bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative analysis of in vivo recording with single-cell RNA-seq data reveals molecular properties of light-sensitive neurons in mouse V1
Authors: Liu Jianwei , Wang Mengdi , Sun Le , Pan Na Clara , Zhang Changjiang , Zhang Junjing , Zuo Zhentao , He Sheng , Wu Qian , Wang Xiaoqun
Published: April 2020

Vision formation is classically based on projections from retinal ganglion cells (RGC) to the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Neurons in the mouse V1 are tuned to light stimuli. Although the cellular information of the retina and the LGN has been widely studied, the transcriptome profiles of single light-stimulated neuron in V1 remain unknown. In our study, in vivo calcium imaging and whole-cell electrophysiological patch-clamp recording were utilized to identify 53 individual cells from layer 2/3 of V1 as light-sensitive (LS) or non-light-sensitive (NS) by single-cell light-evoked calcium evaluation and action potential spiking. The contents of each cell after functional tests were aspiratedin vivothrough a patch-clamp pipette for mRNA sequencing. Moreover, the three-dimensional (3-D) morphological characterizations of the neurons were reconstructed in a live mouse after the whole-cell recordings. Our sequencing results indicated that V1 neurons with a high expression of genes related to transmission regulation, such asRtn4randRgs7,and genes involved in membrane transport, such as Na+/K+ATPase and NMDA-type glutamatergic receptors, preferentially responded to light stimulation. Furthermore, an antagonist that blocksRtn4rsignals could inactivate the neuronal responses to light stimulation in live mice. In conclusion, our findings of thevivo-seq analysis indicate the key role of the strength of synaptic transmission possesses neurons in V1 of light sensory.
Tracking bridge tilt behaviour using sensor fusion techniques
Authors: Faulkner Karen , Brownjohn James Mark William , Wang Ying , Huseynov Farhad
Published: April 2020

The resilience of the built environment to extreme weather events is fundamental for the day-to-day operation of our transport network, with scour representing one of the biggest threats to bridges built over flowing water. Condition monitoring of the bridge using a structural health monitoring system enhances resilience by reducing the time needed to return the bridge to normal use by providing timely information on structural condition and safety. The work presented in this report discusses use of rotational measurements in structural health monitoring. Traditionally tiltmeters (which can be a form of DC accelerometer) are used to measure rotation but are known to be affected by dynamic movements, while gyroscopes react quickly to dynamic motion but drift over time. This review will introduce gyroscopes as a complementary sensor for accelerometer rotational measurements and use sensor fusion techniques to combine the measurements from both sensors to get an optimised rotational result. This method was trialled on a laboratory scaled model, before the system was installed on an in-service single-span skewed railway bridge. The rotational measurements were compared against rotation measurements obtained using a vision-based measurement system to confirm the validity of the results. An introduction to gyroscopes, field test measurement results with the sensors and their correlation with the vision-based measurement results are presented in this article.
Total Energy Intake and Self-Selected Macronutrient Distribution During Wildland Fire Suppression
Authors: Marks Alexander N. , Sol Joseph A. , Domitrovich Joseph W. , West Molly R. , Ruby Brent C.
Published: April 2020

Introduction

Wildland firefighters (WLFF) work long hours in extreme environments, resulting in high daily total energy expenditure. Increasing work-shift eating episodes and/or providing rations that promote convenient eating has shown augmented self-selected work output, as has regular carbohydrate (CHO) consumption. It remains unclear how current WLFF feeding strategies compare to more frequent nutrient delivery. Our aim was to determine WLFFs’ self-selected field total energy intake (TEI), composition, and feeding patterns during wildland fire suppression shifts.

Methods

WLFF were deployed to fire incidents across the United States throughout the 2018 fire season. Preshift food inventories collected at basecamp provided item-specific nutrient content (kilocalories, CHO, fat, protein). Work shift consumption (TEI, feeding frequency, episodic composition) was monitored in real time by field researchers on fireline via observational data capture using mobile tablets. Shift work output was also quantified via actigraph accelerometry.

Results

Eighty-six WLFF (27.5±6.4 y; 16 female, 70 male) worked 14.0±1.1 h shifts, with a TEI of 6.3±2.5 MJ (1494±592 kcal) (51±10, 37±9, 13±4% for CHO, fat, and protein, respectively). WLFF averaged 4.3±1.6 eating episodes (1.4±1.3 MJ [345±306 kcal] and 44±38 g CHO·episode-1). WLFF who consumed >20 kcal·kg-1 averaged less sedentary activity than those consuming <16 kcal·kg-1. Data are presented as mean±SD.

