bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ge/Si Partitioning in Igneous Systems: Constraints From Laser Ablation ICP‐MS Measurements on Natural Samples
Authors: He Detao , Lee Cin‐Ty A. , Yu Xun , Farner Michael 
Published: September 2019

AbstractMineral/melt and intermineral Ge/Si exchange coefficients for nine common rock‐forming silicate minerals were determined by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA‐ICP‐MS). Ge/Si mineral/melt exchange coefficients were found to vary by up to a factor of 10. In mafic and ultramafic systems, Ge/Si mineral/melt exchange coefficients are less than 1 for plagioclase (0.48) and olivine (0.72), close to 1 for clinopyroxene (1.17) and orthopyroxene (1.07), and greater than 1 for garnet (2.69). In felsic and silicic systems, the Ge/Si mineral/melt exchange coefficient is less than 1 for quartz (0.23), plagioclase (0.67), and potassium feldspar (0.67) but much greater than 1 for biotite (4.80) and hornblende (3.95). We show that early, olivine‐dominated fractionation of primitive basalts does not fractionate Ge/Si significantly, but subsequent cotectic crystallization of plagioclase and pyroxene can increase the Ge/Si ratio from 6 × 10−6 to 7 × 10−6. We show that the only way to decrease Ge/Si during magmatic differentiation is by crystallization of hornblende or biotite (though biotite is typically a late crystallizing phase), consistent with hornblende being a major fractionating phase in hydrous intermediate magmas. The high compatibility of Ge in hornblende makes this element, in conjunction with Si, a potentially useful approach for distinguishing between hornblende and garnet in the source regions of intermediate magmas. The high compatibility of Ge in micas suggests that Ge/Si systematics may also be useful in understanding the origin of ultrapotassic magmas, which are often thought to derive from phlogopite‐rich sources.
Distinct Ultrafine‐ and Accumulation‐Mode Particle Properties in Clean and Polluted Urban Environments
Authors: Wang Yuying , Li Zhanqing , Zhang Renyi , Jin Xiaoai , Xu Weiqi , Fan Xinxin , Wu Hao , Zhang Fang , Sun Yele , Wang Qiuyan , Cribb Maureen , Hu Dawei 
Published: September 2019

AbstractIn this study, we report the phenomenon of fast changes in aerosol hygroscopicity between clean and polluted periods observed frequently in urban Beijing during winter using a hygroscopicity tandem mobility analyzer. The cause of this phenomenon and the formation process of particles in different modes are discussed. During clean periods, ultrafine‐mode particles (i.e., nucleation and Aitken modes) stem mainly from nucleation events with subsequent growth. During heavily polluted periods, ultrafine‐mode particles originate chiefly from primary emissions. Larger‐mode particles like accumulation‐mode particles are mainly from primary emissions during clean periods and aqueous reactions during polluted periods. This finding based on hygroscopicity tandem mobility analyzer measurements can make up the deficiency of mass‐dependent instruments in analyzing sources and chemical processes of ultrafine‐mode particles.
Modeling the Electron Flux Enhancement and Butterfly Pitch Angle Distributions on L Shells <2.5
Authors: Hua Man , Li Wen , Ma Qianli , Ni Binbin , Nishimura Yukitoshi , Shen Xiao‐Chen , Li Haimeng 
Published: September 2019

AbstractWe analyze an energetic electron flux enhancement event in the inner radiation belt observed by Van Allen Probes during an intense geomagnetic storm. The energetic electron flux at L~1.5 increased by a factor of 3 with pronounced butterfly pitch angle distributions (PADs). Using a three‐dimensional radiation belt model, we simulate the electron evolution under the impact of radial diffusion, local wave‐particle interactions including hiss, very low frequency transmitters, and magnetosonic waves, as well as Coulomb scattering. Consistency between observation and simulation suggests that inward radial diffusion plays a dominant role in accelerating electrons up to 900 keV and transporting the butterfly PADs from higher L shells to form the butterfly PADs at L~1.5. However, local wave‐particle interactions also contribute to drive butterfly PADs at L ≳ 1.9. Our study provides a feasible mechanism to explain the electron flux enhancement in the inner belt and the persistent presence of the butterfly PADs at L~1.5.
Persistent Supercooled Drizzle at Temperatures Below −25 °C Observed at McMurdo Station, Antarctica
Authors: Silber Israel , Fridlind Ann M. , Verlinde Johannes , Ackerman Andrew S. , Chen Yao‐Sheng , Bromwich David H. , Wang Sheng‐Hung , Cadeddu Maria , Eloranta Edwin W. 
Published: September 2019

