bluuebunny/crossref_metadata_2025_split huggingface dataset:
State strategies to address medicaid prescription spending: negotiated pricing vs price transparency
Authors: Noh Shihyun , Janousek Christian L. , Park Ji Hyung 
Published: April 2020

AbstractThis research longitudinally examines the association between levels of state Medicaid prescription spending and the state strategies intended to constrain cost increases: the negotiated pricing strategy, as indicated by state rebate programs, and the price transparency strategy, as indicated by state operation of All-Payer Claims Databases. The findings demonstrate evidence that state Medicaid prescription spending is influenced by the negotiated pricing strategy, especially Managed Care Organization (MCO) rebates under the Patient Protection and Affordable Care Act, but not influenced by the price transparency strategy. State decisions for MCO rebates, such as carving prescription benefits into managed care benefits, were effective in containing levels of Medicaid prescription spending over time, while other single- and multi-state rebate programs were not. Based on these findings, state policymakers may consider utilizing the MCO rebate program to address increases in Medicaid prescription spending.
Re‐examination of the Population, Stratigraphy, and Sequence of Mercurian Basins: Implications for Mercury's Early Impact History and Comparison With the Moon
Authors: Orgel Csilla , Fassett Caleb I. , Michael Gregory , Riedel Christian , van der Bogert Carolyn H. , Hiesinger Harald 
Published: April 2020

AbstractMercury has one of the best‐preserved impact records in the inner solar system due to the absence of an atmosphere and relatively unmodified ancient surface. However, our knowledge of the early impact record and the nature of the impacting projectiles are far from complete. To get a better understanding of the early impact history, we examined large impact basins (D ≥ 300 km) on Mercury. Here we cataloged 94 basins, 80 of which we classify as certain or probable, 1.7 times more than previously recognized. We re‐evaluate the crater densities of basins using the buffered nonsparseness correction technique, which we successfully applied for the Moon. In contrast with a previous study, we find that basins have a slightly higher N(300) crater density on Mercury than on the Moon, but similar N(500) basin densities. Based on these results and comparison with the Moon, we infer that no more than half of the basin record remains observable and basins older than Borealis have generally been erased from the basin record. Furthermore, we establish the stratigraphic relationships of basins based on N(25) crater frequencies, absolute model ages, and observations of crosscutting relationships. Similarly to our previous study on the Moon, we found no evidence for a change in the size‐frequency distribution of the impacting population; thus, our results are consistent with a single impactor population that bombarded Mercury's surface.
Early Impact Events on Chondritic Parent Bodies: Insights From NWA 11004, Reclassified as an LL7 Breccia
Authors: Li Y. , Rubin A. E. , Hsu W. , Ziegler K. 
Published: April 2020

Key Points

NWA 11004, reclassified as an LL7 breccia, records a partial melting process
NWA 11004 records a late‐stage shock event at 4546 ± 34 Ma that produced undulose to weak mosaic extinction in pyroxene
The presence of type 7 chondrites in the early solar system may be ascribed to impacts on already warm parent bodies
Machine Learning‐Based Prediction of Spatiotemporal Uncertainties in Global Wind Velocity Reanalyses
Authors: Irrgang Christopher , Saynisch‐Wagner Jan , Thomas Maik 
Published: April 2020

AbstractThe characterization of uncertainties in geophysical quantities is an important task with widespread applications for time series prediction, numerical modeling, and data assimilation. In this context, machine learning is a powerful tool for estimating complex patterns and their evolution through time. Here, we utilize a supervised machine learning approach to dynamically predict the spatiotemporal uncertainty of near‐surface wind velocities over the ocean. A recurrent neural network (RNN) is trained with reanalyzed 10 m wind velocities and corresponding precalculated uncertainty estimates during the 2012–2016 time period. Afterward, the neural network's performance is examined by analyzing its prediction for the subsequent year 2017. Our experiments show that a recurrent neural network can capture the globally prevalent wind regimes without prior knowledge about underlying physics and learn to derive wind velocity uncertainty estimates that are only based on wind velocity trajectories. At single training locations, the RNN‐based wind uncertainties closely match with the true reference values, and the corresponding intra‐annual variations are reproduced with high accuracy. Moreover, the neural network can predict global lateral distribution of uncertainties with small mismatch values after being trained only at a few isolated locations in different dynamic regimes. The presented approach can be combined with numerical models for a cost‐efficient generation of ensemble simulations or with ensemble‐based data assimilation to sample and predict dynamically consistent error covariance information of atmospheric boundary forcings.
Assessment and Validation of Three Ionospheric Models (IRI‐2016, NeQuick2, and IGS‐GIM) From 2002 to 2018
Authors: Chen Jun , Ren Xiaodong , Zhang Xiaohong , Zhang Jincheng , Huang Liangke 
Published: April 2020

