The prefrontal cortex (PFC) is involved in working memory and self-regulatory and goal-directed behaviors and displays remarkable structural and functional plasticity over the life course. Neural ...circuitry, molecular profiles, and neurochemistry can be changed by experiences, which influence behavior as well as neuroendocrine and autonomic function. Such effects have a particular impact during infancy and in adolescence. Behavioral stress affects both the structure and function of PFC, though such effects are not necessarily permanent, as young animals show remarkable neuronal resilience if the stress is discontinued. During aging, neurons within the PFC become less resilient to stress. There are also sex differences in the PFC response to stressors. While such stress and sex hormone-related alterations occur in regions mediating the highest levels of cognitive function and self-regulatory control, the fact that they are not necessarily permanent has implications for future behavior-based therapies that harness neural plasticity for recovery.
The PFC is subject to structural and functional modifications in response to the environment, hormones, and age. These effects are both sex and circuit specific. McEwen and Morrison review findings on PFC plasticity in the adult and propose that such plasticity could be harnessed for therapeutic benefit.
Prognostic precipitation is added to a cloud microphysical scheme for global climate models. Results indicate very similar performance to other commonly used mesoscale schemes in an offline driver ...for idealized warm rain cases, better than the previous version of the global model microphysics scheme with diagnostic precipitation. In the mixed phase regime, there is significantly more water and less ice, which may address a common bias seen with the scheme in climate simulations in the Arctic. For steady forcing cases, the scheme has limited sensitivity to time step out to the ∼15-min time steps typical of global models. The scheme is similar to other schemes with moderate sensitivity to vertical resolution. The limited time step sensitivity bodes well for use of the scheme in multiscale models from the mesoscale to the large scale. The scheme is sensitive to idealized perturbations of cloud drop and crystal number. Precipitation decreases and condensate increases with increasing drop number, indicating substantial decreases in precipitation efficiency. The sensitivity is less than with the previous version of the scheme for low drop number concentrations (Nc
< 100 cm−3). Ice condensate increases with ice number, with large decreases in liquid condensate as well for a mixed phase case. As expected with prognostic precipitation, accretion is stronger than with diagnostic precipitation and the accretion to autoconversion ratio increases faster with liquid water path (LWP), in better agreement with idealized models and earlier studies than the previous version.
A new two-moment cloud microphysics scheme predicting the mixing ratios and number concentrations of five species (i.e., cloud droplets, cloud ice, snow, rain, and graupel) has been implemented into ...the Weather Research and Forecasting model (WRF). This scheme is used to investigate the formation and evolution of trailing stratiform precipitation in an idealized two-dimensional squall line. Results are compared to those using a one-moment version of the scheme that predicts only the mixing ratios of the species, and diagnoses the number concentrations from the specified size distribution intercept parameter and predicted mixing ratio. The overall structure of the storm is similar using either the one- or two-moment schemes, although there are notable differences. The two-moment (2-M) scheme produces a widespread region of trailing stratiform precipitation within several hours of the storm formation. In contrast, there is negligible trailing stratiform precipitation using the one-moment (1-M) scheme. The primary reason for this difference are reduced rain evaporation rates in 2-M compared to 1-M in the trailing stratiform region, leading directly to greater rain mixing ratios and surface rainfall rates. Second, increased rain evaporation rates in 2-M compared to 1-M in the convective region at midlevels result in weaker convective updraft cells and increased midlevel detrainment and flux of positively buoyant air from the convective into the stratiform region. This flux is in turn associated with a stronger mesoscale updraft in the stratiform region and enhanced ice growth rates. The reduced (increased) rates of rain evaporation in the stratiform (convective) regions in 2-M are associated with differences in the predicted rain size distribution intercept parameter (which was specified as a constant in 1-M) between the two regions. This variability is consistent with surface disdrometer measurements in previous studies that show a rapid decrease of the rain intercept parameter during the transition from convective to stratiform rainfall. PUBLICATION ABSTRACT
