407 research outputs found

    MODULATION OF STRESS-INDUCED BEHAVIORS THROUGH OREXINERGIC SIGNALING IN THE BASOLATERAL AMYGDALA

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    Stress initiates behavioral disturbances, which are often seen as symptoms of psychiatric disorders, like post-traumatic stress disorder (PTSD), depression, and anxiety. While stress is involved in the formation of disordered states, only certain individuals are vulnerable to, and therefore experience, these outcomes. Further, females are more likely to be diagnosed with stress-induced psychiatric disorders. Elements within stress neurocircuitry offer insight into differential behavioral outcomes associated with stressful experiences; and the basolateral amygdala (BLA), where pro- and anti-stress signals are integrated, is likely an important mediator in phenotype development. The orexin system, too, while being strongly associated with sleep, motivation, and arousal, is critical for directing stress-induced responses. Produced in the hypothalamus, orexins (OrxA and OrxB) are released into the BLA where they target and activate two receptor subtypes: Orx1R and Orx2R. These receptors are found on different cells within BLA microcircuits, with Orx1R predominantly being localized to glutamatergic neurons and Orx2R having slightly higher expression in GABAergic cells. Pharmacological inhibition of Orx1R in the BLA rescues resilient behavior in stress vulnerable mice, while reducing fear freezing behavior, and promoting social learning. Alternatively, Orx2R inhibition in the BLA upsets fear learning in resilient populations, but enhances social avoidance. Alternatively, activation of Orx2R in BLA cells reduces fear freezing and increases social preference. Female mice exhibit unique behavioral patterns as a result of social stress compared to males, but phenotypic responses are observed when females are administered an Orx2R antagonist. While females have higher Orx2R expression in the BLA compared to males, pharmacological intervention with an Orx2R antagonist reveals even further distinctions within female behavioral phenotypes. Together, these results suggest the orexin system is important for defining behavioral outcomes after stress, and while sexual dimorphism exists in behavior and physiology, orexin receptor activity in the BLA appears to be a critical gating mechanism in both male and female stress-induced phenotype development

    Earth as a Transiting Exoplanet: A Validation of Transmission Spectroscopy and Atmospheric Retrieval Methodologies for Terrestrial Exoplanets

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    The James Webb Space Telescope (JWST) will enable the search for and characterization of terrestrial exoplanet atmospheres in the habitable zone via transmission spectroscopy. However, relatively little work has been done to use solar system data, where ground truth is known, to validate spectroscopic retrieval codes intended for exoplanet studies, particularly in the limit of high resolution and high signal-to-noise (S/N). In this work, we perform such a validation by analyzing a high S/N empirical transmission spectrum of Earth using a new terrestrial exoplanet atmospheric retrieval model with heritage in Solar System remote sensing and gaseous exoplanet retrievals. We fit the Earth's 2-14 um transmission spectrum in low resolution (R=250 at 5 um) and high resolution (R=100,000 at 5 um) under a variety of assumptions about the 1D vertical atmospheric structure. In the limit of noiseless transmission spectra, we find excellent agreement between model and data (deviations < 10%) that enable the robust detection of H2O, CO2, O3, CH4, N2, N2O, NO2, HNO3, CFC-11, and CFC-12 thereby providing compelling support for the detection of habitability, biosignature, and technosignature gases in the atmosphere of the planet using an exoplanet-analog transmission spectrum. Our retrievals at high spectral resolution show a marked sensitivity to the thermal structure of the atmosphere, trace gas abundances, density-dependent effects, such as collision-induced absorption and refraction, and even hint at 3D spatial effects. However, we used synthetic observations of TRAPPIST-1e to verify that the use of simple 1D vertically homogeneous atmospheric models will likely suffice for JWST observations of terrestrial exoplanets transiting M dwarfs.Comment: 37 pages, 14 figures, 9 tables. Accepted for publication in PS

