Understanding the enhancement and temperature-dependency of the self-healing and electromechanical properties of dielectric elastomers containing mixed pendant polar groups

High permittivity self-healing dielectric elastomers have the potential to achieve long life, reusability, damage tolerance and enhanced energy density for energy harvesting devices and actuators. The self-healing performance of elastomers and usable temperature range can be affected by the chemical interactions present in the material. Self-healing thermoplastic elastomer styrene-butadiene-styrene (SBS) copolymers were prepared by introducing hydrogen bonding and electrostatic interactions through chemically grafting of polar groups to SBS: methyl thioglycolate (MG) and thioglycolic acid (TG). The mechanical properties were significantly affected by the strength of the hydrogen bonding network in the elastomers, whilst a high relative permittivity of εr ≈ 9.2 with a low loss of tan δ ≈ 0.01 was achieved. In addition, a disorder-to-order phase morphology transition was observed upon increasing the TG content due to the increased hydrogen-bonding network within SBS. At room temperature the self-healed 80/20 MG/TG-SBS exhibited a strain at break of 139% with a recovery ratio of 47.7%, and when healed at 80 °C for 3 hrs exhibited an increased strain at break of 230% with a recovery ratio of 79%. Analysis of FTIR and 1H NMR indicated that the presence of a stronger hydrogen bonding network increased the thermal resistance of the elastomers. The temperature-dependency of the self-healing behaviour was interpreted as the combined effect of hydrogen bonding, electrostatic interactions and chain interdiffusion. This work provides an in-depth understanding of how to tune the electromechanical and self-healing properties of elastomers by tailoring the type and concentration of pendent polar groups. It indicates that intrinsic modification is critical for the development of next generation high performance dielectric elastomers for actuator or energy harvesting devices operating at elevated temperatures

New class of hybrid materials for detection, capture, and "on-demand" release of carbon monoxide

YesCarbon monoxide (CO) is both a substance hazardous to health and a side product of a number of industrial processes, such as methanol steam reforming and large-scale oxidation reactions. The separation of CO from nitrogen (N2) in industrial processes is considered to be difficult because of the similarities of their electronic structures, sizes, and physicochemical properties (e.g., boiling points). Carbon monoxide is also a major poison in fuel cells because of its adsorption onto the active sites of the catalysts. It is therefore of the utmost economic importance to discover new materials that enable effective CO capture and release under mild conditions. However, methods to specifically absorb and easily release CO in the presence of contaminants, such as water, nitrogen, carbon dioxide, and oxygen, at ambient temperature are not available. Here, we report the simple and versatile fabrication of a new class of hybrid materials that allows capture and release of carbon monoxide under mild conditions. We found that carborane-containing metal complexes encapsulated in networks made of poly(dimethylsiloxane) react with CO, even when immersed in water, leading to dramatic color and infrared signature changes. Furthermore, we found that the CO can be easily released from the materials by simply dipping the networks into an organic solvent for less than 1 min, at ambient temperature and pressure, which not only offers a straightforward recycling method, but also a new method for the “on-demand” release of carbon monoxide. We illustrated the utilization of the on-demand release of CO from the networks by carrying out a carbonylation reaction on an electron-deficient metal complex that led to the formation of the CO-adduct, with concomitant recycling of the gel. We anticipate that our sponge-like materials and scalable methodology will open up new avenues for the storage, transport, and controlled release of CO, the silent killer and a major industrial poison.The Royal Society, The Romanian Ministry of Education and Research, The University of Bradford, European Regional Development Fund of the European UnionResearch Development Fund Publication Prize Award winner

Exceptional Performance of Room Temperature Sputtered Flexible Thermoelectric Thin Film Using High Target Utilisation Sputtering Technique

The High Target Utilisation Sputtering technique (HiTUS) is of interest for industrial processes, including in roll-to-roll manufacturing. This study marks the first application of HiTUS to thermoelectric materials, exemplified by bismuth telluride. The HiTUS technique separates the sputtering power into the plasma power and the target power, with additional kinetic energy in the sputtering particles from the applied electrical field, thus enabling a much wider sputter parameter space to modify the film performance. This study investigates how plasma power, target power, and substrate bias in HiTUS intricately influence crystal orientation/size, elemental composition, surface morphology, and other film properties. These factors subsequently affect carrier density/mobility, and consequently the thermoelectric performance of the bismuth telluride film. These deposited films reach a power factor of 6.5 × 10−4 W m−1 K−2 with a figure of merit ≈0.14 at room temperature, the highest value for room-temperature sputtered un-doped bismuth telluride. Subsequent post-deposition annealing significantly enhances the crystallinity of the film (highly polycrystalline), further improving the power factor to 23.5 × 10−4 W m−1 K-2, with a figure of merit ≈0.45 at room temperature. The excellent performance of the HiTUS fabricated thermoelectric film opens opportunities for the large-area manufacture of thin-film thermoelectric materials and devices

