► Introduces the Agricultural Model Intercomparison and Improvement Project (AgMIP). ► Describes AgMIP Protocols for consistent research activities. ► Demonstrates AgMIP approaches using climate, ...crop, and economic model analyses. ► Wheat pilot results elucidate the relative uncertainties from crop and climate models. ► Outlines AgMIP crop-specific, regional, and global research activities.
The Agricultural Model Intercomparison and Improvement Project (AgMIP) is a major international effort linking the climate, crop, and economic modeling communities with cutting-edge information technology to produce improved crop and economic models and the next generation of climate impact projections for the agricultural sector. The goals of AgMIP are to improve substantially the characterization of world food security due to climate change and to enhance adaptation capacity in both developing and developed countries. Analyses of the agricultural impacts of climate variability and change require a transdisciplinary effort to consistently link state-of-the-art climate scenarios to crop and economic models. Crop model outputs are aggregated as inputs to regional and global economic models to determine regional vulnerabilities, changes in comparative advantage, price effects, and potential adaptation strategies in the agricultural sector. Climate, Crop Modeling, Economics, and Information Technology Team Protocols are presented to guide coordinated climate, crop modeling, economics, and information technology research activities around the world, along with AgMIP Cross-Cutting Themes that address uncertainty, aggregation and scaling, and the development of Representative Agricultural Pathways (RAPs) to enable testing of climate change adaptations in the context of other regional and global trends. The organization of research activities by geographic region and specific crops is described, along with project milestones.
Pilot results demonstrate AgMIP's role in assessing climate impacts with explicit representation of uncertainties in climate scenarios and simulations using crop and economic models. An intercomparison of wheat model simulations near Obregón, Mexico reveals inter-model differences in yield sensitivity to CO2 with model uncertainty holding approximately steady as concentrations rise, while uncertainty related to choice of crop model increases with rising temperatures. Wheat model simulations with mid-century climate scenarios project a slight decline in absolute yields that is more sensitive to selection of crop model than to global climate model, emissions scenario, or climate scenario downscaling method. A comparison of regional and national-scale economic simulations finds a large sensitivity of projected yield changes to the simulations’ resolved scales. Finally, a global economic model intercomparison example demonstrates that improvements in the understanding of agriculture futures arise from integration of the range of uncertainty in crop, climate, and economic modeling results in multi-model assessments.
The purpose of this study was to critically examine how people perceive the definitions, differences and similarities of interest and curiosity, and address the subjective boundaries between interest ...and curiosity. We used a qualitative research approach given the research questions and the goal to develop an in-depth understanding of people's meaning of interest and curiosity. We used data from a sample of 126 U.S. adults (48.5% male) recruited through Amazon's Mechanical Turk (M.sub.age = 40.7, SD.sub.age = 11.7). Semi-structured questions were used and thematic analysis was applied. The results showed two themes relating to differences between curiosity and interest; active/stable feelings and certainty/uncertainty. Curiosity was defined as an active feeling (more specifically a first, fleeting feeling) and a child-like emotion that often involves a strong urge to think actively and differently, whereas interest was described as stable and sustainable feeling, which is characterized as involved engagement and personal preferences (e.g., hobbies). In addition, participants related curiosity to uncertainty, e.g., trying new things and risk-taking behaviour. Certainty, on the other hand, was deemed as an important component in the definition of interest, which helps individuals acquire deep knowledge. Both curiosity and interest were reported to be innate and positive feelings that support motivation and knowledge-seeking during the learning process.
Naive T cells undergo metabolic reprogramming to support the increased energetic and biosynthetic demands of effector T cell function. However, how nutrient availability influences T cell metabolism ...and function remains poorly understood. Here we report plasticity in effector T cell metabolism in response to changing nutrient availability. Activated T cells were found to possess a glucose-sensitive metabolic checkpoint controlled by the energy sensor AMP-activated protein kinase (AMPK) that regulated mRNA translation and glutamine-dependent mitochondrial metabolism to maintain T cell bioenergetics and viability. T cells lacking AMPKα1 displayed reduced mitochondrial bioenergetics and cellular ATP in response to glucose limitation in vitro or pathogenic challenge in vivo. Finally, we demonstrated that AMPKα1 is essential for T helper 1 (Th1) and Th17 cell development and primary T cell responses to viral and bacterial infections in vivo. Our data highlight AMPK-dependent regulation of metabolic homeostasis as a key regulator of T cell-mediated adaptive immunity.
