In highly‐productive agricultural areas such as California's Central Valley, where groundwater often supplies the bulk of the water required for irrigation, quantifying rates of groundwater depletion ...remains a challenge owing to a lack of monitoring infrastructure and the absence of water use reporting requirements. Here we use 78 months (October, 2003–March, 2010) of data from the Gravity Recovery and Climate Experiment satellite mission to estimate water storage changes in California's Sacramento and San Joaquin River Basins. We find that the basins are losing water at a rate of 31.0 ± 2.7 mm yr−1 equivalent water height, equal to a volume of 30.9 km3 for the study period, or nearly the capacity of Lake Mead, the largest reservoir in the United States. We use additional observations and hydrological model information to determine that the majority of these losses are due to groundwater depletion in the Central Valley. Our results show that the Central Valley lost 20.4 ± 3.9 mm yr−1 of groundwater during the 78‐month period, or 20.3 km3 in volume. Continued groundwater depletion at this rate may well be unsustainable, with potentially dire consequences for the economic and food security of the United States.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The Klebsiella pneumoniae carbapenem (KPC) β-lactamase occurs in Enterobacteriaceae and can confer resistance to all β-lactam agents including carbapenems. The enzyme may confer low-level carbapenem ...resistance, and the failure of susceptibility methods to identify this resistance has been reported. Automated and nonautomated methods for carbapenem susceptibility were evaluated for identification of KPC-mediated resistance. Ertapenem was a more sensitive indicator of KPC resistance than meropenem and imipenem independently of the method used. Carbapenemase production could be confirmed with the modified Hodge test.
Before the invention of electric lighting, humans were primarily exposed to intense (>300 lux) or dim (<30 lux) environmental light—stimuli at extreme ends of the circadian system’s dose–response ...curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30–300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting. We characterized individual-level dose–response curves to light-induced melatonin suppression using a within-subjects protocol. Fifty-five participants (aged 18–30) were exposed to a dim control (<1 lux) and a range of experimental light levels (10–2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED50) was computed at individual and group levels. The group-level fitted ED50 was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED50 values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock’s role in human health and disease.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Uncertainty and affect are fundamental and interrelated aspects of the human condition. Uncertainty is often associated with negative affect, but in some circumstances, it is associated with positive ...affect. In this article, we review different explanations for the varying relationship between uncertainty and affect. We identify “mental simulation” as a key process that links uncertainty to affective states. We suggest that people have a propensity to simulate negative outcomes, which result in a propensity toward negative affective responses to uncertainty. We also propose the existence of several important moderators of this process, including context and individual differences such as uncertainty tolerance, as well as emotion regulation strategies. Finally, we highlight important knowledge gaps and promising areas for future research, both empirical and conceptual, to further elucidate the relationship between uncertainty and affect.
DNA-based gene therapy has considerable therapeutic potential, but the challenges associated with delivery continue to limit progress. Messenger RNA (mRNA) has the potential to provide for transient ...production of therapeutic proteins, without the need for nuclear delivery and without the risk of insertional mutagenesis. Here we describe the sustained delivery of therapeutic proteins in vivo in both rodents and non-human primates via nanoparticle-formulated mRNA. Nanoparticles formulated with lipids and lipid-like materials were developed for delivery of two separate mRNA transcripts encoding either human erythropoietin (hEPO) or factor IX (hFIX) protein. Dose-dependent protein production was observed for each mRNA construct. Upon delivery of hEPO mRNA in mice, serum EPO protein levels reached several orders of magnitude (>125 000-fold) over normal physiological values. Further, an increase in hematocrit (Hct) was established, demonstrating that the exogenous mRNA-derived protein maintained normal activity. The capacity of producing EPO in non-human primates via delivery of formulated mRNA was also demonstrated as elevated EPO protein levels were observed over a 72-h time course. Exemplifying the possible broad utility of mRNA drugs, therapeutically relevant amounts of human FIX (hFIX) protein were achieved upon a single intravenous dose of hFIX mRNA-loaded lipid nanoparticles in mice. In addition, therapeutic value was established within a hemophilia B (FIX knockout (KO)) mouse model by demonstrating a marked reduction in Hct loss following injury (incision) to FIX KO mice.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Patients with deep brain stimulation (DBS) implants may be subject to heating during MRI due to interaction with excitatory radiofrequency (RF) fields. Parallel RF transmit (pTx) has been proposed to ...minimize such RF-induced heating in preliminary proof-of-concept studies. The present work evaluates the efficacy of pTx technique on realistic lead trajectories obtained from nine DBS patients. Electromagnetic simulations were performed using 4- and 8-element pTx coils compared with a standard birdcage coil excitation using patient models and lead trajectories obtained by segmentation of computed tomography data. Numerical optimization was performed to minimize local specific absorption rate (SAR) surrounding the implant tip while maintaining spatial homogeneity of the transmitted RF magnetic field (B
