bluuebunny/crossref_metadata_2025_split huggingface dataset:
China's Interannual Variability of Net Primary Production Is Dominated by the Central China Region
Authors: Peng Jing , Dan Li , Ying Kairan , Yang Shuai , Tang Xiba , Yang Fuqiang 
Published: December 2020

AbstractIt is important to understand regional contributions to interannual and decadal variabilities of vegetation productivity. However, most studies of regional terrestrial carbon cycles focus on the contributions of regional ecosystems to the mean or trend of net primary production (NPP), rather than its interannual variability (IAV). In this study, the IAV of NPP is explored using the simulation of the Australian Community Atmospheric Biosphere Land Exchange model, version 2.1 (CABLE2.1), compared with an eight‐member Trends in Net Land–Atmosphere Carbon Exchanges (TRENDY) ensemble under present conditions (1951–2010). NPP IAV is also analyzed using only CABLE2.1 under future conditions (2041–2100). Under the present conditions, the Central China region (region CC) contributes the largest fraction (CABLE2.1, 28.2%; TRENDY, 33.3% ± 11.5%) of NPP IAV in China. Such an NPP IAV is strongly associated with circulation‐driven variations in precipitation in most of China (∼85%). During the future period, region CC still plays a key role in the national NPP IAV, at ∼24.6%. Although precipitation IAV is still the main driver regulating the NPP IAV for region CC under the future conditions, climate sensitivity of NPP IAV to precipitation IAV may weaken compared with those under the present conditions. Our results highlight the contribution of region CC to the NPP IAV of China as a whole.
Evaluation of the Forecast Performance for Extreme Cold Events in East Asia With Subseasonal‐to‐Seasonal Data Sets From ECMWF
Authors: Dai Guokun , Mu Mu , Li Chunxiang , Han Zhe , Wang Lei 
Published: December 2020

AbstractUtilizing the subseasonal‐to‐seasonal (S2S) operational forecasts from the European Centre for Medium‐Range Weather Forecasts, the forecast skill for East Asian extreme cold events during 2015–2019 is evaluated. The results from the ensemble mean surface air temperature anomaly, the extreme forecast index, and the continuous ranked probability score skill reveal that extreme cold events can be captured by numerical models with a lead time of 7 days. It is also found that long‐persistent extreme cold events tend to have a longer skillful forecast lead time, which can exceed 10 days. The long skillful forecast lead time indicates that these events have a high intrinsic predictability, and the remote sea surface temperature anomaly, tropical intra‐seasonal oscillation and stratospheric polar vortex may be possible reasons for this predictability. The results suggest that it may be possible to make S2S and beyond skillful forecasts.
Viscoelastic microfluidics: progress and challenges
Authors: Zhou Jian , Papautsky Ian 
Published: December 2020

AbstractThe manipulation of cells and particles suspended in viscoelastic fluids in microchannels has drawn increasing attention, in part due to the ability for single-stream three-dimensional focusing in simple channel geometries. Improvement in the understanding of non-Newtonian effects on particle dynamics has led to expanding exploration of focusing and sorting particles and cells using viscoelastic microfluidics. Multiple factors, such as the driving forces arising from fluid elasticity and inertia, the effect of fluid rheology, the physical properties of particles and cells, and channel geometry, actively interact and compete together to govern the intricate migration behavior of particles and cells in microchannels. Here, we review the viscoelastic fluid physics and the hydrodynamic forces in such flows and identify three pairs of competing forces/effects that collectively govern viscoelastic migration. We discuss migration dynamics, focusing positions, numerical simulations, and recent progress in viscoelastic microfluidic applications as well as the remaining challenges. Finally, we hope that an improved understanding of viscoelastic flows in microfluidics can lead to increased sophistication of microfluidic platforms in clinical diagnostics and biomedical research.
Combinatorial nanodot stripe assay to systematically study cell haptotaxis
Authors: Dlamini Mcolisi , Kennedy Timothy E. , Juncker David 
Published: December 2020

