Abstract
Investigations of the origin and evolution of the Milky Way disc have long relied on chemical and kinematic identifications of its components to reconstruct our Galactic past. Difficulties ...in determining precise stellar ages have restricted most studies to small samples, normally confined to the solar neighbourhood. Here, we break this impasse with the help of asteroseismic inference and perform a chronology of the evolution of the disc throughout the age of the Galaxy. We chemically dissect the Milky Way disc population using a sample of red giant stars spanning out to 2 kpc in the solar annulus observed by the Kepler satellite, with the added dimension of asteroseismic ages. Our results reveal a clear difference in age between the low- and high-α populations, which also show distinct velocity dispersions in the V and W components. We find no tight correlation between age and metallicity nor α/Fe for the high-α disc stars. Our results indicate that this component formed over a period of more than 2 Gyr with a wide range of M/H and α/Fe independent of time. Our findings show that the kinematic properties of young α-rich stars are consistent with the rest of the high-α population and different from the low-α stars of similar age, rendering support to their origin being old stars that went through a mass transfer or stellar merger event, making them appear younger, instead of migration of truly young stars formed close to the Galactic bar.
APOGEE-2 is a high-resolution, near-infrared spectroscopic survey observing ∼3 × 105 stars across the entire sky. It is the successor to APOGEE and is part of the Sloan Digital Sky Survey IV ...(SDSS-IV). APOGEE-2 is expanding on APOGEE's goals of addressing critical questions of stellar astrophysics, stellar populations, and Galactic chemodynamical evolution using (1) an enhanced set of target types and (2) a second spectrograph at Las Campanas Observatory in Chile. APOGEE-2 is targeting red giant branch and red clump stars, RR Lyrae, low-mass dwarf stars, young stellar objects, and numerous other Milky Way and Local Group sources across the entire sky from both hemispheres. In this paper, we describe the APOGEE-2 observational design, target selection catalogs and algorithms, and the targeting-related documentation included in the SDSS data releases.
Facile synthesis of C‐terminal thioesters is integral to native chemical ligation (NCL) strategies for chemical protein synthesis. We introduce a new method of mild peptide activation, which ...leverages solid‐phase peptide synthesis (SPPS) on an established resin linker and classical heterocyclic chemistry to convert C‐terminal peptide hydrazides into their corresponding thioesters via an acyl pyrazole intermediate. Peptide hydrazides, synthesized on established trityl chloride resins, can be activated in solution with stoichiometric acetyl acetone (acac), readily proceed to the peptide acyl pyrazoles. Acyl pyrazoles are mild acylating agents and are efficiently exchanged with an aryl thiol, which can then be directly utilized in NCL. The mild, chemoselective, and stoichiometric activating conditions allow this method to be utilized through multiple sequential ligations without intermediate purification steps.
Mild acac‐tivation: Peptide hydrazides can be activated in solution with stoichiometric acetyl acetone (acac) to give the corresponding peptide acyl pyrazoles. These acyl pyrazoles can be transformed into peptide thioesters, which can then be directly used in native chemical ligation. The mild, chemoselective, and stoichiometric activating conditions allow this method to be used for multiple sequential ligations without intermediate purification steps.
We explore the structure of the element abundance-age-orbit distribution of the stars in the Milky Way's low- disk, by (re-)deriving precise Fe/H, X/Fe, and ages, along with orbits, for red clump ...stars from the apogee survey. There has been a long-standing theoretical expectation and observational evidence that metallicity (Fe/H) and age are informative about a star's orbit, e.g., about its angular momentum and the corresponding mean Galactocentric distance or its vertical motion. Indeed, our analysis of the apogee data confirms that Fe/H or age alone can predict the stars' orbits far less well than a combination of the two. Remarkably, we find and show explicitly that, for known Fe/H and age, the other abundances X/Fe of Galactic disk stars can be predicted well (on average to 0.02 dex) across a wide range of Galactocentric radii, and therefore provide little additional information, e.g., for predicting their orbit. While the age-abundance space for metal-poor stars and potentially for stars near the Galactic center is rich or complex, for the bulk of the Galaxy's low- disk it is simple: Fe/H and age contain most information, unless X/Fe can be measured to 0.02 or better. Consequently, we do not have the precision with current (and likely near-future) data to assign stars to their individual (coeval) birth clusters, from which the disk is presumably formed. We can, however, place strong constraints on future models of Galactic evolution, chemical enrichment, and mixing.
