bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Responses of Mesosphere and Lower Thermosphere Temperatures to Geomagnetic Storms at Low and Middle Latitudes
Authors: Li Jingyuan , Wang Wenbin , Lu Jianyong , Yuan Tao , Yue Jia , Liu Xiao , Zhang Kedeng , Burns Alan G. , Zhang Yongliang , Li Zheng
Published: August 2018

Observations from lidars and satellites have shown that large neutral temperature increases and decreases occur in the middle and low latitudes of the mesosphere and lower thermosphere region during geomagnetic storms. Here we undertake first‐principles simulations of mesosphere and lower thermosphere temperature responses to storms using the Thermosphere Ionosphere Mesosphere Electrodynamics General Circulation Model to elucidate the nature and causes of these changes. Temperature variations were not uniform; instead, nighttime temperatures changed earlier than daytime temperatures, and temperatures changed earlier at high latitudes than at low ones. Furthermore, temperatures increased in some places/times and decreased in others. As the simulation behaves similar to observations, it provides an opportunity to understand physical processes that drive the observed changes. Our analysis has shown that they were produced mainly by adiabatic heating/cooling that was associated with vertical winds resulting from general circulation changes, with additional contributions from vertical heat advection.
Extratropical Cyclone Precipitation Life Cycles: A Satellite‐Based Analysis
Authors: Booth James F. , Naud Catherine M. , Jeyaratnam Jeyavinoth
Published: August 2018

Although extratropical cyclones are the most common midlatitude storms, the relationship between their precipitation life cycle and dynamical strength life cycle has not been thoroughly analyzed. Given that thermodynamic heat exchanges associated with precipitation impact cyclone circulation, there is a need to understand the precipitation/dynamics relationship. Based on Integrated Multi‐satellitE Retrievals for Global Precipitation MeasurementGPM precipitation and Lagrangian cyclone tracks, the precipitation maximum occurs prior to the dynamical strength maximum 70% of the time. The lag in timing is consistent with the difference in cyclone precipitable water vapor at the two peaks. Conditional subsetting of the cyclone composites shows that if the precipitable water vapor distribution is constrained to be equal throughout the composite life cycle, the precipitation peak occurs very near the time of the peak in cyclone dynamical strength. Thus, the boost in dynamical strength caused by latent heat associated with precipitation manifest itself with little to no time lag.
ENSO's Changing Influence on Temperature, Precipitation, and Wildfire in a Warming Climate
Authors: Fasullo J. T. , Otto‐Bliesner B. L. , Stevenson S.
Published: August 2018

On interannual to decadal time scales, the climate mode with many of the strongest societal impacts is the El Niño–Southern Oscillation (ENSO). However, quantifying ENSO's changes in a warming climate remains a formidable challenge, due to both the noise arising from internal variability and the complexity of air‐sea feedbacks in the tropical Pacific Ocean. In this work, we use large (≥30‐member) ensembles of climate simulations to show that anthropogenic climate change can produce systematic increases in ENSO teleconnection strength over many land regions, driving increased interannual variability in regional temperature extremes and wildfire frequency. As the spatial character of this intensification exhibits strong land‐ocean contrasts, a causal role for land‐atmosphere feedbacks is suggested. The identified increase in variance occurs in multiple model ensembles, independent of changes in sea surface temperature variance. This suggests that in addition to changes in the overall likelihoods of heat and wildfire extremes, the variability in these events may also be a robust feature of future climate.
Dynamic Vegetation Simulations of the Mid‐Holocene Green Sahara
Authors: Lu Zhengyao , Miller Paul A. , Zhang Qiong , Zhang Qiang , Wårlind David , Nieradzik Lars , Sjolte Jesper , Smith Benjamin
Published: August 2018

The “Green Sahara” is a period when North Africa was characterized by vegetation cover and wetlands. To qualitatively identify the orbital‐climatic causation of the Green Sahara regime, we performed dynamic vegetation model (LPJ‐GUESS) simulations, driven by climate forcings from coupled general circulation model (EC‐Earth) simulations for the mid‐Holocene, in which the vegetation is prescribed to be either modern desert or artificially vegetated with a reduced dust load. LPJ‐GUESS simulates a vegetated Sahara covered by both herbaceous and woody vegetation types consistent with proxy reconstructions only in the latter scenario. Sensitivity experiments identify interactions required to capture the northward extension of vegetation. Increased precipitation is the main driver of the vegetation extent changes, and the temperature anomalies determine the plant functional types mainly through altered fire disturbance. Furthermore, the simulated vegetation composition also depends on the correct representation of soil texture in a humid environment like Green Sahara.
Devonian Crustal Stretching in the Northern Tasmanides (Australia) and Implications for Oroclinal Bending
Authors: Abdullah Rashed , Rosenbaum Gideon
Published: August 2018

The Tasmanides in eastern Australia exhibit a number of orogenic curvatures (oroclines), and possibly, a continental‐scale bend that defines the continuation of the Delamerian Orogen with the Thomson Orogen. We provide an insight into the geodynamic processes associated with the origin of this orocline. We present interpretations of seismic reflection profiles and potential field data from the Thomson Orogen, which provide information on the crustal architecture and unravel major structures and kinematic relationships. Results show that a large area in the northern Tasmanides is underlain by thinned crust, bounded in the north and south by ~E‐W trending geophysical features with apparent sinistral and dextral sense of kinematics, respectively. Within the highly extended crust of the Thomson Orogen, there is evidence for widespread Devonian basins bounded by normal faults. In stark contrast to the southern Tasmanides, where rocks show evidence for an earlier (Silurian) episode of extension and Devonian contractional deformation, no evidence for Silurian synrift sedimentation is observed in the Thomson Orogen. Evidence for ~E‐W trending sinistral and dextral crustal‐scale shear zones in the northern and southern boundaries of the Thomson Orogen, respectively, may represent tear faults, which were active during the Early Devonian and were possibly accompanied by tear‐related magmatism. We suggest that crustal stretching in the northern Tasmanides was associated with Devonian back‐arc extension in response to trench retreat, bounded by zones of slab‐tearing and crustal segmentation that ultimately led to the development of the Delamerian‐Thomson Orocline.
A Mechanism for Pacific Interdecadal Resonances
Authors: Skákala Jozef , Bruun John T.
Published: August 2018

