Structure and blood compatibility of highly oriented poly(l-lactic acid) chain extended by ethylene glycol diglycidyl ether

YesHighly-oriented poly(l-lactic acid) (PLLA) with fibrillar structure and micro-grooves was fabricated through solid hot drawing technology for further improving the mechanical properties and blood biocompatibility of PLLA as blood-contacting medical devices. In order to enhance the melt strength and thus obtain high orientation degree, PLLA was first chain extended with ethylene glycol diglycidyl ether (EGDE). The extending degree as high as 25.79 mol% can be obtained at 0.7 wt% EGDE content. The complex viscosity, storage and viscous modulus for chain extended PLLA were improved resulting from the enhancement of molecular entanglement, and consequently higher draw ratio can be achieved during the subsequent hot stretching. The tensile strength and modulus of PLLA were improved dramatically by stretching. The stress-induced crystallization of PLLA occurred during drawing. The interfacial tension (γs·blood) between PLLA surface and blood decreased by chain extension and molecular orientation, indicating the weakened interaction between bioactive substance in the blood and the surface of PLLA. Modification and orientation could significantly enhance the blood compatibility of PLLA by prolonging clotting time and decreasing hemolysis ratio, protein adsorption and platelet activation. The bionic character of oriented PLLA and its anti-coagulation mechanism were tried to be explored.This research was supported by National Natural Science Foundation of China (Grant No. 51303109

Structure and blood compatibility of highly oriented PLA/MWNTs composites produced by solid hot drawing

YesHighly oriented poly(lactic acid) (PLA)/multi-walled carbon nanotubes (MWNTs) composites were fabricated through solid hot drawing technology in an effort to improve the mechanical properties and blood biocompatibility of PLA as blood-contacting medical devices. It was found that proper MWNTs content and drawing orientation can improve the tensile strength and modulus of PLA dramatically. With the increase in draw ratio, the cold crystallization peak became smaller, and the glass transition and the melting peak of PLA moved to high temperature, while the crystallinity increased, and the grain size decreased, indicating the stress-induced crystallization of PLA during drawing. MWNTs showed a nucleation effect on PLA, leading to the rise in the melting temperature, increase in crystallinity and reduction of spherulite size for the composites. Moreover, the intensity of (002) diffraction of MWNTs increased with draw ratio, indicating that MWNTs were preferentially aligned and oriented during drawing. Microstructure observation demonstrated that PLA matrix had an ordered fibrillar bundle structure, and MWNTs in the composite tended to align parallel to the drawing direction. In addition, the dispersion of MWNTs in PLA was also improved by orientation. Introduction of MWNTs and drawing orientation could significantly enhance the blood compatibility of PLA by prolonging kinetic clotting time, reducing hemolysis ratio and platelet activation

Solution-Phase Combinatorial Chemistry in Lead Discovery

Solution-phase approaches in combinatorial chemistry complement solid-phase approaches and each can be used to advantage in particular circumstances. Solution-phase synthesis of pools of compounds, whilst allowing successful identification of a selection of good lead structures for medicinal chemistry programmes, also reinforced a number of the disadvantages of such an approach. Solution-phase parallel synthesis of discrete compounds has, however, proved to be a very useful and popular approach both for lead generation and in lead optimisation work. The range of chemistry suitable for use in such approaches is expanding rapidly and some of these chemistries are discussed. The current focus is on enhancing the quality of compounds prepared in array formats, and we describe a number of useful approaches which are being developed to that end

EGFR oligomerization organizes kinase-active dimers into competent signalling platforms

Epidermal growth factor receptor (EGFR) signalling is activated by ligand-induced receptor dimerization. Notably, ligand binding also induces EGFR oligomerization, but the structures and functions of the oligomers are poorly understood. Here, we use fluorophore localization imaging with photobleaching to probe the structure of EGFR oligomers. We find that at physiological epidermal growth factor (EGF) concentrations, EGFR assembles into oligomers, as indicated by pairwise distances of receptor-bound fluorophore-conjugated EGF ligands. The pairwise ligand distances correspond well with the predictions of our structural model of the oligomers constructed from molecular dynamics simulations. The model suggests that oligomerization is mediated extracellularly by unoccupied ligand-binding sites and that oligomerization organizes kinase-active dimers in ways optimal for auto-phosphorylation in trans between neighbouring dimers. We argue that ligand-induced oligomerization is essential to the regulation of EGFR signalling