Conclusions

Not including fire camp meals (breakfast, dinner), the present work-shift TEI approximates 33% of previously determined WLFF total energy expenditure and demonstrates that current WLFF consumption patterns may not deliver adequate nutrients for occupational demands.
A non-exponential extension of Sanov’s theorem via convex duality
Authors: Lacker Daniel
Published: April 2020

This work is devoted to a vast extension of Sanov’s theorem, in Laplace principle form, based on alternatives to the classical convex dual pair of relative entropy and cumulant generating functional. The abstract results give rise to a number of probabilistic limit theorems and asymptotics. For instance, widely applicable non-exponential large deviation upper bounds are derived for empirical distributions and averages of independent and identically distributed samples under minimal integrability assumptions, notably accommodating heavy-tailed distributions. Other interesting manifestations of the abstract results include new results on the rate of convergence of empirical measures in Wasserstein distance, uniform large deviation bounds, and variational problems involving optimal transport costs, as well as an application to error estimates for approximate solutions of stochastic optimization problems. The proofs build on the Dupuis–Ellis weak convergence approach to large deviations as well as the duality theory for convex risk measures.
The potentially negative effects of cooperation in service systems
Authors: Chung Hakjin , Ahn Hyun-Soo , Righter Rhonda
Published: April 2020

The ‘Price of Anarchy’ states that the performance of multi-agent service systems degrades with the agents’ selfishness (anarchy). We investigate a service model in which both customers and the firm are strategic. We find that, for a Stackelberg game in which the server invests in capacity before customers decide whether or not to join, there can be a ‘Benefit of Anarchy’, that is, customers acting selfishly can have a greater overall utility than customers who are coordinated to maximize their overall utility. We also show that customer anarchy can be socially beneficial, resulting in a ‘Social Benefit of Anarchy’. We show that such phenomena are rather general and can arise in multiple settings (e.g. in both profit-maximizing and welfare-maximizing firms, in both capacity-setting and price-setting firms, and in both observable and unobservable queues). However, the underlying mechanism leading to the Benefit of Anarchy can differ significantly from one setting to another.
Market responses to global governance: International climate cooperation and Europe's carbon trading
Authors: Genovese Federica
Published: April 2020

International environmental cooperation can impose significant costs on private firms. Yet, in recent years some companies have been supportive of international climate agreements. This suggests that under certain conditions environmental accords can be profitable. In this paper, I seek to explain this puzzle by focusing on the interaction between domestic regulation and decisions at international climate negotiations. I argue that global climate cooperation hurts the profits of polluting firms if domestic governments do not shield them from international compliance costs. Vice versa, if firms are subject to protective (i.e., insufficiently severe) policy instruments at home, firms can materially gain from international climate agreements that sustain expectations about their profitability. I test the argument with an event study of the effect of decisions at the UN Framework Convention on Climate Change (UNFCCC) on major European firms that received free carbon permits in the early stages of the European Union Emission Trading Scheme (EU ETS). The analysis suggests that financial markets carefully follow the international climate negotiations, and reward the regulated firms based on the outcome of UNFCCC decisions. The evidence also indicates the advantageous interplay between certain types of domestic regulations and international regimes for business. More generally, the results show the perils of privately supported policy for the effectiveness of international public good provision.
(Un)Covering the COVID-19 Pandemic: Framing Analysis of the Crisis in Canada
Authors: Poirier William , Ouellet Catherine , Rancourt Marc-Antoine , Béchard Justine , Dufresne Yannick
Published: April 2020

The current COVID-19 crisis is unprecedented in recent history. On April 1, 2020, the Secretary-General of the United Nations, Antonio Guterres, warned that the world was facing the most challenging crisis since World War II (Associated Press, 2020). With the pandemic taking on an unprecedented magnitude in the twenty-first century, it quickly monopolized media attention. As of early April, Radar+'s large dataset showed that about 65 per cent of headlines on major Canadian media websites were related to the COVID-19 pandemic.
Overusing the pacifier during infancy sets a footprint on abstract words processing
Authors: BARCA Laura , MAZZUCA Claudia , BORGHI Anna M.
Published: April 2020

Perturbations to the speech articulators induced by frequently using an interfering object during infancy (i.e., pacifier) might shape children's language experience and the building of conceptual representations. Seventy-one typically developing third graders performed a semantic categorization task with abstract, concrete and emotional words. Children who used the pacifier for a more extended period were slower than the others. Moreover, overusing the pacifier increased response time of abstract words, whereas emotional and (above all) concrete words were less affected. Results support the view that abstract words are grounded both in perception-action and in linguistic experience.
Syllable duration changes during babbling: a longitudinal study of French infant productions
Authors: CANAULT Mélanie , YAMAGUCHI Naomi , PAILLEREAU Nikola , KRZONOWSKI Jennifer , ROY Johanna-Pascale , DOS SANTOS Christophe , KERN Sophie
Published: April 2020

At the babbling stage, the syllable does not have the temporal characteristics of adult syllables because of the infant's limited oro-motor skills. This research aims to further our knowledge of syllable duration and temporal variability and their evolution with age as an indicator of the development of articulatory skills. The possible impact of syllable position, as well as that of type of intrasyllabic associations and intersyllabic articulatory changes on these parameters has also been tested. Oral productions of 22 French infants were recorded monthly from 8 to 14 months. 11 261 Consonant-Vowel (CV) syllables were annotated and temporally analyzed. The mean duration varied according to syllable position, but not to the intrasyllabic or intersyllabic articulatory changes. Moreover, the syllable duration decreased significantly from the age of 10 months onwards, whereas the temporal variability remained the same.
Laboratory XANES to study vanadium species in vanadium redox flow batteries
Authors: Lutz Christian , Fittschen Ursula Elisabeth Adriane
Published: April 2020

