bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstinence from Masturbation and Hypersexuality
Authors: Zimmer Felix , Imhoff Roland
Published: March 2020

Despite the lack of evidence for negative health effects of masturbation, abstinence from masturbation is frequently recommended as a strategy to improve one’s sexual self-regulation. We adopted a framework of perceived problems with pornography to collect first hints about whether abstinence from masturbation stems from a psychological and behavioral “addiction” or conflicting attitudes. In an online questionnaire survey recruited via a non-thematic Reddit thread (n = 1063), most participants reported that they had tried to be abstinent from masturbation. As visible from zero-order correlations and multiple linear regression, motivation for abstinence was mostly associated with attitudinal correlates, specifically the perception of masturbation as unhealthy. While there were associations with hypersexuality, no significant correlation with behavioral markers such as maximum number of orgasms was found. Higher abstinence motivation was related to a higher perceived impact of masturbation, conservatism, and religiosity and to lower trust in science. We argue that research on abstinence from masturbation can enrich the understanding of whether and how average frequencies of healthy behavior are pathologized.
G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer
Authors: Andreano Kaitlyn J. , Wardell Suzanne E. , Baker Jennifer G. , Desautels Taylor K. , Baldi Robert , Chao Christina A. , Heetderks Kendall A. , Bae Yeeun , Xiong Rui , Tonetti Debra A. , Gutgesell Lauren M. , Zhao Jiong , Sorrentino Jessica A. , Thompson Delita A. , Bisi John E. , Strum Jay C. , Thatcher Gregory R. J. , Norris John D.
Published: March 2020

Purpose

The combination of targeting the CDK4/6 and estrogen receptor (ER) signaling pathways with palbociclib and fulvestrant is a proven therapeutic strategy for the treatment of ER-positive breast cancer. However, the poor physicochemical properties of fulvestrant require monthly intramuscular injections to patients, which limit the pharmacokinetic and pharmacodynamic activity of the compound. Therefore, an orally available compound that more rapidly reaches steady state may lead to a better clinical response in patients. Here, we report the identification of G1T48, a novel orally bioavailable, non-steroidal small molecule antagonist of ER.

Methods

The pharmacological effects and the antineoplastic mechanism of action of G1T48 on tumors was evaluated using human breast cancer cells (in vitro) and xenograft efficacy models (in vivo).

Results

G1T48 is a potent and efficacious inhibitor of estrogen-mediated transcription and proliferation in ER-positive breast cancer cells, similar to the pure antiestrogen fulvestrant. In addition, G1T48 can effectively suppress ER activity in multiple models of endocrine therapy resistance including those harboring ER mutations and growth factor activation. In vivo, G1T48 has robust antitumor activity in a model of estrogen-dependent breast cancer (MCF7) and significantly inhibited the growth of tamoxifen-resistant (TamR), long-term estrogen-deprived (LTED) and patient-derived xenograft tumors with an increased response being observed with the combination of G1T48 and the CDK4/6 inhibitor lerociclib.

Conclusions

These data show that G1T48 has the potential to be an efficacious oral antineoplastic agent in ER-positive breast cancer.
Genome-wide expression profiling reveals increased stability and mitochondrial energy metabolism of the human liver cell line HepaRG-CAR
Authors: Adam Aziza A. A. , Jongejan Aldo , Moerland Perry D. , van der Mark Vincent A. , Oude Elferink Ronald P. , Chamuleau Robert A. F. M. , Hoekstra Ruurdtje
Published: March 2020

Human liver cell line HepaRG is a well-known source of human hepatocyte-like cells which, however, displays limited biotransformation and a tendency to transform after 20 passages. The new HepaRG-CAR cell line overexpressing constitutive androstane receptor (CAR, NR1I3), a regulator of detoxification and energy metabolism outperforms the parental HepaRG cell line in various liver functions. To further characterize this cell line and assess its stability we compared HepaRG-CAR with HepaRG cells at different passages for their expression profile, ammonia and lactate metabolism, bile acid and reactive oxygen species (ROS) production. Transcriptomic profiling of HepaRG-CAR vs. HepaRG early-passage revealed downregulation of hypoxia, glycolysis and proliferation and upregulation of oxidative phosphorylation genesets. In addition CAR overexpression downregulated the mTORC1 signaling pathway, which, as mediator of proliferation and metabolic reprogramming, may play an important role in the establishment of the HepaRG-CAR phenotype. The ammonia and lactate metabolism and bile acid production of HepaRG-CAR cells was stable for 10 additional passages compared to HepaRG cells. Interestingly, bile acid production was 4.5-fold higher in HepaRG-CAR vs. HepaRG cells, whereas lactate and ROS production were 2.7- and 2.0-fold lower, respectively. Principal component analysis showed clustering of HepaRG-CAR (early- and late-passage) and HepaRG early-passage and not with HepaRG late-passage indicating that passaging exerted larger effect on the transcriptional profile of HepaRG than HepaRG-CAR cells. In conclusion, overexpression of CAR in HepaRG cells improves their bile acid production, mitochondrial energy metabolism, and stability, with the latter possibly due to reduced ROS production, resulting in an optimized source of human hepatocytes.
WISP1 and TLR4 on Macrophages Contribute to Ventilator-Induced Lung Injury
Authors: Yu Zhuang , Wang Tingting , Zhang Liming , Yang Xiaohu , Li Quan , Ding Xibing
Published: March 2020

