bluuebunny/crossref_metadata_2025 huggingface dataset:
WHITE OPPOSITION TO NATIVE NATION SOVEREIGNTY
Authors: Davis-Delano Laurel R. , Galliher Renee V. , Carlson Kirsten Matoy , Eason Arianne E. , Fryberg Stephanie A.
Published: August 2020

Since first contact with Europeans, Native American nations have strived to maintain and strengthen their sovereignty. Yet, non-Native individuals and groups, as well as federal, state, and local governments, continue to challenge this sovereignty. Despite the critical importance of sovereignty, the only academic study focused on U.S. public attitudes toward Native nation sovereignty predated the rise of Native nation gaming and relied on samples from three universities. In our study, we surveyed over 2000 White Americans from across the United States to examine attitudes toward Native nation sovereignty. Of the many factors that may influence these attitudes, we focused on three: belief in “the casino Indian” stereotype, the perception that Native American interests conflict with the interests of Whites, and the presence of Native nation gaming in participants’ states.

We find two significant models predicting attitudes towards Native nation sovereignty. First, greater endorsement of the casino Indian stereotype is associated with more negative attitudes toward Native nation sovereignty. This relationship is explained, at least in part, by the perception that Native American interests conflict with the interests of Whites. That is, the more White participants endorsed the casino Indian sterereotype, the more apt they were to believe that their interests conflict with Native Americans, which in turn is related to more negative attitudes towards Native nation sovereignty. The second model revealed that the presence of Native nation gaming in the participant’s state has important indirect implications for attitudes towards Native nation sovereignty. Specifically, White participants living in states with Native nation gaming are more likely to endorse the casino Indian stereotype, which is related to greater perceived conflict of interest with Native Americans, and, ultimately perceived conflict of interest is associated with more negative attitudes toward Native nation sovereignty. We situate our findings relative to group position theory and discuss practical implications for Native nation sovereignty.
Shallow Lower Mantle Viscosity Modulates the Pattern of Mantle Structure
Authors: D. L. Lourenço , M. L. Rudolph
Published: August 2020

Tomographic images of Earth's mantle reveal that structure, even at the largest spatial scales, does not remain correlated across all mantle depths. This is a surprising result given the relationship between a dominantly spherical harmonic degree‐2 pattern in the lower mantle and the pattern of plate motions at the surface, that is, the fact that the two large, low‐shear velocity provinces (LLSVPs) beneath Africa and the Pacific Ocean are located near regions of surface divergence and away from regions of recent and ongoing subduction. Here, we combine analysis of seismic tomography models and numerical simulations of global‐scale mantle circulation to show that the change in correlation in mantle structure across the extended transition zone (400–1,000‐km depth), as revealed by the mantle radial correlation function (RCF), can be attributed primarily to the influence of seismically fast regions in the transition zone beneath the western Pacific subduction zones. Similar changes in the correlation of structure in global models of mantle circulation can be explained by a relatively large increase in viscosity (of at least a hundred times) between the upper mantle and lower mantle. We also demonstrate that a stronger endothermic phase transition at a depth of 660 km helps explain the observed pattern of the mantle RCF and the correlation between geodynamic models and seismic tomography. We account for the differences in resolution and parameterization of geodynamic versus tomographic models through the application of a tomographic resolution operator.
No Cretaceous‐Paleogene Boundary in Exposed Rajahmundry Traps: A Refined Chronology of the Longest Deccan Lava Flows From40Ar/39Ar Dates, Magnetostratigraphy, and Biostratigraphy
Authors: Fendley Isabel M. , Sprain Courtney J. , Renne Paul R. , Arenillas Ignacio , Arz José A. , Gilabert Vicente , Self Stephen , Vanderkluysen Loÿc , Pande Kanchan , Smit Jan , Mittal Tushar
Published: August 2020

Deccan Traps flood basalt volcanism affected ecosystems spanning the end‐Cretaceous mass extinction, with the most significant environmental effects hypothesized to be a consequence of the largest eruptions. The Rajahmundry Traps are the farthest exposures (~1,000 km) of Deccan basalt from the putative eruptive centers in the Western Ghats and hence represent some of the largest volume Deccan eruptions. Although the three subaerial Rajahmundry lava flows have been geochemically correlated to the Wai Subgroup of the Deccan Traps, poor precision associated with previous radioisotopic age constraints has prevented detailed comparison with potential climate effects. In this study, we use new40Ar/39Ar dates, paleomagnetic and volcanological analyses, and biostratigraphic constraints for the Rajahmundry lava flows to ascertain the timing and style of their emplacement. We find that the lower and middle flows (65.92 ± 0.25 and 65.67 ± 0.08 Ma, ±1σsystematic uncertainty) were erupted within magnetochron C29r and were a part of the Ambenali Formation of the Deccan Traps. By contrast, the uppermost flow (65.27 ± 0.08 Ma) was erupted in C29n as part of the Mahabaleshwar Formation. Given these age constraints, the Rajahmundry flows were not involved in the end‐Cretaceous extinction as previously hypothesized. To determine whether the emplacement of the Rajahmundry flows could have affected global climate, we estimated their eruptive CO2release and corresponding climate change using scalings from the LOSCAR carbon cycle model. We find that the eruptive gas emissions of these flows were insufficient to directly cause multi‐degree warming; hence, a causal relationship with significant climate warming requires additional Earth system feedbacks.
Upward Negative Leaders in Positive Upward Lightning in Winter: Propagation Velocities, Electric Field Change Waveforms, and Triggering Mechanism
Authors: Wu Ting , Wang Daohong , Takagi Nobuyuki
Published: August 2020

