Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, ...thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at www.pharmgkb.org).
We describe the simulated data sample for the Photometric Large Synoptic Survey Telescope (LSST) Astronomical Time Series Classification Challenge (PLAsTiCC), a publicly available challenge to ...classify transient and variable events that will be observed by the LSST, a new facility expected to start in the early 2020s. The challenge was hosted by Kaggle, ran from 2018 September 28 to December 17, and included 1094 teams competing for prizes. Here we provide details of the 18 transient and variable source models, which were not revealed until after the challenge, and release the model libraries at https://doi.org/10.5281/zenodo.2612896. We describe the LSST Operations Simulator used to predict realistic observing conditions, and we describe the publicly available SNANA simulation code used to transform the models into observed fluxes and uncertainties in the LSST passbands (ugrizy). Although PLAsTiCC has finished, the publicly available models and simulation tools are being used within the astronomy community to further improve classification, and to study contamination in photometrically identified samples of SN Ia used to measure properties of dark energy. Our simulation framework will continue serving as a platform to improve the PLAsTiCC models, and to develop new models.
How extinct, non-avian theropod dinosaurs moved is a subject of considerable interest and controversy. A better understanding of non-avian theropod locomotion can be achieved by better understanding ...terrestrial locomotor biomechanics in their modern descendants, birds. Despite much research on the subject, avian terrestrial locomotion remains little explored in regards to how kinematic and kinetic factors vary together with speed and body size. Here, terrestrial locomotion was investigated in twelve species of ground-dwelling bird, spanning a 1,780-fold range in body mass, across almost their entire speed range. Particular attention was devoted to the ground reaction force (GRF), the force that the feet exert upon the ground. Comparable data for the only other extant obligate, striding biped, humans, were also collected and studied. In birds, all kinematic and kinetic parameters examined changed continuously with increasing speed, while in humans all but one of those same parameters changed abruptly at the walk-run transition. This result supports previous studies that show birds to have a highly continuous locomotor repertoire compared to humans, where discrete 'walking' and 'running' gaits are not easily distinguished based on kinematic patterns alone. The influences of speed and body size on kinematic and kinetic factors in birds are developed into a set of predictive relationships that may be applied to extinct, non-avian theropods. The resulting predictive model is able to explain 79-93% of the observed variation in kinematics and 69-83% of the observed variation in GRFs, and also performs well in extrapolation tests. However, this study also found that the location of the whole-body centre of mass may exert an important influence on the nature of the GRF, and hence some caution is warranted, in lieu of further investigation.
Calcium signalling in astrocytes couples changes in neural activity to alterations in cerebral blood flow by eliciting vasoconstriction or vasodilation of arterioles. However, the mechanism for how ...these opposite astrocyte influences provide appropriate changes in vessel tone within an environment that has dynamic metabolic requirements remains unclear. Here we show that the ability of astrocytes to induce vasodilations over vasoconstrictions relies on the metabolic state of the rat brain tissue. When oxygen availability is lowered and astrocyte calcium concentration is elevated, astrocyte glycolysis and lactate release are maximized. External lactate attenuates transporter-mediated uptake from the extracellular space of prostaglandin E(2), leading to accumulation and subsequent vasodilation. In conditions of low oxygen concentration extracellular adenosine also increases, which blocks astrocyte-mediated constriction, facilitating dilation. These data reveal the role of metabolic substrates in regulating brain blood flow and provide a mechanism for differential astrocyte control over cerebrovascular diameter during different states of brain activation.
ABSTRACT
We present observations of ASASSN-19dj, a nearby tidal disruption event (TDE) discovered in the post-starburst galaxy KUG 0810+227 by the All-Sky Automated Survey for Supernovae (ASAS-SN) at ...a distance of d ≃ 98 Mpc. We observed ASASSN-19dj from −21 to 392 d relative to peak ultraviolet (UV)/optical emission using high-cadence, multiwavelength spectroscopy and photometry. From the ASAS-SN g-band data, we determine that the TDE began to brighten on 2019 February 6.8 and for the first 16 d the rise was consistent with a flux ∝t2 power law. ASASSN-19dj peaked in the UV/optical on 2019 March 6.5 (MJD = 58548.5) at a bolometric luminosity of L = (6.2 ± 0.2) × 1044 erg s−1. Initially remaining roughly constant in X-rays and slowly fading in the UV/optical, the X-ray flux increased by over an order of magnitude ∼225 d after peak, resulting from the expansion of the X-ray emitting region. The late-time X-ray emission is well fitted by a blackbody with an effective radius of ∼1 × 1012 cm and a temperature of ∼6 × 105 K. The X-ray hardness ratio becomes softer after brightening and then returns to a harder state as the X-rays fade. Analysis of Catalina Real-Time Transient Survey images reveals a nuclear outburst roughly 14.5 yr earlier with a smooth decline and a luminosity of LV ≥ 1.4 × 1043 erg s−1, although the nature of the flare is unknown. ASASSN-19dj occurred in the most extreme post-starburst galaxy yet to host a TDE, with Lick HδA = 7.67 ± 0.17 Å.