AbstractHaptotaxis is critical to cell guidance and development and has been studied in vitro using either gradients or stripe assays that present a binary choice between full and zero coverage of a protein cue. However, stripes offer only a choice between extremes, while for gradients, cell receptor saturation, migration history, and directional persistence confound the interpretation of cellular responses. Here, we introduce nanodot stripe assays (NSAs) formed by adjacent stripes of nanodot arrays with different surface coverage. Twenty-one pairwise combinations were designed using 0, 1, 3, 10, 30, 44 and 100% stripes and were patterned with 200 × 200, 400 × 400 or 800 × 800 nm2 nanodots. We studied the migration choices of C2C12 myoblasts that express neogenin on NSAs (and three-step gradients) of netrin-1. The reference surface between the nanodots was backfilled with a mixture of polyethylene glycol and poly-d-lysine to minimize nonspecific cell response. Unexpectedly, cell response was independent of nanodot size. Relative to a 0% stripe, cells increasingly chose the high-density stripe with up to ~90% of cells on stripes with 10% coverage and higher. Cell preference for higher vs. lower netrin-1 coverage was observed only for coverage ratios >2.3, with cell preference plateauing at ~80% for ratios ≥4. The combinatorial NSA enables quantitative studies of cell haptotaxis over the full range of surface coverages and ratios and provides a means to elucidate haptotactic mechanisms.
A Phase 1 study of RO6870810, a novel bromodomain and extra-terminal protein inhibitor, in patients with NUT carcinoma, other solid tumours, or diffuse large B-cell lymphoma
Authors: Shapiro Geoffrey I. , LoRusso Patricia , Dowlati Afshin , T. Do Khanh , Jacobson Caron A. , Vaishampayan Ulka , Weise Amy , Caimi Paolo F. , Eder Joseph Paul , French Christopher A. , Labriola-Tompkins Emily , Boisserie Frédéric , Pierceall William E. , Zhi Jianguo , Passe Sharon , DeMario Mark , Kornacker Martin , Armand Philippe 
Published: December 2020

Abstract
Background
Bromodomain and extra-terminal (BET) proteins are epigenetic readers that can drive carcinogenesis and therapy resistance. RO6870810 is a novel, small-molecule BET inhibitor.

Methods
We conducted a Phase 1 study of RO6870810 administered subcutaneously for 21 or 14 days of 28- or 21-day cycles, respectively, in patients with the nuclear protein of the testis carcinoma (NC), other solid tumours, or diffuse large B-cell lymphoma (DLBCL) with MYC deregulation.

Results
Fatigue (42%), decreased appetite (35%) and injection-site erythema (35%) were the most common treatment-related adverse events. Pharmacokinetic parameters demonstrated linearity over the dose range tested and support once-daily dosing. Pharmacodynamic assessments demonstrated sustained decreases in CD11b levels in peripheral blood mononuclear cells. Objective response rates were 25% (2/8), 2% (1/47) and 11% (2/19) for patients with NC, other solid tumours and DLBCL, respectively. Responding tumours had evidence of deregulated MYC expression.

Conclusions
This trial establishes the safety, favourable pharmacokinetics, evidence of target engagement and preliminary single-agent activity of RO6870810. Responses in patients with NC, other solid tumours and DLBCL provide proof-of-principle for BET inhibition in MYC-driven cancers. The results support further exploration of RO6870810 as monotherapy and in combinations.

Clinical trials registration
NCT01987362.
Transcriptional factor ATF3 promotes liver fibrosis via activating hepatic stellate cells
Authors: Shi Zhemin , Zhang Kun , Chen Ting , Zhang Yu , Du Xiaoxiao , Zhao Yanmian , Shao Shuai , Zheng Lina , Han Tao , Hong Wei 
Published: December 2020

AbstractThe excessive accumulation of extracellular matrix (ECM) is a key feature of liver fibrosis and the activated hepatic stellate cells (HSCs) are the major producer of ECM proteins. However, the precise mechanisms and target molecules that are involved in liver fibrosis remain unclear. In this study, we reported that activating transcription factor 3 (ATF3) was over-expressed in mice and human fibrotic livers, in activated HSCs and injured hepatocytes (HCs). Both in vivo and in vitro study have revealed that silencing ATF3 reduced the expression of pro-fibrotic genes and inhibited the activation of HSCs, thus alleviating the extent of liver fibrosis, indicating a potential protective role of ATF3 knockdown. However, ATF3 was not involved in either the apoptosis or proliferation of HCs. In addition, our data illustrated that increased nuclear localization of ATF3 promoted the transcription of fibrogenic genes and lnc-SCARNA10, which functioned as a novel positive regulator of TGF-β signaling in liver fibrogenesis by recruiting SMAD3 to the promoter of these genes. Interestingly, further study also demonstrated that lnc-SCARNA10 promoted the expression of ATF3 in a TGF-β/SMAD3-dependent manner, revealing a TGF-β/ATF3/lnc-SCARNA10 axis that contributed to liver fibrosis by activating HSCs. Taken together, our data provide a molecular mechanism implicating induced ATF3 in liver fibrosis, suggesting that ATF3 may represent a useful target in the development of therapeutic strategies for liver fibrosis.
A nuclear-localized cysteine desulfhydrase plays a role in fruit ripening in tomato
Authors: Hu Kang-Di , Zhang Xiao-Yue , Yao Gai-Fang , Rong Yu-Lei , Ding Chen , Tang Jun , Yang Feng , Huang Zhong-Qin , Xu Zi-Mu , Chen Xiao-Yan , Li Yan-Hong , Hu Lan-Ying , Zhang Hua 
Published: December 2020