Upward negative leaders (UNLs) in positive upward lightning are rarely observed. In this study, 24 UNLs observed by the Fast Antenna Lightning Mapping Array during winter thunderstorms in Japan are analyzed. Three‐dimensional velocities of UNLs are calculated, and it is found that velocities during the upward propagation stage range from 1.8 to 27.9 × 105 m/s with a mean value of 10.4 × 105 m/s, and they are always larger than velocities during the following horizontal propagation stage. UNLs produce distinctive electric field change waveforms with V‐shaped overall change trend, with small pulses at the beginning when UNLs start, large pulses during upward propagations, and small pulses again when UNLs turn into horizontal directions. Pulses produced by UNLs are mainly unipolar but sometimes also bipolar. Pulse interval, pulse width, rise time, and fall time are calculated for waveforms produced by five UNLs. Pulse intervals range from 13.7 to 18.9 μs. Pulse width, rise time, and fall time are on average 5.8, 3.3, and 2.4 μs, respectively. All UNLs are preceded by other discharges. Strong negative strokes including some special types of strokes usually precede initiations of UNLs by tens of milliseconds. These negative strokes are usually found only a few kilometers away from UNLs. It is speculated that these negative strokes along with following in‐cloud positive leaders contribute to the depletion of negative charges in thunderclouds, which result in positive electric field changes (atmospheric electricity sign convention) large enough for initiations of UNLs.
The impact of the Syrian conflict on population well-being
Authors: Cheung Felix , Kube Amanda , Tay Louis , Diener Edward , Jackson Joshua J. , Lucas Richard E. , Ni Michael Y. , Leung Gabriel M.
Published: August 2020

The United Nations described the Syrian conflict as the worst man-made disaster since World War II. We adopted a global perspective in examining the impact of the Syrian conflict on Syrians’ physical, mental, and social well-being using the Gallup World Poll. Face-to-face interview data of 11,452 Syrian participants from 2008 to 2015 show that Syrians’ physical (e.g., access to shelter), mental (e.g., life satisfaction), and social (e.g., social support) well-being decline substantially. Syrians who reported being exposed to the conflict are similarly affected compared to those without direct exposure, suggesting country-wide spillover effects. Global data covering 1.7 million participants across 163 countries from 2006 to 2016 show during the conflict, Syria’s precipitous decline in well-being is unparalleled in the world, even when compared to countries similarly experiencing war, protests, and disasters. Our findings reinforce the vital importance of an accelerated peace process to restore well-being in Syria.
On quantum gravity tests with composite particles
Authors: Kumar Shreya P. , Plenio Martin B.
Published: August 2020

Models of quantum gravity imply a fundamental revision of our description of position and momentum that manifests in modifications of the canonical commutation relations. Experimental tests of such modifications remain an outstanding challenge. These corrections scale with the mass of test particles, which motivates experiments using macroscopic composite particles. Here we consider a challenge to such tests, namely that quantum gravity corrections of canonical commutation relations are expected to be suppressed with increasing number of constituent particles. Since the precise scaling of this suppression is unknown, it needs to be bounded experimentally and explicitly incorporated into rigorous analyses of quantum gravity tests. We analyse this scaling based on data from past experiments involving macroscopic pendula, and provide tight bounds that exceed those of current experiments based on quantum mechanical oscillators. Furthermore, we discuss possible experiments that promise even stronger bounds thus bringing rigorous and well-controlled tests of quantum gravity closer to reality.
A lung tropic AAV vector improves survival in a mouse model of surfactant B deficiency
Authors: Kang Martin H. , van Lieshout Laura P. , Xu Liqun , Domm Jakob M. , Vadivel Arul , Renesme Laurent , Mühlfeld Christian , Hurskainen Maria , Mižíková Ivana , Pei Yanlong , van Vloten Jacob P. , Thomas Sylvia P. , Milazzo Claudia , Cyr-Depauw Chanèle , Whitsett Jeffrey A. , Nogee Lawrence M. , Wootton Sarah K. , Thébaud Bernard
Published: August 2020

Surfactant protein B (SP-B) deficiency is an autosomal recessive disorder that impairs surfactant homeostasis and manifests as lethal respiratory distress. A compelling argument exists for gene therapy to treat this disease, as de novo protein synthesis of SP-B in alveolar type 2 epithelial cells is required for proper surfactant production. Here we report a rationally designed adeno-associated virus (AAV) 6 capsid that demonstrates efficiency in lung epithelial cell transduction based on imaging and flow cytometry analysis. Intratracheal administration of this vector delivering murine or human proSFTPB cDNA into SP-B deficient mice restores surfactant homeostasis, prevents lung injury, and improves lung physiology. Untreated SP-B deficient mice develop fatal respiratory distress within two days. Gene therapy results in an improvement in median survival to greater than 200 days. This vector also transduces human lung tissue, demonstrating its potential for clinical translation against this lethal disease.
Unzipping of black phosphorus to form zigzag-phosphorene nanobelts
Authors: Liu Zhifang , Sun Yilin , Cao Huaqiang , Xie Dan , Li Wei , Wang Jiaou , Cheetham Anthony K.
Published: August 2020

