GaN-based cryogenic temperature power electronics for superconducting motors in cryo-electric aircraft

Climate change has spurred a shift to electric transportation, but aviation faces challenges with electric energy storage and propulsion. Cryogenically cooled superconducting motors, along with cryogenically cooled power electronics, offer a solution to increase the efficiency and power density of electric aircraft. This paper evaluates the feasibility of cryogenic power electronics by characterising new technologies (GaN, nanocrystalline) using new experimental techniques. It is found that the on resistance reductions of GaN E-high electron mobility transistors at cryogenic temperatures depend on the maximum blocking voltage of the device, and the size of the gate resistor for ohmic p-GaN devices. Different types of nanocrystalline cores are shown to vary greatly in their behaviour at cryogenic temperatures, which is measured using a modified core loss measurement circuit. Further analysis shows that the losses of a GaN based cryogenic inverter could potentially halve that of an equivalent Si based inverter

Cultivating capacities in community-based researchers in low-resource settings: Lessons from a participatory study on violence and mental health in Sri Lanka

Participatory methods, which rely heavily on community-based data collectors, are growing in popularity to deliver much-needed evidence on violence and mental health in low- and middle-income countries. These settings, along with local researchers, encounter the highest burden of violence and mental ill-health, with the fewest resources to respond. Despite increased focus on wellbeing for research participants and, to a lesser degree, professional researchers in such studies, the role-specific needs of community-based researchers receive scant attention. This co-produced paper draws insights from one group’s experience to identify rewards, challenges, and recommendations for supporting wellbeing and development of community-based researchers in sensitive participatory projects in low-resource settings. Twenty-one community-based researchers supporting a mixed-methods study on youth, violence and mental health in Sri Lanka submitted 63 reflexive structured journal entries across three rounds of data collection. We applied Attride-Stirling’s method for thematic analysis to explore peer researchers’ learning about research, violence and mental health; personal-professional boundaries; challenges in sensitive research; and experiences of support from the core team. Sri Lanka’s first study capturing experiences of diverse community-based researchers aims to inform the growing number of global health and development actors relying on such talent to deliver sensitive and emotionally difficult work in resource-limited and potentially volatile settings. Viewing participatory research as an opportunity for mutual learning among both community-based and professional researchers, we identify practice gaps and opportunities to foster respectful team dynamics and create generative and safe co-production projects for all parties. Intentional choices around communication, training, human and consumable resources, project design, and navigating instable research conditions can strengthen numerous personal and professional capacities across teams. Such individual and collective growth holds potential to benefit short- and long-term quality of evidence and inform action on critical issues, including violence and mental health, facing high-burden, low-resource contexts

Nanotechnology and Nanotoxicology in Retinopathy

Nanoparticles are nanometer-scaled particles, and can be utilized in the form of nanocapsules, nanoconjugates, or nanoparticles themselves for the treatment of retinopathy, including angiogensis-related blindness, retinal degeneration, and uveitis. They are thought to improve the bioavailability in the retina and the permeability of therapeutic molecules across the barriers of the eye, such as the cornea, conjunctiva, and especially, blood-retinal barriers (BRBs). However, consisting of multiple neuronal cells, the retina can be the target of neuronal toxicity of nanoparticles, in common with the central and peripheral nervous system. Furthermore, the ability of nanoparticles to pass through the BRBs might increase the possibility of toxicity, simultaneously promoting distribution in the retinal layers. In this regard, we discussed nanotechnology and nanotoxicology in the treatment of retinopathy

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations : design, characterisation, toxicity and transcorneal permeation studies

This study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using {DSC} and FT-IR. The gelation temperature (Tsol-gel), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. {DSC} and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used. {P188} modified the Tsol/gel of {P407} bringing it close to eye temperature (35°C) compared with the formulation containing {P407} alone. Moreover, gels that comprised {P407} and {P188} exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations {PP11} and PP12, the work of adhesion decreased significantly (P < 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control {KT} release as only 48 of the {KT} released within 12 h. In addition, the HET-CAM and {BCOP} tests confirmed the non-irritancy of {KT} loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. {MTT} assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with {KT} showed reasonable and acceptable percent cell viability compared with control samples

On the barrier properties of the cornea: a microscopy study of the penetration of fluorescently labeled nanoparticles, polymers, and sodium fluorescein

Overcoming the natural defensive barrier functions of the eye remains one of the greatest challenges of ocular drug delivery. Cornea is a chemical and mechanical barrier preventing the passage of any foreign bodies including drugs into the eye, but the factors limiting penetration of permeants and nanoparticulate drug delivery systems through the cornea are still not fully understood. In this study, we investigate these barrier properties of the cornea using thiolated and PEGylated (750 and 5000 Da) nanoparticles, sodium fluorescein, and two linear polymers (dextran and polyethylene glycol). Experiments used intact bovine cornea in addition to bovine cornea de-epithelialized or tissues pretreated with cyclodextrin. It was shown that corneal epithelium is the major barrier for permeation; pretreatment of the cornea with β-cyclodextrin provides higher permeation of low molecular weight compounds, such as sodium fluorescein, but does not enhance penetration of nanoparticles and larger molecules. Studying penetration of thiolated and PEGylated (750 and 5000 Da) nanoparticles into the de-epithelialized ocular tissue revealed that interactions between corneal surface and thiol groups of nanoparticles were more significant determinants of penetration than particle size (for the sizes used here). PEGylation with polyethylene glycol of a higher molecular weight (5000 Da) allows penetration of nanoparticles into the stroma, which proceeds gradually, after an initial 1 h lag phase

A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome highlights the challenges associated with draft genomes and gene prediction in plants

Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164\ua0Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models

Drug discovery in ophthalmology: past success, present challenges, and future opportunities

BACKGROUND: Drug discovery has undergone major transformations in the last century, progressing from the recognition and refinement of natural products with therapeutic benefit, to the systematic screening of molecular libraries on whole organisms or cell lines and more recently to a more target-based approach driven by greater knowledge of the physiological and pathological pathways involved. Despite this evolution increasing challenges within the drug discovery industry are causing escalating rates of failure of development pipelines. DISCUSSION: We review the challenges facing the drug discovery industry, and discuss what attempts are being made to increase the productivity of drug development, including a refocusing on the study of the basic biology of the disease, and an embracing of the concept of ‘translational research’. We consider what ophthalmic drug discovery can learn from the sector in general and discuss strategies to overcome the present limitations. This includes advances in the understanding of the pathogenesis of disease; improvements in animal models of human disease; improvements in ophthalmic drug delivery and attempts at patient stratification within clinical trials. SUMMARY: As we look to the future, we argue that investment in ophthalmic drug development must continue to cover the whole translational spectrum (from ‘bench to bedside and back again’) with recognition that both biological discovery and clinical understanding will drive drug discovery, providing safe and effective therapies for ocular disease