We present the final results from a high sampling rate, multi-month, spectrophotometric reverberation mapping campaign undertaken to obtain either new or improved H{beta} reverberation lag ...measurements for several relatively low-luminosity active galactic nuclei (AGNs). We have reliably measured the time delay between variations in the continuum and H{beta} emission line in six local Seyfert 1 galaxies. These measurements are used to calculate the mass of the supermassive black hole at the center of each of these AGNs. We place our results in context to the most current calibration of the broad-line region (BLR) R{sub BLR}-L relationship, where our results remove outliers and reduce the scatter at the low-luminosity end of this relationship. We also present velocity-resolved H{beta} time-delay measurements for our complete sample, though the clearest velocity-resolved kinematic signatures have already been published.
Background Continual improvements to health systems, products, and services are necessary for improvements in health. However, many of these improvements are not incorporated into everyday practice. ...When designing new health systems, products, and services, involving members of the healthcare community and the public with personal healthcare experience can help to make sure that improvements will be useful and relevant to others like them. Methods Together with healthcare workers and family members with healthcare experience, we developed and applied a step-by-step guide to involving those with personal experience in the design of health system improvements. Results Our guide has three phases- 'Pre-Design', 'Co-Design', and 'Post-Design'. This paper describes each of these phases and illustrates how we applied them to our own project, which is to use virtual healthcare methods to improve care for children with chronic healthcare conditions and their families. In our own work, we found that healthcare workers and family members with personal healthcare experiences were able to use their knowledge and creativity to help us imagine how to improve care for children with chronic healthcare conditions and their families. We have created action items from these family member- and healthcare worker-identified needs, which we will use to shape our virtual healthcare system. Conclusions This paper may be useful for those seeking to involve members of the healthcare community and the public in the creation of better healthcare systems, products, and services. Background Challenges with the adoption, scale, and spread of health innovations represent significant gaps in the evidence-to-practice cycle. In the health innovation design process, a lack of attention paid to the needs of end-users, and subsequent tailoring of innovations to meet these needs, is a possible reason for this deficit. In the creative field of health innovation, which includes the design of healthcare products, systems (governance and organization mechanisms), and services (delivery mechanisms), a framework for both soliciting the needs of end-users and translating these needs into the design of health innovations is needed. Methods To address this gap, our team developed and applied a seven-step methodological framework, called A Generative Co-Design Framework for Healthcare Innovation. This framework was developed by an interdisciplinary team that included patient partners. Results This manuscript contributes a framework and applied exemplar for those seeking to engage end-users in the creative process of healthcare innovation. Through the stages of 'Pre-Design', 'Co-Design', and 'Post-Design', we were able to harness the creative insights of end-users, drawing on their experiences to shape a future state of care. Using an expository example of our own work, the DigiComp Kids project, we illustrate the application of each stage of the Framework. Conclusions A Generative Co-Design Framework for Healthcare Innovation provides healthcare innovators, applied health science researchers, clinicians, and quality improvement specialists with a guide to eliciting and incorporating the viewpoints of end-users while distilling practical considerations for healthcare innovation and design.