Phosphorene, monolayer or few-layer black phosphorus, exhibits fascinating anisotropic properties and shows interesting semiconducting behavior. The synthesis of phosphorene nanosheets is still a hot topic, including the shaping of its two-dimensional structure into nanoribbons or nanobelts. Here we report electrochemical unzipping of single crystalline black phosphorus into zigzag-phosphorene nanobelts, as well as nanosheets and quantum dots, via an oxygen-driven mechanism. The experimental results agree well with our theoretical calculations. The calculation for the unzipping mechanism study suggests that interstitial oxygen-pairs are the critical intermediate species for generating zigzag-phosphorene nanobelts. Although phosphorene oxidation has been reported, lengthwise cutting is hitherto unreported. Our discovery of phosphorene cut upon oxidation represents a previously unknown mechanism for the formation of various dimensions of phosphorene nanostructures, especially zigzag-phosphorene nanobelts. It opens up a way for studying the quantum effects and electronic properties of zigzag-phosphorene nanobelts.
A bilateral interfacial passivation strategy promoting efficiency and stability of perovskite quantum dot light-emitting diodes
Authors: Xu Leimeng , Li Jianhai , Cai Bo , Song Jizhong , Zhang Fengjuan , Fang Tao , Zeng Haibo
Published: August 2020

Perovskite quantum-dot-based light-emitting diodes (QLEDs) possess the features of wide gamut and real color expression, which have been considered as candidates for high-quality lightings and displays. However, massive defects are prone to be reproduced during the quantum dot (QD) film assembly, which would sorely affect carrier injection, transportation and recombination, and finally degrade QLED performances. Here, we propose a bilateral passivation strategy through passivating both top and bottom interfaces of QD film with organic molecules, which has drastically enhanced the efficiency and stability of perovskite QLEDs. Various molecules were applied, and comparison experiments were conducted to verify the necessity of passivation on both interfaces. Eventually, the passivated device achieves a maximum external quantum efficiency (EQE) of 18.7% and current efficiency of 75 cd A−1. Moreover, the operational lifetime of QLEDs is enhanced by 20-fold, reaching 15.8 h. These findings highlight the importance of interface passivation for efficient and stable QD-based optoelectronic devices.
The REGγ inhibitor NIP30 increases sensitivity to chemotherapy in p53-deficient tumor cells
Authors: Gao Xiao , Wang Qingwei , Wang Ying , Liu Jiang , Liu Shuang , Liu Jian , Zhou Xingli , Zhou Li , Chen Hui , Pan Linian , Chen Jiwei , Wang Da , Zhang Qing , Shen Shihui , Xiao Yu , Wu Zhipeng , Cheng Yiyun , Chen Geng , Kubra Syeda , Qin Jun , Huang Lan , Zhang Pei , Wang Chuangui , Moses Robb E. , Lonard David M. , Malley Bert W. O’ , Fares Fuad , Zhang Bianhong , Li Xiaotao , Li Lei , Xiao Jianru
Published: August 2020

A major challenge in chemotherapy is chemotherapy resistance in cells lacking p53. Here we demonstrate that NIP30, an inhibitor of the oncogenic REGγ-proteasome, attenuates cancer cell growth and sensitizes p53-compromised cells to chemotherapeutic agents. NIP30 acts by binding to REGγ via an evolutionarily-conserved serine-rich domain with 4-serine phosphorylation. We find the cyclin-dependent phosphatase CDC25A is a key regulator for NIP30 phosphorylation and modulation of REGγ activity during the cell cycle or after DNA damage. We validate CDC25A-NIP30-REGγ mediated regulation of the REGγ target protein p21 in vivo using p53−/− and p53/REGγ double-deficient mice. Moreover, Phosphor-NIP30 mimetics significantly increase the growth inhibitory effect of chemotherapeutic agents in vitro and in vivo. Given that NIP30 is frequently mutated in the TCGA cancer database, our results provide insight into the regulatory pathway controlling the REGγ-proteasome in carcinogenesis and offer a novel approach to drug-resistant cancer therapy.
ATP-dependent hydroxylation of an unactivated primary carbon with water
Authors: Jacoby Christian , Ferlaino Sascha , Bezold Dominik , Jessen Henning , Müller Michael , Boll Matthias
Published: August 2020

Enzymatic hydroxylation of unactivated primary carbons is generally associated with the use of molecular oxygen as co-substrate for monooxygenases. However, in anaerobic cholesterol-degrading bacteria such as Sterolibacterium denitrificans the primary carbon of the isoprenoid side chain is oxidised to a carboxylate in the absence of oxygen. Here, we identify an enzymatic reaction sequence comprising two molybdenum-dependent hydroxylases and one ATP-dependent dehydratase that accomplish the hydroxylation of unactivated primary C26 methyl group of cholesterol with water: (i) hydroxylation of C25 to a tertiary alcohol, (ii) ATP-dependent dehydration to an alkene via a phosphorylated intermediate, (iii) hydroxylation of C26 to an allylic alcohol that is subsequently oxidised to the carboxylate. The three-step enzymatic reaction cascade divides the high activation energy barrier of primary C–H bond cleavage into three biologically feasible steps. This finding expands our knowledge of biological C–H activations beyond canonical oxygenase-dependent reactions.
Zuo1 supports G4 structure formation and directs repair toward nucleotide excision repair
Authors: De Magis Alessio , Götz Silvia , Hajikazemi Mona , Fekete-Szücs Enikő , Caterino Marco , Juranek Stefan , Paeschke Katrin
Published: August 2020