A wide range of modelling algorithms is used by ecologists, conservation practitioners, and others to predict species ranges from point locality data. Unfortunately, the amount of data available is ...limited for many taxa and regions, making it essential to quantify the sensitivity of these algorithms to sample size. This is the first study to address this need by rigorously evaluating a broad suite of algorithms with independent presence-absence data from multiple species and regions. We evaluated predictions from 12 algorithms for 46 species (from six different regions of the world) at three sample sizes (100, 30, and 10 records). We used data from natural history collections to run the models, and evaluated the quality of model predictions with area under the receiver operating characteristic curve (AUC). With decreasing sample size, model accuracy decreased and variability increased across species and between models. Novel modelling methods that incorporate both interactions between predictor variables and complex response shapes (i.e. GBM, MARS-INT, BRUTO) performed better than most methods at large sample sizes but not at the smallest sample sizes. Other algorithms were much less sensitive to sample size, including an algorithm based on maximum entropy (MAXENT) that had among the best predictive power across all sample sizes. Relative to other algorithms, a distance metric algorithm (DOMAIN) and a genetic algorithm (OM-GARP) had intermediate performance at the largest sample size and among the best performance at the lowest sample size. No algorithm predicted consistently well with small sample size (n < 30) and this should encourage highly conservative use of predictions based on small sample size and restrict their use to exploratory modelling.
We present an analysis of the orbital motion of the four substellar objects orbiting HR 8799. Our study relies on the published astrometric history of this system augmented with an epoch obtained ...with the Project 1640 coronagraph with an integral field spectrograph (IFS) installed at the Palomar Hale telescope. We first focus on the intricacies associated with astrometric estimation using the combination of an extreme adaptive optics system (PALM-3000), a coronagraph, and an IFS. We introduce two new algorithms. The first one retrieves the stellar focal plane position when the star is occulted by a coronagraphic stop. The second one yields precise astrometric and spectrophotometric estimates of faint point sources even when they are initially buried in the speckle noise. The second part of our paper is devoted to studying orbital motion in this system. In order to complement the orbital architectures discussed in the literature, we determine an ensemble of likely Keplerian orbits for HR 8799bcde, using a Bayesian analysis with maximally vague priors regarding the overall configuration of the system. Although the astrometric history is currently too scarce to formally rule out coplanarity, HR 8799d appears to be misaligned with respect to the most likely planes of HR 8799bce orbits. This misalignment is sufficient to question the strictly coplanar assumption made by various authors when identifying a Laplace resonance as a potential architecture. Finally, we establish a high likelihood that HR 8799de have dynamical masses below 13 M sub(jup), using a loose dynamical survival argument based on geometric close encounters. We illustrate how future dynamical analyses will further constrain dynamical masses in the entire system.
Directly detecting thermal emission from young extrasolar planets allows measurement of their atmospheric compositions and luminosities, which are influenced by their formation mechanisms. Using the ...Gemini Planet Imager, we discovered a planet orbiting the ∼20-million-year-old star 51 Eridani at a projected separation of 13 astronomical units. Near-infrared observations show a spectrum with strong methane and water-vapor absorption. Modeling of the spectra and photometry yields a luminosity (normalized by the luminosity of the Sun) of 1.6 to 4.0 × 10–6 and an effective temperature of 600 to 750 kelvin. For this age and luminosity, "hot-start" formation models indicate a mass twice that of Jupiter. This planet also has a sufficiently low luminosity to be consistent with the "cold-start" core-accretion process that may have formed Jupiter.
The "liquid water habitable zone" (HZ) concept is predicated on the ability of the silicate weathering feedback to stabilize climate across a wide range of instellations. However, representations of ...silicate weathering used in current estimates of the effective outer edge of the HZ account for neither the thermodynamic limit on the concentration of weathering products in runoff set by clay precipitation nor the energetic limit on precipitation set by planetary instellation. We find that when the thermodynamic limit is included in an idealized coupled climate/weathering model, the steady-state planetary climate loses sensitivity to silicate dissolution kinetics, becoming sensitive to temperature primarily through the effect of temperature on runoff and to pCO 2 through an effect on solute concentration mediated by pH. This increases sensitivity to land fraction, CO 2 outgassing, and geological factors such as soil age and lithology, all of which are found to have a profound effect on the position of the effective outer edge of the HZ. The interplay between runoff sensitivity and the energetic limit on precipitation leads to novel warm states in the outer reaches of the HZ, owing to the decoupling of temperature and precipitation. We discuss strategies for detecting the signature of the silicate weathering feedback through exoplanet observations in light of insights derived from the revised picture of weathering.
This paper compares laboratory measurements of the vortex-induced vibrations of a riser in a stepped current with blind predictions obtained with 11 different numerical models. Results are included ...on in-line and transverse displacements and curvatures, and dominant frequencies. In general, empirical models were more successful at predicting cross-flow displacements and curvatures than current codes based on CFD. Overall ratios between predictions and measurements of cross-flow displacements were around 95% and 75%, respectively. Predictions of cross-flow curvatures were more scattered, and almost all were unconservative. In-line vortex-induced curvatures, which may cause as much damage as cross-flow curvatures, could not be computed by any of the empirically based codes, and in general those based on CFD were in very poor agreement with the measurements.