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Efficacy and Safety of Bimagrumab in Sporadic Inclusion Body Myositis: Long-Term Extension of RESILIENT
No full textObjective: To assess long-term (2 years) effects of bimagrumab in participants with sporadic inclusion body myositis.Methods: Participants (aged 36–85 years) who completed the core study (RESILIENT) were invited to join an extension study. Individuals continued on same treatment as in the core study (10 mg/kg, 3 mg/kg, 1 mg/kg bimagrumab, or matching placebo administered as intravenous infusions every 4 weeks). The co-primary outcome measures were 6-minute walk distance (6MWD) and safety.Results: Between November 2015 and February 2017, 211 participants entered double-blind placebo-controlled period of the extension study. Mean change in 6MWD from baseline was highly variable across treatment groups, but indicated progressive deterioration from weeks 24 to 104 in all treatment groups. Overall, 91·0%(n=142) participants in the pooled bimagrumab group and 89·1%(n=49) in the placebo group had ≥1 treatment-emergent adverse event (AE). Falls were slightly higher in the bimagrumab 3 mg/kg group versus 10 mg/kg, 1 mg/kg and placebo groups (69·2%[n=36 of 52] vs. 56·6%[n=30 of 53], 58·8%[n=30 of 51], and 61·8%[n=34 of 55], respectively). The most frequently reported AEs in pooled bimagrumab group were diarrhea 14·7%(n=23), involuntary muscle contractions 9·6%(n=15), and rash 5·1%(n=8). Incidence of serious AEs was comparable between the pooled bimagrumab and the placebo group (18·6%[n=29] vs. 14·5%[n=8], respectively).Conclusion: Extended treatment with bimagrumab up to 2 years produced a good safety profile and was well-tolerated, but did not provide clinical benefits in terms of improvement in mobility. The extension study was terminated early due to core study not meeting its primary endpoint.<br/
Effect of Thermal Conduction on Transformer Radiator CFD Modelling
No full textThe lifetime and reliability of power transformersare primarily dependent on the hot-spot temperature in thewindings, as temperature is the most important factordetermining the insulation degradation rate. Key to removingthe heat from the transformer is the radiator which must becarefully designed to keep the temperatures within limits underall operating conditions whilst minimizing the transformer size,weight and cost. This paper compares the analytical methodused to predict the radiator performance with computationalfluid dynamics (CFD) models in terms of heat dissipation. It isfound that the analytical method and CFD models give similarresults in the air natural (AN) cooling modes, whereas theanalytical method overestimates the heat dissipation in the airforced (AF) cooling modes. Moreover, the thermal conductioneffect in the radiator wall is investigated under differentoperating conditions and for different radiator sizes using theCFD models. The simulation results indicate that the radiatorwall contributes to 6%-10% of the total heat dissipation undersome circumstances and therefore should not be simply ignoredin radiator models
Assessing the Impact of Cross-border DSM on Power Transfers in a Regional Transmission System
No full textHigh Resolution Time-to-Digital Converters Implemented on 40, 28 and 20 nm FPGAs
No full textThis work proposed the implementations of high-resolution Time-to-Digital Converters (TDCs) on field-programmable gate array (FPGA) platforms with different manufacturing technologies: 40 nm Virtex-6, 28 nm Kintex-7 and 20 nm Kintex UltraScale. The Large-Scale Multi-Phase Matrix (LSPM) structure is employed, which is different from the commonly used delay line structure. Experimental results have proved that all the three implementations have achieved competitive resolution. Particularly, the Kintex-7 LSPM-TDC has achieved a resolution of 1.29 ps, ranking among the best performing FPGA-based TDCs. The dynamic ranges of the Virtex-6, Kintex-7 and Kintex UltraScale TDCs are 22s, 11s and 18s respectively. The LSPM-TDCs implemented on Virtex-6, Kintex-7 and Kintex UltraScale have demonstrated equivalent dynamic range as the state-of-the-art FPGA-based TDCs, but without using the “two-stage” method which worsens the precision. Moreover, experiment and comparison between implementations with different manufacturing technologies are provided. With the technology advances from 65 nm to 28 nm, steady improvements in resolution are acquired. However, the 20 nm Kintex UltraScale performs not as good as the 28 nm Kintex-7. Experimental results also demonstrate that the phase noise and dynamic power consumption are reduced in platforms with more advanced technology. The discussion of routing delay and jitter of the reference clock provides reference for FPGA designs
Investigation of Novel Drag-Reducing and Atomic Oxygen Resistant Materials in Very Low Earth Orbit using SOAR (Satellite for Orbital Aerodynamics Research)
No full textInterest in operating spacecraft in very low Earth orbits (VLEO), those below approximately 450 km, is growing due to the numerous benefits offered by reducing altitude. For remote sensing and Earth observation applications, improvements in resolution can be achieved or smaller instruments used with associated benefits in cost or mission value. Similarly, for communications applications, link-budgets and data latency can be improved by reducing the operational altitude. However, a key challenge to sustained operations in lower altitude orbits is to minimise and compensate for the aerodynamic drag that is produced by the interaction with the residual atmosphere. A principal aim of the DISCOVERER project is to identify, develop, and characterise materials that can promote specular reflections of the residual atmosphere in VLEO whilst also remaining resistant to the erosive atomic oxygen that is predominant at these altitudes. In combination with geometric design, such materials would be able to reduce the aerodynamic drag experienced by satellites in orbit and would also be able to generate usable aerodynamic lift enabling novel aerodynamic attitude and orbit control. SOAR (Satellite for Orbital Aerodynamics Research) is a 3U CubeSat that has been designed to investigate the aerodynamic performance of different materials in the VLEO environment and provide validation data for further ground-based experiments. To achieve this, the spacecraft features a set of steerable fins that can expose different materials to the oncoming atmospheric flow. A forward-facing ion and neutral mass spectrometer (INMS) provides in-situ measurements of the atmospheric density and flow composition. SOAR is scheduled for launch to the ISS in March 2021. This paper will present the design of the spacecraft, the experimental method that will be used to investigate the aerodynamic properties of materials in orbit, and will provide an update on the status of the spacecraft as it prepares for launch
