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Osteoarthritis treatment via the GLP-1–mediated gut-joint axis targets intestinal FXR signaling
Get PDFWhether a gut-joint axis exists to regulate osteoarthritis is unknown. In two independent cohorts, we identified altered microbial bile acid metabolism with reduced glycoursodeoxycholic acid (GUDCA) in osteoarthritis. Suppressing farnesoid X receptor (FXR)-the receptor of GUDCA-alleviated osteoarthritis through intestine-secreted glucagon-like peptide 1 (GLP-1) in mice. GLP-1 receptor blockade attenuated these effects, whereas GLP-1 receptor activation mitigated osteoarthritis. Osteoarthritis patients exhibited a lower relative abundance of Clostridium bolteae, which promoted the formation of ursodeoxycholic acid (UDCA), a precursor of GUDCA. Treatment with C. bolteae and Food and Drug Administration-approved UDCA alleviated osteoarthritis through the gut FXR-joint GLP-1 axis in mice. UDCA use was associated with lower risk of osteoarthritis-related joint replacement in humans. These findings suggest that orchestrating the gut microbiota-GUDCA-intestinal FXR-GLP-1-joint pathway offers a potential strategy for osteoarthritis treatment
Rapport in same and mixed neurotype groups of autistic and non-autistic adults
Get PDFAlthough autistic adults may establish better dyadic rapport with autistic relative to non-autistic partners, it is unclear whether this extends to group settings. The current study examined whether rapport differs between autistic groups, non-autistic groups, and mixed groups of autistic and non-autistic adults, and whether differing diagnostically from the rest of the group results in lower rapport. One hundred and forty-three adults were assigned to one of four group types of four participants each: all-autistic, all-non-autistic, non-autistic majority (three non-autistic, one autistic), and autistic majority (three autistic, one non-autistic). Groups participated in a 5-minute building activity and afterwards completed a 5-item rapport measure assessing their experience. The all-autistic groups did not differ on overall rapport from the all-non-autistic groups and had significantly higher rapport on two items (enjoying the interaction and friendliness of the group) than both types of mixed groups. At the individual level, autistic participants expressed more ease and enjoyment when interacting with other autistic adults relative to non-autistic adults, and their rapport declined as more non-autistic participants were included in the group. In contrast, rapport for non-autistic participants remained relatively consistent regardless of group composition. We discuss potential reasons why autistic participants were more affected by group composition than non-autistic participants
ROBIN: A unified nanopore-based assay integrating intraoperative methylome classification and next-day comprehensive profiling for ultra-rapid tumor diagnosis
No full textBackgroundAdvances in our technological capacity to interrogate CNS tumor biology have led to the ever increasing use of genomic sequencing in diagnostic decision making. Presently, CNS tumors are classified based on their epigenetic signatures, leading to a paradigm shift in diagnostic pathways. Such testing can be performed so rapidly using nanopore sequencing that results can be provided intraoperatively. This information greatly improves the fidelity of smear diagnosis and can help surgeons tailor their approach, balancing the risks of surgery with the likely benefit. Nevertheless, full integrated diagnosis may require subsequent additional assays to detect pathognomonic somatic mutations and structural variants, thereby delaying the time to final diagnosis.MethodsHere, we present ROBIN, a tool based on PromethION nanopore sequencing technology that can provide both real-time, intraoperative methylome classification and next-day comprehensive molecular profiling within a single assay. ROBIN utilizes 3 methylation classifiers to improve diagnostic performance in the intraoperative setting.ResultsWe demonstrate classifier performance on 50 prospective intraoperative cases, achieving a diagnostic turnaround time under 2 hours and generating robust tumor classifications within minutes of sequencing. Furthermore, ROBIN can detect single nucleotide variants, copy number variants, and structural variants in real time, and is able to inform a complete integrated diagnosis within 24 hours. Classifier performance demonstrated concordance with final integrated diagnosis in 90% of prospective cases.ConclusionNanopore sequencing can greatly improve turnaround times for standard-of-care diagnostic testing and is furthermore able to reliably provide clinically actionable intraoperative tumor classification
A Parallel Input and Versatile Output Dual Active Bridge Converter
Get PDFDue to their easy scalability to high power, simple control mechanism, and effective semiconductor and transformer utilization, H-bridge-derived isolated dc/dc converters have taken a central stage in various power electronics applications such as fast charging stations, dc microgrids and renewable energy integration. Among the bidirectional variants, the dual active bridge (DAB) converter stands out as a common choice due to its direct power flow control mechanism, inherent soft switching realization, symmetric and modular structure, etc. However, the conventional version of the topology exhibits a significant reduction in efficiency when subjected to wide ranges in voltage gain and output power. This limitation can potentially hinder its application in public dc chargers where different charging profiles and vehicle voltage classes are frequently expected. This article proposes a new versatile topology derived from the DAB converter that caters to the requirement of a wide output voltage range and improves the efficiency characteristics while mitigating the current and/or voltage stresses on the semiconductor devices. Furthermore, a suitable modulation strategy is developed that optimizes the soft switching action of the converter in accordance with the load demand. The converter operation is explained and validated through a steady-state model, simulations and an 11kW experimental prototype
Comprehensive performance analysis of a novel closed-loop hydronic cooling of photovoltaic panel with a controlled intermittent flow strategy
