bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer
Authors: Formisano Luigi , Lu Yao , Servetto Alberto , Hanker Ariella B. , Jansen Valerie M. , Bauer Joshua A. , Sudhan Dhivya R. , Guerrero-Zotano Angel L. , Croessmann Sarah , Guo Yan , Ericsson Paula Gonzalez , Lee Kyung-min , Nixon Mellissa J. , Schwarz Luis J. , Sanders Melinda E. , Dugger Teresa C. , Cruz Marcelo Rocha , Behdad Amir , Cristofanilli Massimo , Bardia Aditya , O’Shaughnessy Joyce , Nagy Rebecca J. , Lanman Richard B. , Solovieff Nadia , He Wei , Miller Michelle , Su Fei , Shyr Yu , Mayer Ingrid A. , Balko Justin M. , Arteaga Carlos L. 
Published: March 2019

AbstractUsing an ORF kinome screen in MCF-7 cells treated with the CDK4/6 inhibitor ribociclib plus fulvestrant, we identified FGFR1 as a mechanism of drug resistance. FGFR1-amplified/ER+ breast cancer cells and MCF-7 cells transduced with FGFR1 were resistant to fulvestrant ± ribociclib or palbociclib. This resistance was abrogated by treatment with the FGFR tyrosine kinase inhibitor (TKI) lucitanib. Addition of the FGFR TKI erdafitinib to palbociclib/fulvestrant induced complete responses of FGFR1-amplified/ER+ patient-derived-xenografts. Next generation sequencing of circulating tumor DNA (ctDNA) in 34 patients after progression on CDK4/6 inhibitors identified FGFR1/2 amplification or activating mutations in 14/34 (41%) post-progression specimens. Finally, ctDNA from patients enrolled in MONALEESA-2, the registration trial of ribociclib, showed that patients with FGFR1 amplification exhibited a shorter progression-free survival compared to patients with wild type FGFR1. Thus, we propose breast cancers with FGFR pathway alterations should be considered for trials using combinations of ER, CDK4/6 and FGFR antagonists.
Constructing a synthetic pathway for acetyl-coenzyme A from one-carbon through enzyme design
Authors: Lu Xiaoyun , Liu Yuwan , Yang Yiqun , Wang Shanshan , Wang Qian , Wang Xiya , Yan Zhihui , Cheng Jian , Liu Cui , Yang Xue , Luo Hao , Yang Sheng , Gou Junran , Ye Luzhen , Lu Lina , Zhang Zhidan , Guo Yu , Nie Yan , Lin Jianping , Li Sheng , Tian Chaoguang , Cai Tao , Zhuo Bingzhao , Ma Hongwu , Wang Wen , Ma Yanhe , Liu Yongjun , Li Yin , Jiang Huifeng 
Published: March 2019

AbstractAcetyl-CoA is a fundamental metabolite for all life on Earth, and is also a key starting point for the biosynthesis of a variety of industrial chemicals and natural products. Here we design and construct a Synthetic Acetyl-CoA (SACA) pathway by repurposing glycolaldehyde synthase and acetyl-phosphate synthase. First, we design and engineer glycolaldehyde synthase to improve catalytic activity more than 70-fold, to condense two molecules of formaldehyde into one glycolaldehyde. Second, we repurpose a phosphoketolase to convert glycolaldehyde into acetyl-phosphate. We demonstrated the feasibility of the SACA pathway in vitro, achieving a carbon yield ~50%, and confirmed the SACA pathway by 13C-labeled metabolites. Finally, the SACA pathway was verified by cell growth using glycolaldehyde, formaldehyde and methanol as supplemental carbon source. The SACA pathway is proved to be the shortest, ATP-independent, carbon-conserving and oxygen-insensitive pathway for acetyl-CoA biosynthesis, opening possibilities for producing acetyl-CoA-derived chemicals from one-carbon resources in the future.
Eutrophication will increase methane emissions from lakes and impoundments during the 21st century
Authors: Beaulieu Jake J. , DelSontro Tonya , Downing John A. 
Published: March 2019