Atomic layer deposition of Cu with a carbene-stabilized Cu (i) silylamide

The metal–organic Cu(I) complex 1,3-diisopropyl-imidazolin-2-ylidene copper hexamethyl disilazide has been tested as a novel oxygen-free precursor for atomic layer deposition of Cu with molecular hydrogen. Being a strong Lewis base, the carbene stabilizes the metal centre to form a monomeric compound that can be vaporised and transported without visible degradation. A significant substrate dependence of the growth process not only with respect to the film material but also to the structure of the films was observed. On Pd surfaces continuous films are grown and no phase boundary can be observed between the Cu film and the Pd, while island growth is observed on Ru substrates, which as a consequence requires thicker films in order to achieve a fully coalesced layer. Island growth is also observed for ultra-thin (<10 nm) Pd layers on Si substrates. Possible explanations for the different growth modes observed are discussed

Remote-controlled experiments with cloud chemistry

Developing cleaner chemical processes often involves sophisticated flow-chemistry equipment that is not available in many economically developing countries. For reactions where it is the data that are important rather than the physical product, the networking of chemists across the internet to allow remote experimentation offers a viable solution to this problem

Process Intensification of the Continuous Synthesis of Bio-Derived Monomers for Sustainable Coatings Using a Taylor Vortex Flow Reactor

We describe the optimization and scale-up of two consecutive reaction steps in the synthesis of bio-derived alkoxybutenolide monomers that have been reported as potential replacements for acrylate-based coatings ( Sci. Adv. 2020, 6, eabe0026). These monomers are synthesized by (i) oxidation of furfural with photogenerated singlet oxygen followed by (ii) thermal condensation of the desired 5-hydroxyfuranone intermediate product with an alcohol, a step which until now has involved a lengthy batch reaction. The two steps have been successfully telescoped into a single kilogram-scale process without any need to isolate the 5-hydroxyfuranone between the steps. Our process development involved FTIR reaction monitoring, FTIR data analysis via 2D visualization, and two different photoreactors: (i) a semicontinuous photoreactor based on a modified rotary evaporator, where FTIR and 2D correlation spectroscopy (2D-COS) revealed the loss of the methyl formate coproduct, and (ii) our fully continuous Taylor Vortex photoreactor, which enhanced the mass transfer and permitted the use of near-stoichiometric equivalents of O2. The use of in-line FTIR monitoring and modeling greatly accelerated process optimization in the Vortex reactor. This led to scale-up of the photo-oxidation in 85% yield with a projected productivity of 1.3 kg day–1 and a space-time yield of 0.06 mol day–1 mL–1. Higher productivities could be achieved while sacrificing yield (e.g., 4 kg day–1 at 40% yield). The use of superheated methanol at 200 °C in a pressurized thermal flow reactor accelerated the second step, the thermal condensation of 5-hydroxyfuranone, from a 20 h batch reflux reaction (0.5 L, 85 g) to a space time of 700 g day–1. Proof of concept for telescoping the two steps was established with an overall two-step yield of 67%, producing a process with a projected productivity of 1.1 kg day–1 for the methoxybutenolide monomer without any purification of the 5-hydroxyfuranone intermediate

A note on the primordial abundance of stau NLSPs

In scenarios with a gravitino LSP, there exist strong BBN constraints on the abundance of a possible stau NLSP. We find that in settings with substantial left-right mixing of the stau mass eigenstates these constraints can be evaded even for very long-lived staus.Comment: 17 pages, 5 figures, discussion on vacuum stability adde

A Digital Repository and Execution Platform for Interactive Scholarly Publications in Neuroscience

The CARMEN Virtual Laboratory (VL) is a cloud-based platform which allows neuroscientists to store, share, develop, execute, reproduce and publicise their work. This paper describes new functionality in the CARMEN VL: an interactive publications repository. This new facility allows users to link data and software to publications. This enables other users to examine data and software associated with the publication and execute the associated software within the VL using the same data as the authors used in the publication. The cloud-based architecture and SaaS (Software as a Service) framework allows vast data sets to be uploaded and analysed using software services. Thus, this new interactive publications facility allows others to build on research results through reuse. This aligns with recent developments by funding agencies, institutions, and publishers with a move to open access research. Open access provides reproducibility and verification of research resources and results. Publications and their associated data and software will be assured of long-term preservation and curation in the repository. Further, analysing research data and the evaluations described in publications frequently requires a number of execution stages many of which are iterative. The VL provides a scientific workflow environment to combine software services into a processing tree. These workflows can also be associated with publications and executed by users. The VL also provides a secure environment where users can decide the access rights for each resource to ensure copyright and privacy restrictions are met