    Planet Eclipse Mapping with Long-Term Baseline Drifts

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    High precision lightcurves combined with eclipse mapping techniques can reveal the horizontal and vertical structure of a planet's thermal emission and the dynamics of hot Jupiters. Someday, they even may reveal the surface maps of rocky planets. However, inverting lightcurves into maps requires an understanding of the planet, star and instrumental trends because they can resemble the gradual flux variations as the planet rotates (ie. partial phase curves). In this work, we simulate lightcurves with baseline trends and assess the impact on planet maps. Baseline trends can be erroneously modeled by incorrect astrophysical planet map features, but there are clues to avoid this pitfall in both the residuals of the lightcurve during eclipse and sharp features at the terminator of the planet. Models that use a Gaussian process or polynomial to account for a baseline trend successfully recover the input map even in the presence of systematics but with worse precision for the m=1 spherical harmonic terms. This is also confirmed with the ThERESA eigencurve method where fewer lightcurve terms can model the planet without correlations between the components. These conclusions help aid the decision on how to schedule observations to improve map precision. If the m=1 components are critical, such as measuring the East/West hotspot shift on a hot Jupiter, better characterization of baseline trends can improve the m=1 terms' precision. For latitudinal North/South information from the remaining mapping terms, it is preferable to obtain high signal-to-noise at ingress/egress with more eclipses.Comment: AJ, accepted, 22 page

    Comparison of two commercial ovine Campylobacter vaccines and an experimental bacterin in guinea pigs inoculated with Campylobacter jejuni

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    Objective—To compare efficacy of 2 commercial ovine Campylobacter vaccines and an experimental bacterin in guinea pigs following IP inoculation with Campylobacter jejuni IA3902. Animals—51 female guinea pigs. Procedures—Pregnant and nonpregnant animals were randomly assigned to 1 of 4 treatment groups and administered a commercial Campylobacter vaccine labeled for prevention of campylobacteriosis in sheep via two 5-mL doses 14 days apart (vaccine A; n = 13), another labeled for prevention of campylobacteriosis via two 2-mL doses (vaccine B; 12), an experimental bacterin prepared from the challenge strain (12), or a sham vaccine (14). Ten days later, animals were challenged IP with C jejuni IA3902; 48 hours later, animals were euthanized, complete necropsy was performed, and blood and tissue samples were obtained for bacteriologic culture. Results—Administration of vaccine B or the experimental bacterin, but not vaccine A, significantly reduced 48-hour infection rates versus administration of the sham vaccine. A significantly reduced 48-hour infection rate was associated with administration of vaccine B independent of pregnancy status. Conclusions and Clinical Relevance—Administration of vaccine B significantly reduced infection in guinea pigs challenged with C jejuni IA3902, similar to a homologous bacterin. Results suggested that vaccine B or an autogenous product may be effective in controlling ovine campylobacteriosis caused by this emergent abortifacient strain. Bacteriologic culture of blood, liver, bile, and uterus in nonpregnant guinea pigs 48 hours after inoculation may be a useful screening tool for comparing efficacy of C jejuni vaccines

    Achieving Generalizable Robustness of Deep Neural Networks by Stability Training

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    We study the recently introduced stability training as a general-purpose method to increase the robustness of deep neural networks against input perturbations. In particular, we explore its use as an alternative to data augmentation and validate its performance against a number of distortion types and transformations including adversarial examples. In our image classification experiments using ImageNet data stability training performs on a par or even outperforms data augmentation for specific transformations, while consistently offering improved robustness against a broader range of distortion strengths and types unseen during training, a considerably smaller hyperparameter dependence and less potentially negative side effects compared to data augmentation.Comment: 18 pages, 25 figures; Camera-ready versio

    X-ray lenses fabricated by deep x-ray lithography

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    Refractive x-ray lenses have been fabricated using deep x-ray lithography. Lenses were produced directly in 1- to 6-mm-thick sheets of polymethylmethacrylate (PMMA) with as many as 100 cylindrical lenses along the optical axis. The fabrication process consists of exposing the PMMA sheets to high-energy synchrotron radiation through a mask of 50-micron-thick gold on silicon and subsequent development in ketone. The lenses are suitable for use in synchrotron radiation from a bending magnet at the Advanced Photon Source in the energy range of 8-16 keV. Results of measurements of focus quality, flux density gain, and scatter are presented and discussed with regard to the quality of lens material and fabrication method. Means for improving the performance of the lenses is discussed

