278 research outputs found
What Does it Mean to Teach Interpretively?
The ‘interpretive turn’ has gained traction as a research approach in recent decades in the empirical social sciences. While the contributions of interpretive research and interpretive research methods are clear, we wonder: Does an interpretive perspective lend itself to – or even demand – a particular style of teaching? This question was at the heart of a roundtable discussion we organised at the 2014 Interpretive Policy Analysis (IPA) International Conference. This essay reports on the contours of the discussion, with a focus on our reflections upon what it might mean to teach ‘interpretively’. Prior to outlining these, we introduce the defining characteristics of an interpretive perspective and describe our respective experiences and interests in this conversation. In the hope that this essay might constitute the beginning of a wider conversation, we close it with an invitation for others to respond
The effects of peripheral and central high insulin on brain insulin signaling and amyloid-β in young and old APP/PS1 mice
Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP(swe)/PS1(dE9) transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF Aβ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma Aβ, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on Aβ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate Aβ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma Aβ in young and old mice, independent of neuronal insulin signaling. SIGNIFICANCE STATEMENT The transportation of insulin from blood to brain is a saturable process relevant to understanding the link between hyperinsulinemia and AD. In vitro experiments have found direct connections between high insulin and extracellular Aβ, but these mechanisms presume that peripheral high insulin elevates brain insulin significantly. We found that physiological hyperinsulinemia in awake, behaving mice does not increase CNS insulin to an appreciable level yet modestly increases extracellular Aβ. We also found that the brain of aged APP/PS1 mice was not insulin resistant, contrary to the current state of the literature. These results further elucidate the relationship between insulin, the brain, and AD and its conflicting roles as both a risk factor and potential treatment
Chemical Abundances in Field Red Giants from High-Resolution H-Band Spectra using the APOGEE Spectral Linelist
High-resolution H-band spectra of five bright field K, M, and MS giants,
obtained from the archives of the Kitt Peak National Observatory (KPNO) Fourier
Transform Spectrometer (FTS), are analyzed to determine chemical abundances of
16 elements. The abundances were derived via spectrum synthesis using the
detailed linelist prepared for the SDSS III Apache Point Galactic Evolution
Experiment (APOGEE), which is a high-resolution near-infrared spectroscopic
survey to derive detailed chemical abundance distributions and precise radial
velocities for 100,000 red giants sampling all Galactic stellar populations.
Measured chemical abundances include the cosmochemically important isotopes
12C, 13C, 14N, and 16O, along with Mg, Al, Si, K, Ca, Ti, V, Cr, Mn, Fe, Co,
Ni, and Cu. A comparison of the abundances derived here with published values
for these stars reveals consistent results to ~0.1 dex. The APOGEE spectral
region and linelist is, thus, well-suited for probing both Galactic chemical
evolution, as well as internal nucleosynthesis and mixing in populations of red
giants using high-resolution spectroscopy.Comment: Accepted for publication in The Astrophysical Journal. 42 pages, 12
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Comparison of single-channel EEG, actigraphy, and sleep diary in cognitively normal and mildly impaired older adults
STUDY OBJECTIVES: Multiple methods for monitoring sleep-wake activity have identified sleep disturbances as risk factors for Alzheimer disease (AD). In order to identify the level of agreement between different methods, we compared sleep parameters derived from single-channel EEG (scEEG), actigraphy, and sleep diaries in cognitively normal and mildly impaired older adults.
METHODS: Two hundred ninety-three participants were monitored at home for up to six nights with scEEG, actigraphy, and sleep diaries. Total sleep time (TST), sleep efficiency (SE), sleep onset latency (SOL), and wake after sleep onset (WASO) were calculated using each of these methods. In 109 of the 293 participants, the ratio of cerebrospinal fluid concentrations of phosphorylated tau (p-tau) and amyloid-β-42 (Aβ42) was used as a biomarker for AD pathology.
RESULTS: Agreement was highest for TST across instruments, especially in cognitively normal older adults. Overall, scEEG and actigraphy appeared to have greater agreement for multiple sleep parameters than for scEEG and diary or actigraphy and diary. Levels of agreement between scEEG and actigraphy overall decreased in mildly impaired participants and those with biomarker evidence of AD pathology, especially for measurements of TST.