AbstractIt is important to confirm the accuracy and reliability of commonly used ionosphere models climatologically. In this contribution, International Global Navigation Satellite System Global Ionospheric Maps (IGSG) and two empirical models, that is, NeQuick2 and IRI‐2016, are assessed in detail by applying different assessment methods, for example, Jason2/3 ionospheric data, difference of Slant Total Electron Content (dSTEC) data derived from Global Navigation Satellite System (GNSS) phase observation, and single‐frequency precise point positioning. Compared with IGSG, the biases mainly range from −10 to 10 Total Electron Content Unit (TECU), while they are between −5 and 5 TECU on solar low‐level days for empirical models. The hourly mean biases are about −2.7 and −2.5 TECU for IRI‐2016 and NeQuick2 models, respectively. Over the oceanic region, the mean biases for IRI‐2016 and NeQuick2 models relative to Jason2/3‐Vertical Total Electron Content (VTEC) are smaller than that of IGSG. The Root Mean Square (RMS) values are 4.8 and 6.0 TECU for IGSG and empirical models relative to Jason2‐VTEC while the values are 5.4 and 6.0 TECU with relative to Jason3‐VTEC. Compared with dSTEC values derived from the selected stations, the RMS values are about 1.8 and 2.6 TECU for IGSG and empirical models, respectively. In the positioning domain, the accuracy of single‐frequency precise point positioning corrected by the three models can reach 1 m in three‐dimensional direction. The positioning accuracy is 0.17 m corrected by IGSG and 0.50 m corrected by IRI‐2016 and NeQuick2 in the horizontal direction.
Residuals to the CHAOS‐6 Geomagnetic Field Model Caused by Magnetospheric Currents During Enhanced Magnetic Activity
Authors: Lühr Hermann , Zhou Yun‐Liang 
Published: April 2020

AbstractThanks to mapping missions, like Ørsted, CHAMP, and Swarm, we have gained a detailed understanding of the geomagnetic field. High‐resolution models like POMME, GRIMM, or CHAOS are able to describe the main parts of the Earth's magnetic field reliably. These models represent well contributions from the core and crustal fields. But their validity of describing magnetospheric field effects is limited to low activity periods (Kp ~ 0–2). Here, we study the differences between CHAMP magnetic observations and the predictions from CHAOS‐6‐x9, a recent version, outside this validity range. Systematic residuals appear at times of elevated activity. Mean amplitudes at the equator grow up to 12 nT around 20 hr magnetic local time for magnetic activity around Kp = 4.7. Negative residuals are obtained in the evening to midnight sector and positive ones in the morning. A seasonal dependence of the magnetospheric currents causes more negative deflections of the residuals in the winter than in the summer hemisphere. This hemispheric asymmetry cannot be accounted for by a degree 1 spherical harmonics function. A surprising observation is that the residuals show a clear longitude dependent pattern, which changes with local time. The analysis reveals that this feature can be interpreted as a Universal Time dependence of the residuals with a peak‐to‐peak amplitude of about 8 nT and a period of 12 hr at an activity level of Kp = 4.7. All these results call for a better parameterization of the magnetospheric current effects in a geomagnetic field model that is reliable at least up to moderate activity levels.
Kirigami/origami: unfolding the new regime of advanced 3D microfabrication/nanofabrication with “folding”
Authors: Chen Shanshan , Chen Jianfeng , Zhang Xiangdong , Li Zhi-Yuan , Li Jiafang 
Published: April 2020

