovalbumin is loaded in the glyco‐NPs, the released Ovalbumin in dendritic cells stimulates T cells more efficiently than the free Ovalbumin itself as a result of the enhanced antigen processing and presentation. Thus, the results enlighten a bright future of the glyco‐NPs in immunotherapy.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Densification mechanism during reactive hot pressing of B4C-ZrO2 mixtures

The densification behaviors of pure B₄C and B₄C-ZrO₂ mixtures were compared during hot pressing. The results showed that in-situ formed ZrB₂ effectively enhanced the densification process of B₄C-ZrO₂ mixtures, more significantly during the intermediate stage. Within the relative density ranging from 0.75 to 0.90, the B₄C-15?wt%ZrO₂ mixture (B15Z) achieved the maximum densification rate as twice much as that of pure B₄C. The stress exponent n>3 indicated plastic deformation was the dominant densification mechanism of B15Z. The viscosities of plastic flow were evaluated using Murray-Rodger-William equation and the viscosity of B15Z was only a quarter of that in pure B₄C. The sintering activation energy was calculated to be 305.9?kJ/mol for pure B₄C and 197?kJ/mol for B15Z, respectively. It was proposed that the lower viscosity of plastic flow and activation energy accelerated the sliding and propagating motions of plastic flow, by which underlain the enhanced densification behaviors of B₄C-ZrO₂ mixtures.     

The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship

Breast cancer is the most frequently diagnosed cancer in women worldwide. The disease and its treatments exert profound effects on an individual’s physical and mental health. There are many factors that impact an individual’s risk of developing breast cancer, their response to treatments, and their risk of recurrence. The community of microorganisms inhabiting the gastrointestinal tract, the gut microbiota, affects human health through metabolic, neural, and endocrine signaling, and immune activity. It is through these mechanisms that the gut microbiota appears to influence breast cancer risk, response to treatment, and recurrence. A disrupted gut microbiota or state of ‘dysbiosis’ can contribute to a biological environment associated with higher risk for cancer development as well as contribute to negative treatment side-effects. Many cancer treatments have been shown to shift the gut microbiota toward dysbiosis; however, the microbiota can also be positively manipulated through diet, prebiotic and probiotic supplementation, and exercise. The objective of this review is to provide an overview of the current understanding of the relationship between the gut microbiota and breast cancer and to highlight potential strategies for modulation of the gut microbiota that could lead to improved clinical outcomes and overall health in this population.     

Modeling Impact of ROADM Intra-Node Add/Drop Contention on a Single Node Lightpath Blocking Performance

We propose an analytical model to evaluate the lightpath blocking performance for a single ROADM node with intra-node add/drop contention,in which the number of lightpaths that can be added/dropped with the same wavelength is limited by the add/drop contention factor.Different models of traffic load per nodal degree are considered to validate the effectiveness of the analytical model.The simulation results show that the proposed analytical model is effective in predicting the performance for different values of add/drop contention factor C and for variable offered loads at the node.The add/drop contention factor shows an important impact on the lightpath blocking performance and properly raising the contention factor can significantly improve the lightpath blocking performance.When the add/drop contention factor C exceeds a certain level,the performance of a ROADM with intra-node contention is close to that of a contentionless ROADM.     

Experimental study on the permeability and self-healing capacity of geosynthetic clay liners in heavy metal solutions

Geosynthetic clay liners (GCLs), which have a very low permeability to water and a considerably high self-healing capacity, are widely used in liner systems of landfills. In this study, a series of experimental tests were carried out under complex conditions on typical commercial GCLs from China. In particular, the effects of pH values and lead ions (Pb²⁺) were tested in addition to other factors. The swelling properties of natural bentonite encapsulated between geotextile components in the GCLs were tested first. The swelling capacity was reduced rapidly at pH values < 3 and concentrations of Pb²⁺ >40 mM. Permeability tests on GCLs with different concentrations of lead ions were then performed by using the self-developed multi-link flexible wall permeameter, and data showed that increases in lead ion concentrations greatly improved the permeability. Finally, self-healing capacity tests were conducted on needle-punched GCLs under different levels of damage. Results showed that the GCLs have a good self-healing capacity with small diameter damage holes (2 mm, close to three times the original aperture), but with a damage aperture larger than 15% of the sample area, the self-healing capacity could not prevent leakage; hence, in certain situations it will be necessary to repair the damage to meet the anti-seepage requirement.