AbstractLakes and impoundments are an important source of methane (CH4), a potent greenhouse gas, to the atmosphere. A recent analysis shows aquatic productivity (i.e., eutrophication) is an important driver of CH4 emissions from lentic waters. Considering that aquatic productivity will increase over the next century due to climate change and a growing human population, a concomitant increase in aquatic CH4 emissions may occur. We simulate the eutrophication of lentic waters under scenarios of future nutrient loading to inland waters and show that enhanced eutrophication of lakes and impoundments will substantially increase CH4 emissions from these systems (+30–90%) over the next century. This increased CH4 emission has an atmospheric impact of 1.7–2.6 Pg C-CO2-eq y−1, which is equivalent to 18–33% of annual CO2 emissions from burning fossil fuels. Thus, it is not only important to limit eutrophication to preserve fragile water supplies, but also to avoid acceleration of climate change.
Assessing the Policy gaps for achieving China’s climate targets in the Paris Agreement
Authors: Gallagher Kelly Sims , Zhang Fang , Orvis Robbie , Rissman Jeffrey , Liu Qiang 
Published: March 2019

AbstractChina committed to peak its carbon emissions around 2030, with best efforts to peak early, and also to achieve 20% non-fossil energy as a proportion of primary energy supply by 2030. These commitments were included in China’s nationally-determined contribution to the 2015 Paris Agreement on climate change. We develop and apply a mixed-method methodology for analyzing the likelihood of current Chinese policies reducing greenhouse gas emissions in accordance with China’s Paris commitments. We find that China is likely to peak its emissions well in advance of 2030 and achieve its non-fossil target conditional on full and effective implementation of all current policies, successful conclusion of power-sector reform, and full implementation of a national emissions-trading system (ETS) for the power and additional major industrial sectors after 2020. Several policy gaps are identified and discussed.
Water impacts nutrient dose responses genome-wide to affect crop production
Authors: Swift Joseph , Adame Mark , Tranchina Daniel , Henry Amelia , Coruzzi Gloria M. 
Published: March 2019

AbstractChanges in nutrient dose have dramatic effects on gene expression and development. One outstanding question is whether organisms respond to changes in absolute nutrient amount (moles) vs. its concentration in water (molarity). This question is particularly relevant to plants, as soil drying can alter nutrient concentration, without changing its absolute amount. To compare the effects of amount vs. concentration, we expose rice to a factorial matrix varying the dose of nitrogen (N) and water (W) over a range of combinations, and quantify transcriptome and phenotype responses. Using linear models, we identify distinct dose responses to either N-moles, W-volume, N-molarity (N/W), or their synergistic interaction (N×W). Importantly, genes whose expression patterns are best explained by N-dose and W interactions (N/W or N×W) in seedlings are associated with crop outcomes in replicated field trials. Such N-by-W responsive genes may assist future efforts to develop crops resilient to increasingly arid, low nutrient soils.
Humidity-tolerant rate-dependent capillary viscous adhesion of bee-collected pollen fluids
Authors: Shin Donglee , Choi Won Tae , Lin Haisheng , Qu Zihao , Breedveld Victor , Meredith J. Carson 
Published: March 2019

AbstractWe report a two-phase adhesive fluid recovered from pollen, which displays remarkable rate tunability and humidity stabilization at microscopic and macroscopic scales. These natural materials provide a previously-unknown model for bioinspired humidity-stable and dynamically-tunable adhesive materials. In particular, two immiscible liquid phases are identified in bioadhesive fluid extracted from dandelion pollen taken from honey bees: a sugary adhesive aqueous phase similar to bee nectar and an oily phase consistent with plant pollenkitt. Here we show that the aqueous phase exhibits a rate-dependent capillary adhesion attributed to hydrodynamic forces above a critical separation rate. However, the performance of this adhesive phase alone is very sensitive to humidity due to water loss or uptake. Interestingly, the oily phase contributes scarcely to the wet adhesion. Rather, it spreads over the aqueous phase and functions as a barrier to water vapor that tempers the effects of humidity changes and stabilizes the capillary adhesion.
Far-field coherent thermal emission from polaritonic resonance in individual anisotropic nanoribbons
Authors: Shin Sunmi , Elzouka Mahmoud , Prasher Ravi , Chen Renkun 
Published: March 2019

AbstractCoherent thermal emission deviates from the Planckian blackbody emission with a narrow spectrum and strong directionality. While far-field thermal emission from polaritonic resonance has shown the deviation through modelling and optical characterizations, an approach to achieve and directly measure dominant coherent thermal emission has not materialised. By exploiting the large disparity in the skin depth and wavelength of surface phonon polaritons, we design anisotropic SiO2 nanoribbons to enable independent control of the incoherent and coherent behaviours, which exhibit over 8.5-fold enhancement in the emissivity compared with the thin-film limit. Importantly, this enhancement is attributed to the coherent polaritonic resonant effect, hence, was found to be stronger at lower temperature. A thermometry platform is devised to extract, for the first time, the thermal emissivity from such dielectric nanoemitters with nanowatt-level emitting power. The result provides new insight into the realisation of spatial and spectral distribution control for far-field thermal emission.
Patient reported outcomes for preschool children with recurrent wheeze
Authors: Heidi Makrinioti , Emily Keating , Benjamin Holden , Michael Coren , Robert Klaber , Mitch Blair , Chris Griffiths , Mando Watson , Andrew Bush 
Published: March 2019