AbstractAdvanced kirigami/origami provides an automated technique for modulating the mechanical, electrical, magnetic and optical properties of existing materials, with remarkable flexibility, diversity, functionality, generality, and reconfigurability. In this paper, we review the latest progress in kirigami/origami on the microscale/nanoscale as a new platform for advanced 3D microfabrication/nanofabrication. Various stimuli of kirigami/origami, including capillary forces, residual stress, mechanical stress, responsive forces, and focussed-ion-beam irradiation-induced stress, are introduced in the microscale/nanoscale region. These stimuli enable direct 2D-to-3D transformations through folding, bending, and twisting of microstructures/nanostructures, with which the occupied spatial volume can vary by several orders of magnitude compared to the 2D precursors. As an instant and direct method, ion-beam irradiation-based tree-type and close-loop nano-kirigami is highlighted in particular. The progress in microscale/nanoscale kirigami/origami for reshaping the emerging 2D materials, as well as the potential for biological, optical and reconfigurable applications, is briefly discussed. With the unprecedented physical characteristics and applicable functionalities generated by kirigami/origami, a wide range of applications in the fields of optics, physics, biology, chemistry and engineering can be envisioned.
Autism spectrum heterogeneity: fact or artifact?
Authors: Mottron Laurent , Bzdok Danilo 
Published: April 2020

AbstractThe current diagnostic practices are linked to a 20-fold increase in the reported prevalence of ASD over the last 30 years. Fragmenting the autism phenotype into dimensional “autistic traits” results in the alleged recognition of autism-like symptoms in any psychiatric or neurodevelopemental condition and in individuals decreasingly distant from the typical population, and prematurely dismisses the relevance of a diagnostic threshold. Non-specific socio-communicative and repetitive DSM 5 criteria, combined with four quantitative specifiers as well as all their possible combinations, render limitless variety of presentations consistent with the categorical diagnosis of ASD. We propose several remedies to this problem: maintain a line of research on prototypical autism; limit the heterogeneity compatible with a categorical diagnosis to situations with a phenotypic overlap and a validated etiological link with prototypical autism; reintroduce the qualitative properties of autism presentations and of current dimensional specifiers, language, intelligence, comorbidity, and severity in the criteria used to diagnose autism in replacement of quantitative “social” and “repetitive” criteria; use these qualitative features combined with the clinical intuition of experts and machine-learning algorithms to differentiate coherent subgroups in today’s autism spectrum; study these subgroups separately, and then compare them; and question the autistic nature of “autistic traits”
DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer
Authors: Huang Rui-Xue , Zhou Ping-Kun 
Published: April 2020

AbstractRadiotherapy is one of the most common countermeasures for treating a wide range of tumors. However, the radioresistance of cancer cells is still a major limitation for radiotherapy applications. Efforts are continuously ongoing to explore sensitizing targets and develop radiosensitizers for improving the outcomes of radiotherapy. DNA double-strand breaks are the most lethal lesions induced by ionizing radiation and can trigger a series of cellular DNA damage responses (DDRs), including those helping cells recover from radiation injuries, such as the activation of DNA damage sensing and early transduction pathways, cell cycle arrest, and DNA repair. Obviously, these protective DDRs confer tumor radioresistance. Targeting DDR signaling pathways has become an attractive strategy for overcoming tumor radioresistance, and some important advances and breakthroughs have already been achieved in recent years. On the basis of comprehensively reviewing the DDR signal pathways, we provide an update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for radiosensitization. We further discuss recent advances identified from preclinical studies, current clinical trials, and clinical application of chemical inhibitors targeting key DDR proteins, including DNA-PKcs (DNA-dependent protein kinase, catalytic subunit), ATM/ATR (ataxia–telangiectasia mutated and Rad3-related), the MRN (MRE11-RAD50-NBS1) complex, the PARP (poly[ADP-ribose] polymerase) family, MDC1, Wee1, LIG4 (ligase IV), CDK1, BRCA1 (BRCA1 C terminal), CHK1, and HIF-1 (hypoxia-inducible factor-1). Challenges for ionizing radiation-induced signal transduction and targeted therapy are also discussed based on recent achievements in the biological field of radiotherapy.
CPPU may induce gibberellin-independent parthenocarpy associated with PbRR9 in ‘Dangshansu’ pear
Authors: Cong Liu , Wu Ting , Liu Hanting , Wang Huibin , Zhang Haiqi , Zhao Guangping , Wen Yao , Shi Qianrong , Xu Lingfei , Wang Zhigang 
Published: April 2020

