bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating Water Management Instruments to Reconcile a Hydro‐Economic Water Allocation Strategy With Other Water Preferences
Authors: Dalcin Ana Paula , Fernandes Marques Guilherme 
Published: April 2020

AbstractIncreasing scarcity and pollution has called for changes in water policies, which should reflect society's preferences toward water use, development, and the environment. Water management is still limited in incorporating changing policies and in deriving directives to implement water instruments under long‐term planning. Some examples are water charges that do not reflect watershed externalities and water permits lacking future vision of allocation. Hydro‐economic modeling has explored trade‐offs of water allocation and improved water operations but still does not address instruments' integration. This paper proposes a modeling approach that identifies how to apply water management instruments integrated with each other to deliver a water allocation strategy reconciled with economic development projections and changing water use preferences. This improves our understanding on adjusting the implementation of water management instruments considering future outcomes and trade‐offs. The methodology combines discrete dynamic programming to determine increments in water permits, multiobjective linear programming to generate a Pareto set to model users' water preferences, and nonlinear programming to allocate water permits over different river reaches subject to water quality targets. The reconciliation allowed to identify sustainable water allocation strategies supported by a watershed, and instruments' integration to make it feasible. Strategies imposing limited water permits to economic users and watershed regions indicated where (and when) water conservation programs should be applied, along with quantitative targets (how much). The economic trade‐offs identified reference values for economic instruments to compensate the externalities. Finally, less strict water quality targets did not result in higher economic returns.
Measuring and Modeling Gravel Transport at Caspar Creek, CA, to Detect Changes in Sediment Supply, Storage, and Transport Efficiency
Authors: Richardson P. W. , Wagenbrenner J. W. , Sutherland D. G. , Lisle T. E. 
Published: April 2020

AbstractWe developed a technique for reconstructing annual gravel yields and generated a 55‐year record of gravel transport for the North Fork catchment of the Caspar Creek Experimental Watersheds in Northern California. The technique relies on field data collection including annual surveys of weir pond volumes and suspended sediment measurements, as well as an accounting for settling of suspended sediment and organic matter in the pond. We compared these annual yields to gravel yields predicted by the Wilcock two‐fraction bed load transport model, which we calibrated from measured values at Caspar Creek. We considered three velocity‐discharge relationships and found that values of hydraulic variables measured during storms produced the best fit between reconstructed and predicted annual gravel yields when years with large disturbances were excluded. We also compared predicted gravel transport rates to bed load transport rates measured from 1988 to 1995 with bed load pit samplers. We found that the calibrated model predictions agreed well with the field‐measured bed load transport rates. To investigate the role of supply and storage on gravel transport, we compared the reconstructed gravel yields to predicted gravel yields and found that increased occurrence of landslides and headcut erosion in the 1990s and early 2000s did not lead to an increase in gravel yields. Instead, input of large downed wood in the 1990s created storage space and decreased bed load delivery to the weir pond.
Preferential Flow Enhances Pumping‐Induced Saltwater Intrusion in Volcanic Aquifers
Authors: Geng Xiaolong , Michael Holly A. 
Published: April 2020

AbstractPreferential flow can result in rapid contamination of groundwater resources. This is particularly true in aquifers with connected, high permeability geologic structures and in coastal systems where the oceanic source of contamination is ubiquitous. We consider saltwater intrusion due to pumping in volcanic aquifers with lava tubes represented as connected high‐K structures and compare salinization responses to those of heterogeneous aquifers with different structure and equivalent homogeneous systems. Three‐dimensional simulations of variable‐density groundwater flow and salt transport show that conduits formed by lava flows create preferential groundwater flow in volcanic aquifers. These conduits allow fresh groundwater to extend further offshore than in other systems. However, onshore pumping causes saltwater to migrate landward quickly through the conduits relative to the other models, resulting in more severe saltwater intrusion, particularly at shallow depths. The geometry of geologic heterogeneity in volcanic aquifers leads to increased risk of salinization of fresh groundwater as well as substantial uncertainty due to significant spatial variation in saltwater intrusion. The findings illustrate the importance of considering geologic heterogeneity in assessing the vulnerability of coastal freshwater resources in volcanic and other aquifers with connected high‐permeability geologic structures.
Evaluation of Cloud Microphysical Properties Derived From MODIS and Himawari‐8 Using In Situ Aircraft Measurements Over the Southern Ocean
Authors: Zhao Lijun , Zhao Chuanfeng , Wang Yang , Wang Yuan , Yang Yikun 
Published: April 2020

