Simulation of anyonic statistics and its topological path independence using a 7-qubit quantum simulator

Anyons, quasiparticles living in two-dimensional spaces with exotic exchange statistics, can serve as the fundamental units for fault-tolerant quantum computation. However, experimentally demonstrating anyonic statistics is a challenge due to the technical limitations of current experimental platforms. Here, we take a state perpetration approach to mimic anyons in the Kitaev lattice model using a 7-qubit nuclear magnetic resonance quantum simulator. Anyons are created by dynamically preparing the ground and excited states of the 7-qubit Kitaev lattice model, and are subsequently braided along two distinct, but topologically equivalent, paths. We observe that the phase acquired by the anyons is independent of the path, and coincides with the ideal theoretical predictions when decoherence and implementation errors are taken into account. As the first demonstration of the topological path independence of anyons, our experiment helps to study and exploit the anyonic properties towards the goal of building a topological quantum computer.Comment: 12 pages and 9 figures. All comments are welcome

Targeted delivery of lysosomal enzymes to the endocytic compartment in human cells using engineered extracellular vesicles.

Targeted delivery of lysosomal enzymes to the endocytic compartment of human cells represents a transformative technology for treating a large family of lysosomal storage diseases (LSDs). Gaucher disease is one of the most common types of LSDs caused by mutations to the lysosomal β-glucocerebrosidase (GBA). Here, we describe a genetic strategy to produce engineered exosomes loaded with GBA in two different spatial configurations for targeted delivery to the endocytic compartment of recipient cells. By fusing human GBA to an exosome-anchoring protein: vesicular stomatitis virus glycoprotein (VSVG), we demonstrate that the chimeric proteins were successfully integrated into exosomes which were secreted as extracellular vesicles (EVs) by producer cells. Isolation and molecular characterization of EVs confirmed that the fusion proteins were loaded onto exosomes without altering their surface markers, particle size or distribution. Further, enzyme-loaded exosomes/EVs added to cultured medium were taken up by recipient cells. Further, the endocytosed exosomes/EVs targeted to endocytic compartments exhibited a significant increase in GBA activity. Together, we have developed a novel method for targeting and delivery of lysosomal enzymes to their natural location: the endocytic compartment of recipient cells. Since exosomes/EVs have an intrinsic ability to cross the blood-brain-barrier, our technology may provide a new approach to treat severe types of LSDs, including Gaucher disease with neurological complications

The Language of End-of-Life Decision Making: A Simulation Study

Background: Framing is known to influence decision making. Objective: The study objective was to describe language used by physicians when discussing treatment options with a critically and terminally ill elder. Methods: High-fidelity simulation was used, involving an elder with end-stage cancer and life-threatening hypoxia, followed by a debriefing interview. Subjects were hospitalist, emergency medicine, and critical care physicians from three academic medical centers. Measures were observation of encounters in real time followed by content analysis of simulation and debriefing interview transcripts. During the simulation we identified the first mention (?broaching?) of principal treatment options?intubation and mechanical ventilation (life-sustaining treatment [LST]) and palliation in anticipation of death (palliation)?and used constant comparative methods to identify language used. We identified physician opinions about the use of LST in this clinical context during the debriefing interviews, and compared language used with opinions. Results: Among 114 physician subjects, 106 discussed LST, 86 discussed palliation, and 84 discussed both. We identified five frames: will (decided), must (necessary), should (convention), could (option), and ask (elicitation of preferences). Physicians broached LST differently than palliation (p<0.01), most commonly framing LST as necessary (53%), while framing palliation as optional (49%). Among physicians who framed LST as imperative (will or must), 16 (30%) felt intubation would be inappropriate in this clinical situation. Conclusions: In this high-fidelity simulation experiment involving a critically and terminally ill elder, the majority of physicians framed the available options in ways implying LST was the expected or preferred choice. Framing of treatment options could influence ultimate treatment decisions.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140120/1/jpm.2015.0089.pd

Potential Impact of Time Trend of Life-Style Factors on Cardiovascular Disease Burden in China

Cardiovascular disease (CVD) is a leading cause of death in China. Evaluation of risk factors and their impacts on disease burden is important for future public health initiatives and policy making