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•T cells display metabolic flexibility in response to nutrient limitation•AMPK couples nutrient availability to T cell effector function•T cell metabolic adaptation is AMPKα1-dependent•AMPKα1 is required for primary T cell responses and cellular bioenergetics in vivo
T cells undergo metabolic reprogramming upon activation to fuel T cell growth, proliferation, and effector function. Jones and colleagues show effector T cells adapt their metabolic programs in response to reduced glucose availability, which is regulated by the energy sensor AMPK.
Asteroseismic constraints on K giants make it possible to infer radii, masses and ages of tens of thousands of field stars. Tests against independent estimates of these properties are however scarce, ...especially in the metal-poor regime. Here, we report the detection of solar-like oscillations in eight stars belonging to the red-giant branch (RGB) and red-horizontal branch (RHB) of the globular cluster M4. The detections were made in photometric observations from the K2 Mission during its Campaign 2. Making use of independent constraints on the distance, we estimate masses of the eight stars by utilizing different combinations of seismic and non-seismic inputs. When introducing a correction to the Δν scaling relation as suggested by stellar models, for RGB stars we find excellent agreement with the expected masses from isochrone fitting, and with a distance modulus derived using independent methods. The offset with respect to independent masses is lower, or comparable with, the uncertainties on the average RGB mass (4–10 per cent, depending on the combination of constraints used). Our results lend confidence to asteroseismic masses in the metal-poor regime. We note that a larger sample will be needed to allow more stringent tests to be made of systematic uncertainties in all the observables (both seismic and non-seismic), and to explore the properties of RHB stars, and of different populations in the cluster.
The resident prokaryotic microbiota of the mammalian intestine influences diverse homeostatic functions, including regulation of cellular growth, maintenance of barrier function, and modulation of ...immune responses. However, it is unknown how commensal prokaryotic organisms mechanistically influence eukaryotic signaling networks. Recent data has demonstrated that gut epithelia contacted by enteric commensal bacteria rapidly generate reactive oxygen species (ROS). While the induced generation of ROS via stimulation of formyl peptide receptors is a cardinal feature of the cellular response of phagocytes to pathogenic or commensal bacteria, evidence is accumulating that ROS are also similarly elicited in other cell types, including intestinal epithelia, in response to microbial signals. Additionally, ROS have been shown to serve as critical second messengers in multiple signal transduction pathways stimulated by proinflammatory cytokines and growth factors. This physiologically-generated ROS is known to participate in cellular signaling via the rapid and transient oxidative inactivation of a defined class of sensor proteins bearing oxidant-sensitive thiol groups. These proteins include tyrosine phosphatases that serve as regulators of MAP kinase pathways, cytoskeletal dynamics, as well as components involved in control of ubiquitination-mediated NF-κB activation. Consistently, microbial-elicited ROS has been shown to mediate increased cellular proliferation and motility and to modulate innate immune signaling. These results demonstrate how enteric microbiota influence regulatory networks of the mammalian intestinal epithelia. We hypothesize that many of the known effects of the normal microbiota on intestinal physiology, and potential beneficial effects of candidate probiotic bacteria, may be at least partially mediated by this ROS-dependent mechanism.
Abstract
We report results from continued timing observations of PSR J0740+6620, a high-mass, 2.8 ms radio pulsar in orbit with a likely ultracool white dwarf companion. Our data set consists of ...combined pulse arrival-time measurements made with the 100 m Green Bank Telescope and the Canadian Hydrogen Intensity Mapping Experiment telescope. We explore the significance of timing-based phenomena arising from general relativistic dynamics and variations in pulse dispersion. When using various statistical methods, we find that combining ∼1.5 yr of additional, high-cadence timing data with previous measurements confirms and improves on previous estimates of relativistic effects within the PSR J0740+6620 system, with the pulsar mass
m
p
=
2.08
−
0.07
+
0.07
M
⊙
(68.3% credibility) determined by the relativistic Shapiro time delay. For the first time, we measure secular variation in the orbital period and argue that this effect arises from apparent acceleration due to significant transverse motion. After incorporating contributions from Galactic differential rotation and off-plane acceleration in the Galactic potential, we obtain a model-dependent distance of
d
=
1.14
−
0.15
+
0.17
kpc (68.3% credibility). This improved distance confirms the ultracool nature of the white dwarf companion determined from recent optical observations. We discuss the prospects for future observations with next-generation facilities, which will likely improve the precision on
m
p
for J0740+6620 by an order of magnitude within the next few years.