The Post-Great Recession Geographies of U.S. Municipal Borrowing and Indebtedness
No full textBorrowing from capital markets has long been central to U.S. urban government (Peterson 1981; Sbragia 1996). Over the past five decades, U.S. cities have become even more reliant on borrowing, with local governments becoming more entrepreneurial and Federal authorities withdrawing fiscal support (Harvey 1989; Hackworth 2007). Some also claim this reliance has grown since the Great Recession (Peck 2014). Despite the perceived significance of borrowing to urban government, municipal indebtedness remains a relatively understudied topic within geography. This paper examines post- Great Recession indebtedness changes (2006-2016) in the general funds of U.S. municipalities. We show that general fund indebtedness has not generally increased since the Great Recession, although a complex landscape of divergent borrowing and indebtedness is evident across cities with different populations. The paper uses the Government Finance Database to collect and analyze U.S. Census Bureau data on municipal debt and budget health. We conclude by reflecting on how the analysis can help develop existing understandings of municipal debt and fiscal policy in a post-COVID 19 era
On the Application of BAC-NOMA to 6G umMTC
No full textThis letter studies the application of backscatter communications (BackCom) assisted non-orthogonal multiple access (BAC-NOMA) to the envisioned sixth-generation (6G) ultra-massive machine type communications (umMTC). In particular, the proposed BAC-NOMA transmission scheme can realize simultaneous energy and spectrum cooperation between uplink and downlink users, which is important to support massive connectivity and stringent energy constraints in umMTC. Furthermore, a resource allocation problem for maximizing the uplink throughput and suppressing the interference between downlink and uplink transmission is formulated as an optimization problem and the corresponding optimal resource allocation policy is obtained. Computer simulations are provided to demonstrate the superior performance of BAC-NOMA
Leadership and the hidden politics of co-produced research: a Q-methodology study
No full textCo-production of research has been promoted, but raises many challenges for academic research, including how to balance between scientific methods and the normative values associated with co-production. Involving the public and other stakeholders can imply different purposes for undertaking research, and different perspectives on how to do it. Who leads, and how, can influence how these disputed issues of purpose, practice, and power, are handled. A gap has been identified on the ‘hidden politics’ of leadership in co-produced research. The Q-methodology study presented in this paper offered a means to interrogate the different perspectives on leadership in co-produced research. Through systematic, comparative and empirically-grounded analysis, we identified four distinct viewpoints on leadership in co-production, offering competing perspectives on the practice of leadership, how questions of power should be addressed and contrasting purposes, emphasizing: creativity, outcomes, vision or equality. In reflecting on their divergence, as well as points of commonality, we demonstrate the value of centring questions of otherwise ‘hidden’ politics in debates on co-production and leadership. Our research offers theoretical advance in understanding how leadership in co-production is contested, and practical utility in offering heuristics to help navigate the messy realities of co-production
The Modified Liquid-Liquid Interface: the effect of an interfacial layer of MoS2 on Ion transfer
No full textInspiration from Nature: Influence of Engineered Ligand Scaffolds and Auxiliary Factors on the Reactivity of Biomimetic Oxidants
No full textEnzymes are highly efficient catalysts in Nature that often react with high stereo-, chemo-, and regioselectivity. Usually, enzymes achieve this selectivity through substrate binding and positioning in the active site. The second-coordination sphere effects (also called noncovalent interactions) position the substrate and oxidant in close vicinity, and their effects include electrostatic interactions, hydrogen-bonding interactions, salt-bridges, and also long-range charge-effects from bound cations and anions. Each of these environmental perturbations can affect the kinetics and selectivity of reactions differently. Over the past couple of years, a variety of biomimetic model complexes have been developed and designed that have a similar first-coordination sphere to mononuclear iron-containing enzymes. However, sometimes the reactivity patterns of the biomimetic models in solution are different from the analogous enzymatic systems, and often the selectivity of the reaction is lost. To understand the functional differences between enzymes and biomimetic models, large catalytic clusters have been developed that incorporate second-coordination sphere effects that influence spectroscopic features as well as reactivity patterns. In this Review, we summarize and highlight recent advances in biomimetic chemistry on the creation and design of iron catalysts and the insights that have been obtained when elaborate ligand features are added, which influence the substrate approach to the catalytic center. We start with a highlight of the axial and distal ligand effects of metal centers and how these can be perturbed by hydrogen bonding as well as steric restraints. The syntheses of the active oxidants through the addition of a proton-donating or -accepting groups to the structure have also been discussed in detail in this article. As shown in this work, second-coordination sphere effects can be useful not only to trap and characterize short-lived intermediates but also to enable high selectivity and specificity of a chemical reaction in analogy to enzymatic systems. These biomimetic models appear highly useful for biotechnological and engineering applications with reasonable turnover numbers and consequently have great potential for the future of stereo- and chemoselective synthetic catalytic reactions.</p