AbstractParthenocarpy is a valuable trait in self-incompatible plants, such as pear. N-(2-chloro-4-pyridyl)-N’-phenylurea (CPPU), a synthetic cytokinin analog, can induce parthenocarpy in pear (Pyrus spp.), but the mechanism of induction is unclear. To investigate the role of gibberellin in CPPU-induced parthenocarpy in pear, CPPU supplemented with paclobutrazol (PAC) was sprayed onto ‘Dangshansu’ pear. We found that the fruit set rate of pear treated with CPPU supplemented with PAC was identical to that in a CPPU-alone treatment group. In regard to cell development, CPPU mainly promoted hypanthium cell division and expansion, and PAC application had no influence on CPPU-induced cell development. RNA sequencing revealed that gibberellin 20 oxidase and gibberellin 3 oxidase genes were not differentially expressed following CPPU treatment. According to the analysis of fruit phytohormone content, the CPPU treatments did not induce gibberellin biosynthesis. These results suggest that CPPU-induced parthenocarpy may be gibberellin independent in ‘Dangshansu’ pear. After CPPU treatment, the indole acetic acid (IAA) content in fruit was significantly increased, and the abscisic acid (ABA) content was significantly decreased. Similarly, RNA sequencing revealed that many genes involved in the auxin and ABA pathways were significantly differentially expressed in the CPPU treatment groups; among them, indole-3-pyruvate monooxygenase (YUCCA) was significantly upregulated and 9-cis-epoxycarotenoid dioxygenase (NCED) was significantly downregulated. IAA and ABA may thus play important roles in CPPU-induced parthenocarpy. PbTwo-component response regulator9 (PbRR9), PbYUCCA4, and PbNCED6 were then selected to further elucidate the mechanism of CPPU-induced parthenocarpy. A yeast one-hybrid assay indicated that PbRR9 can combine with the PbYUCCA4 and PbNCED6 promoters. Dual luciferase assays revealed that PbRR9 can promote and repress the activities of the PbYUCCA4 and PbNCED6 promoters, respectively. After the transient expression of PbRR9 in fruits, PbYUCCA4 expression was significantly upregulated, and PbNCED6 expression was significantly downregulated. This study uncovered a CPPU-induced parthenocarpy mechanism that is different from that in tomato. CPPU may upregulate PbYUCCA4 and downregulate PbNCED6 by upregulating PbRR9, thereby increasing IAA content and decreasing ABA content to ultimately induce parthenocarpy in ‘Dangshansu’ pear. However, because only a single time point was used and because ‘botanical’ and ‘accessory’ fruits have different structures, this conclusion is still preliminary.
Transcriptome analysis and metabolic profiling reveal the key role of carotenoids in the petal coloration of Liriodendron tulipifera
Authors: Hao Zhaodong , Liu Siqin , Hu Lingfeng , Shi Jisen , Chen Jinhui 
Published: April 2020

AbstractLiriodendron tulipifera, also known as tuliptree, is a popular ornamental horticultural plant with extraordinary tulip-shaped flowers characterized by an orange band near their base. The mechanisms underlying petal band-specific pigmentation during L. tulipifera flower development are unclear. Here, we combined nontargeted and targeted metabolomics and transcriptomics to identify a pathway cascade leading to carotenoid biosynthesis that is specifically activated in the petal band. The comparative analysis of carotenoid metabolites between L. tulipifera and Liriodendron hybrids indicates that γ-carotene, a rare carotene in plants, is the most likely orange pigment responsible for the coloration of the petal band. Phenotypic and transcriptomic analyses of developing petals reveal that the band area is first predefined by the loss of green color. Later, the band is maintained by locally activating and repressing carotenoid and chlorophyll biosynthesis genes, respectively. Two rate-limiting genes of carotene biosynthesis, carotenoid isomerase (CRTISO) and epsilon lycopene cyclase (ε-LCY), encode the core enzymes responsible for petal band-specific orange pigmentation in L. tulipifera. In particular, a putative additional ε-LCY copy specific to L. tulipifera may contribute to the distinct petal coloration pattern, compared with L. chinense. Taken together, our work provides a first glimpse of the metabolome and transcriptome dynamics in tuliptree flower coloration and provides a valuable resource for flower breeding or metabolic engineering as well as for understanding flower evolution in an early woody angiosperm.
Positron emission tomography imaging of novel AAV capsids maps rapid brain accumulation
Authors: Seo Jai Woong , Ingham Elizabeth S. , Mahakian Lisa , Tumbale Spencer , Wu Bo , Aghevlian Sadaf , Shams Shahin , Baikoghli Mo , Jain Poorva , Ding Xiaozhe , Goeden Nick , Dobreva Tatyana , Flytzanis Nicholas C. , Chavez Michael , Singhal Kratika , Leib Ryan , James Michelle L. , Segal David J. , Cheng R. Holland , Silva Eduardo A. , Gradinaru Viviana , Ferrara Katherine W. 
Published: April 2020