We analyze dispersion measure (DM) variations of 37 millisecond pulsars in the nine-year North American Nanohertz Observatory for Gravitational Waves (NANOGrav) data release and constrain the sources ...of these variations. DM variations can result from a changing distance between Earth and the pulsar, inhomogeneities in the interstellar medium, and solar effects. Variations are significant for nearly all pulsars, with characteristic timescales comparable to or even shorter than the average spacing between observations. Five pulsars have periodic annual variations, 14 pulsars have monotonically increasing or decreasing trends, and 14 pulsars show both effects. Of the four pulsars with linear trends that have line-of-sight velocity measurements, three are consistent with a changing distance and require an overdensity of free electrons local to the pulsar. Several pulsars show correlations between DM excesses and lines of sight that pass close to the Sun. Mapping of the DM variations as a function of the pulsar trajectory can identify localized interstellar medium features and, in one case, an upper limit to the size of the dispersing region of 4 au. Four pulsars show roughly Kolmogorov structure functions (SFs), and another four show SFs less steep than Kolmogorov. One pulsar has too large an uncertainty to allow comparisons. We discuss explanations for apparent departures from a Kolmogorov-like spectrum, and we show that the presence of other trends and localized features or gradients in the interstellar medium is the most likely cause.
During aging, progenitor cells acquire mutations, which may generate clones that colonize the surrounding tissue. By middle age, normal human tissues, including the esophageal epithelium (EE), become ...a patchwork of mutant clones. Despite their relevance for understanding aging and cancer, the processes that underpin mutational selection in normal tissues remain poorly understood. Here, we investigated this issue in the esophageal epithelium of mutagen-treated mice. Deep sequencing identified numerous mutant clones with multiple genes under positive selection, including Notch1, Notch2 and Trp53, which are also selected in human esophageal epithelium. Transgenic lineage tracing revealed strong clonal competition that evolved over time. Clone dynamics were consistent with a simple model in which the proliferative advantage conferred by positively selected mutations depends on the nature of the neighboring cells. When clones with similar competitive fitness collide, mutant cell fate reverts towards homeostasis, a constraint that explains how selection operates in normal-appearing epithelium.
The Global Fire Assimilation System (GFASv1.0) calculates biomass burning emissions by assimilating Fire Radiative Power (FRP) observations from the MODIS instruments onboard the Terra and Aqua ...satellites. It corrects for gaps in the observations, which are mostly due to cloud cover, and filters spurious FRP observations of volcanoes, gas flares and other industrial activity. The combustion rate is subsequently calculated with land cover-specific conversion factors. Emission factors for 40 gas-phase and aerosol trace species have been compiled from a literature survey. The corresponding daily emissions have been calculated on a global 0.5° × 0.5° grid from 2003 to the present. General consistency with the Global Fire Emission Database version 3.1 (GFED3.1) within its accuracy is achieved while maintaining the advantages of an FRP-based approach: GFASv1.0 makes use of the quantitative information on the combustion rate that is contained in the FRP observations, and it detects fires in real time at high spatial and temporal resolution. GFASv1.0 indicates omission errors in GFED3.1 due to undetected small fires. It also exhibits slightly longer fire seasons in South America and North Africa and a slightly shorter fire season in Southeast Asia. GFASv1.0 has already been used for atmospheric reactive gas simulations in an independent study, which found good agreement with atmospheric observations. We have performed simulations of the atmospheric aerosol distribution with and without the assimilation of MODIS aerosol optical depth (AOD). They indicate that the emissions of particulate matter need to be boosted by a factor of 2–4 to reproduce the global distribution of organic matter and black carbon. This discrepancy is also evident in the comparison of previously published top-down and bottom-up estimates. For the time being, a global enhancement of the particulate matter emissions by 3.4 is recommended. Validation with independent AOD and PM10 observations recorded during the Russian fires in summer 2010 show that the global Monitoring Atmospheric Composition and Change (MACC) aerosol model with GFASv1.0 aerosol emissions captures the smoke plume evolution well when organic matter and black carbon are enhanced by the recommended factor. In conjunction with the assimilation of MODIS AOD, the use of GFASv1.0 with enhanced emission factors quantitatively improves the forecast of the aerosol load near the surface sufficiently to allow air quality warnings with a lead time of up to four days.
Background
Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of ...therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety.
Methods
The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy.
Results
The panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy.
Conclusion
The available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in therapeutic response and safety may exist between HTS and mannitol. The use of these agents in these critical clinical situations merits close monitoring for adverse effects. There is a dire need for high-quality research to better inform clinicians of the best options for individualized care of patients with cerebral edema.
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