AbstractChildren with preschool wheeze regularly attend UK emergency departments. There is no international consensus on any specific personalised management approach. This paper describes the first attempt to co-design patient-centred outcomes with families. Preschool wheezers’ parents participated in semi-structured interviews and focus-group discussions to air their concerns and identify potential additional support. Fifty-seven families participated in these interviews. From these, themes were defined through qualitative content analysis. Parental experience was mapped to the patient pathway and seven important personalised outcomes were described. These can be used to inform a tool which following further validation could potentially support management of children with preschool wheeze and provide an additional patient focused clinical outcome measure in audit and research.
Combination of stem cell and gene therapy ameliorates symptoms in Huntington’s disease mice
Authors: Cho In Ki , Hunter Carissa Emerson , Ye Sarah , Pongos Alvince Learnz , Chan Anthony Wing Sang 
Published: March 2019

AbstractHuntington’s disease (HD) is a dominantly inherited monogenetic disorder characterized by motor and cognitive dysfunction due to neurodegeneration. The disease is caused by the polyglutamine (polyQ) expansion at the 5′ terminal of the exon 1 of the huntingtin (HTT) gene, IT15, which results in the accumulation of mutant HTT (mHTT) aggregates in neurons and cell death. The monogenetic cause and the loss of specific neural cell population make HD a suitable candidate for stem cell and gene therapy. In this study, we demonstrate the efficacy of the combination of stem cell and gene therapy in a transgenic HD mouse model (N171-82Q; HD mice) using rhesus monkey (Macaca mulatta) neural progenitor cells (NPCs). We have established monkey NPC cell lines from induced pluripotent stem cells (iPSCs) that can differentiate into GABAergic neurons in vitro as well as in mouse brains without tumor formation. Wild-type monkey NPCs (WT-NPCs), NPCs derived from a transgenic HD monkey (HD-NPCs), and genetically modified HD-NPCs with reduced mHTT levels by stable expression of small-hairpin RNA (HD-shHD-NPCs), were grafted into the striatum of WT and HD mice. Mice that received HD-shHD-NPC grafts showed a significant increase in lifespan compared to the sham injection group and HD mice. Both WT-NPC and HD-shHD-NPC grafts in HD mice showed significant improvement in motor functions assessed by rotarod and grip strength. Also, immunohistochemistry demonstrated the integration and differentiation. Our results suggest the combination of stem cell and gene therapy as a viable therapeutic option for HD treatment.
Dynamic interaction between basin redox and the biogeochemical nitrogen cycle in an unconventional Proterozoic petroleum system
Authors: Cox Grant M. , Sansjofre Pierre , Blades Morgan L. , Farkas Juraj , Collins Alan S. 
Published: March 2019

AbstractPrecambrian hydrocarbons and their corresponding source rocks are distinctly different from their Phanerozoic counterparts, having been deposited in persistently anoxic environments in ecosystems dominated by bacteria. Here, we show that cyclic enrichment of organic matter in the world’s oldest hydrocarbon play (ca. 1.38 Ga), is not associated with flooding surfaces and is unrelated to variations in mineralogy or changes in the relative rate of clastic to biogenic sedimentation—factors typically attributed to organic enrichment in Phanerozoic shales. Instead, the cyclic covariation of total organic carbon, δ15N, δ13C and molybdenum are explained by the feedback between high levels of primary productivity, basin redox and the biogeochemical nitrogen cycle. These factors are important in constraining productivity in the marine biosphere, the development of Precambrian hydrocarbon source rocks, and more generally in understanding oxygenation of the ocean and atmosphere through Earth history; as all are ultimately related to organic carbon burial.
Perception of action-outcomes is shaped by life-long and contextual expectations
Authors: Dogge Myrthel , Custers Ruud , Gayet Surya , Hoijtink Herbert , Aarts Henk 
Published: March 2019