Abstract

Injurious mechanical ventilation has been shown to directly affect pulmonary and systemic immune responses. How these responses propagate or attenuate remains unknown. The goal of this study was to further determine whether toll-like receptor (TLR) 4 and WNT1-inducible signaling pathway protein 1 (WISP1) could contribute to injurious mechanical ventilation, especially focusing on the role of macrophages during experimental ventilator-induced lung injury. A prospective, randomized, and controlled animal study was designed, and male, wild-type (WT) C57BL/6 mice, TLR4 knockout (TLR4−/−), and lyzTLR4 knockout (lyzTLR4−/−) mice aging 8~12 weeks were used. Animals were anesthetized and randomized to spontaneous breathing (SB) group or to high tidal volume (VT, 20 ml/kg) mechanical ventilation (HTV) group. Histological evaluation, alveolar–capillary permeability of Evan’s blue albumin (EBA), WISP1 protein levels, macrophage inflammatory protein-2 (MIP-2), and interleukin-6 (IL-6) in plasma and bronchoalveolar lavage fluid (BALF) concentrations were analyzed. HTV group was associated with a significant increase of WISP1 and EBA ratio in C57BL/6 mice, a significant decrease of WISP1 protein levels, and a significant decrease of IL-6, MIP-2 in plasma, and BALF concentrations of pro-inflammatory cytokines in TLR4−/− and lyzTLR4−/− knockout mice. In TLR4−/− mice and lyzTLR4−/− mice, there were also significant differences between SB group and HTV group in terms of H&E score and EBA ratio and level of pro-inflammation cytokines. The entire TLR4-targeted mice could further improve various inflammatory changes and damages when compared with lyzTLR4-targeted mice. What is more, TLR4−/− mice and lyzTLR4−/− mice reacted differently to rWISP1 and/or BMMC treated. TLR4−/− mice had no response to rWISP1, while lyzTLR4−/− mice still showed drastic response to both treatments. TLR4 and WISP1, especially the former one, on macrophages could contribute to releasing of pro-inflammatory cytokines during ventilator-induced lung injury. Injurious mechanical ventilation may result in an immune response which is similar to that of infection.
Development of new SNPs loci on Quercus robur and Quercus petraea for genetic studies covering the whole species’ distribution range
Authors: Blanc-Jolivet Celine , Bakhtina Svetlana , Yanbaev Ruslan , Yanbaev Yulai , Mader Malte , Guichoux Erwan , Degen Bernd
Published: March 2020

We used double digest restriction site associated DNA sequencing (ddRAD) to develop new geographically informative nuclear SNP loci in Quercus robur and Quercus petraea. Genotypes derived from sequence data of 95 individuals covering the distribution range of the species were analysed to select geographically informative and polymorphic loci within Russia and Germany. We successfully screened a selected set of 119 loci on a MassARRAY® iPLEX™ platform on 190 individuals from 19 locations in Russia. The newly developed loci will be useful for genetic studies over the whole distribution range of both species.
Experimental investigation on bed shear stress distribution in the roughened compound channel
Authors: Abbaspour Akram
Published: March 2020

The roughness in the floodplains in a compound canal and its impact on hydraulic parameters such as the shear stress and their estimation are one of the problems that have attracted the attention of engineers. In this research, the aim is to investigate the effect of artificial on the floodplain of the compound channel on hydraulic parameters. In experiments, slope of channel bed was 0.0015 and three different discharges have been used. The four types of rigid roughness were used to investigate the effect of these parameters. These roughness elements were arranged with zigzag state with two distances of 4 k and 8 k (k is the height of roughness) in the floodplain. A Preston tube with an external diameter of 3 mm that equipped with dynamic pressure sensors was used to compute the shear stress. The Patel calibration curve was used in order to convert the difference between the static and dynamic pressure measured by the Preston tube to the shear stress values. The results showed that for the zigzag arrangement with the density of 4 k, the shear stress is reduced due to the high roughness density and the greater roughened area. In a rough bed, the shear stress in floodplain was significantly higher than smooth bed, and the stress distribution is such that it has descending trend from the main channel toward the wall of the floodplain. The shear stress increase for roughness with a spacing of 8 k is 22–36% higher than the similar hydraulic condition in a smooth bed and the shear stress for condition with the presence of a cylinder with D = 3 cm and roughness spacing of 8 k was 14–18% higher than the shear stress of bed without a cylinder and the same roughness density. The shear stress for condition of the presence of a cylinder with D = 6 cm and roughness spacing of 4 k is 24–30% more than the roughened plain with distances of 4 k.
Evaluation of morphometric parameters and hypsometric curve of Arkavathy river basin using RS and GIS techniques
Authors: Harsha J. , Ravikumar A. S. , Shivakumar B. L.
Published: March 2020