Whole genome sequencing increases molecular diagnostic yield compared with current diagnostic testing for inherited retinal disease

Abstract not availableJamie M. Ellingford, Stephanie Barton, Sanjeev Bhaskar, Simon G. Williams, Panagiotis I. Sergouniotis, James O, Sullivan, Janine A. Lamb, Rahat Perveen, Georgina Hall, William G. Newman, Paul N. Bishop, Stephen A. Roberts, Rick Leach, Rick Tearle, Stuart Bayliss, Simon C. Ramsden, Andrea H. Nemeth, Graeme C.M. Blac

Pathogenic Intronic Splice-Affecting Variants in MYBPC3 in Three Patients with Hypertrophic Cardiomyopathy

From MDPI via Jisc Publications RouterHistory: accepted 2021-05-25, pub-electronic 2021-06-02Publication status: PublishedFunder: Medical Research Council; Grant(s): 1916606, IS-BRC-1215-20007, BB/N000258/1Genetic variants in MYBPC3 are one of the most common causes of hypertrophic cardiomyopathy (HCM). While variants in MYBPC3 affecting canonical splice site dinucleotides are a well-characterised cause of HCM, only recently has work begun to investigate the pathogenicity of more deeply intronic variants. Here, we present three patients with HCM and intronic splice-affecting MYBPC3 variants and analyse the impact of variants on splicing using in vitro minigene assays. We show that the three variants, a novel c.927-8G>A variant and the previously reported c.1624+4A>T and c.3815-10T>G variants, result in MYBPC3 splicing errors. Analysis of blood-derived patient RNA for the c.3815-10T>G variant revealed only wild type spliced product, indicating that mis-spliced transcripts from the mutant allele are degraded. These data indicate that the c.927-8G>A variant of uncertain significance and likely benign c.3815-10T>G should be reclassified as likely pathogenic. Furthermore, we find shortcomings in commonly applied bioinformatics strategies to prioritise variants impacting MYBPC3 splicing and re-emphasise the need for functional assessment of variants of uncertain significance in diagnostic testing

Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development. We employ whole genome sequencing in a discovery family to target association and gene x environment interaction analyses in two large population cohorts; the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK10K. These investigations indicate that USH2A variants are associated with altered low-frequency sound perception which, in turn, increases the risk of developmental language disorder. We further show that Ush2a heterozygote mice have low-level hearing impairments, persistent higher-order acoustic processing deficits and altered vocalizations. These findings provide new insights into the complexity of genetic mechanisms serving language development and disorders and the relationships between developmental auditory and neural systems

Multi-disciplinary team directed analysis of whole genome sequencing reveals pathogenic non-coding variants in molecularly undiagnosed inherited retinal dystrophies

PURPOSE: To identify, using genome sequencing (GS), likely pathogenic non-coding variants in inherited retinal dystrophy (IRD) genes Methods: Patients with IRD were recruited to the study and underwent comprehensive ophthalmological evaluation and GS. The results of GS were investigated through virtual gene panel analysis and plausible pathogenic variants and clinical phenotype evaluated by multi-disciplinary team (MDT) discussion. For unsolved patients in whom a specific gene was suspected to harbour a missed pathogenic variant, targeted re-analysis of non-coding regions was performed on GS data. Candidate variants were functionally tested including by mRNA analysis, minigene and luciferase reporter assays. RESULTS: Previously unreported, likely pathogenic, non-coding variants, in 7 genes (PRPF31, NDP, IFT140, CRB1, USH2A, BBS10, and GUCY2D), were identified in 11 patients. These were shown to lead to mis-splicing (PRPF31, IFT140, CRB1, USH2A) or altered transcription levels (BBS10, GUCY2D). CONCLUSION: MDT-led, phenotype driven, non-coding variant re-analysis of GS is effective in identifying missing causative alleles