AbstractThe rarity of reports in the literature of brief and spatially limited observations of drizzle at temperatures below −20 °C suggest that riming and other temperature‐dependent cloud microphysical processes such as heterogeneous ice nucleation and ice crystal depositional growth prevent drizzle persistence in cold environments. In this study, we report on a persistent drizzle event observed by ground‐based remote sensing measurements at McMurdo Station, Antarctica. The temperatures in the drizzle‐producing cloud were below −25 °C and the drizzle persisted for a period exceeding 7.5 hr. Using ground‐based, satellite, and reanalysis data, we conclude that drizzle was likely present in parts of a widespread cloud field, which stretched more than ~1,000 km along the Ross Ice Shelf coast. Parameter space sensitivity tests using two‐moment bulk microphysics in large eddy simulations constrained by the observations suggest that activated ice freezing nuclei and accumulation‐mode aerosol number concentrations aloft during this persistent drizzle period were likely on the order of 0.2 L−1and 20 cm−3, respectively. In such constrained simulations, the drizzle moisture flux through cloud base exceeds that of ice. The simulations also indicate that drizzle can lead to the formation of multiple peaks in cloud water content profiles. This study suggests that persistent drizzle at these low temperatures may be common at the low aerosol concentrations typical of the Antarctic and Southern Ocean atmospheres.
Systematic Analysis of Machine Learning and Feature Selection Techniques for Prediction of the Kp Index
Authors: Zhelavskaya I. S. , Vasile R. , Shprits Y. Y. , Stolle C. , Matzka J. 
Published: September 2019

AbstractThe Kp index is a measure of the midlatitude global geomagnetic activity and represents short‐term magnetic variations driven by solar wind plasma and interplanetary magnetic field. The Kp index is one of the most widely used indicators for space weather alerts and serves as input to various models, such as for the thermosphere and the radiation belts. It is therefore crucial to predict the Kp index accurately. Previous work in this area has mostly employed artificial neural networks to nowcast Kp, based their inferences on the recent history of Kp and on solar wind measurements at L1. In this study, we systematically test how different machine learning techniques perform on the task of nowcasting and forecasting Kp for prediction horizons of up to 12 hr. Additionally, we investigate different methods of machine learning and information theory for selecting the optimal inputs to a predictive model. We illustrate how these methods can be applied to select the most important inputs to a predictive model of Kp and to significantly reduce input dimensionality. We compare our best performing models based on a reduced set of optimal inputs with the existing models of Kp, using different test intervals, and show how this selection can affect model performance.
Myelofibrosis in 2019: moving beyond JAK2 inhibition
Authors: Schieber Michael , Crispino John D. , Stein Brady 
Published: September 2019

AbstractMyelofibrosis (MF) is a myeloproliferative neoplasm characterized by ineffective clonal hematopoiesis, splenomegaly, bone marrow fibrosis, and the propensity for transformation to acute myeloid leukemia. The discovery of mutations in JAK2, CALR, and MPL have uncovered activated JAK-STAT signaling as a primary driver of MF, supporting a rationale for JAK inhibition. However, JAK inhibition alone is insufficient for long-term remission and offers modest, if any, disease-modifying effects. Given this, there is great interest in identifying mechanisms that cooperate with JAK-STAT signaling to predict disease progression and rationally guide the development of novel therapies. This review outlines the latest discoveries in the biology of MF, discusses current clinical management of patients with MF, and summarizes the ongoing clinical trials that hope to change the landscape of MF treatment.
Inhibition of cyclooxygenase-2 activity in subchondral bone modifies a subtype of osteoarthritis
Authors: Tu Manli , Yang Mi , Yu Nanxi , Zhen Gehua , Wan Mei , Liu Wenlong , Ji Baochao , Ma Hairong , Guo Qiaoyue , Tong Peijian , Cao Li , Luo Xianghang , Cao Xu 
Published: September 2019

AbstractOsteoarthritis (OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there is no effective disease-modifying therapy. Here, we report that elevated cyclooxygenase-2 (COX-2) expression in the osteocytes of subchondral bone causes both spontaneous OA and rheumatoid arthritis (RA). The knockout of COX-2 in osteocytes or treatment with a COX-2 inhibitor effectively rescues the structure of subchondral bone and attenuates cartilage degeneration in spontaneous OA (STR/Ort) mice and tumor necrosis factor-α transgenic RA mice. Thus, elevated COX-2 expression in subchondral bone induces both OA-associated and RA-associated joint cartilage degeneration. The inhibition of COX-2 expression can potentially modify joint destruction in patients with arthritis.
The transcription factor Zfp281 sustains CD4+ T lymphocyte activation through directly repressing Ctla-4 transcription
Authors: Guo Jing , Xue Zhonghui , Ma Ruoyu , Yi Weiwei , Hui Zhaoyuan , Guo Yixin , Yao Yuxi , Cao Wenqiang , Wang Jianli , Ju Zhenyu , Lu Linrong , Wang Lie 
Published: September 2019

