Learning causes a change in how information is processed by neuronal circuits. Whereas synaptic plasticity, an important cellular mechanism, has been studied in great detail, we know much less about ...how learning is implemented at the level of neuronal circuits and, in particular, how interactions between distinct types of neurons within local networks contribute to the process of learning. Here we show that acquisition of associative fear memories depends on the recruitment of a disinhibitory microcircuit in the mouse auditory cortex. Fear-conditioning-associated disinhibition in auditory cortex is driven by foot-shock-mediated cholinergic activation of layer 1 interneurons, in turn generating inhibition of layer 2/3 parvalbumin-positive interneurons. Importantly, pharmacological or optogenetic block of pyramidal neuron disinhibition abolishes fear learning. Together, these data demonstrate that stimulus convergence in the auditory cortex is necessary for associative fear learning to complex tones, define the circuit elements mediating this convergence and suggest that layer-1-mediated disinhibition is an important mechanism underlying learning and information processing in neocortical circuits.
Glyphosate use in the United States increased from less than 5,000 to more than 80,000 metric tons/yr between 1987 and 2007. Glyphosate is popular due to its ease of use on soybean, cotton, and corn ...crops that are genetically modified to tolerate it, utility in no‐till farming practices, utility in urban areas, and the perception that it has low toxicity and little mobility in the environment. This compilation is the largest and most comprehensive assessment of the environmental occurrence of glyphosate and aminomethylphosphonic acid (AMPA) in the United States conducted to date, summarizing the results of 3,732 water and sediment and 1,018 quality assurance samples collected between 2001 and 2010 from 38 states. Results indicate that glyphosate and AMPA are usually detected together, mobile, and occur widely in the environment. Glyphosate was detected without AMPA in only 2.3% of samples, whereas AMPA was detected without glyphosate in 17.9% of samples. Glyphosate and AMPA were detected frequently in soils and sediment, ditches and drains, precipitation, rivers, and streams; and less frequently in lakes, ponds, and wetlands; soil water; and groundwater. Concentrations of glyphosate were below the levels of concern for humans or wildlife; however, pesticides are often detected in mixtures. Ecosystem effects of chronic low‐level exposures to pesticide mixtures are uncertain. The environmental health risk of low‐level detections of glyphosate, AMPA, and associated adjuvants and mixtures remain to be determined.
Unique synergistic effects between phosphonium‐alkylphosphate ionic liquids (ILs) and zinc dialkyldithiophosphate (ZDDP) are discovered when used together as lubricant additives, resulting in ...significant friction and wear reduction along with distinct tribofilm composition and mechanical properties. The synergism is attributed to the remarkably 30–70× higher‐than‐nominal concentrations of hypothetical new compounds (via anion exchange between IL and ZDDP) on the fluid surface/interface.
In recent years, cobalt has become a critical constraint on the supply chain of the Li‐ion battery industry. With the ever‐increasing projections for electric vehicles, the dependency of current ...Li‐ion batteries on the ever‐fluctuating cobalt prices poses serious environmental and sustainability issues. To address these challenges, a new class of cobalt‐free materials with general formula of LiNixFeyAlzO2 (x + y + z = 1), termed as the lithium iron aluminum nickelate (NFA) class of cathodes, is introduced. These cobalt‐free materials are synthesized using the sol–gel process to explore their compositional landscape by varying aluminum and iron. These NFA variants are characterized using electron microscopy, neutron and X‐ray diffraction, and Mössbauer and X‐ray photoelectron spectroscopy to investigate their morphological, physical, and crystal‐structure properties. Operando experiments by X‐ray diffraction, Mössbauer spectroscopy, and galvanostatic intermittent titration have been also used to study the crystallographic transitions, electrochemical activity, and Li‐ion diffusivity upon lithium removal and uptake in the NFA cathodes. NFA compositions yield specific capacities of ≈200 mAh g−1, demonstrating reasonable rate capability and cycling stability with ≈80% capacity retention after 100 charge/discharge cycles. While this is an early stage of research, the potential that these cathodes could have as viable candidates in next‐generation cobalt‐free lithium‐ion batteries is highlighted here.