The speciation of vanadium in the electrolyte of vanadium redox flow batteries (VRFBs) is important to determine the state of charge of the battery. To obtain a better understanding of the transport of the different vanadium species through the separator polymer electrolyte membranes, it is necessary to be able to determine concentration and species of the vanadium ions inside the nanoscopic water body of the membranes. The speciation of V in the electrolyte of VRFBs has been performed by others at the synchrotron by X-ray absorption near-edge structure analysis (XANES). However, the concentrations are quite high and not necessarily justify the use of a large-scale facility. Here, we show that vanadium species in the electrolyte and inside the ionomeric membranes can be determined by laboratory XANES. We were able to determine V species in the 1.6 M electrolyte with a measurement time of 2.3 h and V species having a concentration of 9.8 g kg−1 inside the membranes (178 µm thick) with a measurement time of 5 h. Our results show that laboratory XANES is an appropriate tool to study these kind of samples.
The Diamond I13 full-field transmission X-ray microscope: a Zernike phase-contrast setup for material sciences
Authors: Storm Malte , Döring Florian , Marathe Shashidhara , David Christian , Rau Christoph
Published: April 2020

The I13 transmission X-ray microscope at Diamond Light Source (DLS) has been designed to cover a broad range of energies and field of views. The beamline operates on an undulator source, and a multilayer monochromator can be used to work at a larger bandwidth to enable faster acquisitions. The experimental design includes large working distances for the optics to allow installing in situ sample environments. This paper presents the current state of the experimental system and shows some of the latest results.
An explicit methodology for manufacturing cost–tolerance modeling and optimization using the neural network integrated with the genetic algorithm
Authors: Saravanan A. , Jerald J. , Carolina Rani A. Delphin
Published: April 2020

The objective of the paper is to develop a new method to model the manufacturing cost–tolerance and to optimize the tolerance values along with its manufacturing cost. A cost–tolerance relation has a complex nonlinear correlation among them. The property of a neural network makes it possible to model the complex correlation, and the genetic algorithm (GA) is integrated with the best neural network model to optimize the tolerance values. The proposed method used three types of neural network models (multilayer perceptron, backpropagation network, and radial basis function). These network models were developed separately for prismatic and rotational parts. For the construction of network models, part size and tolerance values were used as input neurons. The reference manufacturing cost was assigned as the output neuron. The qualitative production data set was gathered in a workshop and partitioned into three files for training, testing, and validation, respectively. The architecture of the network model was identified based on the best regression coefficient and the root-mean-square-error value. The best network model was integrated into the GA, and the role of genetic operators was also studied. Finally, two case studies from the literature were demonstrated in order to validate the proposed method. A new methodology based on the neural network model enables the design and process planning engineers to propose an intelligent decision irrespective of their experience.
Managing embryonic and calves losses after twin pregnancies induced by transfer of in vitro-produced Nellore embryos
Authors: Souza Juliano F. , Lubov Rotar , Paiva Clesio J. F. , Tavora Nilda F. C. , Santos Regiane R. , Figueiredo Jose R.
Published: April 2020

Two farms applying reproductive technology for the Nellore beef cattle were selected. Both farms had the same technology programme of oestrous synchronization and embryo transfer, but management was different, especially regarding twins pregnancies. In the present study, we followed the farms from the moment of oestrous synchronization, embryo transfer (two per cow), until delivery and first care of the calves. In farm A, cows presenting twin pregnancies (5 from 13) were submitted to delivery induction, as well as calves and cows were monitored after birth. In farm B, such management was not followed with the twin pregnant cows (31 from 49). In both farms, freemartinism was detected, but this was not a problem as none of the animals would be selected for breeding. No dystocia was observed in farm A, while 48% of the twin pregnancies in farm B ended up in dystocia. Furthermore, the mortality rate of new-born calves in farm A was 10%, while in farm B it reached 32%. Although twin pregnancies remain a concern, we showed here that proper management during and after delivery minimizes animal and economic losses.
Estimating 24-h urinary sodium excretion from casual spot urine specimen among hypertensive patients in Northwest China: the Salt Substitute and Stroke Study
Authors: Zhao Yi , Liu Wanlu , Liu Sha , Li Xiaoxia , Yin Ting , Liu Xiuying , Wang Faxuan , Chang Xiaoyu , Zhang Tianjing , Tian Maoyi , Zhang Yuhong
Published: April 2020

Objective:

To develop an equation that can estimate the 24-h urinary Na excretion by using casual spot urine specimen for older hypertensive participants in rural Ningxia and further to compare with the INTERSALT method, Kawasaki method and Tanaka method.

Design:

Older hypertensive participants in rural Ningxia provided their casual spot urine samples and 24-h urine samples between January 2015 and February 2017. Sex-specific equation was developed using linear forward stepwise regression analysis. Model fit was assessed using adjusted R2. Approximately half of all participants were randomly selected to validate the equation. Mean differences, intraclass correlation coefficients and Bland–Altman plots were used to evaluate the performance of all methods.