Abstract
The expression of coinhibitory receptors, such as CTLA-4, on effector T cells is a key mechanism for the negative regulation of T-cell activation. However, the transcriptional regulation of CTLA-4 is not well understood. Zfp281, a C2H2 zinc finger protein, is a negative regulator of pluripotency maintenance of embryonic stem cells. Nevertheless, the function of Zfp281 in differentiated cells has not been studied. We generated Zfp281 conditional knockout mice in which the function of the Zfp281 gene was conditionally disrupted by the Cd4
Cre transgene to study its impact on T cell function. Zfp281 had no effect on T-cell development, but CD4+ T cell activation and cytokine production were impaired due to diminished T-cell receptor signaling. Furthermore, Zfp281 deficiency inhibited in vivo T cell responses to Listeria monocytogenes infection. Using genome-wide expression profiling assays, we determined that Zfp281 repressed Ctla-4 expression by directly binding to GC-rich sites in its promoter, which inhibited the negative feedback of T cell activation. In line with this result, CTLA-4 blockade and shRNA knockdown partly rescued the reduced cytokine production caused by Zfp281 deficiency. These findings indicate that Zfp281 sustains CD4+ T lymphocyte activation by directly repressing Ctla-4 transcription.
TGFβ blocks IFNα/β release and tumor rejection in spontaneous mammary tumors
Authors: Guerin Marion V. , Regnier Fabienne , Feuillet Vincent , Vimeux Lene , Weiss Julia M. , Bismuth Georges , Altan-Bonnet Gregoire , Guilbert Thomas , Thoreau Maxime , Finisguerra Veronica , Donnadieu Emmanuel , Trautmann Alain , Bercovici Nadège 
Published: September 2019

AbstractType I interferons (IFN) are being rediscovered as potent anti-tumoral agents. Activation of the STimulator of INterferon Genes (STING) by DMXAA (5,6-dimethylxanthenone-4-acetic acid) can induce strong production of IFNα/β and rejection of transplanted primary tumors. In the present study, we address whether targeting STING with DMXAA also leads to the regression of spontaneous MMTV-PyMT mammary tumors. We show that these tumors are refractory to DMXAA-induced regression. This is due to a blockade in the phosphorylation of IRF3 and the ensuing IFNα/β production. Mechanistically, we identify TGFβ, which is abundant in spontaneous tumors, as a key molecule limiting this IFN-induced tumor regression by DMXAA. Finally, blocking TGFβ restores the production of IFNα by activated MHCII+tumor-associated macrophages, and enables tumor regression induced by STING activation. On the basis of these findings, we propose that type I IFN-dependent cancer therapies could be greatly improved by combinations including the blockade of TGFβ.
Bacterial co-culture with cell signaling translator and growth controller modules for autonomously regulated culture composition
Authors: Stephens Kristina , Pozo Maria , Tsao Chen-Yu , Hauk Pricila , Bentley William E. 
Published: September 2019

AbstractSynthetic biology and metabolic engineering have expanded the possibilities for engineered cell-based systems. The addition of non-native biosynthetic and regulatory components can, however, overburden the reprogrammed cells. In order to avoid metabolic overload, an emerging area of focus is on engineering consortia, wherein cell subpopulations work together to carry out a desired function. This strategy requires regulation of the cell populations. Here, we design a synthetic co-culture controller consisting of cell-based signal translator and growth-controller modules that, when implemented, provide for autonomous regulation of the consortia composition. The system co-opts the orthogonal autoinducer AI-1 and AI-2 cell-cell signaling mechanisms of bacterial quorum sensing (QS) to enable cross-talk between strains and a QS signal-controlled growth rate controller to modulate relative population densities. We further develop a simple mathematical model that enables cell and system design for autonomous closed-loop control of population trajectories.
Aluminum with dispersed nanoparticles by laser additive manufacturing
Authors: Lin Ting-Chiang , Cao Chezheng , Sokoluk Maximilian , Jiang Lin , Wang Xin , Schoenung Julie M. , Lavernia Enrique J. , Li Xiaochun 
Published: September 2019

