Materials systems for interleave toughening in polymer composites

We review the literature describing the use of interleaves to increase interlaminar fracture toughness in fibre-reinforced polymer composites and hence to improve damage tolerance. From an analysis of data provided in the literature from the use of microfibre and nanofibre interleaves, we show that the performance of these widely researched systems is clearly differentiated when plotted against the mean coverage of the interleaf. Using a simple analysis, we suggest that this can be attributed to the influence of their porous architectures on the infusion of resin. We show also that the superior toughening performance of microfibre interleaves is only weakly influenced by the choice of fibre. We find also that the inclusion of carbon nanotubes within interleaves to deliver multifunctional composites can be optimised by using a hybrid system with microfibres.

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E7766, a Macrocycle-Bridged Stimulator of Interferon Genes (STING) Agonist with Potent Pan-Genotypic Activity

A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766 , exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.     

A Distinct Cytokine Profile and Stromal Vascular Fraction Metabolic Status without Significant Changes in the Lipid Composition Characterizes Lipedema

Lipedema is an adipose tissue disorder characterized by the disproportionate increase of subcutaneous fat tissue in the lower and/or upper extremities. The underlying pathomechanism remains unclear and no molecular biomarkers to distinguish the disease exist, leading to a large number of undiagnosed and misdiagnosed patients. To unravel the distinct molecular characteristic of lipedema we performed lipidomic analysis of the adipose tissue and serum of lipedema versus anatomically- and body mass index (BMI)-matched control patients. Both tissue groups showed no significant changes regarding lipid composition. As hyperplastic adipose tissue represents low-grade inflammation, the potential systemic effects on circulating cytokines were evaluated in lipedema and control patients using the Multiplex immunoassay system. Interestingly, increased systemic levels of interleukin 11 (p = 0.03), interleukin 28A (p = 0.04) and interleukin 29 (p = 0.04) were observed. As cytokines can influence metabolic activity, the metabolic phenotype of the stromal vascular fraction was examined, revealing significantly increased mitochondrial respiration in lipedema. In conclusion, despite sharing a comparable lipid profile with healthy adipose tissue, lipedema is characterized by a distinct systemic cytokine profile and metabolic activity of the stromal vascular fraction.     

The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.     

The structure,vacancy characteristics,and magnetic properties of GdMn1-xCrxO3 ceramics

To investigate the evolution of the structural and enhanced magnetic properties of GdMnO₃ systems induced by the substitution of Mn with Cr, polycrystalline GdMn_1-xCr_xO₃ samples were synthesized via solid-state reactions. XRD characterization shows that all GdMn_1-xCr_xO₃ compounds with single-phase structures crystallize well and that Cr³⁺ ions entering the lattice sites of GdMnO₃ induce structural distortion. SEM results indicate that the grain size of the synthesized samples (a few microns) decreases as the Cr substitution concentration increases. Positron annihilation lifetime spectroscopy reveals that vacancy-type defects occur in GdMn_1-xCr_xO₃ ceramics and that the vacancy size and concentration clearly change with the Cr content. The temperature and field dependence of the magnetization curves show that Cr substitution significantly influences the magnetic ordering of the gadolinium sublattice, improving the weak ferromagnetic transition temperature and magnetization of GdMn_1-xCr_xO₃. The enhanced magnetization of GdMn_1-xCr_xO₃ is closely related to the vacancy defect concentration.     

Metallocene QACs: The Incorporation of Ferrocene Moieties into monoQAC and bisQAC Structures

Inspired by the incorporation of metallocene functionalities into a variety of bioactive structures, particularly antimicrobial peptides, we endeavored to broaden the structural variety of quaternary ammonium compounds (QACs) by the incorporation of the ferrocene moiety. Accordingly, 23 ferrocene-containing mono- and bisQACs were prepared in high yields and tested for activity against a variety of bacteria, including Gram-negative strains and a panel of clinically isolated MRSA strains. Ferrocene QACs were shown to be effective antiseptics with some displaying single-digit micromolar activity against all bacteria tested, demonstrating yet another step in the expansion of structural variety of antiseptic QACs.     

[2.2]Paracyclophane-Based TCN-201 Analogs as GluN2A-Selective NMDA Receptor Antagonists

Recent studies have shown the involvement of GluN2A subunit-containing NMDA receptors in various neurological and pathological disorders. In the X-ray crystal structure, TCN-201 ( 1 ) and analogous pyrazine derivatives 2 and 3 adopt a U-shape (hairpin) conformation within the binding site formed by the ligand binding domains of the GluN1 and GluN2A subunits. In order to mimic the resulting π/π-interactions of two aromatic rings in the binding site, a [2.2]paracyclophane system was designed to lock these aromatic rings in a parallel orientation. Acylation of [2.2]paracyclophane ( 5 ) with oxalyl chloride and chloroacetyl chloride and subsequent transformations led to the oxalamide 7 , triazole 10 and benzamides 12 . The GluN2A inhibitory activities of the paracyclophane derivatives were tested with two-electrode voltage clamp electrophysiology using Xenopus laevis oocytes expressing selectively functional NMDA receptors with GluN2A subunit. The o-iodobenzamide 12 b with the highest similarity to TCN-201 showed the highest GuN2A inhibitory activity of this series of compounds. At a concentration of 10 μM, 12 b reached 36 % of the inhibitory activity of TCN-201 ( 1 ). This result indicates that the [2.2]paracyclophane system is well accepted by the TCN-201 binding site.     

National-scale implementation of mandatory freshwater farm plans: a mechanism to deliver water quality improvement in productive catchments in New Zealand?

Nutrient Cycling in Agroecosystems - Reducing agriculturally derived diffuse contaminant losses (via non-point sources) from land to water has proven difficult for decades. Owing to the diversity...     

Interfacial microstructure and mechanical properties of Ti3SiC2 ceramic and TC11 alloy joint diffusion bonded with a Cu interlayer

Reliable joints of Ti₃SiC₂ ceramic and TC11 alloy were diffusion bonded with a 50 μm thick Cu interlayer. The typical interfacial structure of the diffusion boned joint, which was dependent on the interdiffusion and chemical reactions between Al, Si and Ti atoms from the base materials and Cu interlayer, was TC11/α-Ti + β-Ti + Ti₂Cu + TiCu/Ti₅Si₄ + TiSiCu/Cu(s, s)/Ti₃SiC₂. The influence of bonding temperature and time on the interfacial structure and mechanical properties of Ti₃SiC₂/Cu/TC11 joint was analyzed. With the increase of bonding temperature and time, the joint shear strength was gradually increased due to enhanced atomic diffusion. However, the thickness of Ti₅Si₄ and TiSiCu layers with high microhardness increased for a long holding time, resulting in the reduction of bonding strength. The maximum shear strength of 251 ± 6 MPa was obtained for the joint diffusion bonded at 850 °C for 60 min, and fracture primarily occurred at the diffusion layer adjacent to the Ti₃SiC₂ substrate. This work provided an economical and convenient solution for broadening the engineering application of Ti₃SiC₂ ceramic.