Water availability and water scarcity in a river basin are influenced by the geomorphological processes occurring within a river basin. Therefore, quantitative evaluation of the river basin shape provides a crucial lead in assessment of the impact of geomorphological processes on the hydrology of the basin. Arkavathy river basin has been selected for the present study. The basin with an annual average rainfall of 874.87 mm is a persistent water scarce basin located in Cauvery river basin in south India. The basin has been subjected to rapid urbanization due to which there is an increased water demand over a period of time. Hence, to tackle the growing water scarcity and reoccurrence of droughts in the basin, an attempt has been made in the present study to investigate and understand the basin morphometry and derivation of hypsometric curve of Arkavathy river basin using remote sensing (RS) and geographic information system (GIS) techniques. Quantitative evaluation of basin morphometry has been made, and the impact of basin morphometry on the peak runoff and flooding in the basin has been assessed. The basin hypsometric curve has aided in assessment of the erosion status of the basin and its impact on the risk of sedimentation on water bodies. The morphometric parameters and hypsometric curve are then analysed to investigate the potential impact of the basin morphometry on the water availability and water scarcity afflicting the basin.
Productivity, competition and bank restructuring process
Authors: Llorens Vanesa , Martín-Oliver Alfredo , Salas-Fumas Vicente
Published: March 2020

This paper analyzes how differences in productivity across banks and the evolution of industry productivity over time might determine the intermediation costs and the restructuring process of the banking industry in the Great Recession. With data of Spanish banks, we find that less productive banks are more likely to exit than more productive banks, and that surviving banks acquire target banks in order to expand their branch network in local markets where they are underrepresented. Competition among banks contributes to the translation of industry productivity growth into lower interest rates of loans. Nonetheless, we find that the industry profit margin in loans increases during the period because of the modest industry productivity growth and the lower intensity of competition from branch closing.
Artificial Erythrina Alkaloids from Three Erythrina Plants, E. variegata, E. crista-galli and E. arborescens
Authors: Zhang Bing-Jie , Wu Jing , Bao Mei-Fen , Wang Fang , Cai Xiang-Hai
Published: March 2020

Fourteen unprecedented artificial Erythrina alkaloids were isolated from the Erythrina variegata, E. crista-galli and E. arborescens (Fabaceae). The structures of these alkaloids were determined by spectroscopic analyses. Their possible formations were proposed. All isolated compounds showed no cytotoxicity and hypoglycemic activity at cell screening bioassay.
Commentary on Jim Tozzi, “Office of Information and Regulatory Affairs: Past, Present, and Future”
Authors: DeMuth Christopher
Published: March 2020

Jim Tozzi is an activist institutional economist. During his 19-year career in the federal civil service, he was a pertinacious institution builder, armed with a PhD in economics but never flaunting it. He gained a reputation, richly deserved in my experience, as a supreme bureaucratic tactician. But he applied his skills to antibureaucratic purposes. Incessantly, and occasionally at professional risk, he promoted and protected internal executive-branch procedures that used economic analysis, and measures of administrative effectiveness, against the incessant forces of political entropy, agency parochialism, and special-interest capture.
Cost-Benefit Analysis Without the B: How Rewriting OIRA’s Past Threatens Its Future
Authors: Katzen Sally
Published: March 2020

Jim Tozzi has a wealth of knowledge and experience with cost-benefit analysis and centralized review of Executive Branch rulemaking. Mine is more limited, but nonetheless significant.1 And while I may agree with much of what he says in his article “Office of Information and Regulatory Affairs: Past, Present and Future,” (Tozzi, 2019) I do see things differently than he does in a number of respects.
Directing Foreign Investments to Eastern Germany: Swiss Engagements after (and before) 1989
Authors: Allen Keith R.
Published: March 2020

This contribution explains how a specific constellation of Swiss consulting experts, financial advisors, and diplomats became involved in the economic restructuring of eastern Germany after November 1989. Swiss engagements reveal that capital did not merely “flow” across unifying Germany's borders, as economists’ definitions of foreign direct investment suggest. Rather, facilitators within and especially beyond Germany actively promoted investments. Business involving foreigners was often grounded in socialist-era trade activities that united profit seekers from East and West Germany, Switzerland, and other nations. As foreign engagements in unifying Germany's economy illustrate, mediators mattered. Pasts persisted. Debt and investment were intertwined. The course of public divesture and state-sponsored private investment in post-Wall Germany suggests future scholars pay closer attention to individuals and entities engaged in exchanging market information, not so much within individual nations as between them.
A Critical Analysis of the Legal and Regulatory Principles for the Declaration and Payment of Company Dividends in Nigeria
Authors: Akaayar Simon Viashima
Published: March 2020

In Nigeria, corporate law and practice are still evolving. Consequently, there is scant literature on some major aspects of corporate law. The focus of this study is on one such area covering dividends and other forms of corporate distribution. In addition to the lack of constructive legal literature on company dividends and other forms of corporate distribution in Nigeria, most of Nigeria's corporate participants and policymakers are still largely uninformed of the fundamental rules and principles on company dividends. Motivated by the foregoing, this research critically examines the theoretical rationale and extant legal principles on company dividends. Its main objectives are to close the gap in the literature and to provoke scholarly discourse that may further enrich policy reform measures in the area of company dividends in Nigeria.
Marine geological investigation of Edward VIII Gulf, Kemp Coast, East Antarctica
Authors: Dove Isabel A. , Leventer Amy , Metcalf Meredith J. , Brachfeld Stefanie A. , Dunbar Robert B. , Manley Patricia , Shevenell Amelia E. , Murray Richard W. , Hommeyer Matthew , Kryc Kelly A. , McLenaghan Natalie , Taylor Fiona , Huber Bruce A.
Published: March 2020