AbstractAdeno-associated viruses (AAVs) are typically single-stranded deoxyribonucleic acid (ssDNA) encapsulated within 25-nm protein capsids. Recently, tissue-specific AAV capsids (e.g. PHP.eB) have been shown to enhance brain delivery in rodents via the LY6A receptor on brain endothelial cells. Here, we create a non-invasive positron emission tomography (PET) methodology to track viruses. To provide the sensitivity required to track AAVs injected at picomolar levels, a unique multichelator construct labeled with a positron emitter (Cu-64, t1/2 = 12.7 h) is coupled to the viral capsid. We find that brain accumulation of the PHP.eB capsid 1) exceeds that reported in any previous PET study of brain uptake of targeted therapies and 2) is correlated with optical reporter gene transduction of the brain. The PHP.eB capsid brain endothelial receptor affinity is nearly 20-fold greater than that of AAV9. The results suggest that novel PET imaging techniques can be applied to inform and optimize capsid design.
Combining high-resolution scanning tunnelling microscopy and first-principles simulations to identify halogen bonding
Authors: Lawrence James , Sosso Gabriele C. , Đorđević Luka , Pinfold Harry , Bonifazi Davide , Costantini Giovanni 
Published: April 2020

AbstractScanning tunnelling microscopy (STM) is commonly used to identify on-surface molecular self-assembled structures. However, its limited ability to reveal only the overall shape of molecules and their relative positions is not always enough to fully solve a supramolecular structure. Here, we analyse the assembly of a brominated polycyclic aromatic molecule on Au(111) and demonstrate that standard STM measurements cannot conclusively establish the nature of the intermolecular interactions. By performing high-resolution STM with a CO-functionalised tip, we clearly identify the location of rings and halogen atoms, determining that halogen bonding governs the assemblies. This is supported by density functional theory calculations that predict a stronger interaction energy for halogen rather than hydrogen bonding and by an electron density topology analysis that identifies characteristic features of halogen bonding. A similar approach should be able to solve many complex 2D supramolecular structures, and we predict its increasing use in molecular nanoscience at surfaces.
The negative regulator SMAX1 controls mycorrhizal symbiosis and strigolactone biosynthesis in rice
Authors: Choi Jeongmin , Lee Tak , Cho Jungnam , Servante Emily K. , Pucker Boas , Summers William , Bowden Sarah , Rahimi Mehran , An Kyungsook , An Gynheung , Bouwmeester Harro J. , Wallington Emma J. , Oldroyd Giles , Paszkowski Uta. 
Published: April 2020

AbstractMost plants associate with beneficial arbuscular mycorrhizal (AM) fungi that facilitate soil nutrient acquisition. Prior to contact, partner recognition triggers reciprocal genetic remodelling to enable colonisation. The plant Dwarf14-Like (D14L) receptor conditions pre-symbiotic perception of AM fungi, and also detects the smoke constituent karrikin. D14L-dependent signalling mechanisms, underpinning AM symbiosis are unknown. Here, we present the identification of a negative regulator from rice, which operates downstream of the D14L receptor, corresponding to the homologue of the Arabidopsis thaliana Suppressor of MAX2-1 (AtSMAX1) that functions in karrikin signalling. We demonstrate that rice SMAX1 is a suppressor of AM symbiosis, negatively regulating fungal colonisation and transcription of crucial signalling components and conserved symbiosis genes. Similarly, rice SMAX1 negatively controls strigolactone biosynthesis, demonstrating an unexpected crosstalk between the strigolactone and karrikin signalling pathways. We conclude that removal of SMAX1, resulting from D14L signalling activation, de-represses essential symbiotic programmes and increases strigolactone hormone production.