AbstractThe way humans perceive the outcomes of their actions is strongly colored by their expectations. These expectations can develop over different timescales and are not always complementary. The present work examines how long-term (structural) expectations – developed over a lifetime - and short-term (contextual) expectations jointly affect perception. In two studies, including a pre-registered replication, participants initiated the movement of an ambiguously rotating sphere by operating a rotary switch. In the absence of any learning, participants predominantly perceived the sphere to rotate in the same direction as their rotary action. This bias toward structural expectations was abolished (but not reversed) when participants were exposed to incompatible action-effect contingencies (e.g., clockwise actions causing counterclockwise percepts) during a preceding learning phase. Exposure to compatible action-effect contingencies, however, did not add to the existing structural bias. Together, these findings reveal that perception of action-outcomes results from the combined influence of both long-term and immediate expectations.
Connectivity differences between consciousness and unconsciousness in non-rapid eye movement sleep: a TMS–EEG study
Authors: Lee Minji , Baird Benjamin , Gosseries Olivia , Nieminen Jaakko O. , Boly Melanie , Postle Bradley R. , Tononi Giulio , Lee Seong-Whan 
Published: March 2019

AbstractThe neuronal connectivity patterns that differentiate consciousness from unconsciousness remain unclear. Previous studies have demonstrated that effective connectivity, as assessed by transcranial magnetic stimulation combined with electroencephalography (TMS–EEG), breaks down during the loss of consciousness. This study investigated changes in EEG connectivity associated with consciousness during non-rapid eye movement (NREM) sleep following parietal TMS. Compared with unconsciousness, conscious experiences during NREM sleep were associated with reduced phase-locking at low frequencies (<4 Hz). Transitivity and clustering coefficient in the delta and theta bands were also significantly lower during consciousness compared to unconsciousness, with differences in the clustering coefficient observed in scalp electrodes over parietal–occipital regions. There were no significant differences in Granger-causality patterns in frontal-to-parietal or parietal-to-frontal connectivity between reported unconsciousness and reported consciousness. Together these results suggest that alterations in spectral and spatial characteristics of network properties in posterior brain areas, in particular decreased local (segregated) connectivity at low frequencies, is a potential indicator of consciousness during sleep.
Band Anti-Crossing Model in Dilute-As GaNAs Alloys
Authors: Goodrich Justin C. , Borovac Damir , Tan Chee-Keong , Tansu Nelson 
Published: March 2019

AbstractThe band structure of the dilute-As GaNAs material is explained by the hybridization of localized As-impurity states with the valance band structure of GaN. Our approach employs the use of Density Functional Theory (DFT) calculated band structures, along with experimental results, to determine the localized As-impurity energy level and coupling parameters in the band anti-crossing (BAC) k ∙ p model for N-rich alloys. This model captures the reduction of bandgap with increasing arsenic incorporation and provides a tool for device-level design with the material within the context of the k ∙ p formalism. The analysis extends to calculating the effect of the arsenic impurities on hole (heavy, light and split-off) effective masses and predicting the trend of the bandgap across the entire composition range.
Strain effect on orbital and magnetic structures of Mn ions in epitaxial Nd0.35Sr0.65MnO3/SrTiO3 films using X-ray diffraction and absorption
Authors: Shao Y. C. , Deshpande N. G. , Chin Y. Y. , Hsieh S. H. , Du C. H. , Wang H. T. , Chiou J. W. , Tsai H. M. , Lin H. J. , Cheng S. L. , Lin J. G. , Asokan K. , Yeh P. H. , Pong W. F. 
Published: March 2019

AbstractThis study probes the temperature-dependent strain that is strongly correlated with the orbital and magnetic structures of epitaxial films of Nd0.35Sr0.65MnO3 (NSMO) that are fabricated by pulsed laser deposition with two thicknesses, 17 (NS17) and 103 nm (NS103) on SrTiO3 (STO) substrate. This investigation is probed using X-ray diffraction (XRD) and absorption-based techniques, X-ray linear dichroism (XLD) and the X-ray magnetic circular dichroism (XMCD). XRD indicates a significant shift in the (004) peak position that is associated with larger strain in NS17 relative to that of NS103 at both 30 and 300 K. Experimental and atomic multiplet simulated temperature-dependent Mn L3,2-edge XLD results reveal that the stronger strain in a thinner NS17 film causes less splitting of Mn 3d eg state at low temperature, indicating an enhancement of orbital fluctuations in the band above the Fermi level. This greater Mn 3d orbital fluctuation can be the cause of both the enhanced ferromagnetism (FM) as a result of spin moments and the reduced Néel temperature of C-type antiferromagnetism (AFM) in NS17, leading to the FM coupling of the canted-antiferromagnetism (FM-cAFM) state in NSMO/STO epitaxial films at low temperature (T = 30 K). These findings are also confirmed by Mn L3,2-edge XMCD measurements.
The Production of Matchout-Deuterated Cholesterol and the Study of Bilayer-Cholesterol Interactions
Authors: Waldie Sarah , Moulin Martine , Porcar Lionel , Pichler Harald , Strohmeier Gernot A. , Skoda Maximilian , Forsyth V. Trevor , Haertlein Michael , Maric Selma , Cárdenas Marité 
Published: March 2019

