bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of a turbulent ExB mixing avalanche mechanism of gas breakdown in strongly magnetized systems
Authors: Yoo Min-Gu , Lee Jeongwon , Kim Young-Gi , Kim Jayhyun , Maviglia Francesco , Sips Adrianus C. C. , Kim Hyun-Tae , Hahm Taik Soo , Hwang Yong-Seok , Lee Hae June , Na Yong-Su 
Published: August 2018

AbstractAlthough gas breakdown phenomena have been intensively studied over 100 years, the breakdown mechanism in a strongly magnetized system, such as tokamak, has been still obscured due to complex electromagnetic topologies. There has been a widespread misconception that the conventional breakdown model of the unmagnetized system can be directly applied to the strongly magnetized system. However, we found clear evidence that existing theories cannot explain the experimental results. Here, we demonstrate the underlying mechanism of gas breakdown in tokamaks, a turbulent ExB mixing avalanche, which systematically considers multi-dimensional plasma dynamics in the complex electromagnetic topology. This mechanism clearly elucidates the experiments by identifying crucial roles of self-electric fields produced by space-charge that decrease the plasma density growth rate and cause a dominant transport via ExB drifts. A comprehensive understanding of plasma dynamics in complex electromagnetic topology provides general design strategy for robust breakdown scenarios in a tokamak fusion reactor.
Reprogramming of the antimycin NRPS-PKS assembly lines inspired by gene evolution
Authors: Awakawa Takayoshi , Fujioka Takuma , Zhang Lihan , Hoshino Shotaro , Hu Zhijuan , Hashimoto Junko , Kozone Ikuko , Ikeda Haruo , Shin-Ya Kazuo , Liu Wen , Abe Ikuro 
Published: August 2018

AbstractReprogramming of the NRPS/PKS assembly line is an attractive method for the production of new bioactive molecules. However, it is usually hampered by the loss of intimate domain/module interactions required for the precise control of chain transfer and elongation reactions. In this study, we first establish heterologous expression systems of the unique antimycin-type cyclic depsipeptides: JBIR-06 (tri-lactone) and neoantimycin (tetra-lactone), and engineer their biosyntheses by taking advantage of bioinformatic analyses and evolutionary insights. As a result, we successfully accomplish three manipulations: (i) ring contraction of neoantimycin (from tetra-lactone to tri-lactone), (ii) ring expansion of JBIR-06 (from tri-lactone to tetra-lactone), and (iii) alkyl chain diversification of JBIR-06 by the incorporation of various alkylmalonyl-CoA extender units, to generate a set of unnatural derivatives in practical yields. This study presents a useful strategy for engineering NRPS-PKS module enzymes, based on nature’s diversification of the domain and module organizations.
Color-stable highly luminescent sky-blue perovskite light-emitting diodes
Authors: Xing Jun , Zhao Yongbiao , Askerka Mikhail , Quan Li Na , Gong Xiwen , Zhao Weijie , Zhao Jiaxin , Tan Hairen , Long Guankui , Gao Liang , Yang Zhenyu , Voznyy Oleksandr , Tang Jiang , Lu Zheng-Hong , Xiong Qihua , Sargent Edward H. 
Published: August 2018

AbstractPerovskite light-emitting diodes (PeLEDs) have shown excellent performance in the green and near-infrared spectral regions, with high color purity, efficiency, and brightness. In order to shift the emission wavelength to the blue, compositional engineering (anion mixing) and quantum-confinement engineering (reduced-dimensionality) have been employed. Unfortunately, LED emission profiles shift with increasing driving voltages due to either phase separation or the coexistence of multiple crystal domains. Here we report color-stable sky-blue PeLEDs achieved by enhancing the phase monodispersity of quasi-2D perovskite thin films. We selected cation combinations that modulate the crystallization and layer thickness distribution of the domains. The perovskite films show a record photoluminescence quantum yield of 88% at 477 nm. The corresponding PeLEDs exhibit stable sky-blue emission under high operation voltages. A maximum luminance of 2480 cd m−2 at 490 nm is achieved, fully one order of magnitude higher than the previous record for quasi-2D blue PeLEDs.
Back to full interseismic plate locking decades after the giant 1960 Chile earthquake
Authors: Melnick Daniel , Li Shaoyang , Moreno Marcos , Cisternas Marco , Jara-Muñoz Julius , Wesson Robert , Nelson Alan , Báez Juan Carlos , Deng Zhiguo 
Published: August 2018