AbstractWhile laser-printed metals do not tend to match the mechanical properties and thermal stability of conventionally-processed metals, incorporating and dispersing nanoparticles in them should enhance their performance. However, this remains difficult to do during laser additive manufacturing. Here, we show that aluminum reinforced by nanoparticles can be deposited layer-by-layer via laser melting of nanocomposite powders, which enhance the laser absorption by almost one order of magnitude compared to pure aluminum powders. The laser printed nanocomposite delivers a yield strength of up to 1000 MPa, plasticity over 10%, and Young’s modulus of approximately 200 GPa, offering one of the highest specific Young’s modulus and specific yield strengths among structural metals, as well as an improved specific strength and thermal stability up to 400 °C compared to other aluminum-based materials. The improved performance is attributed to a high density of well-dispersed nanoparticles, strong interfacial bonding between nanoparticles and Al matrix, and ultrafine grain sizes.
Cooperation of cancer drivers with regulatory germline variants shapes clinical outcomes
Authors: Musa Julian , Cidre-Aranaz Florencia , Aynaud Marie-Ming , Orth Martin F. , Knott Maximilian M. L. , Mirabeau Olivier , Mazor Gal , Varon Mor , Hölting Tilman L. B. , Grossetête Sandrine , Gartlgruber Moritz , Surdez Didier , Gerke Julia S. , Ohmura Shunya , Marchetto Aruna , Dallmayer Marlene , Baldauf Michaela C. , Stein Stefanie , Sannino Giuseppina , Li Jing , Romero-Pérez Laura , Westermann Frank , Hartmann Wolfgang , Dirksen Uta , Gymrek Melissa , Anderson Nathaniel D. , Shlien Adam , Rotblat Barak , Kirchner Thomas , Delattre Olivier , Grünewald Thomas G. P. 
Published: September 2019

AbstractPediatric malignancies including Ewing sarcoma (EwS) feature a paucity of somatic alterations except for pathognomonic driver-mutations that cannot explain overt variations in clinical outcome. Here, we demonstrate in EwS how cooperation of dominant oncogenes and regulatory germline variants determine tumor growth, patient survival and drug response. Binding of the oncogenic EWSR1-FLI1 fusion transcription factor to a polymorphic enhancer-like DNA element controls expression of the transcription factor MYBL2 mediating these phenotypes. Whole-genome and RNA sequencing reveals that variability at this locus is inherited via the germline and is associated with variable inter-tumoral MYBL2 expression. High MYBL2 levels sensitize EwS cells for inhibition of its upstream activating kinase CDK2 in vitro and in vivo, suggesting MYBL2 as a putative biomarker for anti-CDK2-therapy. Collectively, we establish cooperation of somatic mutations and regulatory germline variants as a major determinant of tumor progression and highlight the importance of integrating the regulatory genome in precision medicine.
Reaction selectivity of homochiral versus heterochiral intermolecular reactions of prochiral terminal alkynes on surfaces
Authors: Wang Tao , Lv Haifeng , Huang Jianmin , Shan Huan , Feng Lin , Mao Yahui , Wang Jinyi , Zhang Wenzhao , Han Dong , Xu Qian , Du Pingwu , Zhao Aidi , Wu Xiaojun , Tait Steven L. , Zhu Junfa 
Published: September 2019

AbstractControlling selectivity between homochiral and heterochiral reaction pathways on surfaces remains a great challenge. Here, competing reactions of a prochiral alkyne on Ag(111): two-dimensional (2D) homochiral Glaser coupling and heterochiral cross-coupling with a Bergman cyclization step have been examined. We demonstrate control strategies in steering the reactions between the homochiral and heterochiral pathways by tuning the precursor substituents and the kinetic parameters, as confirmed by high-resolution scanning probe microscopy (SPM). Control experiments and density functional theory (DFT) calculations reveal that the template effect of organometallic chains obtained under specific kinetic conditions enhances Glaser coupling between homochiral molecules. In contrast, for the reaction of free monomers, the kinetically favorable reaction pathway is the cross-coupling between two heterochiral molecules (one of them involving cyclization). This work demonstrates the application of kinetic control to steer chiral organic coupling pathways at surfaces.
Visible light induced alkene aminopyridylation using N-aminopyridinium salts as bifunctional reagents
Authors: Moon Yonghoon , Park Bohyun , Kim Inwon , Kang Gyumin , Shin Sanghoon , Kang Dahye , Baik Mu-Hyun , Hong Sungwoo 
Published: September 2019