A physical oceanographic, geophysical and marine geological survey of Edward VIII Gulf, Kemp Coast, collected data from conductivity–temperature–depth casts, multi-beam bathymetric swath mapping and 3.5 kHz sub-bottom surveying. Modified circumpolar deep water (mCDW) is observed in Edward VIII Gulf, as well as notable bathymetric features including mega-scale glacial lineations and a 1750 m-deep trough. Sedimentological, geochemical, rock-magnetic and micropalaeontological analysis of two kasten cores document regional palaeoclimate and palaeo-oceanographic conditions over the past 8000 years, with a warm period occurring fromc.8 to 4 ka and a shift to cooler conditions beginning atc.4 ka and persisting until at least 0.9 ka. Sediment packages > 40 m thick within deep troughs in Edward VIII Gulf present potential targets for higher-resolution Holocene and deglacial climate studies. Despite the presence of mCDW on the shelf, inland bed topography consisting of highland terrain suggests the likelihood of relative stability of this sector of the East Antarctic Ice Sheet.
Disaster Planning for Homeless Populations: Analysis and Recommendations for Communities
Authors: Morris Stephen C.
Published: March 2020

Homelessness is a growing problem, with perhaps greater than a 150 million homeless people globally. The global community has prioritized the problem, as eradicating homelessness is one of the United Nation’s sustainability goals of 2030. Homelessness is a variable entity with individual, population, cultural, and regional characteristics complicating emergency preparedness. Overall, there are many factors that make homeless individuals and populations more vulnerable to disasters. These include, but are not limited to: shelter concerns, transportation, acute and chronic financial and material resource constraints, mental and physical health concerns, violence, and substance abuse. As such, homeless population classification as a special or vulnerable population with regard to disaster planning is well-accepted. Much work has been done regarding best practices of accounting for and accommodating special populations in all aspects of disaster management. Utilizing what is understood of homeless populations and emergency management for special populations, a review of disaster planning with recommendations for communities was conducted. Much of the literature on this subject generates from urban homeless in the United States, but it is assumed that some lessons learned and guidance will be translatable to other communities and settings.
Unsupervised modeling anomaly detection in discussion forums posts using global vectors for text representation
Authors: Cichosz Paweł
Published: March 2020

Anomaly detection can be seen as an unsupervised learning task in which a predictive model created on historical data is used to detect outlying instances in new data. This work addresses possibly promising but relatively uncommon application of anomaly detection to text data. Two English-language and one Polish-language Internet discussion forums devoted to psychoactive substances received from home-grown plants, such as hashish or marijuana, serve as text sources that are both realistic and possibly interesting on their own, due to potential associations with drug-related crime. The utility of two different vector text representations is examined: the simple bag of words representation and a more refined Global Vectors (GloVe) representation, which is an example of the increasingly popular word embedding approach. They are both combined with two unsupervised anomaly detection methods, based on one-class support vector machines (SVM) and based on dissimilarity to k-medoids clusters. The GloVe representation is found definitely more useful for anomaly detection, permitting better detection quality and ameliorating the curse of dimensionality issues with text clustering. The cluster dissimilarity approach combined with this representation outperforms one-class SVM with respect to detection quality and appears a more promising approach to anomaly detection in text data.
Anacoustic Modes of Sound Construction and the Semiotics of Virtuality
Authors: Seaback Robert
Published: March 2020

This article discusses technical and aesthetic aspects of sound synthesis in the context of anacoustic modes of sound construction – a neologism that underscores the unique ontology of information in the digital domain. Anacoustic modes address the computer at its most fundamental level: the syntactic level of information. This changes the nature of signification as sound is considered first as an informational construct rather than a material circumstance, rupturing the front-loaded meaning that arises from our acoustic experience. Following certain concepts encompassed by N. Katherine Hayles’s posthumanism, anacoustic modes can be viewed as an expression of the materiality of information.
ScreenPlay: A topic-theory-inspired interactive system
Authors: Meikle George
Published: March 2020

ScreenPlay is a unique interactive computer music system (ICMS) that draws upon various computational styles from within the field of human–computer interaction (HCI) in music, allowing it to transcend the socially contextual boundaries that separate different approaches to ICMS design and implementation, as well as the overarching spheres of experimental/academic and popular electronic musics. A key aspect of ScreenPlay’s design in achieving this is the novel inclusion of topic theory, which also enables ScreenPlay to bridge a gap spanning both time and genre between Classical/Romantic era music and contemporary electronic music; providing new and creative insights into the subject of topic theory and its potential for reappropriation within the sonic arts.
Extreme multiexciton emission from deterministically assembled single-emitter subwavelength plasmonic patch antennas
Authors: Dhawan Amit Raj , Belacel Cherif , Esparza-Villa Juan Uriel , Nasilowski Michel , Wang Zhiming , Schwob Catherine , Hugonin Jean-Paul , Coolen Laurent , Dubertret Benoît , Senellart Pascale , Maître Agnès
Published: March 2020