), by varying the input amplitude and phase for each coil element. Local SAR was significantly reduced at the lead tip with both 4-element and 8-element pTx (median decrease of 94% and 97%, respectively), whereas the median coefficient of spatial variation of B
inhomogeneity was moderately increased (30% for 4-element pTx and 20% for 8-element pTx) compared to that of the birdcage coil (17%). Furthermore, the efficacy of optimized 4-element pTx was verified experimentally by imaging a head phantom that included a wire implanted to approximate the worst-case lead trajectory for localized heating, based on the simulations. Negligible temperature elevation was observed at the lead tip, with reasonable image uniformity in the surrounding region. From this experiment and the simulations based on nine DBS patient models, optimized pTx provides a robust approach to minimizing local SAR with respect to lead trajectory.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Large thermospheric neutral density enhancements in the cusp region have been examined for many years. The Challenging Minisatellite Payload (CHAMP) satellite for example has enabled many ...observations of the perturbation, showing that it is mesoscale in size and exists statistically over solar cycle timescales. Further studies examining the relationship with magnetospheric energy input have shown that fine‐scale Poynting fluxes are associated with the density perturbations on a case‐by‐case basis, whilst others have found that mesoscale downward fluxes also exist in the cusp region statistically. In this study, we use nearly 8 years of the overlapping Super Dual Auroral Radar Network and Active Magnetosphere and Planetary Electrodynamics Response Experiment datasets to generate global‐scale patterns of the high‐latitude and height‐integrated Poynting flux into the ionosphere, with a time resolution of 2 min. From these, average patterns are generated based on the interplanetary magnetic field orientation. We show the cusp is indeed an important feature in the Poynting flux maps, but the magnitude does not correlate well with statistical neutral mass density perturbations observed by the CHAMP satellite on similar spatial scales. Importantly, the lack of correlation between mesoscale height‐integrated Poynting fluxes and the cusp neutral mass density enhancement gives possible insight into other processes that may account for the discrepancy, such as energy deposition at finer scale sizes or at higher altitudes than captured.
Key Points
Statistical patterns of the total downward Poynting flux into the atmosphere have been derived using Super Dual Auroral Radar Network and Active Magnetosphere and Planetary Electrodynamics Response Experiment data
Statistical patterns of neutral mass density perturbations as a percentage of the background density have been derived using Challenging Minisatellite Payload data
Mesoscale downward Poynting flux in the cusp region do not correlate very well with neutral mass density enhancements at a similar scale
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Zonal flow appears in toroidal, magnetically confined plasmas as part of the self-regulated interaction of turbulence and transport processes. For toroidal plasmas having a strong toroidal magnetic ...field, the zonal flow is predominately poloidally directed. This Letter reports the first observation of a zonal flow that is toroidally directed. The measurements are made just inside the last closed flux surface of reversed field pinch plasmas that have a dominant poloidal magnetic field. A limit cycle oscillation between the strength of the zonal flow and the amplitude of plasma potential fluctuations is observed, which provides evidence for the self-regulation characteristic of drift-wave-type plasma turbulence. The measurements help advance understanding and gyrokinetic modeling of toroidal plasmas in the pursuit of fusion energy.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Evidence that glial cells influence behavior has been gaining a steady foothold in scientific literature. Out of the five main subtypes of glial cells in the brain, astrocytes and microglia have ...received an outsized share of attention with regard to shaping a wide spectrum of behavioral phenomena and there is growing appreciation that the signals intrinsic to these cells as well as their interactions with surrounding neurons reflect behavioral history in a brain region-specific manner. Considerable regional diversity of glial cell phenotypes is beginning to be recognized and may contribute to behavioral outcomes arising from circuit-specific computations within and across discrete brain nuclei. Here, we summarize current knowledge on the impact of astrocyte and microglia activity on behavioral outcomes, with a specific focus on brain areas relevant to higher cognitive control, reward-seeking, and circadian regulation.
•Astrocytes and microglia display diverse properties across brain regions.•Synaptic and neuronal circuit activity are highly sensitive to astrocyte and microglial signals.•Higher cognitive function, circadian and reward behaviors rely on structurally and functionally dynamic glial cell responses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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