There are a growing number of large-scale, complex hydrologic models that are capable of simulating integrated surface and subsurface flow. Many are coupled to land-surface energy balance models, biogeochemical and ecological process models, and atmospheric models. Although they are being increasingly applied for hydrologic prediction and environmental understanding, very little formal verification and/or benchmarking of these models has been performed. Here we present the results of an intercomparison study of seven coupled surface-subsurface models based on a series of benchmark problems. All the models simultaneously solve adapted forms of the Richards and shallow water equations, based on fully 3-D or mixed (1-D vadose zone and 2-D groundwater) formulations for subsurface flow and 1-D (rill flow) or 2-D (sheet flow) conceptualizations for surface routing. A range of approaches is used for the solution of the coupled equations, including global implicit, sequential iterative, and asynchronous linking, and various strategies are used to enforce flux and pressure continuity at the surface-subsurface interface. The simulation results show good agreement for the simpler test cases, while the more complicated test cases bring out some of the differences in physical process representations and numerical solution approaches between the models. Benchmarks with more traditional runoff generating mechanisms, such as excess infiltration and saturation, demonstrate more agreement between models, while benchmarks with heterogeneity and complex water table dynamics highlight differences in model formulation. In general, all the models demonstrate the same qualitative behavior, thus building confidence in their use for hydrologic applications.
Summary The ability to generate T cells from self-renewing pluripotent stem cells (PSC) has the potential to transform the current practice of autologous T cell immunotherapy into universal off-the-shelf products. However, differentiation of human PSCs into mature, conventional T cells has been challenging with existing methods. We report that a 3D artificial thymic organoid (PSC-ATO) system induced efficient differentiation of human embryonic stem cell and induced pluripotent stem cell-derived mesoderm progenitors to mature, functional T cells with a diverse T cell receptor (TCR) repertoire. This continuous culture system supported both hematopoietic specification and terminal differentiation to naïve CD3+CD8αβ+ and CD3+CD4+ conventional T cells. Introduction of an MHC class I-restricted TCR in PSCs produced naïve, antigen-specific cytotoxic CD8αβ+ T cells which lacked endogenous TCR Vβ expression. Functional assays and RNA sequencing aligned PSC-derived T cells with primary naïve CD8+ T cells. The PSC-ATO system presented here is an efficient platform for generating functional, mature T cells from human PSCs.
SummaryWe demonstrate that dissociated human pluripotent stem cells (PSCs) are intrinsically programmed to form lumens. PSCs form two-cell cysts with a shared apical domain within 20 hr of plating; these cysts collapse to form monolayers after 5 days. Expression of pluripotency markers is maintained throughout this time. In two-cell cysts, an apical domain, marked by EZRIN and atypical PKCζ, is surrounded by apically targeted organelles (early endosomes and Golgi). Molecularly, actin polymerization, regulated by ARP2/3 and mammalian diaphanous-related formin 1 (MDIA), promotes lumen formation, whereas actin contraction, mediated by MYOSIN-II, inhibits this process. Finally, we show that lumenal shape can be manipulated in bioengineered micro-wells. Since lumen formation is an indispensable step in early mammalian development, this system can provide a powerful model for investigation of this process in a controlled environment. Overall, our data establish that lumenogenesis is a fundamental cell biological property of human PSCs.
Cues in the environment can elicit complex emotional states, and thereby maladaptive behavior, as a function of their ascribed value. Here we capture individual variation in the propensity to attribute motivational value to reward-cues using the sign-tracker/goal-tracker animal model. Goal-trackers attribute predictive value to reward-cues, and sign-trackers attribute both predictive and incentive value. Using chemogenetics and microdialysis, we show that, in sign-trackers, stimulation of the neuronal pathway from the prelimbic cortex (PrL) to the paraventricular nucleus of the thalamus (PVT) decreases the incentive value of a reward-cue. In contrast, in goal-trackers, inhibition of the PrL-PVT pathway increases both the incentive value and dopamine levels in the nucleus accumbens shell. The PrL-PVT pathway, therefore, exerts top-down control over the dopamine-dependent process of incentive salience attribution. These results highlight PrL-PVT pathway as a potential target for treating psychopathologies associated with the attribution of excessive incentive value to reward-cues, including addiction.
Core Ideas Burn severity data informed a hydrologic model to assess water balance changes. Loss of vegetation and evapotranspiration exceeded impact of increased runoff. High burn severity may cause drier site conditions due to increased runoff. Change in evapotranspiration acts at long timescales while runoff is event based. Forest fires have a significant impact on hydrology, such as reduced infiltration rates leading to increased flooding. However, post‐fire water balance changes and the competing hydrologic response of increased runoff and evapotranspiration as a function of burn severity are not well understood. Comparing pre‐ and post‐fire water balance changes is challenging because measurements of fire‐disturbed landscapes with the previously undisturbed character are impractical due to non‐repetitive observational conditions. We used a physically based modeling experiment to incorporate burn severity data from the Las Conchas fire to approximate model parameterization to evaluate continuous water balance progression for pre‐ and post‐fire simulations using the same forcing conditions. Fire disturbance decreased evapotranspiration and increased overland flow response to precipitation events. The reduction of evapotranspiration often dominated the new water balance compared with the increase in overland flow, resulting in higher soil moisture. However, this modeling experiment also identified a tipping point where increased overland flow from high burn severity sites eclipses the effect of reduced evapotranspiration on the water balance, causing comparatively drier post‐fire soils. In particular, high burn severity sites approach a threshold that results in larger changes to overland flow than changes in evapotranspiration, potentially moving the site to an overland flow dominated regime. The shifts in water balance components have implications for how site conditions will change under a range of burn severity scenarios.
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