Setting:

Pingluo County and Qingtongxia County in Ningxia Hui Autonomous Region, China.

Participants:

Older hypertensive participants in rural Ningxia.

Results:

Totally, 807 of 1120 invited participants provided qualified 24-h urine samples and spot urine samples. There was no statistical difference comparing the laboratory-based method against the new method and the INTERSALT method, while Kawasaki method had the largest bias with a mean difference of 40·81 g/d (95 % CI 39·27, 42·35 g/d). Bland–Altman plots showed similar pattern of the results.

Conclusion:

The INTERSALT method and the new equation have the potential to estimate the 24-h urinary Na excretion in this study population. However, the extrapolation of the results to other population needs to be careful. Future research is required to establish a more reliable method to estimate 24-h urinary Na excretion.
Esketamine clinical trials: reply to Maju et al.
Authors: Gastaldon C. , Papola D. , Ostuzzi G. , Barbui C.
Published: April 2020

Maju et al. provided clarifications on important and controversial issues related to esketamine clinical trial data, in response to a vivid debate triggered by the marketing authorisation recently granted by this new medicine. In this commentary, we reply to their comments attempting to critically discuss the evidence base needed to obtain regulatory approval.
From Bi-Dimensionality to Uni-Dimensionality in Self-Report	Questionnaires
Authors: Schmalbach Bjarne , Zenger Markus , Michaelides Michalis P. , Schermelleh-Engel Karin , Hinz Andreas , Körner Annett , Beutel Manfred E. , Decker Oliver , Kliem Sören , Brähler Elmar
Published: April 2020

Abstract. The common factor model – by far the most widely used model for factor analysis – assumes equal item intercepts across respondents. Due to idiosyncratic ways of understanding and answering items of a questionnaire, this assumption is often violated, leading to an underestimation of model fit. Maydeu-Olivares and Coffman (2006) suggested the introduction of a random intercept into the model to address this concern. The present study applies this method to six established instruments (measuring depression, procrastination, optimism, self-esteem, core self-evaluations, and self-regulation) with ambiguous factor structures, using data from representative general population samples. In testing and comparing three alternative factor models (one-factor model, two-factor model, and one-factor model with a random intercept) and analyzing differential correlational patterns with an external criterion, we empirically demonstrate the random intercept model’s merit, and clarify the factor structure for the above-mentioned questionnaires. In sum, we recommend the random intercept model for cases in which acquiescence is suspected to affect response behavior.
Volatile‐Rich Magmas Distributed Through the Upper Crust in the Main Ethiopian Rift
Authors: Iddon Fiona , Edmonds Marie
Published: April 2020

Understanding magma storage and differentiation in the East African Rift underpins our understanding of volcanism in continental rift settings. Here, we present the geochemistry of melt inclusions erupted in Main Ethiopian Rift transitional basalts, trachytes, and peralkaline rhyolites, produced by fractional crystallization. Basalts stored on‐ and off‐axis are saturated in an exsolved volatile phase at up to 18 km in the upper crust. Much of the CO2 outgassed from the magmas is likely lost through diffuse degassing. Observed CO2 fluxes require the intrusion of up to 0.14 km3 of basalt beneath the rift each year. On‐axis peralkaline rhyolites are stored shallowly, at ~4–8 km depth. In the Daly Gap, magmas saturate in sulfide and an exsolved volatile phase, which promotes magma rise to shallower levels in the crust. Here, magmas undergo further protracted fractional crystallization and degassing, leading to the formation of a substantial exsolved volatile phase, which may accumulate in a gas‐rich cap. The exsolved volatile phase is rich in sulfur and halogens: their projected loadings into the atmosphere during explosive peralkaline eruptions in the MER are predicted to be substantially higher than their metaluminous counterparts in other settings. The high fraction of exsolved volatiles in the stored magmas enhances their compressibility and must be considered when interpreting ground displacements thought to be caused by magma intrusion at depth; otherwise, intruding volumes will be underestimated. Pockets of exsolved volatiles may be present at the roof zones of magma reservoirs, which may be resolvable using geophysical techniques.
Three‐Dimensional Pore Fluid Pressures in Source Region of 2017 Pohang Earthquake Inferred From Earthquake Focal Mechanisms
Authors: Terakawa Toshiko , Seo Wooseok , Kim Kwang‐Hee , Ree Jin‐Han
Published: April 2020

We analyzed 91 focal mechanism data with relocated hypocenters to estimate the 3‐D pore fluid pressure field in the source region of the 2017 Pohang earthquake in South Korea using the method of focal mechanism tomography. The upper limit of pore fluid pressure was 8 ± 3 MPa in a location northwest of the enhanced geothermal system. The overpressurized fluids were localized in the footwall of the causative fault. It was directly connected to the open hole section of PX2, and fluid injection into this hole could have triggered the mainshock.
A Comparison of the Polarimetric Radar Characteristics of Heavy Rainfall From Hurricanes Harvey (2017) and Florence (2018)
Authors: DeHart Jennifer C. , Bell Michael M.
Published: April 2020