AbstractCloud microphysical properties from aircraft measurements during the Southern Ocean Clouds, Radiation, Aerosol Transport Experimental Study are used to evaluate the cloud products from the geostationary satellite Himawari‐8 (H‐8) and the polar‐orbiting satellite the Moderate Resolution Imaging Spectroradiometer (MODIS). Compared to the in situ aircraft observations when aircraft flew horizontally near cloud tops, the cloud droplet effective radius (re) and number concentration (Nd) from H‐8 (MODIS) are 33% (26%–31%) and 2% (9–13%) larger. Both the H‐8 and MODIS retrievals behave similarly for liquid‐only and mixed‐phase low‐level clouds, indicating the weak sensitivity of the satellite cloud retrieval performance to cloud phase. The re and Nd of the cloud profiles from aircraft measurements were also used to compare with the satellite product. It shows that H‐8 re and Nd agree better with aircraft measurements when considering only the in situ data acquired in the upper portions (highest 20%) of the clouds. Roughly, the re overestimation by H‐8 decreases from 18% to 3% when considering the upper portions of clouds compared to all cloud layer averages, except for one case with drizzles appeared. In addition, the performance of MODIS re and Nd is highly dependent on the wavelengths the retrieval method uses. The droplet re retrievals using wavelength of 1.6 μm have much larger biases than that using the other two channels. The potential effects of the cloud vertical variation and the photon penetration depth, the cloud heterogeneity, the cloud droplet size spectra, and the drizzle on satellite retrievals have also been discussed.
Evidence Is Growing That Alternative Stable States in Semiarid Grasslands Are the Exception, Not the Rule
Authors: Kleinhesselink Andrew 
Published: April 2020

AbstractWoody shrubs have increased in abundance in arid and semiarid grasslands around the globe. This can have negative consequences for communities dependent on grasses for grazing and other ecosystem services. A study by Zheng et al. (2020, https://doi.org/10.1029/2019JG005439) shows that grasslands in Inner Mongolia, China, which have long been invaded by shrubs, may naturally return to a grass‐dominated state when grazing is eliminated. This result emphasizes the primary importance of grazing in driving vegetation change in grasslands and argues against the existence of critical thresholds and alternative stable states in semiarid ecosystems.
Dysregulation of the EphrinB2−EphB4 ratio in pediatric cerebral arteriovenous malformations is associated with endothelial cell dysfunction in vitro and functions as a novel noninvasive biomarker in patients
Authors: Fehnel Katie Pricola , Penn David L. , Duggins-Warf Micah , Gruber Maxwell , Pineda Steven , Sesen Julie , Moses-Gardner Alexander , Shah Nishali , Driscoll Jessica , Zurakowski David , Orbach Darren B. , Smith Edward R. 
Published: April 2020

AbstractWe investigated (1) EphrinB2 and EphB4 receptor expression in cerebral AVMs, (2) the impact of an altered EphrinB2:EphB4 ratio on brain endothelial cell function and (3) potential translational applications of these data. The following parameters were compared between AVM endothelial cells (AVMECs) and human brain microvascular endothelial cells (HBMVECs): quantified EphrinB2 and EphB4 expression, angiogenic potential, and responses to manipulation of the EphrinB2:EphB4 ratio via pharmacologic stimulation/inhibition. To investigate the clinical relevance of these in vitro data, Ephrin expression was assessed in AVM tissue (by immunohistochemistry) and urine (by ELISA) from pediatric patients with AVM (n = 30), other cerebrovascular disease (n = 14) and control patients (n = 29), and the data were subjected to univariate and multivariate statistical analyses. Compared to HBMVECs, AVMECs demonstrated increased invasion (p = 0.04) and migration (p = 0.08), impaired tube formation (p = 0.06) and increased EphrinB2:EphB4 ratios. Altering the EphrinB2:EphB4 ratio (by increasing EphrinB2 or blocking EphB4) in HBMVECs increased invasion (p = 0.03 andp < 0.05, respectively). EphrinB2 expression was increased in AVM tissue, which correlated with increased urinary EphrinB2 levels in AVM patients. Using the optimal urinary cutoff value (EphrinB2 > 25.7 pg/μg), AVMs were detected with high accuracy (80% vs. controls) and were distinguished from other cerebrovascular disease (75% accuracy). Post-treatment urinary EphrinB2 levels normalized in an index patient. In summary, AVMECs have an EphrinB2:EphB4 ratio that is increased compared to that of normal HBMVECs. Changing this ratio in HBMVECs induces AVMEC-like behavior. EphrinB2 is clinically relevant, and its levels are increased in AVM tissue and patient urine. This work suggests that dysregulation of the EphrinB2:EphB4 signaling cascade and increases in EphrinB2 may play a role in AVM development, with potential utility as a diagnostic and therapeutic target.
Towards visible-wavelength passively mode-locked lasers in all-fibre format
Authors: Zou Jinhai , Dong Chuchu , Wang Hongjian , Du Tuanjie , Luo Zhengqian 
Published: April 2020