CONCLUSIONS: Caution should be exercised when comparing scEEG and actigraphy in individuals with mild cognitive impairment or with AD pathology. Sleep diaries may capture different aspects of sleep compared to scEEG and actigraphy. Additional studies comparing different methods of measuring sleep-wake activity in older adults are necessary to allow for comparison between studies using different methods
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Photoacoustic microscopy of human teeth
Photoacoustic microscopy (PAM) utilizes short laser pulses to deposit energy into light absorbers and sensitively detects the ultrasonic waves the absorbers generate in response. PAM directly renders a three-dimensional spatial distribution of sub-surface optical absorbers. Unlike other optical imaging technologies, PAM features label-free optical absorption contrast and excellent imaging depths. Standard dental imaging instruments are limited to X-ray and CCD cameras. Subsurface optical dental imaging is difficult due to the highly-scattering enamel and dentin tissue. Thus, very few imaging methods can detect dental decay or diagnose dental pulp, which is the innermost part of the tooth, containing the nerves, blood vessels, and other cells. Here, we conducted a feasibility study on imaging dental decay and dental pulp with PAM. Our results showed that PAM is sensitive to the color change associated with dental decay. Although the relative PA signal distribution may be affected by surface contours and subsurface reflections from deeper dental tissue, monitoring changes in the PA signals (at the same site) over time is necessary to identify the progress of dental decay. Our results also showed that deep-imaging, near-infrared (NIR) PAM can sensitively image blood in the dental pulp of an in vitro tooth. In conclusion, PAM is a promising tool for imaging both dental decay and dental pulp
Sodium and Oxygen Abundances in the Open Cluster NGC 6791 from APOGEE H-Band Spectroscopy
The open cluster NGC 6791 is among the oldest, most massive and metal-rich
open clusters in the Galaxy. High-resolution -band spectra from the Apache
Point Observatory Galactic Evolution Experiment (APOGEE) of 11 red giants in
NGC 6791 are analyzed for their chemical abundances of iron, oxygen, and
sodium. The abundances of these three elements are found to be homogeneous
(with abundance dispersions at the level of 0.05 - 0.07 dex) in these
cluster red giants, which span much of the red-giant branch (T
3500K - 4600K), and include two red-clump giants. From the infrared
spectra, this cluster is confirmed to be among the most metal-rich clusters in
the Galaxy ( = 0.34 0.06), and is found to have a roughly
solar value of [O/Fe] and slightly enhanced [Na/Fe]. Non-LTE calculations for
the studied Na I lines in the APOGEE spectral region (16373.86\AA\ and
16388.85\AA) indicate only small departures from LTE ( 0.04 dex)
for the parameter range and metallicity of the studied stars. The previously
reported double population of cluster members with different Na abundances is
not found among the studied sample.Comment: Accepted for publication at ApJ Letter
Regulation of the G-protein αi-2 subunit gene in LLC-PK1 renal cells and isolation of porcine genomic clones encoding the gene promoter
Heterotrimeric G-proteins function as signal transducers for a variety of hormone-coupled enzyme and ion transport systems in eukaryotic cells. We have studied G-protein-coupled processes that appear to be developmentally regulated in polarized pig kidney cells (LLC-PK1). Following trypsinization, LLC-PK1 cells differentiate from a rounded cell type to a fully polarized epithelium by 7 days of culture. During this differentiation, the expression of G-protein alpha-i-2 subunit mRNA was not detected until day 4 of culture, it peaked at day 6, and declined thereafter. In contrast, G-protein alpha-(s) subunit mRNA which peaked on day 4 was easily detected on all culture days. The presence of the alpha-i-2 protein on epithelial cell basolateral membranes followed the same pattern of mRNA expression during culture. To understand the developmental expression of the alpha-i-2 subunit in non-polarized cells and its potential regulation by hormones and second messengers in polarized cells at the transcriptional level, genomic DNA segments encoding the alpha-i-2 gene promoter were isolated from an EMBL-3 porcine genomic library. S1 nuclease analysis of LLC-PK1 mRNA with cRNA probes derived from these DNA segments revealed major and a minor transcriptional start sites 131 and 171 base pairs upstream of the translation initiation site. The porcine and human alpha-i-2 subunit genes shared a 78% sequence identity in their 5' flanks which suggested an evolutionary conversation of cis elements required to influence their transcription. The porcine alpha-i-2 gene promoter was identified by fusing DNA segments encoding putative 5'-flanking areas of the gene to a plasmid that contained a firefly luciferase reporter gene but lacked a promoter. The minimal promoter was found between -130 and -60 base pairs from the major transcription start site. No typical "TATA-like" sequences were found. However, a "GC" box and a "TGTGG" sequence were two potential cis elements required for basal transcription of the porcine gene promoter which shared a 76% sequence identity to the promoter of another GTP-binding protein, the human c-Ha-ras proto-oncogene. Transcription of the gene was inhibited following treatment of renal cells with 10(-8) M dexamethasone. These studies suggest that alpha-i-2 gene expression is regulated in LLC-PK1 cells. Identification of the gene's promoter and 5'-flanking sequences provide a basis for elucidating "cis-acting" DNA sequences and "trans-acting" protein factors that act in concert to control the transcriptional regulation of the alpha-i-2 gene which may modulate G-protein coupled effector responses in vasopressin-sensitive renal epithelia
Testing Models of Intrinsic Brightness Variations in Type Ia Supernovae, and their Impact on Measuring Cosmological Parameters
For spectroscopically confirmed Type Ia supernovae we evaluate models of
intrinsic brightness variations with detailed data/Monte Carlo comparisons of
the dispersion in the following quantities: Hubble-diagram scatter, color
difference (B-V-c) between the true B-V color and the fitted color (c) from the
SALT-II light curve model, and photometric redshift residual. The data sample
includes 251 ugriz light curves from the 3-season Sloan Digital Sky Survey-II,
and 191 griz light curves from the Supernova Legacy Survey 3-year data release.
We find that the simplest model of a wavelength-independent (coherent) scatter
is not adequate, and that to describe the data the intrinsic scatter model must
have wavelength-dependent variations. We use Monte Carlo simulations to examine
the standard approach of adding a coherent scatter term in quadrature to the
distance-modulus uncertainty in order to bring the reduced chi2 to unity when
fitting a Hubble diagram. If the light curve fits include model uncertainties
with the correct wavelength dependence of the scatter, we find that the bias on
the dark energy equation of state parameter is negligible. However,
incorrect model uncertainties can lead to a significant bias on the distance
moduli, with up to ~0.05 mag redshift-dependent variation. For the recent SNLS3
cosmology results we estimate that this effect introduces an additional
systematic uncertainty on of ~0.02, well below the total uncertainty.
However, this uncertainty depends on the samples used, and thus this small
-uncertainty is not guaranteed in future cosmology results.Comment: accepted by Ap
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