AbstractHydrogen sulfide (H2S) is a gaseous signaling molecule that plays multiple roles in plant development. However, whether endogenous H2S plays a role in fruit ripening in tomato is still unknown. In this study, we show that the H2S-producing enzyme l-cysteine desulfhydrase SlLCD1 localizes to the nucleus. By constructing mutated forms of SlLCD1, we show that the amino acid residue K24 of SlLCD1 is the key amino acid that determines nuclear localization. Silencing of SlLCD1 by TRV-SlLCD1 accelerated fruit ripening and reduced H2S production compared with the control. A SlLCD1 gene-edited mutant obtained through CRISPR/Cas9 modification displayed a slightly dwarfed phenotype and accelerated fruit ripening. This mutant also showed increased cysteine content and produced less H2S, suggesting a role of SlLCD1 in H2S generation. Chlorophyll degradation and carotenoid accumulation were enhanced in the SlLCD1 mutant. Other ripening-related genes that play roles in chlorophyll degradation, carotenoid biosynthesis, cell wall degradation, ethylene biosynthesis, and the ethylene signaling pathway were enhanced at the transcriptional level in the lcd1 mutant. Total RNA was sequenced from unripe tomato fruit treated with exogenous H2S, and transcriptome analysis showed that ripening-related gene expression was suppressed. Based on the results for a SlLCD1 gene-edited mutant and exogenous H2S application, we propose that the nuclear-localized cysteine desulfhydrase SlLCD1 is required for endogenous H2S generation and participates in the regulation of tomato fruit ripening.
A nonlinear magnonic nano-ring resonator
Authors: Wang Qi , Hamadeh Abbass , Verba Roman , Lomakin Vitaliy , Mohseni Morteza , Hillebrands Burkard , Chumak Andrii V. , Pirro Philipp 
Published: December 2020

AbstractThe field of magnonics, which aims at using spin waves as carriers in data-processing devices, has attracted increasing interest in recent years. We present and study micromagnetically a nonlinear nanoscale magnonic ring resonator device for enabling implementations of magnonic logic gates and neuromorphic magnonic circuits. In the linear regime, this device efficiently suppresses spin-wave transmission using the phenomenon of critical resonant coupling, thus exhibiting the behavior of a notch filter. By increasing the spin-wave input power, the resonance frequency is shifted, leading to transmission curves, depending on the frequency, reminiscent of the activation functions of neurons, or showing the characteristics of a power limiter. An analytical theory is developed to describe the transmission curve of magnonic ring resonators in the linear and nonlinear regimes, and is validated by a comprehensive micromagnetic study. The proposed magnonic ring resonator provides a multi-functional nonlinear building block for unconventional magnonic circuits.
Internal dose assessment of 148Gd using isotope ratios of gamma-emitting 146Gd or 153Gd in accidently released spallation target particles
Authors: Rääf C. , Barkauskas V. , Eriksson Stenström K. , Bernhardsson C. , Pettersson H. B. L. 
Published: December 2020

AbstractThe pure alpha emitter 148Gd may have a significant radiological impact in terms of internal dose to exposed humans in case of accidental releases from a spallation source using a tungsten target, such as the one to be used in the European Spallation Source (ESS). In this work we aim to present an approach to indirectly estimate the whole-body burden of 148Gd and the associated committed effective dose in exposed humans, by means of high-resolution gamma spectrometry of the gamma-emitting radiogadolinium isotopes 146Gd and 153Gd that are accompanied by 148Gd generated from the operation of the tungsten target. Theoretical minimum detectable whole-body activity (MDA) and associated internal doses from 148Gd are calculated using a combination of existing biokinetic models and recent computer simulation studies on the generated isotope ratios of 146Gd/148Gd and 153Gd/148Gd in the ESS target. Of the two gamma-emitting gadolinium isotopes, 146Gd is initially the most sensitive indicator of the presence of 148Gd if whole-body counting is performed within a month after the release, using the twin photo peaks of 146Gd centered at 115.4 keV (MDA < 1 Bq for ingested 148Gd, and < 25 Bq for inhaled 148Gd). The corresponding minimum detectable committed effective doses will be less than 1 µSv for ingested 148Gd, but substantially higher for inhaled 148Gd (up to 0.3 mSv), depending on operation time of the target prior to the release. However, a few months after an atmospheric release, 153Gd becomes a much more sensitive indicator of body burdens of 148Gd, with a minimum detectable committed effective doses ranging from 18 to 77 µSv for chronic ingestion and between 0.65 to 2.7 mSv for acute inhalation in connection to the release. The main issue with this indirect method for 148Gd internal dose estimation, is whether the primary photon peaks from 146 and 153Gd can be detected undisturbed. Preliminary simulations show that nuclides such as 182Ta may potentially create perturbations that could impair this evaluation method, and which impact needs to be further studied in future safety assessments of accidental target releases.
Elucidating the regulatory mechanism of Swi1 prion in global transcription and stress responses
Authors: Du Zhiqiang , Regan Jeniece , Bartom Elizabeth , Wu Wei-Sheng , Zhang Li , Goncharoff Dustin Kenneth , Li Liming 
Published: December 2020