Polarimetric coastal radar data are used to compare the rainfall characteristics of Hurricanes Harvey (2017) and Florence (2018). Intense rainfall was an infrequent yet important contributor to the total rainfall in Harvey, but its relative contribution varied spatially. The total rainfall over land maximized near the coast over Beaumont, TX, due to intense convection resulting from prolonged onshore flow downshear from the circulation center. Overall, polarimetric radar observations in Harvey show a dominance of high concentrations of small‐to‐medium drops, consistent with prior tropical cyclone studies. The microphysical characteristics were spatially and temporally inhomogeneous however, with larger drops more frequent on 27 August and higher number concentrations more frequent on 28 and 30 August. The polarimetric variables and raindrop characteristics observed during Florence share broad similarities to Harvey, but had reduced variability, fewer observations of stronger reflectivity and differential reflectivity, and a lower frequency of high number concentrations and medium‐sized drops. The radar data indicate Florence had reduced coverage of stronger convection compared to Harvey. We hypothesize that differences in storm motion, intensity decay rates, and vertical wind shear produce the distinct precipitation structures and microphysical differences seen in Harvey and Florence.
Unraveling the Mysteries of Asymmetric Topography at Gabilan Mesa, California
Authors: Richardson P. W. , Perron J. T. , Miller S. R. , Kirchner J. W.
Published: April 2020

We investigated the potential causes of topographic asymmetry at Gabilan Mesa, CA, a site that exhibits large aspect‐dependent differences in hillslope gradients and microclimates. Competing hypotheses have been proposed to explain the asymmetry observed at Gabilan Mesa. One hypothesis states that different microclimates on opposing slopes are responsible for differences in runoff or soil strength, which generates asymmetric topography. A second hypothesis states that differences in sediment flux from opposing slopes causes southward lateral channel migration and oversteepening of north facing slopes. To test these hypotheses, we carried out numerical modeling experiments, terrain analysis, and field measurements. We also considered the role of initial tilting in causing the asymmetry. We found that saturated hydraulic conductivity is considerably lower on south facing slopes in one highly asymmetric basin. This is consistent with the hypothesis that aspect‐dependent runoff is responsible for the asymmetry. We also used cosmogenic radionuclide‐derived erosion rates and topographic characteristics at Gabilan Mesa to test predictions from numerical landscape evolution models that incorporate asymmetry‐forming mechanisms. The aspect‐dependent models reproduce the erosional and topographic characteristics of Gabilan Mesa better than the lateral channel migration model. We conclude that aspect‐dependent runoff is the most likely explanation for most of the topographic asymmetry at Gabilan Mesa. Our results do not rule out tilting as a possible influence on the initial development of asymmetry nor do they rule out the possibility that lateral channel migration has contributed to the asymmetry, but we suggest that tilting and lateral channel migration are not primarily responsible for it.
A Data Assimilation Framework for Generating Space‐Time Continuous Daily SWOT River Discharge Data Products
Authors: Li Dongyue , Andreadis Konstantinos M. , Margulis Steven A. , Lettenmaier Dennis P.
Published: April 2020

The Surface Water and Ocean Topography (SWOT) satellite will provide global observations of surface water storage and river discharge at an unprecedented high resolution and accuracy after its scheduled launch in 2021, but a limitation of SWOT observations is their spatial and temporal discontinuity associated with the SWOT orbital characteristics. Here, we describe a prototype data assimilation framework to assimilate synthetic SWOT water surface elevation observations into the LISFLOOD‐FP hydrodynamic model to generate a spatially and temporally continuous SWOT discharge data product. We develop the assimilation system with realistic errors in both the SWOT observations and model predictions. During a 3‐year period (consistent with the designed SWOT mission life), the assimilation effectively fills the observation gaps in both time and space across the 5,094‐km Upper Mississippi river network, where SWOT observations provide an average spatial sampling coverage of 55%. The assimilation results in a posterior discharge estimate agree well with the synthetic truth and better capture the peak flows in the significant 1993 flooding in this region; the daily posterior discharge estimates collectively increase the accuracy of the open‐loop (model‐only) discharge estimate by 41%. The posterior estimates show the largest improvement in areas where SWOT has higher sampling frequency and spatial sampling density and where the river has larger volumetric water storage. The accuracy improvement from the assimilation of SWOT data persists well between subsequent observations. Correcting the effects of bathymetric errors on hydrodynamic modeling prior to the assimilation is critical for the assimilation to improve discharge estimates.
Machine Learning Augmented Time‐Lapse Bathymetric Surveys: A Case Study From the Mississippi River Delta Front
Authors: Obelcz Jeffrey , Wood Warren T. , Phrampus Benjamin J. , Lee Taylor R.
Published: April 2020

