Time Domain Mapping of Spin Torque Oscillator Effective Energy

Stochastic dynamics of spin torque oscillators (STOs) can be described in terms of magnetization drift and diffusion over a current-dependent effective energy surface given by the Fokker-Planck equation. Here we present a method that directly probes this effective energy surface via time-resolved measurements of the microwave voltage generated by a STO. We show that the effective energy approach provides a simple recipe for predicting spectral line widths and line shapes near the generation threshold. Our time domain technique also accurately measures the field-like component of spin torque in a wide range of the voltage bias values.Comment: 5 pages, 3 figures. Supplement included: 7 pages, 6 figure

Simulations of Recovery of Time-Varying Gravity from DECIGO Pathfinder

We simulated time-varying Earth's gravity field recovered from DPF to evaluate an impact of DPF and future satellite gradiometry mission on earth science. From hydrological water movement data and orbit information, gravity gradients to be measured at altitude about ~500km were generated. Errors caused by atmospheric and oceanic variations and instrumental noise were added. Monthly gravity fields were estimated solving normal equations between spherical harmonic coefficients and simulated gravity gradient data. Simulation results show that DPF likely provides monthly hydrological water storage change with spatial scale between 400 and 1000km. Sensitivities to large scale estimates depends on long-term stability of gravity gradient measurement, and errors in short scale estimates are caused by instrumental noise and imperfections in atmospheric and ocean model. With acceleration noise level is lower than ~5 x 10(exp -14) [m/s2/sqrtHz] at frequency higher than 3mHz, water storage changes at limited small basins will be provided by DPF. To monitor continental scale hydrological water movement, noise level must be lower than ~5 x 10(exp -14) [m/s2/sqrtHz] at frequency higher than 1mHz

Pleiotropic Effects of GLP-1 and Analogs on Cell Signaling, Metabolism, and Function

The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its “incretin effect” in restoring glucose homeostasis in diabetics, however, it is now apparent that it has a broader range of physiological effects in the body. Both in vitro and in vivo studies have demonstrated that GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression, and influence neuroprotective pathways. A substantial body of evidence has accumulated with respect to how GLP-1 and its analogs act to restore and maintain normal cellular functions. These findings have prompted several clinical trials which have reported GLP-1 analogs improve cardiac function, restore lung function and reduce mortality in patients with obstructive lung disease, influence blood pressure and lipid storage, and even prevent synaptic loss and neurodegeneration. Mechanistically, GLP-1 elicits its effects via acute elevation in cAMP levels, and subsequent protein kinase(s) activation, pathways well-defined in pancreatic β-cells which stimulate insulin secretion in conjunction with elevated Ca2+ and ATP. More recently, new studies have shed light on additional downstream pathways stimulated by chronic GLP-1 exposure, findings which have direct relevance to our understanding of the potential therapeutic effects of longer lasting analogs recently developed for clinical use. In this review, we provide a comprehensive description of the diverse roles for GLP-1 across multiple tissues, describe downstream pathways stimulated by acute and chronic exposure, and discuss novel pleiotropic applications of GLP-1 mimetics in the treatment of human disease

GLP-1 receptor signalling promotes β-cell glucose metabolism via mTOR-dependent HIF-1α activation

Glucagon-like peptide-1 (GLP-1) promotes insulin secretion from pancreatic β-cells in a glucose dependent manner. Several pathways mediate this action by rapid, kinase phosphorylation-dependent, but gene expression-independent mechanisms. Since GLP-1-induced insulin secretion requires glucose metabolism, we aimed to address the hypothesis that GLP-1 receptor (GLP-1R) signalling can modulate glucose uptake and utilization in β-cells. We have assessed various metabolic parameters after short and long exposure of clonal BRIN-BD11 β-cells and rodent islets to the GLP-1R agonist Exendin-4 (50nM). Here we report for the first time that prolonged stimulation of the GLP-1R for 18hours promotes metabolic reprogramming of β-cells. This is evidenced by up-regulation of glycolytic enzyme expression, increased rates of glucose uptake and consumption, as well as augmented ATP content, insulin secretion and glycolytic flux after removal of Exendin-4. In our model, depletion of HypoxiaInducible Factor 1 alpha (HIF-1α) impaired the effects of Exendin-4 on glucose metabolism, while pharmacological inhibition of Phosphoinositide 3-kinase (PI3K) or mTOR completely abolished such effects. Considering the central role of glucose catabolism for stimulus-secretion coupling in β-cells, our findings suggest that chronic GLP-1 actions on insulin secretion include elevated β-cell glucose metabolism. Moreover, our data reveal novel aspects of GLP-1 stimulated insulin secretion involving de novo gene expression

Adapting student practice placements in response to COVID-19: 'Get there together' a digital stories project for people living with dementia

The impact of COVID-19 has been harshly felt by occupational therapists in practice and students requiring practice education placements. A collaboration between Aneurin Bevan University Health Board (ABUHB) and Cardiff University enabled 10 undergraduate students to undertake their final placement by participating in a Digital Stories Project. This placement was innovatively designed to allow students to meet their learning objectives remotely, reducing clinical days in adherence to social distancing measures. The ‘Get There Together’ project was created by the national steering group after identifying the devastating impact COVID-19 had on people affected by dementia when accessing community occupations. The students collaborated with service users to identify areas that they wanted to visit, creating digital recordings explaining what to expect due to COVID-19 rules. This paper will focus on the conception and development of the Digital Stories Project, which helped increase placement capacity for occupational therapy students, during the COVID-19 pandemic