Nucleic acids can fold into G-quadruplex (G4) structures that can fine-tune biological processes. Proteins are required to recognize G4 structures and coordinate their function. Here we identify Zuo1 as a novel G4-binding protein in vitro and in vivo. In vivo in the absence of Zuo1 fewer G4 structures form, cell growth slows and cells become UV sensitive. Subsequent experiments reveal that these cellular changes are due to reduced levels of G4 structures. Zuo1 function at G4 structures results in the recruitment of nucleotide excision repair (NER) factors, which has a positive effect on genome stability. Cells lacking functional NER, as well as Zuo1, accumulate G4 structures, which become accessible to translesion synthesis. Our results suggest a model in which Zuo1 supports NER function and regulates the choice of the DNA repair pathway nearby G4 structures.
Deep long period volcanic earthquakes generated by degassing of volatile-rich basaltic magmas
Authors: Melnik Oleg , Lyakhovsky Vladimir , Shapiro Nikolai M. , Galina Natalia , Bergal-Kuvikas Olga
Published: August 2020

Deep long-period (DLP) earthquakes observed beneath active volcanoes are sometimes considered as precursors to eruptions. Their origin remains, however, unclear. Here, we present a possible DLP generating mechanism related to the rapid growth of gas bubbles in response to the slow decompression of over-saturated magma. For certain values of the gas and bubble content, the elastic deformation of surrounding rocks forced by the expanding bubbly magma can be fast enough to generate seismic waves. We show that amplitudes and frequencies of DLP earthquakes observed beneath the Klyuchevskoy volcano (Kamchatka, Russia) can be predicted by our model when considering pressure changes of ~107 Pa in a volume of ~103–104 m3 and realistic magma compositions. Our results show importance of the deep degassing in the generation of volcanic seismicity and suggest that the DLP swarms beneath active volcanoes might be related to the pulses of volatile-rich basaltic magmas rising from the mantle.
Dielectric ordering of water molecules arranged in a dipolar lattice
Authors: Belyanchikov M. A. , Savinov M. , Bedran Z. V. , Bednyakov P. , Proschek P. , Prokleska J. , Abalmasov V. A. , Petzelt J. , Zhukova E. S. , Thomas V. G. , Dudka A. , Zhugayevych A. , Prokhorov A. S. , Anzin V. B. , Kremer R. K. , Fischer J. K. H. , Lunkenheimer P. , Loidl A. , Uykur E. , Dressel M. , Gorshunov B.
Published: August 2020

Intermolecular hydrogen bonds impede long-range (anti-)ferroelectric order of water. We confine H2O molecules in nanosized cages formed by ions of a dielectric crystal. Arranging them in channels at a distance of ~5 Å with an interchannel separation of ~10 Å prevents the formation of hydrogen networks while electric dipole-dipole interactions remain effective. Here, we present measurements of the temperature-dependent dielectric permittivity, pyrocurrent, electric polarization and specific heat that indicate an order-disorder ferroelectric phase transition at T0 ≈ 3 K in the water dipolar lattice. Ab initio molecular dynamics and classical Monte Carlo simulations reveal that at low temperatures the water molecules form ferroelectric domains in the ab-plane that order antiferroelectrically along the channel direction. This way we achieve the long-standing goal of arranging water molecules in polar order. This is not only of high relevance in various natural systems but might open an avenue towards future applications in biocompatible nanoelectronics.
Single-cell analysis of two severe COVID-19 patients reveals a monocyte-associated and tocilizumab-responding cytokine storm
Authors: Guo Chuang , Li Bin , Ma Huan , Wang Xiaofang , Cai Pengfei , Yu Qiaoni , Zhu Lin , Jin Liying , Jiang Chen , Fang Jingwen , Liu Qian , Zong Dandan , Zhang Wen , Lu Yichen , Li Kun , Gao Xuyuan , Fu Binqing , Liu Lianxin , Ma Xiaoling , Weng Jianping , Wei Haiming , Jin Tengchuan , Lin Jun , Qu Kun
Published: August 2020

Several studies show that the immunosuppressive drugs targeting the interleukin-6 (IL-6) receptor, including tocilizumab, ameliorate lethal inflammatory responses in COVID-19 patients infected with SARS-CoV-2. Here, by employing single-cell analysis of the immune cell composition of two severe-stage COVID-19 patients prior to and following tocilizumab-induced remission, we identify a monocyte subpopulation that contributes to the inflammatory cytokine storms. Furthermore, although tocilizumab treatment attenuates the inflammation, immune cells, including plasma B cells and CD8+ T cells, still exhibit robust humoral and cellular antiviral immune responses. Thus, in addition to providing a high-dimensional dataset on the immune cell distribution at multiple stages of the COVID-19, our work also provides insights into the therapeutic effects of tocilizumab, and identifies potential target cell populations for treating COVID-19-related cytokine storms.
Author Correction: Sulcal organization in the medial frontal cortex provides insights into primate brain evolution
Authors: Amiez Céline , Sallet Jérôme , Hopkins William D. , Meguerditchian Adrien , Hadj-Bouziane Fadila , Hamed Suliann Ben , Wilson Charles R. E. , Procyk Emmanuel , Petrides Michael
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A database of battery materials auto-generated using ChemDataExtractor
Authors: Huang Shu , Cole Jacqueline M.
Published: August 2020