AbstractTranscriptional regulators are prevalent among identified prions in Saccharomyces cerevisiae, however, it is unclear how prions affect genome-wide transcription. We show here that the prion ([SWI+]) and mutant (swi1∆) forms of Swi1, a subunit of the SWI/SNF chromatin-remodeling complex, confer dramatically distinct transcriptomic profiles. In [SWI+] cells, genes encoding for 34 transcription factors (TFs) and 24 Swi1-interacting proteins can undergo transcriptional modifications. Several TFs show enhanced aggregation in [SWI+] cells. Further analyses suggest that such alterations are key factors in specifying the transcriptomic signatures of [SWI+] cells. Interestingly, swi1∆ and [SWI+] impose distinct and oftentimes opposite effects on cellular functions. Translation-associated activities, in particular, are significantly reduced in swi1∆ cells. Although both swi1∆ and [SWI+] cells are similarly sensitive to thermal, osmotic and drought stresses, harmful, neutral or beneficial effects were observed for a panel of tested chemical stressors. Further analyses suggest that the environmental stress response (ESR) is mechanistically different between swi1∆ and [SWI+] cells—stress-inducible ESR (iESR) are repressed by [SWI+] but unchanged by swi1∆ while stress-repressible ESR (rESR) are induced by [SWI+] but repressed by swi1∆. Our work thus demonstrates primarily gain-of-function outcomes through transcriptomic modifications by [SWI+] and highlights a prion-mediated regulation of transcription and phenotypes in yeast.
Chain architectures of various cellulose-based antiscalants on the inhibition of calcium carbonate scale
Authors: Yu Wei , Yang Hu 
Published: December 2020

AbstractTwo series of cellulose-based antiscalants with different chain architectures, i.e., linear carboxymethyl cellulose (CMC) and branch-shaped carboxymethyl cellulose-graft-poly(acrylic acid) (CMC-g-PAA), were synthesized. The carboxyl groups were distributed on CMC backbone but mainly on the grafted chains of CMC-g-PAA. The addition of CMC and CMC-g-PAA can both increase the surface energy of CaCO3 scale and decrease its crystal nucleation rate, thereby inhibiting CaCO3 scale formation. The structural effects of these cellulose-based antiscalants, especially the chain architectures, on the scale inhibition were investigated in detail. High degree of carboxymethyl substitution caused better inhibition effect of linear CMC. However, CMC-g-PAA with an appropriate content of carboxyl groups but high average number of PAA grafted chains can achieve high inhibition performance. Besides, with similar contents of carboxyl groups, CMC-g-PAA showed much better inhibition performance than CMC due to the distinct multi-dimensional spatial structure of graft copolymer in solution, causing the enhanced chelation and dispersion effects. Characterization of CaCO3 crystal by scanning electron microscopy and X-ray diffraction confirmed that crystal distortion effect obviously existed in CMC but quite minor in CMC-g-PAA. The differences between the scale-inhibition performance of CMC and CMC-g-PAA should be attributed to the different scale-inhibition mechanisms originated in their distinct chain architectures.
The role of microRNA-3085 in chondrocyte function
Authors: Le Linh , Niu Lingzi , Barter Matthew J. , Young David A. , Dalmay Tamas , Clark Ian M. , Swingler Tracey E. 
Published: December 2020