AbstractMode-locked fibre lasers (MLFLs) are fundamental building blocks of many photonic systems used in industrial, scientific and biomedical applications. To date, 1–2 μm MLFLs have been well developed; however, passively mode-locked fibre lasers in the visible region (380–760 nm) have never been reported. Here, we address this challenge by demonstrating an all-fibre visible-wavelength passively mode-locked picosecond laser at 635 nm. The 635 nm mode-locked laser with an all-fibre figure-eight cavity uses a Pr/Yb codoped ZBLAN fibre as the visible gain medium and a nonlinear amplifying loop mirror as the mode-locking element. First, we theoretically predict and analyse the formation and evolution of 635 nm mode-locked pulses in the dissipative soliton resonance (DSR) regime by solving the Ginzburg-Landau equation. Then, we experimentally demonstrate the stable generation of 635 nm DSR mode-locked pulses with a pulse duration as short as ~96 ps, a radio-frequency signal-to-noise ratio of 67 dB and a narrow spectral bandwidth of <0.1 nm. The experimental results are in excellent agreement with our numerical simulations. In addition, we also observe 635 nm noise-like pulse operation with a wide (>1 nm) and modulated optical spectrum. This work represents an important step towards miniaturized ultrafast fibre lasers in the visible spectral region.
Characterization of viruses in a tapeworm: phylogenetic position, vertical transmission, and transmission to the parasitized host
Authors: Hahn Megan A , Rosario Karyna , Lucas Pierrick , Dheilly Nolwenn M 
Published: April 2020

Abstract
Parasitic flatworms (Neodermata) infect all vertebrates and represent a significant health and economic burden worldwide due to the debilitating diseases they cause. This study sheds light for the first time into the virome of a tapeworm by describing six novel RNA virus candidate species associated with Schistocephalus solidus, including three negative-strand RNA viruses (order Jingchuvirales, Mononegavirales, and Bunyavirales) and three double-stranded RNA viruses. Using in vitro culture of S. solidus, controlled experimental infections and field sampling, we demonstrate that five of these viruses are vertically transmitted, and persist throughout the S. solidus complex life cycle. Moreover, we show that one of the viruses, named Schistocephalus solidus rhabdovirus (SsRV1), is excreted by the parasite and transmitted to parasitized hosts indicating that it may impact S. solidus–host interactions. In addition, SsRV1 has a basal phylogenetic position relative to vertebrate rhabdoviruses suggesting that parasitic flatworms could have contributed to virus emergence. Viruses similar to four of the S. solidus viruses identified here were found in geographically distant S. solidus populations through data mining. Further studies are necessary to determine if flatworm viruses can replicate in parasitized hosts, how they contribute to parasite infection dynamics and if these viruses could be targeted for treatment of parasitic disease.
Transcriptome signatures from discordant sibling pairs reveal changes in peripheral blood immune cell composition in Autism Spectrum Disorder
Authors: Filosi Michele , Kam-Thong Tony , Essioux Laurent , Muglia Pierandrea , Trabetti Elisabetta , Spooren Will , Müller-Myshok Bertram ,   Italian Autism Network, Alibrio Giovanni , Anchisi Laura , Andruccioli Milena , Benvenuto Arianna , Battistella Pier Antonio , Boscaini Flavio , Bravaccio Carmela , Ceppi Elisa , Cosentino Diego , Curatolo Paolo , Da Ros Lucio , Bernardina Bernardo Dalla , De Giacomo Andrea , Di Vita Giuseppa , Domenici Enrico , Elia Massimo , Gitti Filippo , Grittani Serenella , Lamanna Anna Linda , Mani Elisa , Manzi Barbara , Margari Lucia , Masi Gabriele , Molteni Massimo , Muglia Pierandrea , Nardocci Franco , Pascotto Antonio , Parmeggiani Antonia , Pignatti Pier Franco , Piroddi Tiziana , Prandini Paola , Ratti Emiliangelo , Rizzini Paolo , Russo Sebastiano , Scifo Renato , Tancredi Raffaella , Tiberti Alessandra , Trabetti Elisabetta , Zoccante Leonardo , Zuddas Alessandro , Domenici Enrico 
Published: April 2020