A database of battery materials is presented which comprises a total of 292,313 data records, with 214,617 unique chemical-property data relations between 17,354 unique chemicals and up to five material properties: capacity, voltage, conductivity, Coulombic efficiency and energy. 117,403 data are multivariate on a property where it is the dependent variable in part of a data series. The database was auto-generated by mining text from 229,061 academic papers using the chemistry-aware natural language processing toolkit, ChemDataExtractor version 1.5, which was modified for the specific domain of batteries. The collected data can be used as a representative overview of battery material information that is contained within text of scientific papers. Public availability of these data will also enable battery materials design and prediction via data-science methods. To the best of our knowledge, this is the first auto-generated database of battery materials extracted from a relatively large number of scientific papers. We also provide a Graphical User Interface (GUI) to aid the use of this database.
Novel protein pathways in development and progression of pulmonary sarcoidosis
Authors: Bhargava Maneesh , Viken K. J. , Barkes B. , Griffin T. J. , Gillespie M. , Jagtap P. D. , Sajulga R. , Peterson E. J. , Dincer H. E. , Li L. , Restrepo C. I. , O’Connor B. P. , Fingerlin T. E. , Perlman D. M. , Maier L. A.
Published: August 2020

Pulmonary involvement occurs in up to 95% of sarcoidosis cases. In this pilot study, we examine lung compartment-specific protein expression to identify pathways linked to development and progression of pulmonary sarcoidosis. We characterized bronchoalveolar lavage (BAL) cells and fluid (BALF) proteins in recently diagnosed sarcoidosis cases. We identified 4,306 proteins in BAL cells, of which 272 proteins were differentially expressed in sarcoidosis compared to controls. These proteins map to novel pathways such as integrin-linked kinase and IL-8 signaling and previously implicated pathways in sarcoidosis, including phagosome maturation, clathrin-mediated endocytic signaling and redox balance. In the BALF, the differentially expressed proteins map to several pathways identified in the BAL cells. The differentially expressed BALF proteins also map to aryl hydrocarbon signaling, communication between innate and adaptive immune response, integrin, PTEN and phospholipase C signaling, serotonin and tryptophan metabolism, autophagy, and B cell receptor signaling. Additional pathways that were different between progressive and non-progressive sarcoidosis in the BALF included CD28 signaling and PFKFB4 signaling. Our studies demonstrate the power of contemporary proteomics to reveal novel mechanisms operational in sarcoidosis. Application of our workflows in well-phenotyped large cohorts maybe beneficial to identify biomarkers for diagnosis and prognosis and therapeutically tenable molecular mechanisms.
Tales of 1,008 small molecules: phenomic profiling through live-cell imaging in a panel of reporter cell lines
Authors: Cox Michael J. , Jaensch Steffen , Van de Waeter Jelle , Cougnaud Laure , Seynaeve Daan , Benalla Soulaiman , Koo Seong Joo , Van Den Wyngaert Ilse , Neefs Jean-Marc , Malkov Dmitry , Bittremieux Mart , Steemans Margino , Peeters Pieter J. , Wegner Jörg Kurt , Ceulemans Hugo , Gustin Emmanuel , Chong Yolanda T. , Göhlmann Hinrich W. H.
Published: August 2020

Phenomic profiles are high-dimensional sets of readouts that can comprehensively capture the biological impact of chemical and genetic perturbations in cellular assay systems. Phenomic profiling of compound libraries can be used for compound target identification or mechanism of action (MoA) prediction and other applications in drug discovery. To devise an economical set of phenomic profiling assays, we assembled a library of 1,008 approved drugs and well-characterized tool compounds manually annotated to 218 unique MoAs, and we profiled each compound at four concentrations in live-cell, high-content imaging screens against a panel of 15 reporter cell lines, which expressed a diverse set of fluorescent organelle and pathway markers in three distinct cell lineages. For 41 of 83 testable MoAs, phenomic profiles accurately ranked the reference compounds (AUC-ROC ≥ 0.9). MoAs could be better resolved by screening compounds at multiple concentrations than by including replicates at a single concentration. Screening additional cell lineages and fluorescent markers increased the number of distinguishable MoAs but this effect quickly plateaued. There remains a substantial number of MoAs that were hard to distinguish from others under the current study’s conditions. We discuss ways to close this gap, which will inform the design of future phenomic profiling efforts.
Relationship of morphometrics, total carotenoids, and total lipids with activity and sexual and spatial features in Euphausia superba
Authors: Färber Lorda Jaime , Ceccaldi Hubert J.
Published: August 2020

Morphological differences associated with sex or stage, together with total lipids and carotenoids, were studied in Euphausia superba as possible indicators of physiological condition. E. superba displays sexual dimorphism during growth. A group of mature males, called Males II herein, has a greater abdominal length, suggesting that they are faster swimmers, a feature implying higher metabolic rates and a higher demand for protecting pigments like carotenoids. Mature Males II have proportionally lower lipids but higher total lipid-soluble carotenoids, a counterintuitive finding. Males II also have bigger eyes. Significant regressions with carotenoids were found for wet weight, abdominal length, and eye diameter. On a spatial analysis, population composition reflects reproductive activity. Males II would be in search of females for fecundation and, thus, are dominant in some areas. The PCA analysis of 10 allometric and biochemical variables show a distinct Males II group differing in morphology, carotenoids, and lipid contents. The carotenoid:lipid ratio was highest for Males II, supporting the hypothesis of the role of carotenoids in the activity of the species. Mature males may experience physiological stress during reproduction and probably die shortly afterwards. A relationship between activity, morphometrics, and carotenoid content seems evident, deserving further investigation.
Cardiorenal metabolic biomarkers link early life stress to risk of non-communicable diseases and adverse mental health outcomes
Authors: Poplawski Janet , Radmilovic Ana , Montina Tony D. , Metz Gerlinde A. S.
Published: August 2020