A cloud system-resolving model (the Weather Research and Forecasting model) with 1 km horizontal grid spacing is used to investigate the response of an idealized supercell storm to increased cloud ...droplet concentrations associated with polluted conditions. The primary focus is on exploring robustness of simulated aerosol effects in the face of complex process interactions and feedbacks between the cloud microphysics and dynamics. Simulations are run using sixteen different model configurations with various microphysical or thermodynamic processes modified or turned off. Robustness of the storm response to polluted conditions is also explored for each configuration by performing additional simulations with small perturbations to the initial conditions. Differences in the domain-mean accumulated surface precipitation and convective mass flux between polluted and pristine conditions are small for almost all model configurations, with relative differences in each quantity generally less than 15%. Configurations that produce a decrease (increase) in cold pool strength in polluted conditions also tend to simulate a decrease (increase) in surface precipitation and convective mass flux. Combined with an analysis of the dynamical and thermodynamic fields, these results indicate the importance of interactions between microphysics, cold pool evolution, and dynamics along outflow boundaries in explaining the system response. Several model configurations, including the baseline, produce an overall similar storm response (weakening) in polluted conditions despite having different microphysical or thermodynamic processes turned off. With hail initiation turned off or the hail fallspeed-size relation set to that of snow, the model produces an invigoration instead of weakening of the storm in polluted conditions. These results highlight the difficulty of foreseeing impacts of changes to model parameterizations and isolating process interactions that drive the system response to aerosols. Overall, these findings are robust, in a qualitative sense, to small perturbations in the initial conditions. However, there is sensitivity in the magnitude, and in some cases sign, of the storm response to polluted conditions with small perturbations in the temperature of the thermal used to initiate convection (less than 0.5 K) or the vertical shear of the environmental wind ( 5%). It is concluded that reducing uncertainty in simulations of aerosol effects on individual deep convective storms will likely require ensemble methods in addition to continued improvement of model parameterizations.
The predicted particle properties (P3) scheme introduced in Part I of this series represents all ice hydrometeors using a single "free" category, in which the bulk properties evolve smoothly through ...changes in the prognostic variables, allowing for the representation of any type of ice particle. In this study, P3 has been expanded to include multiple free ice-phase categories allowing particle populations with different sets of bulk properties to coexist, thereby reducing the detrimental effects of property dilution. The modified version of P3 is the first scheme to parameterize ice-phase microphysics using multiple free categories. The multicategory P3 scheme is described and its overall behavior is illustrated. It is shown using an idealized 1D kinematic model that the overall simulation of total ice mass, reflectivity, and surface precipitation converges with additional categories. The correct treatment of the rime splintering process, which promotes multiple ice modes, is shown to require at least two categories in order to be included without introducing problems associated with property dilution. Squall-line simulations using a 3D dynamical model with one, two, and three ice categories produce reasonable reflectivity structures and precipitation rates compared to radar observations. In the multicategory simulations, ice hydrometeors from different categories and with different bulk properties are shown to coexist at the same points, with effects on reflectivity structure and precipitation. The new scheme thus appears to work reasonably in a full 3D model and is ready to be tested more widely for research and operational applications.
Abstract
The sensitivity of an idealized squall line to horizontal and vertical grid spacing is investigated using a new approach. Simulations are first performed at a horizontal grid spacing of 1 km ...until the storm reaches its mature stage. The model output is then interpolated to smaller (and larger) grid spacings, and the model is restarted using the interpolated state plus small thermodynamic perturbations to spin up small-scale motions. This framework allows an investigation of the sensitivity of the storm to changes in without complications from differences in storm initiation and early evolution. The restarted simulations reach a quasi steady state within approximately 1 h. Results demonstrate that there are two -dependent regimes with the transition between regimes occurring for between 250 and 500 m. Some storm characteristics, such as the mean convective core area, change substantially for 250 m but show limited sensitivity as is decreased below 250 m, despite better resolving smaller-scale turbulent motions. This transition is found to be independent of the chosen . Mixing in the context of varying and is also investigated via passive tracers that are initialized 1 h after restarting the simulations (i.e., after the spin up of small-scale motions). The tracer field at the end of the simulations reveals that entrainment and detrainment are suppressed in the simulations with 500 m. For decreasing , entrainment and detrainment are substantially more important, limiting the flux of low-level tracer to the upper troposphere, which has important implications for modeling studies of convective transport from the boundary layer through the troposphere.