AbstractGreat megathrust earthquakes arise from the sudden release of energy accumulated during centuries of interseismic plate convergence. The moment deficit (energy available for future earthquakes) is commonly inferred by integrating the rate of interseismic plate locking over the time since the previous great earthquake. But accurate integration requires knowledge of how interseismic plate locking changes decades after earthquakes, measurements not available for most great earthquakes. Here we reconstruct the post-earthquake history of plate locking at Guafo Island, above the seismogenic zone of the giant 1960 (Mw = 9.5) Chile earthquake, through forward modeling of land-level changes inferred from aerial imagery (since 1974) and measured by GPS (since 1994). We find that interseismic locking increased to ~70% in the decade following the 1960 earthquake and then gradually to 100% by 2005. Our findings illustrate the transient evolution of plate locking in Chile, and suggest a similarly complex evolution elsewhere, with implications for the time- and magnitude-dependent probability of future events.
Restricted cell cycle is essential for clonal evolution and therapeutic resistance of pre-leukemic stem cells
Authors: Tremblay Cedric S. , Saw Jesslyn , Chiu Sung Kai , Wong Nicholas C. , Tsyganov Kirill , Ghotb Sarah , Graham Alison N. , Yan Feng , Guirguis Andrew A. , Sonderegger Stefan E. , Lee Nicole , Kalitsis Paul , Reynolds John , Ting Stephen B. , Powell David R. , Jane Stephen M. , Curtis David J. 
Published: August 2018

AbstractPre-leukemic stem cells (pre-LSCs) give rise to leukemic stem cells through acquisition of additional gene mutations and are an important source of relapse following chemotherapy. We postulated that cell-cycle kinetics of pre-LSCs may be an important determinant of clonal evolution and therapeutic resistance. Using a doxycycline-inducible H2B-GFP transgene in a mouse model of T-cell acute lymphoblastic leukemia to study cell cycle in vivo, we show that self-renewal, clonal evolution and therapeutic resistance are limited to a rare population of pre-LSCs with restricted cell cycle. We show that proliferative pre-LSCs are unable to return to a cell cycle-restricted state. Cell cycle-restricted pre-LSCs have activation of p53 and its downstream cell-cycle inhibitor p21. Furthermore, absence of p21 leads to proliferation of pre-LSCs, with clonal extinction through loss of asymmetric cell division and terminal differentiation. Thus, inducing proliferation of pre-LSCs represents a promising strategy to increase cure rates for acute leukemia.
Multidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains
Authors: Huang Wei , Peng Yi , Kiselar Janna , Zhao Xuan , Albaqami Aljawharah , Mendez Daniel , Chen Yinghua , Chakravarthy Srinivas , Gupta Sayan , Ralston Corie , Kao Hung-Ying , Chance Mark R. , Yang Sichun 
Published: August 2018

AbstractHuman estrogen receptor alpha (hERα) is a hormone-responsive nuclear receptor (NR) involved in cell growth and survival that contains both a DNA-binding domain (DBD) and a ligand-binding domain (LBD). Functionally relevant inter-domain interactions between the DBD and LBD have been observed in several other NRs, but for hERα, the detailed structural architecture of the complex is unknown. By utilizing integrated complementary techniques of small-angle X-ray scattering, hydroxyl radical protein footprinting and computational modeling, here we report an asymmetric L-shaped “boot” structure of the multidomain hERα and identify the specific sites on each domain at the domain interface involved in DBD–LBD interactions. We demonstrate the functional role of the proposed DBD–LBD domain interface through site-specific mutagenesis altering the hERα interfacial structure and allosteric signaling. The L-shaped structure of hERα is a distinctive DBD–LBD organization of NR complexes and more importantly, reveals a signaling mechanism mediated by inter-domain crosstalk that regulates this receptor’s allosteric function.
Clampdown of inflammation in aging and anticancer therapies by limiting upregulation and activation of GPCR, CXCR4
Authors: Nair Raji R. , Madiwale Shreyas V. , Saini Deepak Kumar 
Published: August 2018