Stress is one of the most critical determinants of lifetime health and increases the risk of chronic non-communicable diseases. To gain insight into underlying environment-gene interactions, we analyzed the cardiorenal metabolome of adult mice exposed to multidimensional early-life transportation stress. Using proton nuclear magnetic resonance (1H NMR) spectroscopy, we show that early life stress permanently programs metabolic pathways in somatic organs linked to cardiorenal and mental health disorders in later life. Heart and kidneys of stressed mice revealed robust metabolic markers linked to abnormal energy metabolism, branched-chain amino acid biosynthesis and degradation, methylhistidine metabolism, arginine and proline metabolism, glycine and serine metabolism, and aminoacyl-tRNA biosynthesis. These markers were strongly associated with anxiety-like behaviours. Dysregulation of energy and protein metabolism suggests an increased risk of metabolic diseases like insulin resistance, cardiorenal syndrome, diabetes, and obesity. These findings provide novel insights into the direct effects of early life stress on cardiorenal metabolism and are consistent with prior observations of increased non-communicable disease risk in stressed populations. Thus, stress-associated metabolic signatures in somatic organs may provide early predictors of health risks in later life and reveal new candidates for peripheral biomarker detection with diagnostic value.
Author Correction: Holocene centennial to millennial shifts in North-Atlantic storminess and ocean dynamics
Authors: Goslin Jérôme , Fruergaard Mikkel , Sander Lasse , Gałka Mariusz , Menviel Laurie , Monkenbusch Johannes , Thibault Nicolas , Clemmensen Lars B.
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Absolute spectroscopy near 7.8 μm with a comb-locked extended-cavity quantum-cascade-laser
Authors: Lamperti Marco , AlSaif Bidoor , Gatti Davide , Fermann Martin , Laporta Paolo , Farooq Aamir , Marangoni Marco
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Increased expression of secreted frizzled related protein 1 (SFRP1) predicts ampullary adenocarcinoma recurrence
Authors: Cheng Li-Chin , Chao Ying- Jui , Overman Michael J. , Wang Chih -Yang , Phan Nam Nhut , Chen Yi-Ling , Wang Tzu-Wen , Hsu Hui-Ping , Shan Yan-Shen , Lai Ming- Derg
Published: August 2020

Ampullary adenocarcinoma is a rare gastrointestinal cancer in which WNT signalling dysregulation has been previously reported. Secreted frizzled related protein 1 (SFRP1) is one of the extracellular ligands of WNT signalling. We performed bioinformatics analyses of SFRP1 expression in human cancer. Microarray analysis of SFRP1 in periampullary adenocarcinoma was obtained from the Gene Expression Omnibus GSE39409 dataset. SFRP1 expression in ampullary adenocarcinoma was detected by immunohistochemistry staining and correlated with patients’ clinical outcomes. Our results showed that SFRP1 expression had different clinical applications in all types of human cancer. No detected alteration of SFPR1 gene and SFRP1 expression in ampullary adenocarcinoma was lower than that in other periampullary adenocarcinomas. However, high expression levels of SFRP1 protein were correlated with cancer recurrence, peritoneal carcinomatosis and poor patient prognosis. Gene set enrichment analysis showed downregulation of multiple WNT-related genes in primary culture cells from ampullary adenocarcinoma, but SFRP1 expression was increased. We found an interaction between WNT, bone morphogenetic protein and hedgehog signalling with SFRP1. Furthermore, a high expression of SFRP1 predicted poor prognosis for ampullary adenocarcinoma patients. Because it is a multifunctional protein, SFRP1 targeting serves as a potential therapy for ampullary adenocarcinoma patients.
Spreading of soap bubbles on dry and wet surfaces
Authors: Pfeiffer Patricia , Ohl Claus-Dieter
Published: August 2020

The spreading of soap bubbles after forming contact with a substrate is experimentally studied. We find for dry glass substrate that the rim of the spreading soap bubble follows the well known scaling law for inertia dominated spreading $$r \sim t^{1/2}$$

r
∼

t

1
/
2

[Eggers, J., Lister, J., and Stone, H., J. Fluid Mech. 401, 293–310 (1999)]. Varying the viscosity of the soap solutions and the coating of the glass does not affect this spreading behavior qualitatively. Yet, on a wetted surface, the rim obtains a constant radial velocity. Here, the rim splits into two and this new rim trails the main rim. Interestingly, the central film enclosed by the two rims develops radially oriented wrinkles.
Sibling validation of polygenic risk scores and complex trait prediction
Authors: Lello Louis , Raben Timothy G. , Hsu Stephen D. H.
Published: August 2020

