Low cost patterning of thin film

A novel route for the low-cost patterning of electrical thin films has been established. The process has been developed principally for the manufacture of thermocouples using high-speed reel-to-reel industrial techniques, but could be applied to the manufacture of a wide range of electronic devices including radio frequency identification (RFID) antennae, electrical interconnect, and passive electronic components. The procedure exploits high-volume processes directly to print self-removing masking layers. The process offers substantial advantages over traditional thin-film patterning methods including faster, cheaper production runs. Raw material use and wastage are greatly reduced, affording environmental benefits

Printed thick-film thermocouple sensors

Thermocouples have been printed using thick-film processes, which demonstrate a repeatable and stable reaction to temperature and a potential difference per degree temperature change comparable to conventional commercial couples. The potential for this novel approach is to offer a rapid, low-cost, low-temperature manufacturing process for electrical temperature monitoring

Printed thermocouple devices

A novel process for the fabrication of thermocouples using thick-film techniques has been developed. Thermoelectric reactions of 22 μV/°C per couple have been observed which are comparable to those of conventional thermocouples. This work outlines the potential for a rapid, lowcost, low temperature manufacturing solution for the production of electrical temperature sensors

MED12 regulates a transcriptional network of calcium-handling genes in the heart

The Mediator complex regulates gene transcription by linking basal transcriptional machinery with DNA-bound transcription factors. The activity of the Mediator complex is mainly controlled by a kinase submodule that is composed of 4 proteins, including MED12. Although ubiquitously expressed, Mediator subunits can differentially regulate gene expression in a tissue-specific manner. Here, we report that MED12 is required for normal cardiac function, such that mice with conditional cardiac-specific deletion of MED12 display progressive dilated cardiomyopathy. Loss of MED12 perturbs expression of calcium-handling genes in the heart, consequently altering calcium cycling in cardiomyocytes and disrupting cardiac electrical activity. We identified transcription factors that regulate expression of calcium-handling genes that are downregulated in the heart in the absence of MED12, and we found that MED12 localizes to transcription factor consensus sequences within calcium-handling genes. We showed that MED12 interacts with one such transcription factor, MEF2, in cardiomyocytes and that MED12 and MEF2 co-occupy promoters of calcium-handling genes. Furthermore, we demonstrated that MED12 enhances MEF2 transcriptional activity and that overexpression of both increases expression of calcium-handling genes in cardiomyocytes. Our data support a role for MED12 as a coordinator of transcription through MEF2 and other transcription factors. We conclude that MED12 is a regulator of a network of calcium-handling genes, consequently mediating contractility in the mammalian heart

Ablation of CaMKIId oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease

CRISPR-Cas9 gene editing is emerging as a prospective therapy for genomic mutations. However, current editing approaches are directed primarily toward relatively small cohorts of patients with specific mutations. Here, we describe a cardioprotective strategy potentially applicable to a broad range of patients with heart disease. We used base editing to ablate the oxidative activation sites of CaMKIId, a primary driver of cardiac disease. We show in cardiomyocytes derived from human induced pluripotent stem cells that editing the CaMKIId gene to eliminate oxidation-sensitive methionine residues confers protection from ischemia/reperfusion (IR) injury. Moreover, CaMKIId editing in mice at the time of IR enables the heart to recover function from otherwise severe damage. CaMKIId gene editing may thus represent a permanent and advanced strategy for heart disease therapy

Dynamic Modulation of Thymic MicroRNAs in Response to Stress

thymocyte subsets. Several of the differentially regulated murine thymic miRs are also stress responsive in the heart, kidney, liver, brain, and/or spleen. The most dramatic thymic microRNA down modulated is miR-181d, exhibiting a 15-fold reduction following stress. This miR has both similar and distinct gene targets as miR-181a, another member of miR-181 family. Many of the differentially regulated microRNAs have known functions in thymopoiesis, indicating that their dysregulation will alter T cell repertoire selection and the formation of naïve T cells. This data has implications for clinical treatments involving anti-inflammatory steroids, ablation therapies, and provides mechanistic insights into the consequences of infections

A renewable energy-centred research agenda for planning and financing Nexus development objectives in rural sub-Saharan Africa

In rural sub-Saharan Africa – the global poverty hotspot – the vast majority of cropland is rainfed only, resulting in reduced and unstable yields. Smallholder farmers account for 80% of agricultural production but they have limited access to relevant services to support both commercial operations and their livelihoods: more than two-thirds of rural dwellers have no access to electricity (crucial for crop irrigation, processing, and storage) and about 40% have no access to clean water. Previous research has analysed integrated technological and resource management approaches to tackle these overlapping development gaps. To finance and implement such transformations in resource-constrained settings, it is now crucial to understand the business and investment implications, also considering the strong regional population growth and the increasing frequency and intensity of climate extremes. Here, we lay out a research agenda that promotes the integration of multi-scale modelling excellence along the climate-water-renewable energy-agriculture-development Nexus and the creation of robust business models for private companies that can sustainably support private smallholder farmers of SSAin their effort to eradicate poverty and inequality. The proposed agenda is a cornerstone of the EC-H2020 project LEAP-RE RE4AFAGRI (“Renewable Energy for African Agriculture: Integrating Modelling Excellence and Robust Business Models”). In proposing the agenda, we highlight the importance of integrating energy access into the Nexus framework from both research and investment perspectives

Muscle RING-finger 2 and 3 maintain striated-muscle structure and function

Background: The Muscle-specific RING-finger (MuRF) protein family of E3 ubiquitin ligases is important for maintenance of muscular structure and function. MuRF proteins mediate adaptation of striated muscles to stress. MuRF2 and MuRF3 bind to microtubules and are implicated in sarcomere formation with noticeable functional redundancy. However, if this redundancy is important for muscle function in vivo is unknown. Our objective was to investigate cooperative function of MuRF2 and MuRF3 in the skeletal muscle and the heart in vivo. Methods: MuRF2 and MuRF3 double knockout mice (DKO) were generated and phenotypically characterized. Skeletal muscle and the heart were investigated by morphological measurements, histological analyses, electron microscopy, immunoblotting, and real-time PCR. Isolated muscles were subjected to in vitro force measurements. Cardiac function was determined by echocardiography and working heart preparations. Function of cardiomyocytes was measured in vitro. Cell culture experiments and mass-spectrometry were used for mechanistic analyses. Results: DKO mice showed a protein aggregate myopathy in skeletal muscle. Maximal force development was reduced in DKO soleus and extensor digitorum longus. Additionally, a fibre type shift towards slow/type I fibres occurred in DKO soleus and extensor digitorum longus. MuRF2 and MuRF3-deficient hearts showed decreased systolic and diastolic function. Further analyses revealed an increased expression of the myosin heavy chain isoform beta/slow and disturbed calcium handling as potential causes for the phenotype in DKO hearts. Conclusions: The redundant function of MuRF2 and MuRF3 is important for maintenance of skeletal muscle and cardiac structure and function in vivo