Coupling nano-emitters to plasmonic antennas is a key milestone for the development of nanoscale quantum light sources. One challenge, however, is the precise nanoscale positioning of the emitter in the structure. Here, we present a laser etching protocol that deterministically positions a single colloidal CdSe/CdS core/shell quantum dot emitter inside a subwavelength plasmonic patch antenna with three-dimensional nanoscale control. By exploiting the properties of metal–insulator–metal structures at the nanoscale, the fabricated single-emitter antenna exhibits a very high-Purcell factor (>72) and a brightness enhancement of a factor of 70. Due to the unprecedented quenching of Auger processes and the strong acceleration of the multiexciton emission, more than 4 photons per pulse can be emitted by a single quantum dot, thus increasing the device yield. Our technology can be applied to a wide range of photonic nanostructures and emitters, paving the way for scalable and reliable fabrication of ultra-compact light sources.
Comparative performance of rural water supplies during drought
Authors: MacAllister D. J. , MacDonald A. M. , Kebede S. , Godfrey S. , Calow R.
Published: March 2020

As rural African communities experience more frequent and extreme droughts, it is increasingly important that water supplies are climate resilient. Using a unique temporal dataset we explore rural water supply (n = 5196) performance during the 2015–16 drought in Ethiopia. Mean functionality ranged from 60% for motorised boreholes to 75% for hand-pumped boreholes. Real-time monitoring and responsive operation and maintenance led to rapid increases in functionality of hand-pumped and, to a lesser extent, motorised boreholes. Increased demand was placed on motorised boreholes in lowland areas as springs, hand-dug-wells and open sources failed. Most users travelled >1 h to access motorised boreholes but <30 min, increasing to 30-60 mins, for hand-pumped boreholes. Boreholes accessing deep (>30 m) groundwater performed best during the drought. Prioritising access to groundwater via multiple improved sources and a portfolio of technologies, such as hand-pumped and motorised boreholes, supported by responsive and proactive operation and maintenance, increases rural water supply resilience.
Ratiometric population sensing by a pump-probe signaling system in Bacillus subtilis
Authors: Babel Heiko , Naranjo-Meneses Pablo , Trauth Stephanie , Schulmeister Sonja , Malengo Gabriele , Sourjik Victor , Bischofs Ilka B.
Published: March 2020

Communication by means of diffusible signaling molecules facilitates higher-level organization of cellular populations. Gram-positive bacteria frequently use signaling peptides, which are either detected at the cell surface or ‘probed’ by intracellular receptors after being pumped into the cytoplasm. While the former type is used to monitor cell density, the functions of pump-probe networks are less clear. Here we show that pump-probe networks can, in principle, perform different tasks and mediate quorum-sensing, chronometric and ratiometric control. We characterize the properties of the prototypical PhrA-RapA system in Bacillus subtilis using FRET. We find that changes in extracellular PhrA concentrations are tracked rather poorly; instead, cells accumulate and strongly amplify the signal in a dose-dependent manner. This suggests that the PhrA-RapA system, and others like it, have evolved to sense changes in the composition of heterogeneous populations and infer the fraction of signal-producing cells in a mixed population to coordinate cellular behaviors.
Nanoelectromechanical relay without pull-in instability for high-temperature non-volatile memory
Authors: Rana Sunil , Mouro João , Bleiker Simon J. , Reynolds Jamie D. , Chong Harold M. H. , Niklaus Frank , Pamunuwa Dinesh
Published: March 2020

Emerging applications such as the Internet-of-Things and more-electric aircraft require electronics with integrated data storage that can operate in extreme temperatures with high energy efficiency. As transistor leakage current increases with temperature, nanoelectromechanical relays have emerged as a promising alternative. However, a reliable and scalable non-volatile relay that retains its state when powered off has not been demonstrated. Part of the challenge is electromechanical pull-in instability, causing the beam to snap in after traversing a section of the airgap. Here we demonstrate an electrostatically actuated nanoelectromechanical relay that eliminates electromechanical pull-in instability without restricting the dynamic range of motion. It has several advantages over conventional electrostatic relays, including low actuation voltages without extreme reduction in critical dimensions and near constant actuation airgap while the device moves, for improved electrostatic control. With this nanoelectromechanical relay we demonstrate the first high-temperature non-volatile relay operation, with over 40 non-volatile cycles at 200 ∘C.
A generalizable 29-mRNA neural-network classifier for acute bacterial and viral infections
Authors: Mayhew Michael B. , Buturovic Ljubomir , Luethy Roland , Midic Uros , Moore Andrew R. , Roque Jonasel A. , Shaller Brian D. , Asuni Tola , Rawling David , Remmel Melissa , Choi Kirindi , Wacker James , Khatri Purvesh , Rogers Angela J. , Sweeney Timothy E.
Published: March 2020