Cobalt has become a critical constraint on the supply chain of the Li‐ion battery industry due to the dependency of current Li‐ion batteries on the ever‐fluctuating cobalt prices. To overcome this cobalt conundrum, a new class of cobalt‐free layered cathodes with a general formula of LiNixFeyAlzO2 (x + y + z = 1) is introduced, termed as the lithium iron aluminum nickelate (NFA) class.
The stability and kinetics of the Li–Li7La3Zr2O12 (LLZO) interface were characterized as a function of temperature and current density. Polycrystalline LLZO was densified using a rapid hot-pressing ...technique achieving 97 ± 1% relative density, and <10% grain boundary resistance; effectively consisting of an ensemble of single LLZO crystals. It was determined that by heating to 175 °C, the room temperature Li-LLZO interface resistance decreases dramatically from 5822 (as-assembled) to 514 Ω cm2; a > 10-fold decrease. In characterizing the maximum sustainable current density (or critical current density – CCD) of the Li-LLZO interface, several signs of degradation were observed. In DC cycling tests, significant deviation from Ohmic behavior was observed. In post-cycling tests, regions of metallic Li were observed; propagating parallel to the ionic current. For the cells cycled at 30, 70, 100, 130 and 160 °C, the CCD was determined to be 50, 200, 800, 3500, and 20000 μA cm−2, respectively. The relationships and phenomena observed in this work can be used to better understand the Li-LLZO interface stability, enabling the use of batteries employing Li metal anodes.
•The Li-LLZO interface kinetics and stability are affected by temperature.•The Li-LLZO interface resistance decreases by >10-fold upon heating to 175 °C.•Reducing the charge-transfer resistance increased the maximum current density.•Exceeding the maximum current density resulted in metallic Li propagation.
Abstract
The surroundings of massive protostars constitute an accretion disc which has numerically been shown to be subject to fragmentation and responsible for luminous accretion-driven outbursts. ...Moreover, it is suspected to produce close binary companions which will later strongly influence the star's future evolution in the Hertzsprung–Russel diagram. We present three-dimensional gravitation-radiation-hydrodynamic numerical simulations of 100 M⊙ pre-stellar cores. We find that accretion discs of young massive stars violently fragment without preventing the (highly variable) accretion of gaseous clumps on to the protostars. While acquiring the characteristics of a nascent low-mass companion, some disc fragments migrate on to the central massive protostar with dynamical properties showing that its final Keplerian orbit is close enough to constitute a close massive protobinary system, having a young high- and a low-mass components. We conclude on the viability of the disc fragmentation channel for the formation of such short-period binaries, and that both processes – close massive binary formation and accretion bursts – may happen at the same time. FU-Orionis-type bursts, such as observed in the young high-mass star S255IR−NIRS3, may not only indicate ongoing disc fragmentation, but also be considered as a tracer for the formation of close massive binaries – progenitors of the subsequent massive spectroscopic binaries – once the high-mass component of the system will enter the main-sequence phase of its evolution. Finally, we investigate the Atacama Large (sub-)Millimeter Array observability of the disc fragments.
Design studies are an increasingly popular form of problem-driven visualization research, yet there is little guidance available about how to do them effectively. In this paper we reflect on our ...combined experience of conducting twenty-one design studies, as well as reading and reviewing many more, and on an extensive literature review of other field work methods and methodologies. Based on this foundation we provide definitions, propose a methodological framework, and provide practical guidance for conducting design studies. We define a design study as a project in which visualization researchers analyze a specific real-world problem faced by domain experts, design a visualization system that supports solving this problem, validate the design, and reflect about lessons learned in order to refine visualization design guidelines. We characterize two axes - a task clarity axis from fuzzy to crisp and an information location axis from the domain expert's head to the computer - and use these axes to reason about design study contributions, their suitability, and uniqueness from other approaches. The proposed methodological framework consists of 9 stages: learn, winnow, cast, discover, design, implement, deploy, reflect, and write. For each stage we provide practical guidance and outline potential pitfalls. We also conducted an extensive literature survey of related methodological approaches that involve a significant amount of qualitative field work, and compare design study methodology to that of ethnography, grounded theory, and action research.