AbstractOne of the major pathological outcomes of DNA damage during aging or anticancer therapy is enhanced inflammation. However, the underlying signaling mechanism that drives this is not well understood. Here, we show that in response to DNA damage, ubiquitously expressed GPCR, CXCR4 is upregulated through the ATM kinase-HIF1α dependent DNA damage response (DDR) signaling, and enhances inflammatory response when activated by its ligand, chemokine CXCL12. A pharmacologically active compound screen revealed that this increased inflammation is dependent on reduction in cAMP levels achieved through activation of Gαi through CXCR4 receptor and PDE4A. Through in vivo analysis in mice where DNA damage was induced by irradiation, we validated that CXCR4 is induced systemically after DNA damage and inhibition of its activity or its induction blocked inflammation as well as tissue injury. We thus report a unique DNA damage-linked inflammatory cascade, which is mediated by expression level changes in a GPCR and can be targeted to counteract inflammation during anticancer therapies as well as aging.
The stability of educational achievement across school years is largely explained by genetic factors
Authors: Rimfeld Kaili , Malanchini Margherita , Krapohl Eva , Hannigan Laurie J. , Dale Philip S. , Plomin Robert 
Published: August 2018

AbstractLittle is known about the etiology of developmental change and continuity in educational achievement. Here, we study achievement from primary school to the end of compulsory education for 6000 twin pairs in the UK-representative Twins Early Development Study sample. Results showed that educational achievement is highly heritable across school years and across subjects studied at school (twin heritability ~60%; SNP heritability ~30%); achievement is highly stable (phenotypic correlations ~0.70 from ages 7 to 16). Twin analyses, applying simplex and common pathway models, showed that genetic factors accounted for most of this stability (70%), even after controlling for intelligence (60%). Shared environmental factors also contributed to the stability, while change was mostly accounted for by individual-specific environmental factors. Polygenic scores, derived from a genome-wide association analysis of adult years of education, also showed stable effects on school achievement. We conclude that the remarkable stability of achievement is largely driven genetically even after accounting for intelligence.
A deconvolutional Bayesian mixing model approach for river basin sediment source apportionment
Authors: Blake William H. , Boeckx Pascal , Stock Brian C. , Smith Hugh G. , Bodé Samuel , Upadhayay Hari R. , Gaspar Leticia , Goddard Rupert , Lennard Amy T. , Lizaga Ivan , Lobb David A. , Owens Philip N. , Petticrew Ellen L. , Kuzyk Zou Zou A. , Gari Bayu D. , Munishi Linus , Mtei Kelvin , Nebiyu Amsalu , Mabit Lionel , Navas Ana , Semmens Brice X. 
Published: August 2018

AbstractIncreasing complexity in human-environment interactions at multiple watershed scales presents major challenges to sediment source apportionment data acquisition and analysis. Herein, we present a step-change in the application of Bayesian mixing models: Deconvolutional-MixSIAR (D-MIXSIAR) to underpin sustainable management of soil and sediment. This new mixing model approach allows users to directly account for the ‘structural hierarchy’ of a river basin in terms of sub-watershed distribution. It works by deconvoluting apportionment data derived for multiple nodes along the stream-river network where sources are stratified by sub-watershed. Source and mixture samples were collected from two watersheds that represented (i) a longitudinal mixed agricultural watershed in the south west of England which had a distinct upper and lower zone related to topography and (ii) a distributed mixed agricultural and forested watershed in the mid-hills of Nepal with two distinct sub-watersheds. In the former, geochemical fingerprints were based upon weathering profiles and anthropogenic soil amendments. In the latter compound-specific stable isotope markers based on soil vegetation cover were applied. Mixing model posterior distributions of proportional sediment source contributions differed when sources were pooled across the watersheds (pooled-MixSIAR) compared to those where source terms were stratified by sub-watershed and the outputs deconvoluted (D-MixSIAR). In the first example, the stratified source data and the deconvolutional approach provided greater distinction between pasture and cultivated topsoil source signatures resulting in a different posterior distribution to non-deconvolutional model (conventional approaches over-estimated the contribution of cultivated land to downstream sediment by 2 to 5 times). In the second example, the deconvolutional model elucidated a large input of sediment delivered from a small tributary resulting in differences in the reported contribution of a discrete mixed forest source. Overall D-MixSIAR model posterior distributions had lower (by ca 25–50%) uncertainty and quicker model run times. In both cases, the structured, deconvoluted output cohered more closely with field observations and local knowledge underpinning the need for closer attention to hierarchy in source and mixture terms in river basin source apportionment. Soil erosion and siltation challenge the energy-food-water-environment nexus. This new tool for source apportionment offers wider application across complex environmental systems affected by natural and human-induced change and the lessons learned are relevant to source apportionment applications in other disciplines.
Subcontinental heat wave triggers terrestrial and marine, multi-taxa responses
Authors: Ruthrof Katinka X. , Breshears David D. , Fontaine Joseph B. , Froend Ray H. , Matusick George , Kala Jatin , Miller Ben P. , Mitchell Patrick J. , Wilson Shaun K. , van Keulen Mike , Enright Neal J. , Law Darin J. , Wernberg Thomas , Hardy Giles E. St. J. 
Published: August 2018