AbstractNotwithstanding several research efforts in the past years, robust and replicable molecular signatures for autism spectrum disorders from peripheral blood remain elusive. The available literature on blood transcriptome in ASD suggests that through accurate experimental design it is possible to extract important information on the disease pathophysiology at the peripheral level. Here we exploit the availability of a resource for molecular biomarkers in ASD, the Italian Autism Network (ITAN) collection, for the investigation of transcriptomic signatures in ASD based on a discordant sibling pair design. Whole blood samples from 75 discordant sibling pairs selected from the ITAN network where submitted to RNASeq analysis and data analyzed by complementary approaches. Overall, differences in gene expression between affected and unaffected siblings were small. In order to assess the contribution of differences in the relative proportion of blood cells between discordant siblings, we have applied two different cell deconvolution algorithms, showing that the observed molecular signatures mainly reflect changes in peripheral blood immune cell composition, in particular NK cells. The results obtained by the cell deconvolution approach are supported by the analysis performed by WGCNA. Our report describes the largest differential gene expression profiling in peripheral blood of ASD subjects and controls conducted by RNASeq. The observed signatures are consistent with the hypothesis of immune alterations in autism and an increased risk of developing autism in subjects exposed to prenatal infections or stress. Our study also points to a potential role of NMUR1, HMGB3, and PTPRN2 in ASD.
IDH mutation in glioma: molecular mechanisms and potential therapeutic targets
Authors: Han Sue , Liu Yang , Cai Sabrina J. , Qian Mingyu , Ding Jianyi , Larion Mioara , Gilbert Mark R. , Yang Chunzhang 
Published: April 2020

AbstractIsocitrate dehydrogenase (IDH) enzymes catalyse the oxidative decarboxylation of isocitrate and therefore play key roles in the Krebs cycle and cellular homoeostasis. Major advances in cancer genetics over the past decade have revealed that the genes encoding IDHs are frequently mutated in a variety of human malignancies, including gliomas, acute myeloid leukaemia, cholangiocarcinoma, chondrosarcoma and thyroid carcinoma. A series of seminal studies further elucidated the biological impact of the IDH mutation and uncovered the potential role of IDH mutants in oncogenesis. Notably, the neomorphic activity of the IDH mutants establishes distinctive patterns in cancer metabolism, epigenetic shift and therapy resistance. Novel molecular targeting approaches have been developed to improve the efficacy of therapeutics against IDH-mutated cancers. Here we provide an overview of the latest findings in IDH-mutated human malignancies, with a focus on glioma, discussing unique biological signatures and proceedings in translational research.
Identification of a novel tumor angiogenesis inhibitor targeting Shh/Gli1 signaling pathway in Non-small cell lung cancer
Authors: Lei Xueping , Zhong Yihang , Huang Lijuan , Li Songpei , Fu Jijun , Zhang Lingmin , Zhang Yu , Deng Qiudi , Yu Xiyong 
Published: April 2020

AbstractAlthough angiogenesis inhibitors targeting VEGF/VEGFR2 have been applied for tumor therapy, the outcomes are still unsatisfactory. Thus, it is urgent to develop novel angiogenesis inhibitor for cancer therapy from new perspectives. Identification of novel angiogenesis inhibitor from natural products is believed to be one of most promising strategy. In this study, we showed that pristimerin, an active agent isolated from traditional Chinese herbal medicine Celastrus aculeatus Merr, was a novel tumor angiogenesis inhibitor that targeting sonic hedgehog (Shh)/glioma associated oncogene 1 (Gli1) signaling pathway in non-small cell lung cancer (NSCLC). We showed that pristimerin affected both the early- and late-stage of angiogenesis, suggesting by that pristimerin inhibited Shh-induced endothelial cells proliferation, migration, invasion as well as pericytes recruitment to the endothelial tubes, which is critical for the new blood vessel maturation. It also suppressed tube formation, vessel sprouts formation and neovascularization in chicken embryo chorioallantoic membrane (CAM). Moreover, it significantly decreased microvessel density (MVD) and pericyte coverage in NCI-H1299 xenografts, resulting in tumor growth inhibition. Further research revealed that pristimerin suppressed tumor angiogenesis by inhibiting the nucleus distribution of Gli1, leading to inactivation of Shh/Gli1 and its downstream signaling pathway. Taken together, our study showed that pristimerin was a promising novel anti-angiogenic agent for the NSCLC therapy and targeting Shh/Gli1 signaling pathway was an effective approach to suppress tumor angiogenesis.
Bacterial type III effector protein HopQ inhibits melanoma motility through autophagic degradation of vimentin
Authors: Park Seung-Ho , Yoon Sung-Jin , Choi Song , Kim Jun-Seob , Lee Moo-Seung , Lee Seon-Jin , Lee Sang-Hyun , Min Jeong-Ki , Son Mi-Young , Ryu Choong-Min , Yoo Jiyun , Park Young-Jun 
Published: April 2020