Orchestrating Extracellular Vesicle With Dual Reporters for Imaging and Capturing in Mammalian Cell Culture

Background: Recent technological advancements have enabled live-cell imaging of intracellular organelles to monitor their biogenesis in mammalian cells. However, applying this method to gain insight into extracellular organelles, such as extracellular vesicles (EVs), presents unique challenges that require special considerations in design and engineering.Results: We have developed a dual-reporter system that combines genetic fusion, fluorescence microcopy and magnetic beads capture of EVs to study the biogenesis of EVs in mammalian cell cultures. First, we genetically produced a series of reporters by fusing a green fluorescent protein (GFP) and an affinity peptide (6xHis), with either the endogenous transmembrane protein, CD63, or EVs targeting vesicular stomatitis viral glycoprotein (VSVG). Transfection of these reporters into human 293T cells resulted in expression and integration of these reporters into pre-exosome compartments, which were subsequently released into the culture medium. Confocal imaging and nano-particle tracking analysis demonstrated that EVs were appropriately labeled and exhibited a single dominant peak in the 80–110 nm size range, indicating that isolated EVs were comprised of micro-vesicles and/or exosome subpopulations. Incubation of isolated EVs with nickel-coated magnetic beads resulted in successful capture of GFP-positive EVs. Finally, addition of EVs into culture medium was able to reveal the cellular uptake of GFP-labeled EVs by recipient cells. Taken together, our dual-reporter system provides a powerful method for both monitoring and capturing of EVs in mammalian cell culture systems.Conclusion: A dual-reporter system provides a robust tool to study the life cycle of EVs in mammalian cells from biogenesis and excretion to cellular uptake

Multiple enzymatic approaches to hydrolysis of fungal beta-glucans by the soil bacterium Chitinophaga pinensis

The genome of the soil Bacteroidota Chitinophaga pinensis encodes a large number of glycoside hydrolases (GHs) with noteworthy features and potentially novel functions. Several are predicted to be active on polysaccharide components of fungal and oomycete cell walls, such as chitin, beta-1,3-glucan and beta-1,6-glucan. While several fungal beta-1,6-glucanase enzymes are known, relatively few bacterial examples have been characterised to date. We have previously demonstrated that C. pinensis shows strong growth using beta-1,6-glucan as the sole carbon source, with the efficient release of oligosaccharides from the polymer. We here characterise the capacity of the C. pinensis secretome to hydrolyse the beta-1,6-glucan pustulan and describe three distinct enzymes encoded by its genome, all of which show different levels of beta-1,6-glucanase activity and which are classified into different GH families. Our data show that C. pinensis has multiple tools to deconstruct pustulan, allowing the species' broad utility of this substrate, with potential implications for bacterial biocontrol of pathogens via cell wall disruption. Oligosaccharides derived from fungal beta-1,6-glucans are valuable in biomedical research and drug synthesis, and these enzymes could be useful tools for releasing such molecules from microbial biomass, an underexploited source of complex carbohydrates

Examining the impact of a universal social and emotional learning intervention (Passport) on internalising symptoms and other outcomes among children, compared to the usual school curriculum: study protocol for a school-based cluster randomised trial.

Background: School-based universal social and emotional learning (SEL) interventions implemented during the transition to adolescence may be efficacious in preventing the development of mental health difficulties. This protocol describes a two-arm parallel cluster randomised controlled trial to investigate the impact of a universal SEL intervention (Passport, compared to usual provision) on internalising symptoms (primary outcome), emotion regulation, well-being, loneliness, social support, bullying, academic attainment, and health-related quality of life in English primary school pupils aged 9-11 years. A developer-led trial demonstrated the feasibility, acceptability, and utility of Passport; this will be the first independent trial.Methods: Sixty primary schools will be recruited across the Greater Manchester city region and surrounding areas, involving 2400 pupils aged 8-9 at baseline. Schools will be allocated to the intervention arm to implement Passport over 18 weekly sessions or to the control arm to implement the usual school curriculum. Random allocation will be at school level following completion of baseline measures, with minimisation to ensure balance across trial arms in school size and free school meal eligibility. Measures will be collected at baseline, post-intervention (12 months post-baseline), and at 12 months follow-up (24 months post-baseline). The primary outcome analysis (intervention effects on internalising symptoms at post-intervention) will comprise a two-level (school, child) hierarchical linear model, following the intention-to-treat principle. Additional analyses will be undertaken to assess intervention effects on secondary outcomes, maintenance effects for all outcomes, intervention compliance moderator effects, subgroup moderator effects, and mechanisms underpinning intervention effects on the primary outcome. A mixed-methods implementation and process evaluation will examine factors that influence implementation, and a health economic evaluation will assess the cost-effectiveness of the intervention.Discussion: Findings will provide educators with crucial knowledge of whether and how increasing emotion regulation through a universal intervention impacts internalising symptoms and a range of related outcomes. Findings will also inform policy related to the promotion of mental health among children and young people. If the intervention is found to be efficacious in reducing internalising symptoms and is also cost-effective, it may offer high potential as a preventative intervention for widespread implementation.Trial Registration: ISRCTN12875599; registered on 24 November 2022.</p