Pacific interdecadal variability (PIV) is an important large‐scale climate phenomenon. There is growing evidence that PIV contains three spectral resonances: a decadal (13 ± 1‐year) spectral peak, bidecadal (20 ± 5‐year) resonance, and a pentadecadal (60 ± 10‐year) resonance. Although much has been clarified about mechanisms behind PIV, there are still many open questions about the origin of these resonant modes (especially the pentadecadal mode). We describe dynamics in the Pacific basin by a toy (delayed oscillator) model that sheds light on the nature of these resonant peaks. The model suggests that unlike the bidecadal resonance, which results from local atmosphere‐ocean coupling in the extratropics, the pentadecadal and possibly also decadal resonances result from atmospheric and oceanic teleconnections between the extratropics and tropics. We show that a tiny coupling between extratropics and tropics through the ocean tunnel is sufficient to trigger the pentadecadal oscillation in the Pacific basin. Our model also explains (a) the observed three‐period locking between the bidecadal and pentadecadal modes and (b) the synchronization of anomalies in the central eastern tropics and central North Pacific with the opposite relative sign. We conclude that the role of oceanic teleconnections is probably underestimated in the current literature on PIV.
Particulate Trace Metal Composition and Sources in the Kuroshio Adjacent to the East China Sea: The Importance of Aerosol Deposition
Authors: Liao Wen‐Hsuan , Ho Tung‐Yuan
Published: August 2018

The Kuroshio, flowing through the eastern end of the East China Sea, transports terrestrial material to the Northwestern Pacific Ocean. Along the Kuroshio path, we collected size‐fractionated suspended particles in the upper 200 m to investigate the composition and sources of particulate trace metals. Demonstrated by Al‐ and P‐normalized elemental ratios, we found that anthropogenic aerosol deposition was the major source of most particulate trace metals in the Kuroshio region although the impact of bottom resuspension and riverine input may be significant at some specific regions. As seen in our previous studies in the South China Sea and the Western Philippine Sea, this study concluded that anthropogenic aerosol deposition is the dominant particulate trace metal source in the surface water of the Northwestern Pacific Ocean and its marginal seas. Compared to particulate trace metal composition obtained in other open oceans, we found that the distribution patterns of particulate trace metal composition in the surface waters are closely associated with aerosol deposition fluxes. In regions with low deposition, the particulate trace metal concentrations were extremely low and metal to P ratios were all comparable to their intracellular quota previously proposed. In regions with high deposition, metal to P ratios were highly elevated in comparison to their intracellular quota and metal to Al ratios were deviated from lithogenic ratios to various extents. The globally consistent distribution patterns validate trace metal stoichiometry concept in plankton intracellularly and the primary role of aerosol deposition on deciding particulate trace metal composition in oceanic surface water globally.
SO2 Oxidation Kinetics Leave a Consistent Isotopic Imprint on Volcanic Ice Core Sulfate
Authors: Gautier Elsa , Savarino Joel , Erbland Joseph , Farquhar James
Published: August 2018

This work presents measurements of time‐resolved mass‐independently fractionated sulfate of volcanic origin from Antarctic ice core records that cover the last 2,600 years. These measurements are used to evaluate the time dependence of the deposited isotopic signal and to extract the isotopic characteristics of the reactions yielding sulfate from stratospheric volcanic eruptions in the modern atmosphere. Time evolution of the signal in snow (years) with respect to the fast SO2 oxidation in the stratosphere suggests that photochemically produced condensed phase is rapidly and continuously separated from the gas phase and preserved during transportation and deposition on the polar ice cap. On some eruptions, a nonzero isotopic mass balance highlights that a part of the signal can be lost during transport and/or deposition. The large number of volcanic events studied allows the Δ33S versus Δ36S and δ34S versus Δ33S slopes to be constrained at −1.56 (1σ = 0.25) and 0.09 (1σ = 0.02), respectively. The Δ33S versus Δ36S slope refines a prior determinations of Δ36S/Δ33S = −4 and overlaps the range observed for sulfur seen in early Earth samples (Archean). In recent volcanogenic sulfate, the Δ33S versus δ34S differs, however, from the Archean record. The similitude for Δ36S/Δ33S and the difference for Δ33S/δ34S suggest similar mass‐independently fractionated sulfate processes to the Archean atmosphere. Using a simple model, we highlight that a combination of several mechanisms is needed to reproduce the observed isotopic trends and suggest a greater contribution from mass‐dependent oxidation by OH in the modern atmosphere.
Diel Stream Temperature Effects on Nitrogen Cycling in Hyporheic Zones
Authors: Zheng Lizhi , Bayani Cardenas M.
Published: August 2018

