Covalent polyester colouration by in situ chromophore creation

The permanent colouration of a polyester by straightforward azo coupling is disclosed. Uniquely, the chromophore is created only upon successful polymer modification with a non-coloured molecule (in situ colouration), which confirms successful polymer adaptation and ensures that coloured waste is not produced. The method of colouration, which may feasibly be applied for the coloration of a wide-range of step-growth polyesters, yielded a polymer capable of preventing indigo deposition onto a range of fabrics, offering potential use within advanced detergent formulations

A macroscale finite element approach for simulating the bending behaviour of biaxial fabrics

A macroscale finite element (FE) model was developed to simulate the forming behaviour of biaxial fabrics, incorporating the effects of bending stiffness to predict fabric wrinkling. The dependency of the bending stiffness on the fibre orientation was addressed by extending a non-orthogonal constitutive framework previously developed for biaxial fabric materials. The nonlinear bending behaviour of a biaxial non-crimp fabric (NCF) with pillar stitches was characterised by a revised cantilever test using structured light scanning to measure specimen curvature, providing input data for the material model. Simulations were performed to replicate the bias-extension behaviour of the NCF material, showing good agreement with experimental data. Wrinkles were observed within the central area of the specimen at low extension, which consequently affect the uniformity of the shear angle distribution in the region where pure shear is expected.EPRSC Doctoral Training Partnership awar

Correction: Thermoresponsive polysarcosine-based nanoparticles

Correction for ‘Thermoresponsive polysarcosine-based nanoparticles’ by Huayang Yu et al., J. Mater. Chem. B, 2019, 7, 4217–4223

Meticulous Doxorubicin Release from pH‐responsive Nanoparticles Entrapped within an Injectable Thermoresponsive Depot.

The dual stimuli‐controlled release of doxorubicin from gel‐embedded nanoparticles is reported. Non‐cytotoxic polymer nanoparticles are formed from poly(ethylene glycol)‐ b ‐poly(benzyl glutamate) that, uniquely, contain a central ester link. This connection renders the nanoparticles pH‐responsive, enabling extensive doxorubicin release in acidic solutions (pH 6.5), but not in solutions of physiological pH (pH 7.4). Doxorubicin loaded nanoparticles were found to be stable for at least 31 days and lethal against the three breast cancer cell lines tested. Furthermore, doxorubicin loaded nanoparticles could be incorporated within a thermoresponsive poly(2‐hydroxypropyl methacrylate) gel depot, which forms immediately upon injection of poly(2‐hydroxypropyl methacrylate) in DMSO solution into aqueous solution. The combination of the poly(2‐hydroxypropyl methacrylate) gel and poly(ethylene glycol)‐ b ‐poly(benzyl glutamate) nanoparticles yields an injectable doxorubicin delivery system that facilities near‐complete drug release when maintained at elevated temperatures (37 °C) in acidic solution (pH 6.5). In contrast, negligible payload release occurs when the material is stored at room temperature in non‐acidic solution (pH 7.4). The system has great potential as a vehicle for the prolonged, site‐specific, release of chemotherapeutics

Effect of Silicon Content on Carbide Precipitation and Low-Temperature Toughness of Pressure Vessel Steels

Cr – Mn – Mo – Ni pressure vessel steels containing 0.54 and 1.55% Si are studied. Metallographic and fractographic analyses of the steels after tempering at 650 and 700°C are performed. The impact toughness at – 30°C and the hardness of the steels are determined. The mass fraction of the carbide phase in the steels is computed with the help of the J-MatPro 4.0 software

Differentiation potential of STRO-1+ dental pulp stem cells changes during cell passaging

<p>Abstract</p> <p>Background</p> <p>Dental pulp stem cells (DPSCs) can be driven into odontoblast, osteoblast, and chondrocyte lineages in different inductive media. However, the differentiation potential of naive DPSCs after serial passaging in the routine culture system has not been fully elucidated.</p> <p>Results</p> <p>DPSCs were isolated from human/rat dental pulps by the magnetic activated cell sorting based on STRO-1 expression, cultured and passaged in the conventional culture media. The biological features of STRO-1⁺DPSCs at the 1^stand 9^thpassages were investigated. During the long-term passage, the proliferation ability of human STRO-1⁺DPSCs was downregulated as indicated by the growth kinetics. When compared with STRO-1⁺DPSCs at the 1^stpassage (DPSC-P1), the expression of mature osteoblast-specific genes/proteins (alkaline phosphatase, bone sialoprotein, osterix, and osteopontin), odontoblast-specific gene/protein (dentin sialophosphoprotein and dentin sialoprotein), and chondrocyte-specific gene/protein (type II collagen) was significantly upregulated in human STRO-1⁺DPSCs at the 9^thpassage (DPSC-P9). Furthermore, human DPSC-P9 cells in the mineralization-inducing media presented higher levels of alkaline phosphatase at day 3 and day 7 respectively, and produced more mineralized matrix than DPSC-P9 cells at day 14. <it>In vivo </it>transplantation results showed that rat DPSC-P1 cell pellets developed into dentin, bone and cartilage structures respectively, while DPSC-P9 cells can only generate bone tissues.</p> <p>Conclusions</p> <p>These findings suggest that STRO-1⁺DPSCs consist of several interrelated subpopulations which can spontaneously differentiate into odontoblasts, osteoblasts, and chondrocytes. The differentiation capacity of these DPSCs changes during cell passaging, and DPSCs at the 9^thpassage restrict their differentiation potential to the osteoblast lineage <it>in vivo</it>.</p

In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis

Abstract Background Sustained drug delivery is a large unmet clinical need in glaucoma. Here, we incorporated a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor, CCG-222740, into slow release large unilamellar vesicles derived from the liposomes DOTMA (1,2-di-O-octadecenyl-3-trimethylammonium propane) and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), and tested their effects in vitro and in vivo. Results The vesicles were spherical particles of around 130 nm and were strongly cationic. A large amount of inhibitor could be incorporated into the vesicles. We showed that the nanocarrier CCG-222740 formulation gradually released the inhibitor over 14 days using high performance liquid chromatography. Nanocarrier CCG-222740 significantly decreased ACTA2 gene expression and was not cytotoxic in human conjunctival fibroblasts. In vivo, nanocarrier CCG-222740 doubled the bleb survival from 11.0 ± 0.6 days to 22.0 ± 1.3 days (p = 0.001), decreased conjunctival scarring and did not have any local or systemic adverse effects in a rabbit model of glaucoma filtration surgery. Conclusions Our study demonstrates proof-of-concept that a nanocarrier-based formulation efficiently achieves a sustained release of a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor and prevents conjunctival fibrosis in an established rabbit model of glaucoma filtration surgery.https://deepblue.lib.umich.edu/bitstream/2027.42/146540/1/12951_2018_Article_425.pd

Proteomics: in pursuit of effective traumatic brain injury therapeutics

Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients

Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP

Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)