The subaqueous Mississippi River Delta Front is prone to seabed instabilities >1 m of vertical bathymetric change per year, but the ability to predict the location and magnitude of instability‐driven depth change is limited. Here we demonstrate that data‐driven geospatial models can predict MRDF depth change from a small amount (1% of full coverage) of training data. We predict depth change at 100 m2 resolution between 2005 and 2017 over a ~100 km2 area. Models trained on ~1% of full‐coverage depth change data produce comparable and relatively low average predicted depth change errors (1–2 cm). K‐nearest neighbors best reproduce the spatial variability of depth change and can interpolate and extrapolate from training data. This approach has immediate applications for geohazard monitoring on the MRDF and other geologically similar settings and can be applied in other settings if the drivers of depth change variance are well known.
Thank You to Our 2019 Reviewers
Authors: Clark Martyn , Bahr Jean , Bierkens Marc F. P. , Hall Jim , Kollet Stefan , Luce Charles H. , Lundquist Jessica , Mackay D. Scott , van Meerveld Ilja , Sanchez‐Vila Xavier , Troch Peter A. , Wohl Ellen
Published: April 2020

The editors of Water Resources Research (WRR) express their appreciation to the reviewers of articles submitted to the journal in 2019. We are proud of the rigorous WRR review process, where reviewers habitually go out of their way to improve the caliber and impact of WRR papers. Of the 2,640 reviewers listed below for the 2,034 new papers and 1,129 revised papers submitted to the journal, 398 people reviewed three or more papers. On behalf of the journal and the authors, we thank all reviewers for their service and dedication to the scientific community. We look forward to the exciting advances that will be published in WRR in 2020.
Stearoyl-CoA-desaturase-1 regulates gastric cancer stem-like properties and promotes tumour metastasis via Hippo/YAP pathway
Authors: Gao Yunhe , Li Jiyang , Xi Hongqing , Cui Jianxin , Zhang Kecheng , Zhang Jiabing , Zhang Yanmei , Xu Wei , Liang Wenquan , Zhuang Ziwei , Wang Pengpeng , Qiao Zhi , Wei Bo , Chen Lin
Published: April 2020

Background

Stearoyl-CoA desaturase-1 (SCD1) is reported to play essential roles in cancer stemness among several cancers. Our previous research revealed significant overexpression of SCD1 in primary gastric cancer stem cells (GCSCs), with its functional role still unknown.

Methods

We stably established three primary GCSCs by sphere-forming assays and flow cytometry. Protein quantification and bioinformatics analysis were performed to reveal the differential protein pattern. Lentivirus-based small-interfering RNA (siRNA) knockdown and pharmacological inhibition approaches were used to characterise the function and molecular mechanism role of SCD1 in the regulation of GC stemness and tumour metastasis capacity both in vitro and in vivo.

Results

SCD1 was found to increase the population of GCSCs, whereas its suppression by an SCD1 inhibitor or knockdown by siRNA attenuated the stemness of GCSCs, including chemotherapy resistance and sphere-forming ability. Furthermore, SCD1 suppression reversed epithelial-to-mesenchymal transition and reduced the GC metastasis probability both in vitro and in vivo. Downregulation of SCD1 in GCSCs was associated with the expression of Yes-associated protein (YAP), a key protein in the Hippo pathway, and nuclear YAP translocation was also blocked by the SCD1 decrease.

Conclusions

SCD1 promotes GCSC stemness through the Hippo/YAP pathway. Targeting SCD1 might be a novel therapeutic strategy, especially to suppress GC metastasis and sensitise chemotherapy.
Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma
Authors: Corrie P. G. , Qian W. , Basu B. , Valle J. W. , Falk S. , lwuji C. , Wasan H. , Palmer D. , Scott-Brown M. , Wadsley J. , Arif S. , Bridgewater J. , Propper D. , Gillmore R. , Gopinathan A. , Skells R. , Bundi P. , Brais R. , Dalchau K. , Bax L. , Chhabra A. , Machin A. , Dayim A. , McAdam K. , Cummins S. , Wall L. , Ellis R. , Anthoney A. , Evans J. , Ma Y. T. , Isherwood C. , Neesse A. , Tuveson D. , Jodrell D. I.
Published: April 2020

Background

Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial.

Methods

Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers.

Results

In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47–0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65–1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13–0.70).

Conclusions

SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS.

Clinical trial registration

ISRCTN71070888; ClinialTrials.gov (NCT03529175).
A live cell reporter of exosome secretion and uptake reveals pathfinding behavior of migrating cells
Authors: Sung Bong Hwan , von Lersner Ariana , Guerrero Jorge , Krystofiak Evan S. , Inman David , Pelletier Roxanne , Zijlstra Andries , Ponik Suzanne M. , Weaver Alissa M.
Published: April 2020