Stream temperature often varies diurnally and seasonally, and these variations propagate into hyporheic zones (HZs), forming dynamic and heterogeneous thermal patterns. The complex thermal distribution creates potential biogeochemical hotspots and hot moments. Yet, how diel temperature variations affect HZ nitrogen cycling is unknown. We thus conducted a series of multiphysics numerical simulations of nonisothermal fluid flow and multicomponent reactive solute transport to investigate this problem. We imposed a sinusoidally varying stream temperature representing diel warming and cooling and studied the effects of different temperature means and amplitudes on HZ nitrate removal efficiency inside a streambed with a dune. The results showed that the time‐variable nitrification, denitrification, and nitrate removal efficiency responded differently to the diel stream temperature signal. The temporal variation of spatially averaged nitrification rate tracks the stream temperature signal, whereas the spatially averaged denitrification variation pattern has a more complex connection to temperature. We observed a persistent hotspot where significant denitrification rates are present over the 24‐hr period. We further evaluated and estimated the bulk nitrate removal efficiency calculated by time integration of spatially averaged reaction rates over a day. For denitrification‐dominant systems, the bulk nitrate removal efficiency for cases with dynamic stream temperature was effectively the same as those with an equivalent constant mean temperature. Therefore, the bulk removal efficiency of a thermally dynamic diel system may be represented by an equivalent isothermal system given stable flow conditions. However, since large instantaneous variations in various rates were observed, the results imply that randomly timed field measurements are unlikely to be representative. This has to be considered for both past and future synoptic observational studies.
Application of Discrete Element Methods to Approximate Sea Ice Dynamics
Authors: Damsgaard A. , Adcroft A. , Sergienko O.
Published: August 2018

Lagrangian models of sea ice dynamics have several advantages over Eulerian continuum models. Spatial discretization on the ice floe scale is natural for Lagrangian models and offers exact solutions for mechanical nonlinearities with arbitrary sea ice concentrations. This allows for improved model performance in ice‐marginal zones, where sea ice is fragmented. Furthermore, Lagrangian models can explicitly simulate jamming processes that occur when sea ice moves through narrow confinements. While difficult to parameterize in continuum formulations, jamming emerges spontaneously in dense granular systems simulated in a Lagrangian framework. Here we present a flexible discrete element framework for approximating Lagrangian sea ice mechanics at the ice floe scale, forced by ocean and atmosphere velocity fields. Our goal is to evaluate the potential of models simpler than the traditional discrete element methods for granular dynamics. We demonstrate that frictionless contact models based on compressive stiffness alone are unlikely to produce jamming and describe two different approaches based on Coulomb friction and cohesion which both result in increased bulk shear strength of the granular assemblage. The frictionless but cohesive contact model displays jamming behavior which is similar to the more complex model with Coulomb friction and ice floe rotation at larger scales and has significantly lower computational cost.
“To Be, or Not to Be, That Is the Question”—The Cretan Extensional Detachment, Greece
Authors: Ring Uwe , Yngwe Frej
Published: August 2018

We present new structural data from the contact zone between the high‐pressure Phyllite‐Quartzite unit (PQ) and the overlying non‐high‐pressure Tripolitza unit in east‐central Crete for testing propositions that this contact represents the top‐to‐the‐north Cretan extensional detachment. Detailed mapping in the Neapoli valley shows that the PQ/Tripolitza contact is associated with a shallowly dipping penetrative foliation and associated south‐southwest (SSW)‐trending stretching lineation in the PQ. Kinematic indicators yielded a consistent top‐to‐the‐SSW sense of shear. The Tripolitza unit above was brittlely deformed, and top‐to‐the‐SSW thrust faults sole out in the contact zone. Undoing the effects of subsequent large‐wavelength, low‐amplitude folding about west‐northwest‐trending axes of the contact indicates that the top‐to‐the‐SSW kinematics resulted from crustal shortening. Therefore, the PQ/Tripolitza contact in the Neapoli valley is an out‐of‐sequence thrust, the Tripolitza thrust. We discuss a tectonic model in which the high‐pressure PQ was first exhumed in a shortening‐related extrusion wedge between about 22 and 17 Ma. The top of the exhuming extrusion wedge was then cut off by out‐of‐sequence thrusts in the upper crust at ≥17–11 Ma during sustained N‐S shortening. Subsequently, extensional graben in Crete formed after 11 Ma.
Modeling of Interactions Between Floating Particles and Emergent Stems in Slow Open Channel Flow
Authors: Liu Xiaoguang , Zeng Yuhong , Huai Wenxin
Published: August 2018

In slow open channel flow that features emergent vegetation, the dispersal of floating particles is affected by hydrodynamic characteristics at the free surface (e.g., surface tension), fluid drag, and inertial impaction. We investigated the interaction mechanism between floating particles and emergent stems. A mechanical model that considers the combined effect of fluid drag and inertial impaction has been presented to predict the probability that a particle collides with emergent stems. This model correctly captures the expected positive correlation between collision probability and vegetation density for dense emergent canopies. Furthermore, a new definition of the probability that a floating particle interacts with a stem is proposed. A statistical model to predict the probability that particles are permanently captured by stems is also proposed where the physical characteristics of particles (such as density and shape) are explicitly treated. Flume experiments have been conducted to explore the simultaneous effects of stem density and flow velocity on the approach and retention of slow‐moving inertial particles. These experiments are used to evaluate the scaling assumptions and the proposed model performance.
Water Repellency Decreases Vapor Sorption of Clay Minerals
Authors: Chen Jingjing , Shang Chao , Eick Matthew J. , Stewart Ryan D.
Published: August 2018