We test 26 polygenic predictors using tens of thousands of genetic siblings from the UK Biobank (UKB), for whom we have SNP genotypes, health status, and phenotype information in late adulthood. Siblings have typically experienced similar environments during childhood, and exhibit negligible population stratification relative to each other. Therefore, the ability to predict differences in disease risk or complex trait values between siblings is a strong test of genomic prediction in humans. We compare validation results obtained using non-sibling subjects to those obtained among siblings and find that typically most of the predictive power persists in between-sibling designs. In the case of disease risk we test the extent to which higher polygenic risk score (PRS) identifies the affected sibling, and also compute Relative Risk Reduction as a function of risk score threshold. For quantitative traits we examine between-sibling differences in trait values as a function of predicted differences, and compare to performance in non-sibling pairs. Example results: Given 1 sibling with normal-range PRS score (< 84 percentile, < + 1 SD) and 1 sibling with high PRS score (top few percentiles, i.e. > + 2 SD), the predictors identify the affected sibling about 70–90% of the time across a variety of disease conditions, including Breast Cancer, Heart Attack, Diabetes, etc. 55–65% of the time the higher PRS sibling is the case. For quantitative traits such as height, the predictor correctly identifies the taller sibling roughly 80 percent of the time when the (male) height difference is 2 inches or more.
Synthesis of glycoconjugates utilizing the regioselectivity of a lytic polysaccharide monooxygenase
Authors: Westereng Bjørge , Kračun Stjepan K. , Leivers Shaun , Arntzen Magnus Ø. , Aachmann Finn L. , Eijsink Vincent G. H.
Published: August 2020

Polysaccharides from plant biomass are the most abundant renewable chemicals on Earth and can potentially be converted to a wide variety of useful glycoconjugates. Potential applications of glycoconjugates include therapeutics and drug delivery, vaccine development and as fine chemicals. While anomeric hydroxyl groups of carbohydrates are amenable to a variety of useful chemical modifications, selective cross-coupling to non-reducing ends has remained challenging. Several lytic polysaccharide monooxygenases (LPMOs), powerful enzymes known for their application in cellulose degradation, specifically oxidize non-reducing ends, introducing carbonyl groups that can be utilized for chemical coupling. This study provides a simple and highly specific approach to produce oxime-based glycoconjugates from LPMO-functionalized oligosaccharides. The products are evaluated by HPLC, mass spectrometry and NMR. Furthermore, we demonstrate potential biodegradability of these glycoconjugates using selective enzymes.
Long-term in vivo imaging reveals tumor-specific dissemination and captures host tumor interaction in zebrafish xenografts
Authors: Asokan Nandini , Daetwyler Stephan , Bernas Stefanie N. , Schmied Christopher , Vogler Steffen , Lambert Katrin , Wobus Manja , Wermke Martin , Kempermann Gerd , Huisken Jan , Brand Michael , Bornhäuser Martin
Published: August 2020

Understanding mechanisms mediating tumor metastasis is crucial for diagnostic and therapeutic targeting. Here, we take advantage of a transparent embryonic zebrafish xenograft model (eZXM) to visualize and track metastatic cells in real time using selective plane illumination microscopy (SPIM) for up to 30 h. Injected human leukemic and breast cancer cells exhibited cell-type specific patterns of intravascular distribution with leukemic cells moving faster than breast cancer cells. Tracking of tumor cells from high-resolution images revealed acute differences in intravascular speed and distance covered by cells. While the majority of injected breast cancer cells predominantly adhered to nearby vasculature, about 30% invaded the non-vascularized tissue, reminiscent of their metastatic phenotype. Survival of the injected tumor cells appeared to be partially inhibited and time-lapse imaging showed a possible role for host macrophages of the recipient embryos. Leukemic cell dissemination could be effectively blocked by pharmacological ROCK1 inhibition using Fasudil. These observations, and the ability to image several embryos simultaneously, support the use of eZXM and SPIM imaging as a functional screening platform to identify compounds that suppress cancer cell spread and invasion.
Elevation in the counts of IL-35-producing B cells infiltrating into lung tissue in mycobacterial infection is associated with the downregulation of Th1/Th17 and upregulation of Foxp3+Treg
Authors: Chen Chen , Xu Huan , Peng Ying , Luo Hong , Huang Gui-Xian , Wu Xian-Jin , Dai You-Chao , Luo Hou-Long , Zhang Jun-Ai , Zheng Bi-Ying , Zhang Xiang-Ning , Chen Zheng W. , Xu Jun-Fa
Published: August 2020

IL-35 is an anti-inflammatory cytokine and is thought to be produced by regulatory T (Treg) cells. A previous study found that IL-35 was upregulated in the serum of patients with active tuberculosis (ATB), and IL-35-producing B cells infiltrated to tuberculous granuloma of patients with ATB. Purified B cells from such patients generated more IL-35 after stimulation by antigens of Mycobacterium tuberculosis and secreted more IL-10. However, the function and the underlying mechanisms of IL-35-producing B cells in TB progression have not been investigated. The present study found that the expression of mRNA of IL-35 subsets Ebi3 and p35 was elevated in mononuclear cells from peripheral blood, spleen, bone marrow, and lung tissue in a mouse model infected with Mycobacterium bovis BCG, as tested by real-time polymerase chain reaction. Accordingly, the flow cytometry analysis showed that the counts of a subset of IL-35+ B cells were elevated in the circulating blood and in the spleen, bone marrow, and lung tissue in BCG-infected mice, whereas anti-TB therapy reduced IL-35-producing B cells. Interestingly, BCG infection could drive the infiltration of IL-35-producing B cells into the lung tissue, and the elevated counts of IL-35-producing B cells positively correlated with the bacterial load in the lungs. Importantly, the injection of exogenous IL-35 stimulated the elevation in the counts of IL-35-producing B cells and was associated with the downregulation of Th1/Th17 and upregulation of Foxp3+Treg.The study showed that a subset of IL-35-producing B cells might take part in the downregulation of immune response in mycobacterial infection.
Grating-based spectral X-ray dark-field imaging for correlation with structural size measures
Authors: Taphorn Kirsten , De Marco Fabio , Andrejewski Jana , Sellerer Thorsten , Pfeiffer Franz , Herzen Julia
Published: August 2020

