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    A coarse-grained model of room-temperature ionic liquids between metal electrodes: a molecular dynamics study

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    Recent mean-field theories predict that room-temperature ionic liquid (RTIL) electric double-layer capacitors (EDLCs) undergo a spontaneous surface charge separation (SSCS) with no applied potential. In this study, we construct a coarse-grained molecular model that corresponds to the mean-field models to directly simulate the behavior of RTILs without invoking mean-field approximations. In addition to observing the SSCS transition, we highlight the importance of the image charge interactions and explore the enhanced in-plane ordering on the electrodes, two effects not accounted for by the mean-field theories. By calculating and comparing the differential capacitance for RTILs confined between perfectly conducting and non-metal electrodes, we show that the image charge interactions drastically improve the energy storage properties of RTIL EDLCs

    Neural, physiological, and psychological markers of appetitive conditioning in anorexia nervosa: a study protocol

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    Background. Anorexia nervosa (AN) is a chronic and disabling psychiatric condition characterized by low hedonic drive towards food, and is thought to be inclusive of altered dimensions of reward processing. Whether there exists a fundamental aberrancy in the capacity to acquire and maintain de novo hedonic associations—a critical component of hedonic responding—has never been studied in AN. Methods. This multi-modal study will employ a 2-day Pavlovian appetitive conditioning paradigm to interrogate the (1) acquisition, (2) extinction, (3) spontaneous recovery and (4) reinstatement of appetitive learning in adolescents and young adults with AN. Participants will be 30 currently ill, underweight individuals with AN; 30 weight-restored individuals with AN; and 30 age-matched healthy controls, all aged 12–22 years. All subjects will undergo clinical assessment, followed by the 2-day appetitive conditioning task during which fMRI, pupillometry, heart rate deceleration, and subjective ratings will be acquired. Discussion. This study will be the first to interrogate appetitive conditioning in AN—a disorder characterized by altered hedonic responding to food. Results will help establish objective biomarkers of appetitive conditioning in AN and lay the groundwork for developing novel lines of treatment for AN and other psychiatric disorders involving diminished ability to experience pleasure and reward. Trial registration: Pending. Intended registry: Clinicaltrials.gov

    Validation of Candidate Sleep Disorder Risk Genes Using Zebrafish

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    Sleep disorders and chronic sleep disturbances are common and are associated with cardio-metabolic diseases and neuropsychiatric disorders. Several genetic pathways and neuronal mechanisms that regulate sleep have been described in animal models, but the genes underlying human sleep variation and sleep disorders are largely unknown. Identifying these genes is essential in order to develop effective therapies for sleep disorders and their associated comorbidities. To address this unmet health problem, genome-wide association studies (GWAS) have identified numerous genetic variants associated with human sleep traits and sleep disorders. However, in most cases, it is unclear which gene is responsible for a sleep phenotype that is associated with a genetic variant. As a result, it is necessary to experimentally validate candidate genes identified by GWAS using an animal model. Rodents are ill-suited for this endeavor due to their poor amenability to high-throughput sleep assays and the high costs associated with generating, maintaining, and testing large numbers of mutant lines. Zebrafish (Danio rerio), an alternative vertebrate model for studying sleep, allows for the rapid and cost-effective generation of mutant lines using the CRISPR/Cas9 system. Numerous zebrafish mutant lines can then be tested in parallel using high-throughput behavioral assays to identify genes whose loss affects sleep. This process identifies a gene associated with each GWAS hit that is likely responsible for the human sleep phenotype. This strategy is a powerful complement to GWAS approaches and holds great promise to identify the genetic basis for common human sleep disorders

    Oral short-chain fatty acids administration regulates innate anxiety in adult microbiome-depleted mice

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    Anxiety is characterized by feelings of tension and worry even in the absence of threatening stimulus. Pathological condition of anxiety elicits defensive behavior and aversive reaction ultimately impacting individuals and society. The gut microbiota has been shown to contribute to the modulation of anxiety-like behavior in rodents through the gut-brain axis. Several studies observed that germ-free (GF) and the broad spectrum of antibiotic cocktail (ABX)-treated rodents display lowered anxiety-like behavior. We speculate that gut microbial short-chain fatty acids (SCFA) modulate the innate anxiety response. Herein, we administered SCFA in the drinking water in adult mice treated with ABX to deplete the microbiota and tested their anxiety-like behavior. To further augment the innate fear response, we enhanced the aversive stimulus of the anxiety-like behavior tests. Strikingly, we found that the anxiety-like behavior in ABX mice was not altered when enhanced aversive stimulus, while control and ABX mice supplemented with SCFA displayed increased anxiety-like behavior. Vagus nerve serves as a promising signaling pathway in the gut-brain axis. We determined the role of vagus nerve by subdiaphragmatic vagotomy (SDV) in ABX mice supplemented with SCFA. We found that the restored anxiety-like behavior in ABX mice by SCFA was unaffected by SDV. These findings suggest that gut microbiota can regulate anxiety-like behavior through their fermentation products SCFA