Hormones in the hypothalamus-pituitary-adrenal (HPA) axis mediate many of the bodily responses to stressors, yet there is no clear relationship between the levels of these hormones and ...stress-associated mental illnesses such as posttraumatic stress disorder (PTSD). Therefore, other hormones are likely to be involved in this effect of stress. Here we used a rodent model of PTSD in which rats repeatedly exposed to a stressor display heightened fear learning following auditory Pavlovian fear conditioning. Our results show that stress-related increases in circulating ghrelin, a peptide hormone, are necessary and sufficient for stress-associated vulnerability to exacerbated fear learning and these actions of ghrelin occur in the amygdala. Importantly, these actions are also independent of the classic HPA stress axis. Repeated systemic administration of a ghrelin receptor agonist enhanced fear memory but did not increase either corticotropin-releasing factor (CRF) or corticosterone. Repeated intraamygdala infusion of a ghrelin receptor agonist produced a similar enhancement of fear memory. Ghrelin receptor antagonism during repeated stress abolished stress-related enhancement of fear memory without blunting stress-induced corticosterone release. We also examined links between ghrelin and growth hormone (GH), a major downstream effector of the ghrelin receptor. GH protein was upregulated in the amygdala following chronic stress, and its release from amygdala neurons was enhanced by ghrelin receptor stimulation. Virus-mediated overexpression of GH in the amygdala was also sufficient to increase fear. Finally, virus-mediated overexpression of a GH receptor antagonist was sufficient to block the fear-enhancing effects of repeated ghrelin receptor stimulation. Thus, ghrelin requires GH in the amygdala to exert fear-enhancing effects. These results suggest that ghrelin mediates a novel branch of the stress response and highlight a previously unrecognized role for ghrelin and growth hormone in maladaptive changes following prolonged stress.
The development of 3D in vitro models capable of recapitulating native tumor microenvironments could improve the translatability of potential anticancer drugs and treatments. Here, 3D bioprinting ...techniques are used to build tumor constructs via precise placement of living cells, functional biomaterials, and programmable release capsules. This enables the spatiotemporal control of signaling molecular gradients, thereby dynamically modulating cellular behaviors at a local level. Vascularized tumor models are created to mimic key steps of cancer dissemination (invasion, intravasation, and angiogenesis), based on guided migration of tumor cells and endothelial cells in the context of stromal cells and growth factors. The utility of the metastatic models for drug screening is demonstrated by evaluating the anticancer efficacy of immunotoxins. These 3D vascularized tumor tissues provide a proof‐of‐concept platform to i) fundamentally explore the molecular mechanisms of tumor progression and metastasis, and ii) preclinically identify therapeutic agents and screen anticancer drugs.
A migration‐inducing, vascularized tumor model platform is created via 3D bioprinting of cells, natural hydrogels, and programmable release capsules. These cell‐laden architectures are designed to recapitulate the primary characteristics of metastasis. The 3D models both physically and chemically reconstruct the tumor microenvironments with high spatiotemporal resolution, offering a tool to bridge the gap between monolayer cell culture and animal models.
ABSTRACT
A very small fraction of (runaway) massive stars have masses exceeding $60\!-\!70\, \rm M_{\odot }$ and are predicted to evolve as luminous blue variable and Wolf–Rayet stars before ending ...their lives as core-collapse supernovae. Our 2D axisymmetric hydrodynamical simulations explore how a fast wind ($2000\, \rm km\, \rm s^{-1}$) and high mass-loss rate ($10^{-5}\, \rm M_{\odot }\, \rm yr^{-1}$) can impact the morphology of the circumstellar medium. It is shaped as 100 pc-scale wind nebula that can be pierced by the driving star when it supersonically moves with velocity $20\!-\!40\, \rm km\, \rm s^{-1}$ through the interstellar medium (ISM) in the Galactic plane. The motion of such runaway stars displaces the position of the supernova explosion out of their bow shock nebula, imposing asymmetries to the eventual shock wave expansion and engendering Cygnus-loop-like supernova remnants. We conclude that the size (up to more than $200\, \rm pc$) of the filamentary wind cavity in which the chemically enriched supernova ejecta expand, mixing efficiently the wind and ISM materials by at least $10{{\ \rm per\ cent}}$ in number density, can be used as a tracer of the runaway nature of the very massive progenitors of such $0.1\, \rm Myr$ old remnants. Our results motivate further observational campaigns devoted to the bow shock of the very massive stars BD+43°3654 and to the close surroundings of the synchrotron-emitting Wolf–Rayet shell G2.4+1.4.
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