X-ray dark-field (XDF) imaging accesses information on the small-angle scattering properties of the sample. With grating interferometry, the measured scattering signal is related to the sample’s autocorrelation function, which was previously demonstrated for simple samples, such as mono-dispersed microspheres for which the autocorrelation function is mathematically given. However, in potential clinical applications of XDF imaging, complex microstructures, such as lung parenchyma are under investigation. Their bahaviour in XDF imaging is not yet known and no mathematical description of the autocorrelation function is derived so far. In this work we demonstrate the previously established correlation of the XDF data of complex sample structures with their autocorrelation function to be impractical. Furthermore, we propose an applicable correlation between XDF and the sample’s structural parameter on the basis of mean chord length, a medically-approved measure for alveolar structure, known to be affected by structural lung diseases. Our findings reveal a correlation between energy-dependent XDF imaging and the sample’s mean chord length. By that, a connection between a medical measure for alveoli and XDF is achieved, which is particularly important regarding potential future XDF lung imaging applications for the assessment of alveoli size in diagnostic lung imaging.
Production and purification of higher molecular weight chondroitin by metabolically engineered Escherichia coli K4 strains
Authors: D’ambrosio S. , Alfano A. , Cassese E. , Restaino O. F. , Barbuto Ferraiuolo S. , Finamore R. , Cammarota M. , Schiraldi C. , Cimini D.
Published: August 2020

The capsular polysaccharide obtained from Escherichia coli K4 is a glycosaminoglycan-like molecule, similar to chondroitin sulphate, that has established applications in the biomedical field. Recent efforts focused on the development of strategies to increase K4 polysaccharide fermentation titers up to technologically attractive levels, but an aspect that has not been investigated so far, is how changes in the molecular machinery that produces this biopolymer affect its molecular weight. In this work, we took advantage of recombinant E. coli K4 strains that overproduce capsular polysaccharide, to study whether the inferred pathway modifications also influenced the size of the produced polymer. Fed-batch fermentations were performed up to the 22 L scale, in potentially industrially applicable conditions, and a purification protocol that allows in particular the recovery of high molecular weight unsulphated chondroitin, was developed next. This approach allowed to determine the molecular weight of the purified polysaccharide, demonstrating that kfoF overexpression increased polymer size up to 133 kDa. Higher polysaccharide titers and size were also correlated to increased concentrations of UDP-GlcA and decreased concentrations of UDP-GalNAc during growth. These results are interesting also in view of novel potential applications of higher molecular weight chondroitin and chondroitin sulphate in the biomedical field.
Bright-light detector control emulates the local bounds of Bell-type inequalities
Authors: Sajeed Shihan , Sultana Nigar , Lim Charles Ci Wen , Makarov Vadim
Published: August 2020

It is well-known that no local model—in theory—can simulate the outcome statistics of a Bell-type experiment as long as the detection efficiency is higher than a threshold value. For the Clauser–Horne–Shimony–Holt (CHSH) Bell inequality this theoretical threshold value is $$\eta _{\text {T}} = 2 (\sqrt{2}-1) \approx 0.8284$$

η
T

=
2

(

2

-
1
)

≈
0.8284

. On the other hand, Phys. Rev. Lett. 107, 170404 (2011) outlined an explicit practical model that can fake the CHSH inequality for a detection efficiency of up to 0.5. In this work, we close this gap. More specifically, we propose a method to emulate a Bell inequality at the threshold detection efficiency using existing optical detector control techniques. For a Clauser–Horne–Shimony–Holt inequality, it emulates the CHSH violation predicted by quantum mechanics up to $$\eta _{\text {T}}$$

η
T

. For the Garg–Mermin inequality—re-calibrated by incorporating non-detection events—our method emulates its exact local bound at any efficiency above the threshold. This confirms that attacks on secure quantum communication protocols based on Bell violation is a real threat if the detection efficiency loophole is not closed.
Forecasting low flow conditions months in advance through teleconnection patterns, with a special focus on summer 2018
Authors: Ionita M. , Nagavciuc V.
Published: August 2020

Over the past decades, Europe has been affected by several low flow periods which had substantial impacts on the hydrology of the rivers themselves as well as on the society and economy. Low flow periods have a direct impact on the environment, on the inland waterway navigation, on the hydropower production as well as on the sediment management, among others. Similar to floods, low flows are naturally occurring phenomena which can significantly hinder different uses and functions of the rivers and impact the aquatic system and the water quality. Moreover, it is projected that, in the future, climate change might lead to drier summers over the European region and therefore to more frequent and severe low flow periods. The results presented here show that the summer 2018 low flow situation, over the Rhine and Elbe Rivers basin, could have been predicted up to two seasons ahead by using previous months' sea surface temperature, sea level pressure, precipitation, mean air temperature and soil moisture. The lagged relationship between the predictand (e.g. seasonal streamflow) and the climate and oceanic predictors varies between 1 month (e.g. precipitation) up to 6 months (e.g. sea surface temperature). Taking into account that all predictors are available in real-time, the forecast scheme can be used to provide early warnings for the upcoming low flow situations, thus offering the possibility for better management of the water resources.