Expanding the genotypic spectrum of TXNL4A variants in Burn‐McKeown syndrome

From Wiley via Jisc Publications RouterHistory: received 2021-09-06, rev-recd 2021-10-21, accepted 2021-10-23, pub-electronic 2021-11-05Article version: VoRPublication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; Id: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/N000358/1Funder: Health Education England Genomics Education ProgrammeFunder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100007155; Grant(s): 1916606Funder: National Institute for Health Manchester Biomedical Research Centre; Grant(s): IS‐BRC‐1215‐20007Abstract: The developmental disorder Burn‐McKeown Syndrome (BMKS) is characterised by choanal atresia and specific craniofacial features. BMKS is caused by biallelic variants in the pre‐messenger RNA splicing factor TXNL4A. Most patients have a loss‐of‐function variant in trans with a 34‐base pair (bp) deletion (type 1 Δ34) in the promoter region. Here, we identified two patients with BMKS. One individual has a TXNL4A c.93_94delCC, p.His32Argfs *21 variant combined with a type 1 Δ34 promoter deletion. The other has an intronic TXNL4A splice site variant (c.258‐3C>G) and a type 1 Δ34 promoter deletion. We show the c.258‐3C>G variant and a previously reported c.258‐2A>G variant, cause skipping of the final exon of TXNL4A in a minigene splicing assay. Furthermore, we identify putative transcription factor binding sites within the 56 bp of the TXNL4A promoter affected by the type 1 and type 2 Δ34 and use dual luciferase assays to identify a 22 bp repeated motif essential for TXNL4A expression within this promoter region. We propose that additional variants affecting critical transcription factor binding nucleotides within the 22 bp repeated motif could be relevant to BMKS aetiology. Finally, our data emphasises the need to analyse the non‐coding sequence in individuals where a single likely pathogenic coding variant is identified in an autosomal recessive disorder consistent with the clinical presentation

Combining a prioritization strategy and functional studies nominates 5’UTR variants underlying inherited retinal disease

BACKGROUND: 5’ untranslated regions (5’UTRs) are essential modulators of protein translation. Predicting the impact of 5’UTR variants is challenging and rarely performed in routine diagnostics. Here, we present a combined approach of a comprehensive prioritization strategy and functional assays to evaluate 5’UTR variation in two large cohorts of patients with inherited retinal diseases (IRDs). METHODS: We performed an isoform-level re-analysis of retinal RNA-seq data to identify the protein-coding transcripts of 378 IRD genes with highest expression in retina. We evaluated the coverage of their 5’UTRs by different whole exome sequencing (WES) kits. The selected 5’UTRs were analyzed in whole genome sequencing (WGS) and WES data from IRD sub-cohorts from the 100,000 Genomes Project (n = 2397 WGS) and an in-house database (n = 1682 WES), respectively. Identified variants were annotated for 5’UTR-relevant features and classified into seven categories based on their predicted functional consequence. We developed a variant prioritization strategy by integrating population frequency, specific criteria for each category, and family and phenotypic data. A selection of candidate variants underwent functional validation using diverse approaches. RESULTS: Isoform-level re-quantification of retinal gene expression revealed 76 IRD genes with a non-canonical retina-enriched isoform, of which 20 display a fully distinct 5’UTR compared to that of their canonical isoform. Depending on the probe design, 3–20% of IRD genes have 5’UTRs fully captured by WES. After analyzing these regions in both cohorts, we prioritized 11 (likely) pathogenic variants in 10 genes (ARL3, MERTK, NDP, NMNAT1, NPHP4, PAX6, PRPF31, PRPF4, RDH12, RD3), of which 7 were novel. Functional analyses further supported the pathogenicity of three variants. Mis-splicing was demonstrated for the PRPF31:c.-9+1G>T variant. The MERTK:c.-125G>A variant, overlapping a transcriptional start site, was shown to significantly reduce both luciferase mRNA levels and activity. The RDH12:c.-123C>T variant was found in cis with the hypomorphic RDH12:c.701G>A (p.Arg234His) variant in 11 patients. This 5’UTR variant, predicted to introduce an upstream open reading frame, was shown to result in reduced RDH12 protein but unaltered mRNA levels. CONCLUSIONS: This study demonstrates the importance of 5’UTR variants implicated in IRDs and provides a systematic approach for 5’UTR annotation and validation that is applicable to other inherited diseases