Improved identification of bacterial and viral infections would reduce morbidity from sepsis, reduce antibiotic overuse, and lower healthcare costs. Here, we develop a generalizable host-gene-expression-based classifier for acute bacterial and viral infections. We use training data (N = 1069) from 18 retrospective transcriptomic studies. Using only 29 preselected host mRNAs, we train a neural-network classifier with a bacterial-vs-other area under the receiver-operating characteristic curve (AUROC) 0.92 (95% CI 0.90–0.93) and a viral-vs-other AUROC 0.92 (95% CI 0.90–0.93). We then apply this classifier, inflammatix-bacterial-viral-noninfected-version 1 (IMX-BVN-1), without retraining, to an independent cohort (N = 163). In this cohort, IMX-BVN-1 AUROCs are: bacterial-vs.-other 0.86 (95% CI 0.77–0.93), and viral-vs.-other 0.85 (95% CI 0.76–0.93). In patients enrolled within 36 h of hospital admission (N = 70), IMX-BVN-1 AUROCs are: bacterial-vs.-other 0.92 (95% CI 0.83–0.99), and viral-vs.-other 0.91 (95% CI 0.82–0.98). With further study, IMX-BVN-1 could provide a tool for assessing patients with suspected infection and sepsis at hospital admission.
Marker-free carotenoid-enriched rice generated through targeted gene insertion using CRISPR-Cas9
Authors: Dong Oliver Xiaoou , Yu Shu , Jain Rashmi , Zhang Nan , Duong Phat Q. , Butler Corinne , Li Yan , Lipzen Anna , Martin Joel A. , Barry Kerrie W. , Schmutz Jeremy , Tian Li , Ronald Pamela C.
Published: March 2020

Targeted insertion of transgenes at pre-determined plant genomic safe harbors provides a desirable alternative to insertions at random sites achieved through conventional methods. Most existing cases of targeted gene insertion in plants have either relied on the presence of a selectable marker gene in the insertion cassette or occurred at low frequency with relatively small DNA fragments (<1.8 kb). Here, we report the use of an optimized CRISPR-Cas9-based method to achieve the targeted insertion of a 5.2 kb carotenoid biosynthesis cassette at two genomic safe harbors in rice. We obtain marker-free rice plants with high carotenoid content in the seeds and no detectable penalty in morphology or yield. Whole-genome sequencing reveals the absence of off-target mutations by Cas9 in the engineered plants. These results demonstrate targeted gene insertion of marker-free DNA in rice using CRISPR-Cas9 genome editing, and offer a promising strategy for genetic improvement of rice and other crops.
Directed self-assembly of viologen-based 2D semiconductors with intrinsic UV–SWIR photoresponse after photo/thermo activation
Authors: Yu Xiao-Qing , Sun Cai , Liu Bin-Wen , Wang Ming-Sheng , Guo Guo-Cong
Published: March 2020

Extending photoresponse ranges of semiconductors to the entire ultraviolet–visible (UV)–shortwave near-infrared (SWIR) region (ca. 200–3000 nm) is highly desirable to reduce complexity and cost of photodetectors or to promote power conversion efficiency of solar cells. The observed up limit of photoresponse for organic-based semiconductors is about 1800 nm, far from covering the UV–SWIR region. Here we develop a cyanide-bridged layer-directed intercalation approach and obtain a series of two viologen-based 2D semiconductors with multispectral photoresponse. In these compounds, infinitely π-stacked redox-active N-methyl bipyridinium cations with near-planar structures are sandwiched by cyanide-bridged MnII–FeIII or ZnII–FeIII layers. Radical–π interactions among the infinitely π-stacked N-methyl bipyridinium components favor the extension of absorption range. Both semiconductors show light/thermo-induced color change with the formation of stable radicals. They have intrinsic photocurrent response in the range of at least 355–2400 nm, which exceeds all reported values for known single-component organic-based semiconductors.
Soft three-dimensional network materials with rational bio-mimetic designs
Authors: Yan Dongjia , Chang Jiahui , Zhang Hang , Liu Jianxing , Song Honglie , Xue Zhaoguo , Zhang Fan , Zhang Yihui
Published: March 2020

Many biological tissues offer J-shaped stress–strain responses, since their microstructures exhibit a three-dimensional (3D) network construction of curvy filamentary structures that lead to a bending-to-stretching transition of the deformation mode under an external tension. The development of artificial 3D soft materials and device systems that can reproduce the nonlinear, anisotropic mechanical properties of biological tissues remains challenging. Here we report a class of soft 3D network materials that can offer defect-insensitive, nonlinear mechanical responses closely matched with those of biological tissues. This material system exploits a lattice configuration with different 3D topologies, where 3D helical microstructures that connect the lattice nodes serve as building blocks of the network. By tailoring geometries of helical microstructures or lattice topologies, a wide range of desired anisotropic J-shaped stress–strain curves can be achieved. Demonstrative applications of the developed conducting 3D network materials with bio-mimetic mechanical properties suggest potential uses in flexible bio-integrated devices.
Room-temperature liquid diffused separation induced crystallization for high-quality perovskite single crystals
Authors: Yao Fang , Peng Jiali , Li Ruiming , Li Wenjing , Gui Pengbin , Li Borui , Liu Chang , Tao Chen , Lin Qianqian , Fang Guojia
Published: March 2020