As soils become dry, water primarily exists as vapor that adsorbs to and desorbs from particle surfaces. The drying process also often enhances soil water repellency, yet the effects of repellency on soil water vapor sorption and exchange are not well understood. The objective of this study was to quantify the water vapor sorption dynamics of two minerals (Ca2+ saturated kaolinite and montmorillonite), in which water repellency was induced using two organic agents: cetyl trimethylammonium bromide (~4% by mass) and stearic acid (0.5%, 5%, 10%, 20%, and 35% by mass). Samples were then analyzed for water vapor sorption isotherms, solid‐water contact angles, organic carbon content, mineral surface morphology, hydrophobic functional groups (using Fourier transform infrared spectroscopy), zeta potential, and particle size distributions. The results showed that the water repellent treatments altered particle surface potentials and decreased surface areas relative to the controls. As a result, those samples adsorbed significantly less water and had less hysteresis between adsorption and desorption isotherms than the nontreated controls (p < 0.05). Differences in water adsorption were most pronounced for water activities >0.6, where hydrophobic compounds may have inhibited water vapor condensation, even at low concentrations. In contrast, solid‐water contact angles were small in montmorillonite treatments with <10% stearic acid, suggesting that low levels of hydrophobic compounds may have greater effect on vapor sorption compared to liquid water imbibition. Altogether, these results imply that repellency may reduce water retention in dry soils and enhance water vapor losses.
Effectiveness of EGFR/HER2-targeted drugs is influenced by the downstream interaction shifts of PTPIP51 in HER2-amplified breast cancer cells
Authors: Dietel Eric , Brobeil Alexander , Tag Claudia , Gattenloehner Stefan , Wimmer Monika
Published: August 2018

Breast cancer is the most common female cancerous disease and the second most cause of cancer death in women. About 20–30% of these tumors exhibit an amplification of the HER2/ErbB2 receptor, which is coupled to a more aggressive and invasive growth of the cancer cells. Recently developed tyrosine kinase inhibitors and therapeutic antibodies targeting the HER2 receptor improved the overall survival time compared with sole radio- and chemotherapy. Upcoming resistances against the HER2-targeted therapy make a better understanding of the receptor associated downstream pathways an absolute need. In earlier studies, we showed the involvement of Protein Tyrosine Phosphatase Interacting Protein 51 (PTPIP51) in the mitogen-activated protein kinase (MAPK) pathway. The MAPK pathway is one of the most frequently overactivated pathways in HER2-amplified breast cancer cells. This study is aimed to elucidate the effects of four different TKIs on the interactome of PTPIP51, namely with the receptors EGFR and HER2, 14-3-3/Raf1 (MAPK pathway), its regulating enzymes, and the mitochondria-associated interaction partners in HER2 breast cancer cell lines (SK-BR3 and BT474) by using the Duolink proximity ligation assay, immunoblotting and knockdown of PTPIP51. Inhibition of both EGFR and HER2/ErbB2R shifted PTPIP51 into the MAPK pathway, but left the mitochondria-associated interactome of PTPIP51 unattended. Exclusively inhibiting HER2/ErbB2 by Mubritinib did not affect the interaction of PTPIP51 with the MAPK signaling. Selective inhibition of HER2 induced great alterations of mitochondria-associated interactions of PTPIP51, which ultimately led to the most-effective reduction of cell viability of SK-BR3 cells of all tested TKIs. The results clearly reveal the importance of knowing the exact mechanisms of the inhibitors affecting receptor tyrosine kinases in order to develop more efficient anti-HER2-targeted therapies.
Correction: Population pharmacokinetics of fludarabine in patients with aplastic anemia and Fanconi anemia undergoing allogeneic hematopoietic stem cell transplantation
Authors: Mohanan E. , Panetta J. C. , Lakshmi K. M. , Edison E. S. , Korula A. , Fouzia N. A. , Abraham A. , Viswabandya A. , Mathews V. , George B. , Srivastava A. , Balasubramanian P.
Published: August 2018

This article was originally published under a CC BY-NC-ND 4.0 license, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the article have been modified accordingly.
Divergent accumulation of microbial necromass and plant lignin components in grassland soils
Authors: Ma Tian , Zhu Shanshan , Wang Zhiheng , Chen Dima , Dai Guohua , Feng Bowei , Su Xiangyan , Hu Huifeng , Li Kaihui , Han Wenxuan , Liang Chao , Bai Yongfei , Feng Xiaojuan
Published: August 2018

The means through which microbes and plants contribute to soil organic carbon (SOC) accumulation remain elusive due to challenges in disentangling the complex components of SOC. Here we use amino sugars and lignin phenols as tracers for microbial necromass and plant lignin components, respectively, and investigate their distribution in the surface soils across Mongolian grasslands in comparison with published data for other grassland soils of the world. While lignin phenols decrease, amino sugars increase with SOC contents in all examined grassland soils, providing continental-scale evidence for the key role of microbial necromass in SOC accumulation. Moreover, in contrast to clay’s control on amino sugar accumulation in fine-textured soils, aridity plays a central role in amino sugar accrual and lignin decomposition in the coarse-textured Mongolian soils. Hence, aridity shifts may have differential impacts on microbial-mediated SOC accumulation in grassland soils of varied textures.
Intermolecular selective carboacylation of alkenes via nickel-catalyzed reductive radical relay
Authors: Zhao Xian , Tu Hai-Yong , Guo Lei , Zhu Shengqing , Qing Feng-Ling , Chu Lingling
Published: August 2018