AbstractMalignant melanoma is a fatal disease that rapidly spreads to the whole body. Treatments have limited efficiency owing to drug resistance and various side effects. Pseudomonas syringae pv. tomato (Pto) is a model bacterial pathogen capable of systemic infection in plants. Pto injects the effector protein HopQ into the plant cytosol via a type III secretion machinery and suppresses the host immunity. Intriguingly, host plant proteins regulated by HopQ are conserved even in humans and conferred in tumor metastasis. Nevertheless, the potential for HopQ to regulate human cancer metastasis was unknown. In this study, we addressed the suitability of HopQ as a possible drug against melanoma metastasis. In melanoma cells, overexpressed HopQ is phosphorylated and bound to 14-3-3 through its N-terminal domain, resulting in stronger interaction between HopQ and vimentin. The binding of HopQ to vimentin allowed for degradation of vimentin via p62-dependent selective autophagy. Attenuation of vimentin expression by HopQ inhibited melanoma motility and in vivo metastasis. These findings demonstrated that HopQ directly degraded vimentin in melanoma cells and could be applied to an inhibitor of melanoma metastasis.
Potent BRD4 inhibitor suppresses cancer cell-macrophage interaction
Authors: Yin Mingzhu , Guo Ying , Hu Rui , Cai Wesley L. , Li Yao , Pei Shiyao , Sun Hongyin , Peng Cong , Li Jiali , Ye Rui , Yang Qiaohong , Wang Nenghui , Tao Yongguang , Chen Xiang , Yan Qin 
Published: April 2020

AbstractSmall molecule inhibitor of the bromodomain and extraterminal domain (BET) family proteins is a promising option for cancer treatment. However, current BET inhibitors are limited by their potency or oral bioavailability. Here we report the discovery and characterization of NHWD-870, a BET inhibitor that is more potent than three major clinical stage BET inhibitors BMS-986158, OTX-015, and GSK-525762. NHWD-870 causes tumor shrinkage or significantly suppresses tumor growth in nine xenograft or syngeneic models. In addition to its ability to downregulate c-MYC and directly inhibit tumor cell proliferation, NHWD-870 blocks the proliferation of tumor associated macrophages (TAMs) through multiple mechanisms, partly by reducing the expression and secretion of macrophage colony-stimulating factor CSF1 by tumor cells. NHWD-870 inhibits CSF1 expression through suppressing BRD4 and its target HIF1α. Taken together, these results reveal a mechanism by which BRD4 inhibition suppresses tumor growth, and support further development of NHWD-870 to treat solid tumors.
Imaging small molecule-induced endosomal escape of siRNA
Authors: Du Rietz Hampus , Hedlund Hampus , Wilhelmson Sten , Nordenfelt Pontus , Wittrup Anders 
Published: April 2020

AbstractSmall interfering RNAs (siRNAs) are a new class of promising therapeutic molecules that can be used for sequence-specific downregulation of disease-causing genes. However, endosomal entrapment of siRNA is a key hurdle for most delivery strategies, limiting the therapeutic effect. Here, we use live-cell microscopy and cytosolic galectin-9 as a sensor of membrane damage, to probe fundamental properties of endosomal escape of cholesterol-conjugated siRNA induced by endosome-disrupting compounds. We demonstrate efficient release of ligand-conjugated siRNA from vesicles damaged by small molecules, enhancing target knockdown up to ∼47-fold in tumor cells. Still, mismatch between siRNA-containing and drug-targeted endolysosomal compartments limits siRNA activity improvement. We also show widespread endosomal damage in macroscopic tumor spheroids after small molecule treatment, substantially improving siRNA delivery and knockdown throughout the spheroid. We believe the strategy to characterize endosomal escape presented here will be widely applicable, facilitating efforts to improve delivery of siRNA and other nucleic acid-based therapeutics.