Large single crystals serve as an ideal platform for investigating intrinsic material properties and optoelectronic applications. Here we develop a method, namely, room-temperature liquid diffused separation induced crystallization that uses silicone oil to separate the solvent from the perovskite precursors, to grow high-quality perovskite single crystals. The growth kinetics of perovskite single crystals using this method is elucidated, and their structural and optoelectronic properties are carefully characterized. The resultant perovskite single crystals, taking CH3NH3PbBr3 as an example, exhibit approximately 1 µs lifetime, a low trap density of 4.4 × 109 cm−3, and high yield of 92%, which are appealing for visible light or X-ray detection. We hope our findings will be of great significance for the continued advancement of high-quality perovskite single crystals, through a better understanding of growth mechanisms and their deployment in various optoelectronics. The diffused separation induced crystallization strategy presents a major step forward for advancing the field on perovskite single crystals.
Gene clustering and copy number variation in alkaloid metabolic pathways of opium poppy
Authors: Li Qiushi , Ramasamy Sukanya , Singh Pooja , Hagel Jillian M. , Dunemann Sonja M. , Chen Xue , Chen Rongji , Yu Lisa , Tucker Joseph E. , Facchini Peter J. , Yeaman Sam
Published: March 2020

Genes in plant secondary metabolic pathways enable biosynthesis of a range of medically and industrially important compounds, and are often clustered on chromosomes. Here, we study genomic clustering in the benzylisoquinoline alkaloid (BIA) pathway in opium poppy (Papaver somniferum), exploring relationships between gene expression, copy number variation, and metabolite production. We use Hi-C to improve the existing draft genome assembly, yielding chromosome-scale scaffolds that include 35 previously unanchored BIA genes. We find that co-expression of BIA genes increases within clusters and identify candidates with unknown function based on clustering and covariation in expression and alkaloid production. Copy number variation in critical BIA genes correlates with stark differences in alkaloid production, linking noscapine production with an 11-gene deletion, and increased thebaine/decreased morphine production with deletion of a T6ODM cluster. Our results show that the opium poppy genome is still dynamically evolving in ways that contribute to medically and industrially important phenotypes.
Highly enantioselective photo-polymerization enhanced by chiral nanoparticles and in situ photopatterning of chirality
Authors: He Chenlu , Feng Zeyu , Shan Sizhen , Wang Mengqiao , Chen Xin , Zou Gang
Published: March 2020

Chiral noble metal nanoparticles has recently gained great interest due to their potential applications including ultrasensitive chiral recognition and asymmetric synthesis. We anticipate that they could be utilized to induce asymmetric photo-polymerization reactions with high enantioselectivity and reactivity. Here, we report such a system. By employing silver nanoparticles modified with cysteine as the chiral inducer, polydiacetylene (PDA) with high chiral asymmetry was obtained from achiral diacetylene monomers triggered with unpolarized UV light. Furthermore, the helical sense of chirality can be controlled by varying the wavelength of UV irradiation. This enables a feasible and economical method to fabricate programmable 2D patterns of chiral PDA with tailored chirality distributions, such as smooth gradients in chirality and micropatterns with tailorable circularly polarized luminescence. Our finding not only opens a pathway for producing programmable chiroptical micropatterns, but also is highly valuable for deeper understanding of symmetry breaking in enantioselective photochemical reactions.
Author Correction: Deep learning analysis of defect and phase evolution during electron beam-induced transformations in WS2
Authors: Maksov Artem , Dyck Ondrej , Wang Kai , Xiao Kai , Geohegan David B. , Sumpter Bobby G. , Vasudevan Rama K. , Jesse Stephen , Kalinin Sergei V. , Ziatdinov Maxim
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The range of non-Kitaev terms and fractional particles in α-RuCl3
Authors: Wang Yiping , Osterhoudt Gavin B. , Tian Yao , Lampen-Kelley Paige , Banerjee Arnab , Goldstein Thomas , Yan Jun , Knolle Johannes , Ji Huiwen , Cava Robert J. , Nasu Joji , Motome Yukitoshi , Nagler Stephen E. , Mandrus David , Burch Kenneth S.
Published: March 2020

Significant efforts have focused on the magnetic excitations of relativistic Mott insulators, predicted to realize the Kitaev quantum spin liquid (QSL). This exactly solvable model involves a highly entangled state resulting from bond-dependent Ising interactions that produce excitations which are non-local in terms of spin flips. A key challenge in real materials is identifying the relative size of the non-Kitaev terms and their role in the emergence or suppression of fractional excitations. Here, we identify the energy and temperature boundaries of non-Kitaev interactions by direct comparison of the Raman susceptibility of α-RuCl3 with quantum Monte Carlo (QMC) results for the Kitaev QSL. Moreover, we further confirm the fractional nature of the magnetic excitations, which is given by creating a pair of fermionic quasiparticles. Interestingly, this fermionic response remains valid in the non-Kitaev range. Our results and focus on the use of the Raman susceptibility provide a stringent new test for future theoretical and experimental studies of QSLs.
Cardiac dysregulation following intrahippocampal kainate-induced status epilepticus
Authors: Levine Amber T. , Born Heather A. , Landstrom Andrew P. , Larson Samuel , Lee Wai Ling , Dao An T. , Wehrens Xander H. , Lai Yi-Chen , Anderson Anne E.
Published: March 2020