Small extracellular vesicles called exosomes affect multiple autocrine and paracrine cellular phenotypes. Understanding the function of exosomes requires a variety of tools, including live imaging. Our previous live-cell reporter, pHluorin-CD63, allows dynamic subcellular monitoring of exosome secretion in migrating and spreading cells. However, dim fluorescence and the inability to make stably-expressing cell lines limit its use. We incorporated a stabilizing mutation in the pHluorin moiety, M153R, which now exhibits higher, stable expression in cells and superior monitoring of exosome secretion. Using this improved construct, we visualize secreted exosomes in 3D culture and in vivo and identify a role for exosomes in promoting leader–follower behavior in 2D and 3D migration. Incorporating an additional non-pH-sensitive red fluorescent tag allows visualization of the exosome lifecycle, including multivesicular body (MVB) trafficking, MVB fusion, exosome uptake and endosome acidification. This reporter will be a useful tool for understanding both autocrine and paracrine roles of exosomes.
MALT-1 mediates IL-17 neural signaling to regulate C. elegans behavior, immunity and longevity
Authors: Flynn Sean M. , Chen Changchun , Artan Murat , Barratt Stephen , Crisp Alastair , Nelson Geoffrey M. , Peak-Chew Sew-Yeu , Begum Farida , Skehel Mark , de Bono Mario
Published: April 2020

Besides pro-inflammatory roles, the ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate IL-17 signaling in neurons, and the extent it can alter organismal phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C. elegans neurons. We identify the paracaspase MALT-1 as a critical output of the pathway. MALT1 mediates signaling from many immune receptors in mammals, but was not previously implicated in IL-17 signaling or nervous system function. C. elegans MALT-1 forms a complex with homologs of Act1 and IRAK and appears to function both as a scaffold and a protease. MALT-1 is expressed broadly in the C. elegans nervous system, and neuronal IL-17–MALT-1 signaling regulates multiple phenotypes, including escape behavior, associative learning, immunity and longevity. Our data suggest MALT1 has an ancient role modulating neural circuit function downstream of IL-17 to remodel physiology and behavior.
Multi-model functionalization of disease-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction
Authors: Post Kathryn L. , Belmadani Manuel , Ganguly Payel , Meili Fabian , Dingwall Riki , McDiarmid Troy A. , Meyers Warren M. , Herrington Caitlin , Young Barry P. , Callaghan Daniel B. , Rogic Sanja , Edwards Matthew , Niciforovic Ana , Cau Alessandro , Rankin Catharine H. , O’Connor Timothy P. , Bamji Shernaz X. , Loewen Christopher J. R. , Allan Douglas W. , Pavlidis Paul , Haas Kurt
Published: April 2020

Functional variomics provides the foundation for personalized medicine by linking genetic variation to disease expression, outcome and treatment, yet its utility is dependent on appropriate assays to evaluate mutation impact on protein function. To fully assess the effects of 106 missense and nonsense variants of PTEN associated with autism spectrum disorder, somatic cancer and PTEN hamartoma syndrome (PHTS), we take a deep phenotypic profiling approach using 18 assays in 5 model systems spanning diverse cellular environments ranging from molecular function to neuronal morphogenesis and behavior. Variants inducing instability occur across the protein, resulting in partial-to-complete loss-of-function (LoF), which is well correlated across models. However, assays are selectively sensitive to variants located in substrate binding and catalytic domains, which exhibit complete LoF or dominant negativity independent of effects on stability. Our results indicate that full characterization of variant impact requires assays sensitive to instability and a range of protein functions.
Non-Invasive MRI of Blood–Cerebrospinal Fluid Barrier Function
Authors: Evans P. G. , Sokolska M. , Alves A. , Harrison I. F. , Ohene Y. , Nahavandi P. , Ismail O. , Miranda E. , Lythgoe M. F. , Thomas D. L. , Wells J. A.
Published: April 2020

The blood–cerebrospinal fluid barrier (BCSFB) is a highly dynamic transport interface that serves brain homeostasis. To date, however, understanding of its role in brain development and pathology has been hindered by the absence of a non-invasive technique for functional assessment. Here we describe a method for non-invasive measurement of BSCFB function by using tracer-free MRI to quantify rates of water delivery from arterial blood to ventricular cerebrospinal fluid. Using this method, we record a 36% decrease in BCSFB function in aged mice, compared to a 13% decrease in parenchymal blood flow, itself a leading candidate biomarker of early neurodegenerative processes. We then apply the method to explore the relationship between BCSFB function and ventricular morphology. Finally, we provide proof of application to the human brain. Our findings position the BCSFB as a promising new diagnostic and therapeutic target, the function of which can now be safely quantified using non-invasive MRI.
LSD1-mediated enhancer silencing attenuates retinoic acid signalling during pancreatic endocrine cell development
Authors: Vinckier Nicholas K. , Patel Nisha A. , Geusz Ryan J. , Wang Allen , Wang Jinzhao , Matta Ileana , Harrington Austin R. , Wortham Matthew , Wetton Nichole , Wang Jianxun , Jhala Ulupi S. , Rosenfeld Michael G. , Benner Christopher W. , Shih Hung-Ping , Sander Maike
Published: April 2020

