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    33676 research outputs found

    Tunable valley splitting and bipolar operation in graphene quantum dots

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    Quantum states in graphene are two-fold degenerate in spins, and two-fold in valleys. Both degrees of freedom can be utilized for qubit preparations. In our bilayer graphene quantum dots, we demonstrate that the valley g-factor gv, dened analogously to the spin g-factor gs for valley splitting in perpendicular magnetic field, is tunable by over a factor of four from 20 to 90, by gate voltage adjustments only. Larger gv resultsfrom larger electronic dot sizes, determined from the charging energy. On our versatile device, bipolar operation, charging our quantum dot with charge carriers of the same or the opposite polarity as the leads, can be performed. Dots of both polarities are tunable to the first charge carrier, such that the transition from an electron to a hole dot by action of the plunger gate can be observed. Addition of gates easily extends the system to host tunable double dots

    Immune Response and Safety of Viral Vaccines in Children with Autoimmune Diseases on Immune Modulatory Drug Therapy

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    Introduction: Children with autoimmune diseases often require treatment with systemic immunosuppressives. There are ongoing concerns regarding the efficacy and safety of vaccination, particularly live-attenuated viral vaccines in these patients.Areas covered: To evaluate the immunogenicity and safety of viral vaccines in children and young people treated with systemic immunosuppressive drugs for autoimmune diseases. A systemic literature review was performed using Pubmed and the following terms: virus, vaccination, autoimmune diseases, immunogenicity. English papers in subjects less than 21 years old were included. A total of 37 original articles were available, 25 on inactivated vaccines (influenza; hepatitis A virus; hepatitis B virus; human papillomavirus), and 12 on live-attenuated vaccines (varicella zoster virus; measles, mumps, and rubella). Viral vaccines were generally immunogenic and safe in children receiving immunosuppressive drugs including biologics. Use of low-dose glucocorticosteroids, disease-modifying antirheumatic drugs did not have a significant detrimental effect on vaccine immunogenicity, although there was anecdotal evidence of reduced immunogenicity in patients receiving high dose glucocorticoids and pulse cyclophosphamide. Patients on biologics mounted adequate seroprotective responses, but antibody titres tended to be lower. Both live-attenuated and inactivated vaccines were well tolerated and did not cause serious adverse events. Autoimmune disease activity was not adversely affected by vaccination.Expert commentary: Current evidence indicates that administration of viral vaccines to children and young people with autoimmune diseases receiving most systemic immunosuppressive drugs are immunogenic and safe. Patients on biologicals tend to have lower antibody titres. Those on high-dose glucocorticoids and pulse cyclophosphamide should avoid live viral vaccines

    Non-viral reprogramming of human nucleus pulposus cells with FOXF1 via extracellular vesicle delivery: an in-vitro and in-vivo study

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    Intervertebral disc (IVD) degeneration is characterized by decreased cellularity, decreased proteoglycan synthesis and increased inflammation, catabolism, and neural/vascular ingrowth. Current regenerative methods for IVD degeneration are largely cell therapy based or involve viral vectors which are associated with mutagenesis and undesired immune responses. This novel study uses bulk electroporation and engineered extracellular vesicles (EVs) to deliver the transcription factor FOXF1 mRNA to degenerate human nucleus pulposus (NP) cells as a minimally invasive therapeutic strategy for regeneration of the IVD. Bulk-electroporation was used to investigate the effects of FOXF1 on human NP cells with 4-week culture in 3D agarose constructs. Engineered EV delivery of FOXF1 into human IVD cells in monolayer was determined with subsequent in-vivo validation in a pilot mouse IVD puncture model. Transfection of FOXF1 significantly altered gene expression via upregulating healthy NP markers (FOXF1, KRT19), decreasing inflammatory cytokines (IL-1β, IL6), catabolic enzymes (MMP13) and nerve growth factor (NGF) with significant increases in glycosaminoglycan accumulation in human NP cells. Engineered EVs loaded with FOXF1 demonstrated successful encapsulation of FOXF1 cargo and effective uptake by human NP cells cultured in monolayer. Injection of EVs loaded with FOXF1 into the mouse IVD in-vivo resulted in significant upregulation of FOXF1 and Brachyury compared to controls at 7-days post-injection, with no evidence of cytotoxicity. This is the first study to demonstrate non-viral delivery of FOXF1 and reprogramming of human NP cells in-vitro and mouse IVD cells in-vivo. We highlight this strategy as a non-addictive approach for treating IVD degeneration and associated back pain

    What health policy makers need to know about mismatches between public perceptions of disease risk, prevalence and severity: A national survey