    Reference Ranges of Left Ventricular Strain Measures by Two-Dimensional Speckle-Tracking Echocardiography in Children: A Systematic Review and Meta-Analysis

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    BACKGROUND: Establishment of the range of reference values and associated variations of two-dimensional speckle-tracking echocardiography (2DSTE)-derived left ventricular (LV) strain is a prerequisite for its routine clinical adoption in pediatrics. The aims of this study were to perform a meta-analysis of normal ranges of LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) measurements derived by 2DSTE in children and to identify confounding factors that may contribute to variance in reported measures. METHODS: A systematic review was launched in MEDLINE, Embase, Scopus, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library. Search hedges were created to cover the concepts of pediatrics, STE, and left-heart ventricle. Two investigators independently identified and included studies if they reported 2DSTE-derived LV GLS, GCS, or GRS. The weighted mean was estimated by using random effects models with 95% CIs, heterogeneity was assessed using the Cochran Q statistic and the inconsistency index (I(2)), and publication bias was evaluated using the Egger test. Effects of demographic (age), clinical, and vendor variables were assessed in a metaregression. RESULTS: The search identified 2,325 children from 43 data sets. The reported normal mean values of GLS among the studies varied from -16.7% to -23.6% (mean, -20.2%; 95% CI, -19.5% to -20.8%), GCS varied from -12.9% to -31.4% (mean, -22.3%; 95% CI, -19.9% to -24.6%), and GRS varied from 33.9% to 54.5% (mean, 45.2%; 95% CI, 38.3% to 51.7%). Twenty-six studies reported longitudinal strain only from the apical four-chamber view, with a mean of -20.4% (95% CI, -19.8% to -21.7%). Twenty-three studies reported circumferential strain (mean, -20.3%; 95% CI, -19.4% to -21.2%) and radial strain (mean, 46.7%; 95% CI, 42.3% to 51.1%) from the short-axis view at the midventricular level. A significant apex-to-base segmental longitudinal strain gradient (P 94% and P < .001 for each strain measure), which was not explained by age, gender, body surface area, blood pressure, heart rate, frame rate, frame rate/heart rate ratio, tissue-tracking methodology, location of reported strain value along the strain curve, ultrasound equipment, or software. The metaregression showed that these effects were not significant determinants of variations among normal ranges of strain values. There was no evidence of publication bias (P = .40). CONCLUSIONS: This study defines reference values of 2DSTE-derived LV strain in children on the basis of a meta-analysis. In healthy children, mean LV GLS was -20.2% (95% CI, -19.5% to -20.8%), mean GCS was -22.3% (95% CI, -19.9% to -24.6%), and mean GRS was 45.2% (95% CI, 38.3% to 51.7%). LV segmental longitudinal strain has a stable apex-to-base gradient that is preserved throughout maturation. Although variations among different reference ranges in this meta-analysis were not dependent on differences in demographic, clinical, or vendor parameters, age- and vendor-specific referenced ranges were established as well

    Eigenspectra: A Framework for Identifying Spectra from 3D Eclipse Mapping

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    Planetary atmospheres are inherently 3D objects that can have strong gradients in latitude, longitude, and altitude. Secondary eclipse mapping is a powerful way to map the 3D distribution of the atmosphere, but the data can have large correlations and errors in the presence of photon and instrument noise. We develop a technique to mitigate the large uncertainties of eclipse maps by identifying a small number of dominant spectra to make them more tractable for individual analysis via atmospheric retrieval. We use the eigencurves method to infer a multi-wavelength map of a planet from spectroscopic secondary eclipse light curves. We then apply a clustering algorithm to the planet map to identify several regions with similar emergent spectra. We combine the similar spectra together to construct an "eigenspectrum" for each distinct region on the planetary map. We demonstrate how this approach could be used to isolate hot from cold regions and/or regions with different chemical compositions in observations of hot Jupiters with the James Webb Space Telescope (JWST). We find that our method struggles to identify sharp edges in maps with sudden discontinuities, but generally can be used as a first step before a more physically motivated modeling approach to determine the primary features observed on the planet.Comment: 13 pages, 17 figures, accepted to MNRA
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