Developmental progression depends on temporally defined changes in gene expression mediated by transient exposure of lineage intermediates to signals in the progenitor niche. To determine whether cell-intrinsic epigenetic mechanisms contribute to signal-induced transcriptional responses, here we manipulate the signalling environment and activity of the histone demethylase LSD1 during differentiation of hESC-gut tube intermediates into pancreatic endocrine cells. We identify a transient requirement for LSD1 in endocrine cell differentiation spanning a short time-window early in pancreas development, a phenotype we reproduced in mice. Examination of enhancer and transcriptome landscapes revealed that LSD1 silences transiently active retinoic acid (RA)-induced enhancers and their target genes. Furthermore, prolonged RA exposure phenocopies LSD1 inhibition, suggesting that LSD1 regulates endocrine cell differentiation by limiting the duration of RA signalling. Our findings identify LSD1-mediated enhancer silencing as a cell-intrinsic epigenetic feedback mechanism by which the duration of the transcriptional response to a developmental signal is limited.
Goteo.org civic crowdfunding and match-funding data connecting Sustainable Development Goals
Authors: Fuster Morell Mayo , Senabre Hidalgo Enric , Rodríguez Enrique
Published: April 2020

The United Nations’ Sustainable Development Goals (SDGs) highlight priority areas for global sustainable development, such as reducing inequalities and protecting the environment. Digital platforms, such as Goteo.org, facilitate financial support from individuals for SDG-related initiatives through crowdfunding and match-funding campaigns. Match-funding is a type of crowdfunding, where individual donations are matched or multiplied by public and private organizations. There remains a lack of open data, however, to study the effectiveness of match-funding as a way to finance these civic initiatives. The Goteo.org platform’s approach to data transparency and open source principles have allowed these data to be collected, and here we present a dataset for 487 civic crowdfunding campaigns. This dataset presents a unique opportunity to compare the behaviour of different crowdfunding modalities in parallel with the SDGs.
Differential Impact of Sleep Deprivation and Circadian Timing on Reflexive Versus Inhibitory Control of Attention
Authors: Collet Jinny , Ftouni Suzanne , Clough Meaghan , Cain Sean W. , Fielding Joanne , Anderson Clare
Published: April 2020

In a visually stimulating environment with competing stimuli, we continually choose where to allocate attention, and what to ignore. Wake and circadian-dependent modulation of attentional control and resolution of conflict is poorly understood. Twenty-two participants (17males; 25.6 ± 5.6 years) completed ocular motor tasks throughout 40 hours of sleep deprivation under constant routine conditions. A prosaccade task required a reflexive saccade toward a stimulus (no conflict), while an antisaccade task required inhibiting a reflexive saccade to the peripheral stimulus, and looking in the mirror opposite instead (conflict resolution). Antisaccade inhibitory errors showed circadian modulation, being highest in the morning, progressively decreasing until melatonin onset, before returning to the prior morning’s peak throughout the biological night. This diurnal rhythm was blunted by sleep loss (>24 hours), with inhibitory control remaining impaired across the second biological day. For prosaccade, responses slowed down during the biological night. Taken together, we provide evidence for a circadian modulation of attentional bias: the morning being biased toward reflexive responding, and the evening toward higher inhibitory control. Our data show that sleep loss and circadian timing differentially impact attention, depending on whether a response conflict is present (antisaccade) or absent (prosaccade).
Airborne Optical Sectioning for Nesting Observation
Authors: Schedl David C. , Kurmi Indrajit , Bimber Oliver
Published: April 2020

We describe how a new and low-cost aerial scanning technique, airborne optical sectioning (AOS), can support ornithologists in nesting observation. After capturing thermal and color images during a seven minutes drone flight over a 40 × 12 m patch of the nesting site of Austria’s largest heron population, a total of 65 herons and 27 nests could be identified, classified, and localized in a sparse 3D reconstruction of the forest. AOS is a synthetic aperture imaging technique that removes occlusion caused by leaves and branches. It registers recorded images to a common 3D coordinate system to support the reconstruction and analysis of the entire forest volume, which is impossible with conventional 2D or 3D imaging techniques. The recorded data is published with open access.
Gamma-Ray and Radio-Frequency Radiation from Thunderstorms Observed from Space and Ground
Authors: Mailyan B. G. , Nag A. , Dwyer J. R. , Said R. K. , Briggs M. S. , Roberts O. J. , Stanbro M. , Rassoul H. K.
Published: April 2020

Terrestrial gamma ray flashes (TGFs) are a class of enigmatic electrical discharges in the Earth’s atmosphere. In this study, we analyze an unprecedentedly large dataset comprised of 2188 TGFs whose signatures were simultaneously measured using space- and ground-based detectors over a five-year period. The Gamma-ray Burst Monitor (GBM) on board the Fermi spacecraft provided the energetic radiation measurements. Radio frequency (RF) measurements were obtained from the Global Lightning Dataset (GLD360). Here we show the existence of two categories of TGFs − those that were accompanied by quasi-simultaneous electromagnetic pulses (EMPs) detected by the GLD360 and those without such simultaneous EMPs. We examined, for the first time, the dependence of the TGF-associated EMP-peak-amplitude on the horizontal offset distance between the Fermi spacecraft and the TGF source. TGFs detected by the GBM with sources at farther horizontal distances are expected to be intrinsically brighter and were found to be associated with EMPs having larger median peak-amplitudes. This provides independent evidence that the EMPs and TGFs are produced by the same phenomenon, rather than the EMPs being from “regular” lightning in TGF-producing thunderstorms.