The development of catalytic carboacylation of simple olefins, which would enable the rapid construction of ketones with high levels of complexity and diversity, is very challenging. To date, the vast majority of alkene carboacylation reactions are typically restricted to single- and two-component methodologies. Here we describe a three-component carboacylation of alkenes via the merger of radical chemistry with nickel catalysis. This reaction manifold utilizes a radical relay strategy involving radical addition to an alkene followed by alkyl radical capture by an acyl-nickel complex to forge two vicinal C−C bonds under mild conditions. Excellent chemoselectivity and regioselectivity have been achieved by utilizing a pendant weakly chelating group. This versatile protocol allows for facile access to a wide range of important β-fluoroalkyl ketones from simple starting materials.
Megahertz data collection from protein microcrystals at an X-ray free-electron laser
Authors: Grünbein Marie Luise , Bielecki Johan , Gorel Alexander , Stricker Miriam , Bean Richard , Cammarata Marco , Dörner Katerina , Fröhlich Lars , Hartmann Elisabeth , Hauf Steffen , Hilpert Mario , Kim Yoonhee , Kloos Marco , Letrun Romain , Messerschmidt Marc , Mills Grant , Nass Kovacs Gabriela , Ramilli Marco , Roome Christopher M. , Sato Tokushi , Scholz Matthias , Sliwa Michel , Sztuk-Dambietz Jolanta , Weik Martin , Weinhausen Britta , Al-Qudami Nasser , Boukhelef Djelloul , Brockhauser Sandor , Ehsan Wajid , Emons Moritz , Esenov Sergey , Fangohr Hans , Kaukher Alexander , Kluyver Thomas , Lederer Max , Maia Luis , Manetti Maurizio , Michelat Thomas , Münnich Astrid , Pallas Florent , Palmer Guido , Previtali Gianpietro , Raab Natascha , Silenzi Alessandro , Szuba Janusz , Venkatesan Sandhya , Wrona Krzysztof , Zhu Jun , Doak R. Bruce , Shoeman Robert L. , Foucar Lutz , Colletier Jacques-Philippe , Mancuso Adrian P. , Barends Thomas R. M. , Stan Claudiu A. , Schlichting Ilme
Published: August 2018

X-ray free-electron lasers (XFELs) enable novel experiments because of their high peak brilliance and femtosecond pulse duration. However, non-superconducting XFELs offer repetition rates of only 10–120 Hz, placing significant demands on beam time and sample consumption. We describe serial femtosecond crystallography experiments performed at the European XFEL, the first MHz repetition rate XFEL, delivering 1.128 MHz X-ray pulse trains at 10 Hz. Given the short spacing between pulses, damage caused by shock waves launched by one XFEL pulse on sample probed by subsequent pulses is a concern. To investigate this issue, we collected data from lysozyme microcrystals, exposed to a ~15 μm XFEL beam. Under these conditions, data quality is independent of whether the first or subsequent pulses of the train were used for data collection. We also analyzed a mixture of microcrystals of jack bean proteins, from which the structure of native, magnesium-containing concanavalin A was determined.
Redox-responsive self-assembly PEG nanoparticle enhanced triptolide for efficient antitumor treatment
Authors: Wang Yanchun , Liu Xuewei , Wang Xuemei , Zheng Wei , Zhang Junping , Shi Feng , Liu Junbao
Published: August 2018

Chemotherapy induces tumor cell death by directly damaging DNA or hindering cell mitosis. Some of the drawbacks of most chemotherapy are lack of target selectivity to tumor cells, and adverse drug reaction, which limit the treatment intensity and frequency. Herein, we synthesized the prodrug of triptolide (TP) coupled to vitamin E (VE) using dithiodiglycolic acid and co-dissolved with PEG2000- linoleic acid (MPEG200-LD) in ethanol. The PEGylated TP prodrug self-assembly nanoparticles (PTPPSN) were prepared via nanoprecipitation method. Besides, characterization, stability and in vitro release of the PEGylated nanometer prodrug were investigated. Furthermore, in vitro and in vivo antitumor efficacy of PTPPSN explored showed that the cytotoxicity of triptolide was significantly reduced in vitro preparation. However, in vitro and in vivo antitumor effect of PTPPSN was significantly improved compared to the original triptolide. In summary, the PEGylated nanoparticle successfully encapsulated triptolide yielded suitable cell microenvironment, and nanotechnology-related achievements. This study, therefore, provides a new method for antitumor research as well as an innovative technology for clinical treatment of malignant tumor.
Human Plasma Metabolomics Implicates Modified 9-cis-Retinoic Acid in the Phenotype of Left Main Artery Lesions in Acute ST-Segment Elevated Myocardial Infarction
Authors: Huang Lei , Zhang Lei , Li Tong , Liu Ying-wu , Wang Yu , Liu Bo-jiang
Published: August 2018

The detection of left main coronary artery disease (LMCAD) is crucial before ST-segment elevated myocardial infarction (STEMI) or sudden cardiac death. The aim of this study was to identify characteristic metabolite modifications in the LMCAD phenotype, using the metabolomics technique. Metabolic profiles were generated based on ultra-performance liquid chromatography and mass spectrometry, combined with multivariate statistical analysis. Plasma samples were collected prospectively from a propensity-score matched cohort including 44 STEMI patients (22 consecutive LMCAD and 22 non-LMCAD), and 22 healthy controls. A comprehensive metabolomics data analysis was performed with Metaboanalyst 3.0 version. The retinol metabolism pathway was shown to have the strongest discriminative power for the LMCAD phenotype. According to biomarker analysis through receiver-operating characteristic curves, 9-cis-retinoic acid (9cRA) dominated the first page of biomarkers, with area under the curve (AUC) value 0.888. Next highest were a biomarker panel consisting of 9cRA, dehydrophytosphingosine, 1H-Indole-3-carboxaldehyde, and another seven variants of lysophosphatidylcholines, exhibiting the highest AUC (0.933). These novel data propose that the retinol metabolism pathway was the strongest differential pathway for the LMCAD phenotype. 9cRA was the most critical biomarker of LMCAD, and a ten-metabolite plasma biomarker panel, in which 9cRA remained the weightiest, may help develop a potent predictive model for LMCAD in clinic.
Energy metabolism in the intestinal crypt epithelial cells of piglets during the suckling period
Authors: Wang Qiye , Xiong Xia , Li Jianzhong , Tu Qiang , Yang Huansheng , Yin Yulong
Published: August 2018