Get PDFPhotovoltaic (PV) technology has seen rapid development in hot and arid regions due to intense solar radiation. However, extreme weather conditions pose challenges for PV applications in terms of efficiency and lifespan. A new closed-loop hydronic cooling system for PV panels, designed for 24-h continuous operation, was developed to address these challenges. However, a circulation pump can consume a considerable amount of electricity due to 24-h continuous operation, resulting in substantial wastage. This study proposes a controlled intermittent flow (CIF) strategy for the pump to optimize operation hours and minimize energy consumption under favourable PV temperature conditions. A dynamic 3D simulation model was developed and validated to numerically analyse the performance metrics of the proposed PV cooling method with CIF. The yearly performance of PV panel cooling systems with continuous flow (CF) and CIF, as well as common PV panels, was comprehensively evaluated and compared. The results showed that the CIF strategy effectively reduces the pump's operating hours and energy consumption while minimally impacting the system's net electricity output. The CIF strategy is found to yield a significant enhancement in seasonal net power output, with a 0.57 % increase during winter and a 0.83 % increase in summer compared to the CF system. Moreover, employing the CIF strategy with a setpoint of 35 °C results in a consistent 0.96 % rise in annual net power output across all months compared to the CF system, except for the lifespan, the CF is better. For Basra's local climatic condition in Iraq, the CF and CIF closed-loop photovoltaic cooling systems show significant lifetime improvements of up to 34.3 % and 41 % over common PV panels, while for Hong Kong's local climatic condition, the CIF system outperforms by 4.9 % and 22.2 % compared to CF system and common PV panel, respectively. The proposed closed-loop hydronic cooling method for PV panels with CIF exhibits the best performance among the three types of PV systems, making it particularly suitable for regions with hot and arid climates
Second-Carrier Harmonic Cancellation for a DC Bus Fed by Multiple Dual Active Bridges in More Electric Aircraft Applications
Get PDFThis paper develops a mechanism to suppress second-carrier harmonics on a common DC bus fed by multiple dual-active bridge (DAB) converters. A mathematical model of dc-link current harmonic components of a DAB is derived. Using this model, it is found that the magnitude and the phase angle of the second-carrier harmonic are mainly determined by the phase shift ratio of the DAB converter. Based on this conclusion, a harmonic suppression control scheme has been developed to manage the phase shifts in carrier waves of the two converters. To mitigate the impacts of differences in leakage inductances, voltage source types and levels, an enhanced harmonic cancellation scheme has been developed using an extra control loop to coordinate the duty cycles between DABs to achieve entire harmonic cancellation in general cases. The proposed method demonstrates a significant reduction of second-carrier harmonics and has been validated in both simulation and experiment results
Critical Teacher Education for Social Sustainability: Voices from Zambian Student Teachers and Tutors
Get PDFThis study aims to reveal the contributions of teacher education to social sustainability in an African context. The study explored the gaps and connections between multiple layers of policy, global, regional, and national educational targets, and the voices of teacher education tutors and students from a local teacher education college in the Copperbelt region of Zambia. Semi-structured interviews were employed to gather participants’ views on their aspiration, knowledge transformation and professional capacity. Employing a critical realist approach, the study identifies four key ‘moments’ in teacher education (Robertson and Dale, 2015) and reveals dedicated teacher education practices that aim to support national economic development local demands for specialised subject knowledge, along with family and individual human needs within communities. The findings lead to a discussion mapping critical teacher education that promotes social sustainability within the Global South, emphasising the significant roles of teacher education in fostering a comprehensive understanding of societies and human well-being, encouraging reciprocal knowledge exchange within communities, and supporting the continued professional development of teachers
Transfer of congruency effects between Stroop and multiplication tasks: Evidence that retrieval of multiplication facts requires inhibitory control
Get PDFInhibitory control is classically considered a domain-general process, yet recent findings suggest it may operate in context-specific ways. This has important implications for theories in other cognitive domains, such as mathematics, in which inhibitory control is proposed to play a key role. Inhibitory control has been implicated in resolving interference between competing number facts when retrieving them from memory, yet clear evidence for this is lacking. Here we report two pre-registered experiments with adults that investigated transfer of inhibitory control between interleaved Stroop and multiplication fact retrieval trials. Experiment 1 (n = 450) measured the congruency sequence effect, where transfer of inhibitory control between trials leads to a reduced congruency effect following an incongruent trial. Experiment 2 (n = 370) measured transfer of the list-wide proportion congruency effect, where the congruency effect is reduced when incongruent trials are more frequent. We found evidence of transfer of the congruency sequence effect between Stroop and multiplication. This did not differ depending on whether the Stroop task used number or animal stimuli. There was no transfer of the list-wide proportion congruency effect. These results suggest that reactive, transient domain-general inhibitory control processes are involved in retrieving multiplication facts from memory. Our findings have implications for theories of cognitive control and mathematical cognition, but caution should be taken in interpreting implications for educational interventions
On face value: a ghost driver field study investigating interactions between pedestrians and a driverless vehicle with anthropomorphic displays
Get PDFIn a novel, on-road study, using a ‘Ghost Driver’ to emulate an automated vehicle (AV), we captured over 10 hours of video (n = 520) and 64 survey responses documenting the behaviour and attitudes of pedestrians in response to the AV. Three prototype external human-machine interfaces (eHMIs) described the AV’s behaviour, awareness and intention using elements of anthropomorphism: High (human face), Low (car motif), Abstract (partial representation of human features that lacked precise visual reference); these were evaluated against a (no eHMI) baseline. Despite many pedestrians reporting that they still relied on vehicular cues to negotiate their crossing, there was a desire/expectation expressed for explicit communication with future AVs. High and Low anthropomorphism eHMIs received the most positive responses for clarity, confidence and trust, with High also attracting significantly more/longer glances and the highest preference rating. In contrast, Abstract was considered least clear and subsequently invited the lowest confidence and trust ratings
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