AbstractHeat waves have profoundly impacted biota globally over the past decade, especially where their ecological impacts are rapid, diverse, and broad-scale. Although usually considered in isolation for either terrestrial or marine ecosystems, heat waves can straddle ecosystems of both types at subcontinental scales, potentially impacting larger areas and taxonomic breadth than previously envisioned. Using climatic and multi-species demographic data collected in Western Australia, we show that a massive heat wave event straddling terrestrial and maritime ecosystems triggered abrupt, synchronous, and multi-trophic ecological disruptions, including mortality, demographic shifts and altered species distributions. Tree die-off and coral bleaching occurred concurrently in response to the heat wave, and were accompanied by terrestrial plant mortality, seagrass and kelp loss, population crash of an endangered terrestrial bird species, plummeting breeding success in marine penguins, and outbreaks of terrestrial wood-boring insects. These multiple taxa and trophic-level impacts spanned >300,000 km2—comparable to the size of California—encompassing one terrestrial Global Biodiversity Hotspot and two marine World Heritage Areas. The subcontinental multi-taxa context documented here reveals that terrestrial and marine biotic responses to heat waves do not occur in isolation, implying that the extent of ecological vulnerability to projected increases in heat waves is underestimated.
Effects of Synchronous Electrode Pulses on Neural Recruitment During Multichannel Microstimulation
Authors: Hokanson James A. , Gaunt Robert A. , Weber Douglas J. 
Published: August 2018

AbstractThe recent proliferation of high-density microelectrode arrays has inspired several new applications of electrical microstimulation, including restoration of sensory functions in the visual, auditory, and somatosensory systems. In each case, the goal is to achieve precisely targeted activation of neurons, while patterning the location and timing of stimulation across the array to mimic naturalistic patterns of neural activity. However, when two or more electrodes deliver stimulation pulses at the same time, the electric fields created by each electrode interact. The effects of field interactions on neuronal recruitment depend on several factors, which have been studied extensively at the macro-scale but have been overlooked in the case of high density arrays. Here, we report that field interactions can significantly affect neural recruitment, even with low amplitude stimulation. We created a computational model of peripheral nerve axons to estimate stimulation parameters sufficient to generate neural recruitment during synchronous and asynchronous stimulation on two microelectrodes located within the peripheral nerve. Across a range of stimulus amplitudes, the model predicted that synchronous stimulation on adjacent electrodes (400 µm separation), would recruit 2–3 times more neurons than during asynchronous stimulation. Our results suggest that field interactions should not be ignored when designing multichannel microstimulation paradigms, even at threshold-level stimulus amplitudes.
Detection of antibiotics synthetized in microfluidic picolitre-droplets by various actinobacteria
Authors: Mahler Lisa , Wink Konstantin , Beulig R. Julia , Scherlach Kirstin , Tovar Miguel , Zang Emerson , Martin Karin , Hertweck Christian , Belder Detlev , Roth Martin 
Published: August 2018