We tested the hypothesis that energy metabolism in the intestinal crypt epithelial cells of piglets changes during the suckling period. The experiment began with 24 piglets from 8 litters (3 piglets per litter). One piglet from each litter was randomly selected and euthanized at 7, 14, or 21 d of age, respectively. Crypt cells were isolated from the mid-jejunum and protein synthesis was analyzed using isobaric tags for relative and absolute quantification. The production of proteins related to glycolysis was mainly decreased from Days 7 to 14 before increasing up to Day 21. Synthesis of proteins involved in fatty acids, amino acids (glutamate and glutamine), and citrate cycle metabolism was generally down-regulated for samples collected on Days 14 and 21 when compared with levels on Day 7. These results indicate that energy metabolism in the intestinal crypt epithelial cells changes during the suckling period. Furthermore, this pattern of metabolism varies among glucose, fatty acids, and amino acids. Therefore, these findings may be useful in efforts to regulate the intestinal development of piglets.
Structural basis of cell wall peptidoglycan amidation by the GatD/MurT complex of Staphylococcus aureus
Authors: Nöldeke Erik R. , Muckenfuss Lena M. , Niemann Volker , Müller Anna , Störk Elena , Zocher Georg , Schneider Tanja , Stehle Thilo
Published: August 2018

The peptidoglycan of Staphylococcus aureus is highly amidated. Amidation of α-D-isoglutamic acid in position 2 of the stem peptide plays a decisive role in the polymerization of cell wall building blocks. S. aureus mutants with a reduced degree of amidation are less viable and show increased susceptibility to methicillin, indicating that targeting the amidation reaction could be a useful strategy to combat this pathogen. The enzyme complex that catalyzes the formation of α-D-isoglutamine in the Lipid II stem peptide was identified recently and shown to consist of two subunits, the glutamine amidotransferase-like protein GatD and the Mur ligase homolog MurT. We have solved the crystal structure of the GatD/MurT complex at high resolution, revealing an open, boomerang-shaped conformation in which GatD is docked onto one end of MurT. Putative active site residues cluster at the interface between GatD and MurT and are contributed by both proteins, thus explaining the requirement for the assembled complex to carry out the reaction. Site-directed mutagenesis experiments confirm the validity of the observed interactions. Small-angle X-ray scattering data show that the complex has a similar conformation in solution, although some movement at domain interfaces can occur, allowing the two proteins to approach each other during catalysis. Several other Gram-positive pathogens, including Streptococcus pneumoniae, Clostridium perfringens and Mycobacterium tuberculosis have homologous enzyme complexes. Combined with established biochemical assays, the structure of the GatD/MurT complex provides a solid basis for inhibitor screening in S. aureus and other pathogens.
Association of plasma microRNA expression with age, genetic background and functional traits in dairy cattle
Authors: Ioannidis Jason , Sánchez-Molano Enrique , Psifidi Androniki , Donadeu F. Xavier , Banos Georgios
Published: August 2018

A number of blood circulating microRNAs (miRNAs) are proven disease biomarkers and have been associated with ageing and longevity in multiple species. However, the role of circulating miRNAs in livestock species has not been fully studied. We hypothesise that plasma miRNA expression profiles are affected by age and genetic background, and associated with health and production traits in dairy cattle. Using PCR arrays, we assessed 306 plasma miRNAs for effects of age (calves vs mature cows) and genetic background (control vs select lines) in 18 animals. We identified miRNAs which were significantly affected by age (26 miRNAs) and genetic line (5 miRNAs). Using RT-qPCR in a larger cow population (n = 73) we successfully validated array data for 12 age-related miRNAs, one genetic line-related miRNA, and utilised expression data to associate their levels in circulation with functional traits in these animals. Plasma miRNA levels were associated with telomere length (ageing/longevity indicator), milk production and composition, milk somatic cell count (mastitis indicator), fertility, lameness, and blood metabolites linked with body energy balance and metabolic stress. In conclusion, circulating miRNAs could provide useful selection markers for dairy cows to help improve health, welfare and production performance.
Correlation of Color Fundus Photograph Grading with Risks of Early Age-related Macular Degeneration by using Automated OCT-derived Drusen Measurements
Authors: Cheung Chui Ming Gemmy , Shi Yuan , Tham Yih Chung , Sabanayagam Charumathi , Neelam Kumari , Wang Jie Jin , Mitchell Paul , Cheng Ching-Yu , Wong Tien Yin , Cheung Carol Yim Lui
Published: August 2018