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    OBJECTIVES To assess people’s perceptions of their personal risk, population prevalence and perceived severity in relation to three key health conditions (cancer, heart disease and hearing loss), gauge the size of any misperceptions, and identify correlates of such misperceptions. DESIGN Cross-sectional survey. STUDY SAMPLE 10,401 adults representative of the UK population. RESULTS Clear majorities of people incorrectly believe that they are at greater personal risk of cancer (>75%), that cancer is more prevalent in the population (>50%) and that cancer is more disabling (>65%), than either heart disease or hearing loss. In turn, people consistently regard their personal risk of hearing loss, the population prevalence of hearing loss and the severity of hearing loss as lower than either cancer or heart disease. Multiple regression analyses showed inconsistent patterns of relationships between people’s beliefs, sociodemographic characteristics and their health behaviours. CONCLUSIONS Accuracy in beliefs about cancer, heart disease and hearing loss is low, and the relationships between these beliefs, their potential antecedents and consequences are complex. Policy makers should ensure close adherence to evidence or risk making decisions that are costly both in financial terms and in terms of suboptimal population subjective well-being

    Hydrocracking of virgin and Post-Consumer Polymers

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    With the growing concern around polymer waste sent to landfill and its environmental release, one effective route for polymer recycling is hydrocracking over bifunctional zeolites. Zeolite Beta impregnated with 1% Pt has demonstrated high conversion of single and mixed streams of virgin and post-consumer polymers, LDPE, HDPE, PP and PS under mild reaction conditions of 330°C, 20 bar H2 and a 30 minute reaction time. The PE and PP streams giving a similar mix of low molecular weight hydrocarbons with higher selectivity toward gases (typically, C3-C4) and also, obtaining high iso- to normal paraffin ratio. PS was readily converted into an aromatic-rich product under these mild conditions and demonstrated the ability to be a source of benzene and ethylbenzene for use as raw materials in further polymer production. Dealuminated zeolite USY with 1% Pt increased the selectivity toward liquid products and resulting in more naphtha (C5-C12) and heavier liquids (C13-C20)

    A SPECTRAL-IN-TIME NEWTON-KRYLOV METHOD FOR NONLINEAR PDE-CONSTRAINED OPTIMIZATION

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    We devise a method for nonlinear time-dependent PDE-constrained optimization problems that uses a spectral-in-time representation of the residual, combined with a Newton-Krylov method to drive the residual to zero. We also propose a preconditioner to accelerate this scheme. Numerical results indicate that this method can achieve fast and accurate solution of nonlinear problems for a range of mesh sizes and problem parameters, the numbers of outer Newton and inner Krylov iterations required to reach the attainable accuracy of a spatial discretization are robust with respect to the number of collocation points in time, and also do not change substantially when other problem parameters are varied

    Soil microbial diversity-biomass relationships are driven by soil carbon content across global biomes

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    The relationship between biodiversity and biomass has been a long standing debate in ecology. Soil biodiversity and biomass are essential drivers of ecosystem functions. However, unlike plant communities, little is known about how the diversity and biomass of soil microbial communities are interlinked across globally distributed biomes, and how variations in this relationship influence ecosystem function. To fill this knowledge gap, we conducted a field survey across global biomes, with contrasting vegetation and climate types. We show that soil carbon (C) content is associated to the microbial diversity-biomass relationship and ratio in soils across global biomes. This ratio provides an integrative index to identify those locations on Earth wherein diversity is much higher compared with biomass and vice versa. The soil microbial diversity-to biomass ratio peaks in arid environments with low C content, and is very low in C-rich cold environments. Our study further advances that reductions in soil C content associated with land use intensification and climate change could cause dramatic shifts in the microbial diversity-biomass ratio, with potential consequences for broad soil processes

    Mobility and healthy ageing in the city: exploring opportunities and challenges of autonomous vehicles for older adults’ outdoor mobility

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    Older adults face outdoor mobility challenges due to age-related changes and problems linked to the transportation system. The advent of fully-autonomous vehicles (AVs) is expected to benefit older adults by facilitating their outdoor mobility. However, research exploring the implications of AVs from older adults’ perspective is limited. This study explores older adults’ perception of the opportunities and concerns regarding AVs, in relation to their outdoor mobility needs and challenges. Using a qualitative design, we explore these issues based on in-depth interviews conducted with participants (≥ 65 years) in Greater Manchester, UK. The results revealed that older adults perceive opportunities in AVs enhancing their physical activity, promoting social interaction and offering stress-free door-to-door mobility. They, however, expressed concerns including safety, cost, possible erosion of road etiquettes and a desirable driving culture as a result of automation, a lack of social interaction with a human driver, and possible difficulties in using AVs. The participants’ most preferred use options (i.e., public transport and shared autonomous services) are grounded in their need for social interaction, physical activity, safe and less stressful, and affordable travel. The implications of these findings for policy at the intersection of mobility and healthy ageing in future cities are discussed

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