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.

Highlights d M-ATOs mimic the different stages of normal murine thymopoiesis in multiple strains d M-ATOs support the key transcriptional transitions during T cell development d M-ATOs generate mature T cells with a diverse TCR repertoire d M-ATOs generate the complete trajectory of thymopoiesis from a single HSC

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.

This work is motivated by our goal of determining why individuals with stroke are impaired when locating their arms in space. We assessed the ability of individuals without neurological impairments to mirror their forearms during various motor tasks so that we could identify baseline performance in an unimpaired population. Nine right-hand dominant participants without neurological impairments mirrored forearm positions bi-directionally (i.e., right forearm mirrors left forearm, vice versa) for three motor tasks (i.e., passive, passive/active, and active) and two position identification modes (i.e., mirroring to a position stored in working memory versus concurrently felt by the opposite arm). During each trial, the participant's reference forearm moved to a flexion ([Formula: see text]) or extension ([Formula: see text]) position, and then, their opposite forearm mirrored the position of their reference forearm. The main finding across all tested conditions is that participants mirrored forearm positions with an average magnitude of error [Formula: see text]. When controlling their forearms' movements (active motor task), participants mirrored forearm positions more accurately by up to, on average, [Formula: see text] at the flexion location than at the extension location. Moreover, participants mirrored forearm positions more accurately by up to, on average, [Formula: see text] when their forearms were moved for them rather than when they controlled their forearms' movements. Task directionality and position identification mode did not significantly affect participant arm mirroring accuracy. These findings are relevant for interpreting in future work the reason why impairments occur, on similar tasks, in individuals with altered motor commands, working memory, and arm impedance, e.g., post-stroke hemiparesis.

Stimuli or 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 signtracker/goal-tracker animal model. Goal-trackers attribute predictive value to rewardcues, 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 goaltrackers, 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. independent delivery of food-US, distinct conditioned responses emerge. Some rats, goal-trackers (GTs), approach the location of impending food delivery upon the lever-CS presentation, while others, sign-trackers (STs), approach and interact with the lever-CS itself. For both GTs and STs the lever-CS acquires predictive value and elicits a conditioned response, but for STs, the CS also acquires incentive value. This animal model, therefore, provides a unique platform to investigate the neurobiological determinants of individual differences in the propensity to attribute incentive salience to reward-cues.Previous studies suggest that sign-tracking behavior results from enhanced activity in subcortical brain circuits known to mediate motivated behaviors, including the striatal dopamine system, the amygdala, and the hypothalamus 22,23,28-31 . In addition, relative to GTs, STs appear to have deficits in top-down cognitive control originating in the prefrontal cortex 32 . Thus, we hypothesize that sign-tracking behavior arises from an imbalance between top-down cognitive control and bottom-up motivational processes.One brain region that is ideally situated to act as a fulcrum between cortical, limbic and homeostatic circuits is the paraventricular nucleus of the thalamus (PVT). The PVT has, in fact, come to be known as the "thalamic gateway" 33 for appetitive motivation; acting to integrate cognitive, emotional, motivational and viscerosensitive information, and, in turn, guide behavioral responses 33,34 . Consistent with this view, the PVT has been implicated in the propensity to attribute incentive motivational value to reward-cues [35][36][37] .The functional connectivity of the PVT in response to cue-induced neuronal activity differentiates STs from GTs 28,29,35 . In STs, cue-induced activity in the PVT is correlated with activity in subcortical areas, including the nucleus accumbens (NAc); whereas in GTs, cue-...