Neurons in the primate dorsolateral prefrontal cortex (dlPFC) generate persistent firing in the absence of sensory stimulation, the foundation of mental representation. Persistent firing arises from ...recurrent excitation within a network of pyramidal Delay cells. Here, we examined glutamate receptor influences underlying persistent firing in primate dlPFC during a spatial working memory task. Computational models predicted dependence on NMDA receptor (NMDAR) NR2B stimulation, and Delay cell persistent firing was abolished by local NR2B NMDAR blockade or by systemic ketamine administration. AMPA receptors (AMPARs) contributed background depolarization to sustain network firing. In contrast, many Response cells were sensitive to AMPAR blockade and increased firing after systemic ketamine, indicating that models of ketamine actions should be refined to reflect neuronal heterogeneity. The reliance of Delay cells on NMDAR may explain why insults to NMDARs in schizophrenia or Alzheimer’s disease profoundly impair cognition.
► Primate prefrontal cortical working memory circuits require NMDA NR2B receptors ► Blocking NMDA, but not AMPA receptors, markedly reduced Delay cell firing ► Systemic ketamine also reduced Delay cell firing but increased Response cell firing ► These primate data should redefine NMDA glutamate theories of cognitive disorders
Wang et al. assess the effect of blocking glutamate receptors on working memory and neuronal firing in primate dlPFC. Delay cell firing is abolished by NMDAR block, while many Response cells are sensitive to AMPAR block. Blocking NR2B receptors impairs working memory, underscoring their role in cognitive function.
Pancreatic cancer is the third-leading cause of cancer mortality in the USA, recently surpassing breast cancer. A key component of pancreatic cancer's lethality is its acquired immune privilege, ...which is driven by an immunosuppressive microenvironment, poor T cell infiltration, and a low mutational burden. Although immunotherapies such as checkpoint blockade or engineered T cells have yet to demonstrate efficacy, a growing body of evidence suggests that orthogonal combinations of these and other strategies could unlock immunotherapy in pancreatic cancer. In this Review article, we discuss promising immunotherapies currently under investigation in pancreatic cancer and provide a roadmap for the development of prevention vaccines for this and other cancers.
Estrogen facilitates higher cognitive functions by exerting effects on brain regions such as the prefrontal cortex and hippocampus. Estrogen induces spinogenesis and synaptogenesis in these two brain ...regions and also initiates a complex set of signal transduction pathways via estrogen receptors (ERs). Along with the classical genomic effects mediated by activation of ER α and ER β, there are membrane-bound ER α, ER β, and G protein-coupled estrogen receptor 1 (GPER1) that can mediate rapid nongenomic effects. All key ERs present throughout the body are also present in synapses of the hippocampus and prefrontal cortex. This review summarizes estrogen actions in the brain from the standpoint of their effects on synapse structure and function, noting also the synergistic role of progesterone. We first begin with a review of ER subtypes in the brain and how their abundance and distributions are altered with aging and estrogen loss (e.g., ovariectomy or menopause) in the rodent, monkey, and human brain. As there is much evidence that estrogen loss induced by menopause can exacerbate the effects of aging on cognitive functions, we then review the clinical trials of hormone replacement therapies and their effectiveness on cognitive symptoms experienced by women. Finally, we summarize studies carried out in nonhuman primate models of age- and menopause-related cognitive decline that are highly relevant for developing effective interventions for menopausal women. Together, we highlight a new understanding of how estrogen affects higher cognitive functions and synaptic health that go well beyond its effects on reproduction.
The notion of transformation is gaining traction in contemporary sustainability debates. New ways of theorising and supporting transformations are emerging and, so the argument goes, opening exciting ...spaces to (re)imagine and (re)structure radically different futures. Yet, questions remain about how the term is being translated from an academic concept into an assemblage of normative policies and practices, and how this process might shape social, political, and environmental change. Motivated by these questions, we identify five latent risks associated with discourse that frames transformation as apolitical and/or inevitable. We refer to these risks as the dark side of transformation. While we cannot predict the future of radical transformations towards sustainability, we suggest that scientists, policymakers, and practitioners need to consider such change in more inherently plural and political ways.
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