We evaluated automated OCT-derived drusen volume measures in a population-based study (n = 4,512) aged ≥40 years, and its correlation with conventional color fundus photographs (CFP)-derived early AMD features. Participants had protocol-based assessment to capture medical and ocular history, genotyping for SNPs in CFH, ARMS2, and CETP, CFP-based AMD grading and automated drusen volume based on SD-OCT using built-in software (Cirrus OCT advanced RPE analysis software). Significantly fewer eyes with early AMD features (drusen, hyperpigmentation, soft or reticular drusen) had drusen volume = 0 mm3 (p < 0.001). In eyes with drusen volume > 0 mm3, increasing AMD severity was associated with increase in drusen volume (correlation coefficient 0.17, p < 0.001). However 220 (59.14%) of 372 participants with AMD based on CFP grading had drusen volume = 0 mm3. Factors associated with drusen volume included age (OR 1.42 per 5 years, 95% confidence interval [CI] 2.76, 4.48), systolic blood pressure (OR1.00, 95% CI 1.00, 1.01), ethnic Malay (OR 1.54, 95% CI 1.29, 1.83) and Chinese (OR 1.66, 95% CI 1.37, 2.01) compared to Indian. The ARMS2 rs10490924 T allele was associated with increased drusen volume in subjects with AMD (multivariable adjusted OR1.54, 95% CI 1.08, 2.19). Automated OCT-derived drusen volume is correlated with CFP-based AMD grading in many, but not all subjects. However the agreement is not good. These two modalities provide complementary information and should be incorporated into future studies.
Disruption of mesoderm formation during cardiac differentiation due to developmental exposure to 13-cis-retinoic acid
Authors: Liu Qing , Van Bortle Kevin , Zhang Yue , Zhao Ming-Tao , Zhang Joe Z. , Geller Benjamin S. , Gruber Joshua J. , Jiang Chao , Wu Joseph C. , Snyder Michael P.
Published: August 2018

13-cis-retinoic acid (isotretinoin, INN) is an oral pharmaceutical drug used for the treatment of skin acne, and is also a known teratogen. In this study, the molecular mechanisms underlying INN-induced developmental toxicity during early cardiac differentiation were investigated using both human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs). Pre-exposure of hiPSCs and hESCs to a sublethal concentration of INN did not influence cell proliferation and pluripotency. However, mesodermal differentiation was disrupted when INN was included in the medium during differentiation. Transcriptomic profiling by RNA-seq revealed that INN exposure leads to aberrant expression of genes involved in several signaling pathways that control early mesoderm differentiation, such as TGF-beta signaling. In addition, genome-wide chromatin accessibility profiling by ATAC-seq suggested that INN-exposure leads to enhanced DNA-binding of specific transcription factors (TFs), including HNF1B, SOX10 and NFIC, often in close spatial proximity to genes that are dysregulated in response to INN treatment. Altogether, these results identify potential molecular mechanisms underlying INN-induced perturbation during mesodermal differentiation in the context of cardiac development. This study further highlights the utility of human stem cells as an alternative system for investigating congenital diseases of newborns that arise as a result of maternal drug exposure during pregnancy.
Phosphorylation promotes binding affinity of Rap-Raf complex by allosteric modulation of switch loop dynamics
Authors: T Devanand , Venkatraman Prasanna , Vemparala Satyavani
Published: August 2018

The effects of phosphorylation of a serine residue on the structural and dynamic properties of Ras-like protein, Rap, and its interactions with effector protein Ras binding domain (RBD) of Raf kinase, in the presence of GTP, are investigated via molecular dynamics simulations. The simulations show that phosphorylation significantly effects the dynamics of functional loops of Rap which participate in the stability of the complex with effector proteins. The effects of phosphorylation on Rap are significant and detailed conformational analysis suggest that the Rap protein, when phosphorylated and with GTP ligand, samples different conformational space as compared to non-phosphorylated protein. In addition, phosphorylation of SER11 opens up a new cavity in the Rap protein which can be further explored for possible drug interactions. Residue network analysis shows that the phosphorylation of Rap results in a community spanning both Rap and RBD and strongly suggests transmission of allosteric effects of local alterations in Rap to distal regions of RBD, potentially affecting the downstream signalling. Binding free energy calculations suggest that phosphorylation of SER11 residue increases the binding between Rap and Raf corroborating the network analysis results. The increased binding of the Rap-Raf complex can have cascading effects along the signalling pathways where availability of Raf can influence the oncogenic effects of Ras proteins. These simulations underscore the importance of post translational modifications like phosphorylation on the functional dynamics in proteins and can be an alternative to drug-targeting, especially in notoriously undruggable oncoproteins belonging to Ras-like GTPase family.
Rhythmic synchronization and hybrid collective states of globally coupled oscillators
Authors: Qiu Tian , Bonamassa Ivan , Boccaletti Stefano , Liu Zonghua , Guan Shuguang
Published: August 2018

Macroscopic rhythms are often signatures of healthy functioning in living organisms, but they are still poorly understood on their microscopic bases. Globally interacting oscillators with heterogeneous couplings are here considered. Thorough theoretical and numerical analyses indicate the presence of multiple phase transitions between different collective states, with regions of bi-stability. Novel coherent phases are unveiled, and evidence is given of the spontaneous emergence of macroscopic rhythms where oscillators’ phases are always found to be self-organized as in Bellerophon states, i.e. in multiple clusters with quantized values of their average frequencies. Due to their rather unconditional appearance, the circumstance is paved that the Bellerophon states grasp the microscopic essentials behind collective rhythms in more general systems of interacting oscillators.
Publisher Correction: Symbiodinium genomes reveal adaptive evolution of functions related to coral-dinoflagellate symbiosis
Authors: Liu Huanle , Stephens Timothy G. , González-Pech Raúl A. , Beltran Victor H. , Lapeyre Bruno , Bongaerts Pim , Cooke Ira , Aranda Manuel , Bourne David G. , Forêt Sylvain , Miller David J. , van Oppen Madeleine J. H. , Voolstra Christian R. , Ragan Mark A. , Chan Cheong Xin
Published: August 2018