AbstractThe development of intermolecular alkene aminopyridylation has great potential for quickly increasing molecular complexity with two valuable groups. Here we report a strategy for the photocatalytic aminopyridylation of alkenes using a variety of N-aminopyridinium salts as both aminating and pyridylating reagents. Using Eosin Y as a photocatalyst, amino and pyridyl groups are simultaneously incorporated into alkenes, affording synthetically useful aminoethyl pyridine derivatives under mild reaction conditions. Remarkably, the C4-regioselectivity in radical trapping with N-aminopyridinium salt can be controlled by electrostatic interaction between the pyridinium nitrogen and sulfonyl group of β-amino radical. This transformation is characterized by a broad substrate scope, good functional group compatibility, and the utility of this transformation was further demonstrated by late-stage functionalization of complex biorelevant molecules. Combining experiments and DFT calculations on the mechanism of the reaction is investigated to propose a complete mechanism and regioselectivity.
Early induction of C/EBPβ expression as a potential marker of steroid responsive colitis
Authors: Assas Mushref Bakri , Levison Scott , Pennock Joanne L. 
Published: September 2019

AbstractThe precise mechanism of hydrocortisone immune regulation in the management of colitis is poorly understood. Whilst not without limitations, its ability to suppress pathology and rapidly improve patient clinical outcome is key. We were interested in identifying early markers of therapeutic responsiveness in order to identify patients’ refractory to therapy. Chronic Th1-driven colitis was induced in AKR/J mice using a parasite infection,Trichuris muris. 35 days post infection, mice were treated with low dose hydrocortisone (2 mg/kg/) i.p. on alternate days. Response to therapy was assessed at a systemic and tissue level day 45 post infection. Histopathology, gene and protein analysis was conducted to determine cytokine and transcriptional profiles. The colonic transcriptional profile in steroid treated mice showed significant upregulation of a small subset of T cell associated genes, in particular C/EBPβ, CD4, IL7R and STAT5a. Despite no change in either transcription or protein production in downstream cytokines IFN γ, TNFα IL-17 and IL-10, hydrocortisone treatment significantly reduced colonic pathology and restored colonic length to naïve levels. As expected, steroid treatment of chronic gut inflammation generated significant immunosuppressive effects characterized by histological improvement. Low dose hydrocortisone induced significant upregulation of a subset of genes associated with T cell maintenance and regulation, including C/EBPβ. These data suggest that enhanced expression of C/EBPβ may be one of a subset of early markers demonstrating an immune regulatory response to hydrocortisone therapy, potentially by stabilization of Treg function. These observations contribute to our understanding of the immune landscape after steroid therapy, providing a potential markers of therapeutic responders and those refractory to hydrocortisone treatment.
E40, a novel microbial protease efficiently detoxifying gluten proteins, for the dietary management of gluten intolerance
Authors: Cavaletti Linda , Taravella Anna , Carrano Lucia , Carenzi Giacomo , Sigurtà Alessandro , Solinas Nicola , Caro Salvatore De , Stasio Luigia Di , Picascia Stefania , Laezza Mariavittoria , Troncone Riccardo , Gianfrani Carmen , Mamone Gianfranco 
Published: September 2019

AbstractGluten proteins are the causative agent of Celiac Disease (CD), a life-long food intolerance characterized by an autoimmune enteropathy. Inadvertent gluten exposure is frequent even in celiac patients complying with a gluten-free diet, and the supplementation of exogenous gluten-digestive enzymes (glutenases) is indeed a promising approach to reduce the risk of dietary gluten boost. Here we describe Endopeptidase 40, a novel glutenase discovered as secreted protein from the soil actinomycete Actinoallomurus A8, and its recombinant active form produced by Streptomyces lividans TK24. E40 is resistant to pepsin and trypsin, and active in the acidic pH range 3 to 6. E40 efficiently degrades the most immunogenic 33-mer as well as the whole gliadin proteins, as demonstrated by SDS-PAGE, HPLC, LC-MS/MS, and ELISA. T lymphocytes from duodenal biopsies of celiac patients showed a strongly reduced or absent release of IFN-γ when exposed to gluten digested with E40. Data in gastrointestinal simulated conditions suggest that no toxic peptides are freed during gluten digestion by E40 into the stomach to enter the small intestine, thus counteracting the intestinal inflammatory cascade to occur in CD patients. E40 is proposed as a novel candidate in Oral Enzymatic Therapy for the dietary management of gluten toxicity.