AbstractMicroRNAs have been shown to play a role in cartilage development, homeostasis and breakdown during osteoarthritis. We previously identified miR-3085 in humans as a chondrocyte-selective microRNA, however it could not be detected by Northern blot. The aim of the current study was to prove that miR-3085 is a microRNA and to investigate the function of miR-3085 in signaling pathways relevant to cartilage homeostasis and osteoarthritis. Here, we confirm that miR-3085 is a microRNA and not another class of small RNA using (1) a pre-miR hairpin maturation assay, (2) expression levels in a Dicer null cell line, and (3) Ago2 pulldown. MicroRNA-3085-3p is expressed more highly in micromass than monolayer cultured chondrocytes. Transfection of miR-3085-3p into chondrocytes decreases expression of COL2A1 and ACAN, both of which are validated as direct targets of miR-3085-3p. Interleukin-1 induces the expression of miR-3085-3p, at least in part via NFκB. In a feed-forward mechanism, miR-3085-3p then potentiates NFκB signaling. However, at early time points after transfection, its action appears to be inhibitory. MyD88 has been shown to be a direct target of miR-3085-3p and may be responsible for the early inhibition of NFκB signaling. However, at later time points, MyD88 knockdown remains inhibitory and so other functions of miR-3085-3p are clearly dominant. TGFβ1 also induces the expression of miR-3085-3p, but in this instance, it exerts a feedback inhibition on signaling with SMAD3 and SMAD4 shown to be direct targets. This in vitro analysis shows that miR-3085-3p functions in chondrocytes to induce IL-1-signaling, reduce TGFβ1 signaling, and inhibit expression of matrix genes. These data suggest that miR-3085-3p has a role in chondrocyte function and could contribute to the process of osteoarthritis.
Activation of NLRP3 by uropathogenic Escherichia coli is associated with IL-1β release and regulation of antimicrobial properties in human neutrophils
Authors: Demirel Isak , Persson Alexander , Brauner Annelie , Särndahl Eva , Kruse Robert , Persson Katarina 
Published: December 2020

AbstractThe NLRP3 inflammasome and IL-1β have recently been linked to the severity of uropathogenic Escherichia coli (UPEC)-mediated urinary tract infection (UTI). However, not much is known about the contribution of NLRP3 to the antimicrobial properties of neutrophils and the release of IL-1β during UPEC infection. The purpose of this study was to elucidate the mechanisms behind UPEC-induced IL-1β release from human neutrophils, and to investigate the contribution of the NLRP3 inflammasome in neutrophil-mediated inhibition of UPEC growth. We found that the UPEC strain CFT073 increased the expression of NLRP3 and increased caspase-1 activation and IL-1β release from human neutrophils. The IL-1β release was mediated by the NLRP3 inflammasome and by serine proteases in an NF-κB-and cathepsin B-dependent manner. The UPEC virulence factors α-hemolysin, type-1 fimbriae and p-fimbriae were all shown to contribute to UPEC mediated IL-1β release from neutrophils. Furthermore, inhibition of caspase-1 and NLRP3 activation increased neutrophil ROS-production, phagocytosis and the ability of neutrophils to suppress UPEC growth. In conclusion, this study demonstrates that UPEC can induce NLRP3 and serine protease-dependent release of IL-1β from human neutrophils and that NLRP3 and caspase-1 can regulate the antimicrobial activity of human neutrophils against UPEC.
Strip-width determines competitive strengths and grain yields of intercrop species in relay intercropping system
Authors: Raza Muhammad Ali , Cui Liang , Qin Ruijun , Yang Feng , Yang Wenyu 
Published: December 2020

AbstractMaize/soybean relay intercropping system (MSR) is a popular cultivation method to obtain high yields of both crops with reduced inputs. However, in MSR, the effects of different strip widths on competitive strengths and grain yields of intercrop species are still unclear. Therefore, in a two-year field experiment, soybean was relay-intercropped with maize in three different strip-width arrangements (narrow-strips, 180 cm; medium-strips, 200 cm; and wide-strips, 220 cm), and all intercropping results were compared with sole maize (SM) and sole soybean (SS). Results showed that the optimum strip-width for obtaining high grain yields of maize and soybean was 200 cm (medium-strips), which improved the competitive-ability of soybean by maintaining the competitive-ability of maize in MSR. On average, maize and soybean produced 98% and 77% of SM and SS yield, respectively, in medium-strips. The improved grain yields of intercrop species in medium-strips increased the total grain yield of MSR by 15% and land equivalent ratio by 22%, which enhanced the net-income of medium-strips (by 99%, from 620 US $ ha−1 in wide-strips to 1233 US $ ha−1 in medium-strips). Overall, these findings imply that following the optimum strip-width in MSR, i. e., strip-width of 200 cm, grain yields, and competitive interactions of intercrop species can be improved.