In the original HTML version of the paper, the following affiliation was missing for author Cheong Xin Chan: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia. This affiliation was incorrectly assigned to author Pim Bongaerts as “Present Address”. All affiliations were published correctly in the PDF version of the paper and have now been corrected in the HTML.
A comprehensive urinary steroid analysis strategy using two-dimensional gas chromatography – time of flight mass spectrometry
Authors: Bileck Andrea , Verouti Sophia N. , Escher Genevieve , Vogt Bruno , Groessl Michael
Published: August 2018

Steroids are key players in a high variety of physiological processes and are typically analyzed for the diagnosis of hormonal disorders.
Single-cell assay on microfluidic devices
Authors: Huang Qiushi , Mao Sifeng , Khan Mashooq , Lin Jin-Ming
Published: August 2018

Advances in microfluidic techniques have prompted researchers to study the inherent heterogeneity of single cells in cell populations.
Oxygen producing microscale spheres affect cell survival in conditions of oxygen-glucose deprivation in a cell specific manner: implications for cell transplantation
Authors: Newland Heike , Eigel Dimitri , Rosser Anne E. , Werner Carsten , Newland Ben
Published: August 2018

Oxygen-glucose deprivation detrimentally affected mesenchymal stem cells, which could be reversed by the addition of oxygen producing spheres.
Is it possible to control kinetic rates of radical polymerisation in ionic liquids?
Authors: Low Kaycee , Wylie Luke , Scarborough David L. A. , Izgorodina Ekaterina I.
Published: August 2018

This work predicted propagation rates of free radical polymerisation in clusters of ionic liquids: stabilisation of the propagating radical and deactivation of the monomer were found to be the main factors in controlling kinetic rates, allowing for controlled free radical polymerisation in ionic liquids.
The p-sc structure in phosphorus: bringing order to the high pressure phases of group 15 elements
Authors: Scelta Demetrio , Baldassarre Adhara , Serrano-Ruiz Manuel , Dziubek Kamil , Cairns Andrew B. , Peruzzini Maurizio , Bini Roberto , Ceppatelli Matteo
Published: August 2018

High pressure state-of-the-art synchrotron XRD in black-phosphorus has solved apparent contradictions about the stability of the A7 layered structure in pnictogens, highlighting the importance of the s–p orbital mixing in the formation of the p-sc structure.
{Np38} clusters: the missing link in the largest poly-oxo cluster series of tetravalent actinides
Authors: Martin Nicolas P. , Volkringer Christophe , Roussel Pascal , März Juliane , Hennig Christoph , Loiseau Thierry , Ikeda-Ohno Atsushi
Published: August 2018

The poly-oxo clusters of neptunium, {Np38}, fill the gap in the largest poly-oxo cluster series of tetravalent actinides.
Deciphering micro-polarity inside the endoplasmic reticulum using a two-photon active solvatofluorochromic probe
Authors: Pal Kaushik , Samanta Indranil , Gupta Rahul Kumar , Goswami Debabrata , Koner Apurba Lal
Published: August 2018

A new class of two-photon active and solvatofluorochromic dyes for the determination of ER polarity is reported.
Exploring the intramolecular catalysis of the proton exchange process to modulate the relaxivity of Gd(iii)-complexes of HP-DO3A-like ligands
Authors: Carnovale Irene Maria , Lolli Marco Lucio , Serra Sonia Colombo , Mingo Alberto Fringuello , Napolitano Roberta , Boi Valeria , Guidolin Nicol , Lattuada Luciano , Tedoldi Fabio , Baranyai Zsolt , Aime Silvio
Published: August 2018

The GdIII complex of Ph-HP-DO3A shows the highest contribution to the relaxivity by the intramolecular proton exchange of the –OH group.
Rational design of a ratiometric two-photon fluorescent probe for real-time visualization of apoptosis
Authors: Huang Yinliang , Zhou Qin , Feng Yan , Zhang Wan , Fang Guoshun , Fang Min , Chen Man , Xu Changzhi , Meng Xiangming
Published: August 2018

A ratiometric two-photon fluorescent probe (Mito-DCHO) was rationally designed for real-time assessing and dual-color visualization of the early stage of apoptosis.
1,1-Diphosphines and divinylphosphines via base catalyzed hydrophosphination
Authors: Coles N. T. , Mahon M. F. , Webster R. L.
Published: August 2018

A homologous series of 1,1-diphosphines have been prepared by alkyne hydrophosphination using catalytic KHMDS at room temperature.
Modulation of the optical color of Au nanoclusters and its application in ratiometric photoluminescence detection
Authors: Xiao Yan , Zhou Jie , Chen Miaomiao , Wen Wei , Zhang Xiuhua , Wang Shengfu
Published: August 2018

A novel strategy for the optical color modulation of glutathione stabilized Au nanoclusters is reported and applied in ratiometric photoluminescence detection.
Electronic-dimensionality reduction of bulk MoS2 by hydrogen treatment
Authors: Cho Soohyun , Kim Beom Seo , Kim Beomyoung , Kyung Wonshik , Seo Jeongjin , Park Min , Jeon Jun Woo , Tanaka Kiyohisa , Denlinger Jonathan D. , Kim Changyoung , Odkhuu Dorj , Kim Byung Hoon , Park Seung Ryong
Published: August 2018

Quantum well states in bulk-formed 2H-MoS2 after hydrogen-treatment were revealed by angle-resolved photoemission spectroscopy.
Trap-controlled proton hopping: interpretation of low-temperature dielectric relaxation of ice Ih
Authors: Khamzin A. A. , Nasybullin A. I.
Published: August 2018

A microscopic model of the dielectric relaxation of ice at low temperatures is proposed.