Electric fields induce motion in many fluid systems, including polymer melts, surfactant micelles and colloidal suspensions. Likewise, electric fields can be used to move liquid drops. Electrically ...induced droplet motion manifests itself in processes as diverse as storm cloud formation, commercial ink-jet printing, petroleum and vegetable oil dehydration, electrospray ionization for use in mass spectrometry, electrowetting and lab-on-a-chip manipulations. An important issue in practical applications is the tendency for adjacent drops to coalesce, and oppositely charged drops have long been assumed to experience an attractive force that favours their coalescence. Here we report the existence of a critical field strength above which oppositely charged drops do not coalesce. We observe that appropriately positioned and oppositely charged drops migrate towards one another in an applied electric field; but whereas the drops coalesce as expected at low field strengths, they are repelled from one another after contact at higher field strengths. Qualitatively, the drops appear to 'bounce' off one another. We directly image the transient formation of a meniscus bridge between the bouncing drops, and propose that this temporary bridge is unstable with respect to capillary pressure when it forms in an electric field exceeding a critical strength. The observation of oppositely charged drops bouncing rather than coalescing in strong electric fields should affect our understanding of any process involving charged liquid drops, including de-emulsification, electrospray ionization and atmospheric conduction.
Alzheimer disease (AD) is associated with aberrant processing of the amyloid precursor protein (APP) by γ‐secretase, via an unknown mechanism. We recently showed that presenilin‐1 and ‐2, the ...catalytic components of γ‐secretase, and γ‐secretase activity itself, are highly enriched in a subcompartment of the endoplasmic reticulum (ER) that is physically and biochemically connected to mitochondria, called mitochondria‐associated ER membranes (MAMs). We now show that MAM function and ER–mitochondrial communication—as measured by cholesteryl ester and phospholipid synthesis, respectively—are increased significantly in presenilin‐mutant cells and in fibroblasts from patients with both the familial and sporadic forms of AD. We also show that MAM is an intracellular detergent‐resistant lipid raft (LR)‐like domain, consistent with the known presence of presenilins and γ‐secretase activity in rafts. These findings may help explain not only the aberrant APP processing but also a number of other biochemical features of AD, including altered lipid metabolism and calcium homeostasis. We propose that upregulated MAM function at the ER–mitochondrial interface, and increased cross‐talk between these two organelles, may play a hitherto unrecognized role in the pathogenesis of AD.
Alzheimer disease (AD) associated (gamma)‐secretase components presenilin‐1 and ‐2 accumulate in MAM, an LR‐like ER subcompartment connected to mitochondria. MAM function increases in patients with familial or sporadic AD and may be linked to AD pathogenesis.
Background/aims: There is evidence that smoking is a risk factor for age related macular degeneration (AMD). However, not all studies have demonstrated this association and several key questions ...about the role of smoking in AMD have still to be determined. The aim of this study was to further investigate this relation for both choroidal neovascularisation (CNV) and geographic atrophy (GA). Methods: To investigate the relation between smoking and the risk of developing age related macular degeneration (AMD) in white people, 435 cases with end stage AMD were compared with 280 controls. All subjects had graded stereoscopic colour fundus photography and AMD was defined as the presence of GA or CNV. Smoking history was assessed using multiple parameters in a detailed questionnaire. Results: Comparison of current and former smokers with non-smokers was consistent with smoking being a risk factor for AMD but did not reach statistical significance. There was a strong association between AMD and pack years of cigarette smoking (p = 0.002), the odds ratio increasing with the amount smoked; for subjects with more than 40 pack years of smoking the odds ratio was 2.75 (95% CI 1.22 to 6.20) compared with non-smokers. Both types of AMD showed a similar relation; smoking more than 40 pack years of cigarettes was associated with an odds ratio of 3.43 (95% CI 1.28 to 9.20) for GA and 2.49 (95% CI 1.06 to 5.82) for CNV. Stopping smoking was associated with reduced odds of AMD and the risk in those who had not smoked for over 20 years was comparable to non-smokers. The risk profile was similar for males and females. Passive smoking exposure was associated with an increased risk of AMD (OR 1.87; 95% CI 1.03 to 3.40) in non-smokers. Conclusions: The authors have demonstrated a strong association between the risk of both GA and CNV and pack years of cigarette smoking. This provides support for a causal relation between smoking and AMD. They also show an increased risk for AMD in non-smokers exposed to passive smoking. Stopping smoking appears to reduce the risk of developing AMD.
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