AbstractThe natural bacterial diversity is regarded as a treasure trove for natural products. However, accessing complex cell mixtures derived from environmental samples in standardized high-throughput screenings is challenging. Here, we present a droplet-based microfluidic platform for ultrahigh-throughput screenings able to directly harness the diversity of entire microbial communities. This platform combines extensive cultivation protocols in aqueous droplets starting from single cells or spores with modular detection methods for produced antimicrobial compounds. After long-term incubation for bacterial cell propagation and metabolite production, we implemented a setup for mass spectrometric analysis relying on direct electrospray ionization and injection of single droplets. Even in the presence of dense biomass we show robust detection of streptomycin on the single droplet level. Furthermore, we developed an ultrahigh-throughput screening based on a functional whole-cell assay by picoinjecting reporter cells into droplets. Depending on the survival of reporter cells, droplets were selected for the isolation of producing bacteria, which we demonstrated for a microbial soil community. The established ultrahigh-throughput screening for producers of antibiotics in miniaturized bioreactors in which diverse cell mixtures can be screened on the single cell level is a promising approach to find novel antimicrobial scaffolds.
Predictions of novel Schistosoma mansoni - human protein interactions consistent with experimental data
Authors: White Bear J. , Long Thavy , Skinner Danielle , McKerrow James H. 
Published: August 2018

AbstractInfection by the human blood fluke, Schistosoma mansoni involves a variety of cross-species protein- protein interactions. The pathogen expresses a diverse arsenal of proteins that facilitate the breach of physical and biochemical barriers present in skin evasion of the immune system, and digestion of human plasma proteins including albumin and hemoglobin, allowing schistosomes to reside in the host for years. However, only a small number of specific interactions between S. mansoni and human proteins have been identified. We present and apply a protocol that generates testable predictions of S. mansoni-human protein interactions. In this study, we have preliminary predictions of novel interactions between schistosome and human proteins relevant to infection and the ability of the parasite to evade the immune system. We applied a computational whole-genome comparative approach to predict potential S. mansoni-human protein interactions based on similarity to known protein complexes. We first predict S. mansoni -human protein interactions based on similarity to known protein complexes. Putative interactions were then scored and assessed using several contextual filters, including the use of annotation automatically derived from literature using a simple natural language processing methodology. Next, in vitro experiments were carried out between schistosome and host proteins to validate several prospective predictions. Our method predicted 7 out of the 10 previously known cross-species interactions involved in pathogenesis between S. mansoni and its human host. Interestingly, two novel putative interactions involving Schistosoma proteins, the cercarial elastase SmCE, and the adult tegument surface protein Sm29, were also predicted and experimentally characterized. Preliminary data suggest that elafin, a host endogenous serine protease inhibitor, may be a novel substrate for SmCE. Additionally, CD59, an inhibitor of the membrane attack complex, could interact with Sm29. Furthermore, the application framework provides an integrated methodology for investigation of host-pathogen interactions and an extensive source of orthogonal data for experimental analysis. We have made the predictions available for community perusal.
Exploring Exemplary Optoelectronic and Charge Transport Properties of KCuX(X=Se,Te)
Authors: Parveen Atahar , Vaitheeswaran G. 
Published: August 2018

AbstractWe report the electronic structure, optical and charge transport properties of the unexplored ternary Zintl phases KCuX(X=Se,Te) from the first principles calculations employing the full-potential linearized augmented plane-wave (FLAPW) method with the Tran Blaha modified Becke-Johnson (TBmBJ) potential. It is demonstrated that the materials are direct band gap (1.13, 1.38 eV) semiconductors with covalent bonding between Cu and (Se/Te). The calculated low effective mass and high carrier mobility (over 105 cm2/V.s) accentuate that KCuX have good carrier transport and the materials may have possible applications in solar cell absorbers and nanoelectronic devices. Absorption spectra indicates that the ternary crystals are UV-A light absorbers and could be useful in photovoltaic and photodetector applications. A study on the effect of pressure (till 5 GPa) is carried out in order to further explore the materials for their electronic band gaps and charge transport properties as they are proposed to be useful in future contemporary electronic devices. It is observed that pressure enhances the intrinsic carrier mobility and thermal stability of KCuX, indicating that the materials can withstand robust external conditions.