Schopenhauer on the Rights of Animals

I argue that Schopenhauer’s ascription of (moral) rights to animals flows naturally from his distinctive analysis of the concept of a right. In contrast to those who regard rights as fundamental and then cast wrongdoing as a matter of violating rights, he takes wrong (Unrecht) to be the more fundamental notion and defines the concept of a right (Recht) in its terms. He then offers an account of wrongdoing which makes it plausible to suppose that at least many animals can be wronged and thus, by extension, have rights. The result, I argue, is a perspective on the nature of moral rights in general, and the idea of animal rights in particular, that constitutes an important and plausible alternative to the more familiar views advanced by philosophers in recent decades

Forging networks and mixing ores: rethinking the social landscapes of iron metallurgy

This research explores the networks of technological knowledge that influenced changes in the iron production practices of western Uganda in the second half of the second millennium AD. Temporal and spatial variability in technological processes were observed within the research area, in terms of the style and construction of the furnaces, the use of a manganese-rich flux, and the configuration of tuyères. These shifts were considered in relation to the social dimensions of iron production, specifically the protection of technical knowledge. Informed by ethnographic data from the study area, variations were noted in the participation in, or exclusion from, iron production activity on the basis of gender and clan affiliation. This stands in contrast to ethno-historic accounts that speak of a strongly regulated production environment. This paper considers that an uncritical emphasis on conservatism provides an inadequate framework for addressing long-term change in iron production technologies. It suggests that constellations of knowledge in western Uganda fostered the potential for innovation and experimentation, resulting in dynamic technological practice. This paper urges a more nuanced discussion of how complex metallurgical technologies transform and move within cultural and physical landscapes, with ramifications for how we conceptualize the emergence and adoption of early technologies

Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial

\ua9 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Background: Individuals with serum antibodies to citrullinated protein antigens (ACPA), rheumatoid factor, and symptoms, such as inflammatory joint pain, are at high risk of developing rheumatoid arthritis. In the arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept (APIPPRA) trial, we aimed to evaluate the feasibility, efficacy, and acceptability of treating high risk individuals with the T-cell co-stimulation modulator abatacept. Methods: The APIPPRA study was a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial done in 28 hospital-based early arthritis clinics in the UK and three in the Netherlands. Participants (aged ≥18 years) at risk of rheumatoid arthritis positive for ACPA and rheumatoid factor with inflammatory joint pain were recruited. Exclusion criteria included previous episodes of clinical synovitis and previous use of corticosteroids or disease-modifying antirheumatic drugs. Participants were randomly assigned (1:1) using a computer-generated permuted block randomisation (block sizes of 2 and 4) stratified by sex, smoking, and country, to 125 mg abatacept subcutaneous injections weekly or placebo for 12 months, and then followed up for 12 months. Masking was achieved by providing four kits (identical in appearance and packaging) with pre-filled syringes with coded labels of abatacept or placebo every 3 months. The primary endpoint was the time to development of clinical synovitis in three or more joints or rheumatoid arthritis according to American College of Rheumatology and European Alliance of Associations for Rheumatology 2010 criteria, whichever was met first. Synovitis was confirmed by ultrasonography. Follow-up was completed on Jan 13, 2021. All participants meeting the intention-to-treat principle were included in the analysis. This trial was registered with EudraCT (2013–003413–18). Findings: Between Dec 22, 2014, and Jan 14, 2019, 280 individuals were evaluated for eligibility and, of 213 participants, 110 were randomly assigned to abatacept and 103 to placebo. During the treatment period, seven (6%) of 110 participants in the abatacept group and 30 (29%) of 103 participants in the placebo group met the primary endpoint. At 24 months, 27 (25%) of 110 participants in the abatacept group had progressed to rheumatoid arthritis, compared with 38 (37%) of 103 in the placebo group. The estimated proportion of participants remaining arthritis-free at 12 months was 92\ub78% (SE 2\ub76) in the abatacept group and 69\ub72% (4\ub77) in the placebo group. Kaplan–Meier arthritis-free survival plots over 24 months favoured abatacept (log-rank test p=0\ub7044). The difference in restricted mean survival time between groups was 53 days (95% CI 28–78; p<0\ub70001) at 12 months and 99 days (95% CI 38–161; p=0\ub70016) at 24 months in favour of abatacept. During treatment, abatacept was associated with improvements in pain scores, functional wellbeing, and quality-of-life measurements, as well as low scores of subclinical synovitis by ultrasonography, compared with placebo. However, the effects were not sustained at 24 months. Seven serious adverse events occurred in the abatacept group and 11 in the placebo group, including one death in each group deemed unrelated to treatment. Interpretation: Therapeutic intervention during the at-risk phase of rheumatoid arthritis is feasible, with acceptable safety profiles. T-cell co-stimulation modulation with abatacept for 12 months reduces progression to rheumatoid arthritis, with evidence of sustained efficacy beyond the treatment period, and with no new safety signals. Funding: Bristol Myers Squibb

The Fifteenth Data Release of the Sloan Digital Sky Surveys: First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library

Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July–2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA—we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020–2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data