AbstractThe deuteration of biomolecules provides advanced opportunities for neutron scattering studies. For low resolution studies using techniques such as small-angle neutron scattering and neutron reflection, the level of deuteration of a sample can be varied to match the scattering length density of a specific D2O/H2O solvent mixture. This can be of major value in structural studies where specific regions of a complex system can be highlighted, and others rendered invisible. This is especially useful in analyses of the structure and dynamics of membrane components. In mammalian membranes, the presence of cholesterol is crucial in modulating the properties of lipids and in their interaction with proteins. Here, a protocol is described for the production of partially deuterated cholesterol which has a neutron scattering length density that matches that of 100% D2O solvent (hereby named matchout cholesterol). The level of deuteration was determined by mass spectrometry and nuclear magnetic resonance. The cholesterol match-point was verified experimentally using small angle neutron scattering. The matchout cholesterol was used to investigate the incorporation of cholesterol in various phosphatidylcholine supported lipid bilayers by neutron reflectometry. The study included both saturated and unsaturated lipids, as well as lipids with varying chain lengths. It was found that cholesterol is distributed asymmetrically within the bilayer, positioned closer to the headgroups of the lipids than to the middle of the tail core, regardless of the phosphatidylcholine species.
Acoustic recordings provide detailed information regarding the behavior of cryptic wildlife to support conservation translocations
Authors: Yan Xiao , Zhang Hemin , Li Desheng , Wu Daifu , Zhou Shiqiang , Sun Mengmeng , Hu Haiping , Liu Xiaoqiang , Mou Shijie , He Shengshan , Owen Megan A. , Huang Yan 
Published: March 2019

AbstractFor translocated animals, behavioral competence may be key to post-release survival. However, monitoring behavior is typically limited to tracking movements or inferring behavior at a gross scale via collar-mounted sensors. Animal-bourne acoustic monitoring may provide a unique opportunity to monitor behavior at a finer scale. The giant panda is an elusive species of Ursid that is vulnerable to extinction. Translocation is an important aspect of the species’ recovery, and survival and recruitment for pandas likely hinge on behavioral competence. Here we tested the efficacy of a collar-mounted acoustic recording unit (ARU) to remotely monitor the behavior of panda mothers and their dependent young. We found that trained human listeners could reliably identify 10 behaviors from acoustic recordings. Through visual inspection of spectrograms we further identified 5 behavioral categories that may be detectable by automated pattern recognition, an approach that is essential for the practical application of ARU. These results suggest that ARU are a viable method for remotely observing behaviors, including feeding. With targeted effort directed towards instrumentation and computing advances, ARU could be used to document how behavioral competence supports or challenges post-release survival and recruitment, and allow for research findings to be adaptively integrated into future translocation efforts.
A Fully Automated System Using A Convolutional Neural Network to Predict Renal Allograft Rejection: Extra-validation with Giga-pixel Immunostained Slides
Authors: Kim Young-Gon , Choi Gyuheon , Go Heounjeong , Cho Yongwon , Lee Hyunna , Lee A-Reum , Park Beomhee , Kim Namkug 
Published: March 2019

AbstractPathologic diagnoses mainly depend on visual scoring by pathologists, a process that can be time-consuming, laborious, and susceptible to inter- and/or intra-observer variations. This study proposes a novel method to enhance pathologic scoring of renal allograft rejection. A fully automated system using a convolutional neural network (CNN) was developed to identify regions of interest (ROIs) and to detect C4d positive and negative peritubular capillaries (PTCs) in giga-pixel immunostained slides. The performance of faster R-CNN was evaluated using optimal parameters of the novel method to enlarge the size of labeled masks. Fifty and forty pixels of the enlarged size images showed the best performance in detecting C4d positive and negative PTCs, respectively. Additionally, the feasibility of deep-learning-assisted labeling as independent dataset to enhance detection in this model was evaluated. Based on these two CNN methods, a fully automated system for renal allograft rejection was developed. This system was highly reliable, efficient, and effective, making it applicable to real clinical workflow.