Examining the impact of a universal social and emotional learning intervention (Passport) on internalising symptoms and other outcomes among children, compared to the usual school curriculum:study protocol for a school-based cluster randomised trial

BACKGROUND: School-based universal social and emotional learning (SEL) interventions implemented during the transition to adolescence may be efficacious in preventing the development of mental health difficulties. This protocol describes a two-arm parallel cluster randomised controlled trial to investigate the impact of a universal SEL intervention (Passport, compared to usual provision) on internalising symptoms (primary outcome), emotion regulation, well-being, loneliness, social support, bullying, academic attainment, and health-related quality of life in English primary school pupils aged 9-11 years. A developer-led trial demonstrated the feasibility, acceptability, and utility of Passport; this will be the first independent trial.METHODS: Sixty primary schools will be recruited across the Greater Manchester city region and surrounding areas, involving 2400 pupils aged 8-9 at baseline. Schools will be allocated to the intervention arm to implement Passport over 18 weekly sessions or to the control arm to implement the usual school curriculum. Random allocation will be at school level following completion of baseline measures, with minimisation to ensure balance across trial arms in school size and free school meal eligibility. Measures will be collected at baseline, post-intervention (12 months post-baseline), and at 12 months follow-up (24 months post-baseline). The primary outcome analysis (intervention effects on internalising symptoms at post-intervention) will comprise a two-level (school, child) hierarchical linear model, following the intention-to-treat principle. Additional analyses will be undertaken to assess intervention effects on secondary outcomes, maintenance effects for all outcomes, intervention compliance moderator effects, subgroup moderator effects, and mechanisms underpinning intervention effects on the primary outcome. A mixed-methods implementation and process evaluation will examine factors that influence implementation, and a health economic evaluation will assess the cost-effectiveness of the intervention.DISCUSSION: Findings will provide educators with crucial knowledge of whether and how increasing emotion regulation through a universal intervention impacts internalising symptoms and a range of related outcomes. Findings will also inform policy related to the promotion of mental health among children and young people. If the intervention is found to be efficacious in reducing internalising symptoms and is also cost-effective, it may offer high potential as a preventative intervention for widespread implementation.TRIAL REGISTRATION: ISRCTN12875599; registered on 24 November 2022.</p

Association analysis of complex diseases using triads, parent-child dyads and singleton monads

Background: Triad families are routinely used to test association between genetic variants and complex diseases. Triad studies are important and popular since they are robust in terms of being less prone to false positives due to population structure. In practice, one may collect not only complete triads, but also incomplete families such as dyads (affected child with one parent) and singleton monads (affected child without parents). Since there is a lack of convenient algorithms and software to analyze the incomplete data, dyads and monads are usually discarded. This may lead to loss of power and insufficient utilization of genetic information in a study. Results: We develop likelihood-based statistical models and likelihood ratio tests to test for association between complex diseases and genetic markers by using combinations of full triads, parent-child dyads, and affected singleton monads for a unified analysis. A likelihood is calculated directly to facilitate the data analysis without imputation and to avoid computational complexity. This makes it easy to implement the models and to explain the results. Conclusion: By simulation studies, we show that the proposed models and tests are very robust in terms of accurately controlling type I error evaluations, and are powerful by empirical power evaluations. The methods are applied to test for association between transforming growth factor alpha (TGFA) gene and cleft palate in an Irish study