    Viscous and centrifugal instabilities of massive stars

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    Massive stars exhibit a variety of instabilities, many of which are poorly understood. We explore instabilities induced by centrifugal forces and angular momentum transport in massive rotating stars. First, we derive and numerically solve linearized oscillation equations for adiabatic radial modes in polytropic stellar models. In the presence of differential rotation, we show that centrifugal and Coriolis forces combined with viscous angular momentum transport can excite stellar pulsation modes, under both low- or high-viscosity conditions. In the low-viscosity limit, which is common in real stars, we demonstrate how to compute mode growth/damping rates via a work integral. Finally, we build realistic rotating 30 M_⊙ star models and show that overstable (growing) radial modes are predicted to exist for most of the star’s life, in the absence of non-adiabatic effects. Peak growth rates are predicted to occur while the star is crossing the Hertzsprung–Russell gap, though non-adiabatic damping may dominate over viscous driving, depending on the effective viscosity produced by convective and/or magnetic torques. Viscous instability could be a new mechanism to drive massive star pulsations and is possibly related to instabilities of luminous blue variable stars

    Tidally Tilted Pulsators

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    The tidally tilted pulsators are a new type of oscillating star in close binary systems that have their pulsation axis in the orbital plane because of the tidal distortion caused by their companion. We describe this group of stars on the basis of the first three representatives discovered and illustrate the basic methods used for their analysis. Their value for astrophysical study is rooted in the combination of the strengths of binary star and asteroseismic analyses; pulsational mode identifications can be achieved because the oscillations are visible over nearly 360 degrees of aspect throughout the orbital cycle. An illustrative case of a particularly interesting system is presented

    Fossil biomolecules reveal an avian metabolism in the ancestral dinosaur

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    Birds and mammals independently evolved the highest metabolic rates among living animals. Their metabolism generates heat that enables active thermoregulation, shaping the ecological niches they can occupy and their adaptability to environmental change. The metabolic performance of birds, which exceeds that of mammals, is thought to have evolved along their stem lineage. However, there is no proxy that enables the direct reconstruction of metabolic rates from fossils. Here we use in situ Raman and Fourier-transform infrared spectroscopy to quantify the in vivo accumulation of metabolic lipoxidation signals in modern and fossil amniote bones. We observe no correlation between atmospheric oxygen concentrations and metabolic rates. Inferred ancestral states reveal that the metabolic rates consistent with endothermy evolved independently in mammals and plesiosaurs, and are ancestral to ornithodirans, with increasing rates along the avian lineage. High metabolic rates were acquired in pterosaurs, ornithischians, sauropods and theropods well before the advent of energetically costly adaptations, such as flight in birds. Although they had higher metabolic rates ancestrally, ornithischians reduced their metabolic abilities towards ectothermy. The physiological activities of such ectotherms were dependent on environmental and behavioural thermoregulation, in contrast to the active lifestyles of endotherms1. Giant sauropods and theropods were not gigantothermic, but true endotherms. Endothermy in many Late Cretaceous taxa, in addition to crown mammals and birds, suggests that attributes other than metabolism determined their fate during the terminal Cretaceous mass extinction

    Discretization of annular-ring diffraction pattern for large-scale photonics beamforming

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    A solid-state active beamformer based on the annular-ring diffraction pattern is demonstrated in an integrated photonic platform. Such a circularly symmetric annular-ring aperture achieves a radiating element limited field of view. Furthermore, it is demonstrated that a multi-annular-ring aperture with a fixed linear density of elements maintains the beam efficiency for larger apertures while reducing the beamwidth and side-lobe level. A 255-element multi-annular-ring optical phased array with active beamforming is implemented in a standard photonics process. A total of 510 phase and amplitude modulators enable beamforming and beam steering using this aperture. A row–column drive methodology reduces the required electrical drivers by more than a factor of 5

    Structurally derived universal mechanism for the catalytic cycle of the tail-anchored targeting factor Get3

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    Tail-anchored (TA) membrane proteins, accounting for roughly 2% of proteomes, are primarily targeted posttranslationally to the endoplasmic reticulum membrane by the guided entry of TA proteins (GET) pathway. For this complicated process, it remains unknown how the central targeting factor Get3 uses nucleotide to facilitate large conformational changes to recognize then bind clients while also preventing exposure of hydrophobic surfaces. Here, we identify the GET pathway in Giardia intestinalis and present the structure of the Get3–client complex in the critical postnucleotide-hydrolysis state, demonstrating that Get3 reorganizes the client-binding domain (CBD) to accommodate and shield the client transmembrane helix. Four additional structures of GiGet3, spanning the nucleotide-free (apo) open to closed transition and the ATP-bound state, reveal the details of nucleotide stabilization and occluded CBD. This work resolves key conundrums and allows for a complete model of the dramatic conformational landscape of Get3

    The Shuram excursion: A response to climate extremes at the dawn of animal life

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    The Ediacaran-aged Shuram excursion was the last and largest of the Neoproterozoic negative carbon isotope anomalies. Recognized in stratigraphic successions around the globe, it precedes diverse evidence for macroscopic, multicellular life, and follows the Cryogenian global glaciations and Ediacaran Gaskiers glaciation. Hypotheses for the cause of the Shuram excursion can be broadly grouped into those that argue for post-depositional diagenetic alteration of the carbon isotope record and those that argue the extremely low δ¹³C values reflect a primary perturbation to the carbon cycle. Given the timing and magnitude of this event, distinguishing between these disparate hypotheses, or combining them, is critical for reconstructing the environmental conditions under which complex life evolved on Earth. We test specific predictions of each model using a range of stratigraphic observations and micro- and macro-analytical techniques. We find that the type sections in Oman where the Shuram excursion was first described are well preserved and contain a range of features difficult to reconcile with a post-depositional origin. However, many salient features are consistent with an extreme warming event coupled to a carbon cycle perturbation, analogous to the Paleocene-Eocene Thermal Maximum (PETM), and increased middle Ediacaran volcanism. We propose that cooling associated with the recovery was critical for origination rates of macroscopic soft-bodied organisms

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