Status epilepticus (SE) is a prevalent disorder associated with significant morbidity, including the development of epilepsy and mortality. Cardiac arrhythmias (i.e. inappropriate sinus tachycardia and bradycardia, asystole, and atrioventricular blocks) are observed in patients following SE. We characterized ictal (during a seizure) and interictal (between seizure) cardiac arrhythmogenesis following SE using continuous electrocardiography and video electroencephalography (vEEG) recordings throughout a 14-day monitoring period in an intrahippocampal chemoconvulsant mouse model that develops epilepsy. We quantified heart rhythm abnormalities and examined whether the frequency of cardiac events correlated with epileptiform activity, circadian (light/dark) cycle, the presence of seizures, and survival during this period of early epileptogenesis (the development of epilepsy) following SE. Shortly following SE, mice developed an increased interictal heart rate and heart rhythm abnormalities (i.e. sinus pause and sinus arrhythmias) when compared to control mice. Heart rhythm abnormalities were more frequent during the light cycle and were not correlated with increased epileptiform activity or seizure frequency. Finally, SE animals had early mortality, and a death event captured during vEEG recording demonstrated severe bradycardia prior to death. These cardiac changes occurred within 14 days after SE and may represent an early risk factor for sudden death following SE.
Author Correction: Canonical germinant receptor is dispensable for spore germination in Clostridium botulinum group II strain NCTC 11219
Authors: Clauwers Charlien , Lood Cédric , Van den Bergh Bram , van Noort Vera , Michiels Chris W.
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Profiling the susceptibility of Pseudomonas aeruginosa strains from acute and chronic infections to cell-wall-targeting immune proteins
Authors: Torrens Gabriel , Barceló Isabel M. , Pérez-Gallego Marcelo , Escobar-Salom Maria , Tur-Gracia Sara , Munar-Bestard Marta , González-Nicolau María del Mar , Cabrera-Venegas Yoandy José , Rigo-Rumbos Estefany Nayarith , Cabot Gabriel , López-Causapé Carla , Rojo-Molinero Estrella , Oliver Antonio , Juan Carlos
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Stable isotope metabolomics of pulmonary artery smooth muscle and endothelial cells in pulmonary hypertension and with TGF-beta treatment
Authors: Hernandez-Saavedra Daniel , Sanders Linda , Freeman Scott , Reisz Julie A. , Lee Michael H. , Mickael Claudia , Kumar Rahul , Kassa Biruk , Gu Sue , D’ Alessandro Angelo , Stenmark Kurt R. , Tuder Rubin M. , Graham Brian B.
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Selective Targeting of Virus Replication by Proton Pump Inhibitors
Authors: Watanabe Susan M. , Ehrlich Lorna S. , Strickland Madeleine , Li Xiaofan , Soloveva Veronica , Goff Arthur J. , Stauft Charles B. , Bhaduri-McIntosh Sumita , Tjandra Nico , Carter Carol
Published: March 2020

Two proton pump inhibitors, tenatoprazole and esomeprazole, were previously shown to inhibit HIV-1 egress by blocking the interaction between Tsg101, a member of the ESCRT-I complex, and ubiquitin. Here, we deepen our understanding of prazole budding inhibition by studying a range of viruses in the presence of tenatoprazole. Furthermore, we investigate the relationship between the chemistry of prodrug activation and HIV-1 inhibition for diverse prazoles currently on the market. We report that tenatoprazole is capable of inhibiting the replication of members of the enveloped filo, alpha, and herpes virus families but not the flavivirus group and not the non-enveloped poliovirus. Another key finding is that prazole prodrugs must be activated inside the cell, while their rate of activation in vitro correlated to their efficacy in cells. Our study lays the groundwork for future efforts to repurpose prazole-based compounds as antivirals that are both broad-spectrum and selective in nature.
Temporal discounting correlates with directed exploration but not with random exploration
Authors: Sadeghiyeh Hashem , Wang Siyu , Alberhasky Maxwell R. , Kyllo Hannah M. , Shenhav Amitai , Wilson Robert C.
Published: March 2020

The explore-exploit dilemma describes the trade off that occurs any time we must choose between exploring unknown options and exploiting options we know well. Implicit in this trade off is how we value future rewards — exploiting is usually better in the short term, but in the longer term the benefits of exploration can be huge. Thus, in theory there should be a tight connection between how much people value future rewards, i.e. how much they discount future rewards relative to immediate rewards, and how likely they are to explore, with less ‘temporal discounting’ associated with more exploration. By measuring individual differences in temporal discounting and correlating them with explore-exploit behavior, we tested whether this theoretical prediction holds in practice. We used the 27-item Delay-Discounting Questionnaire to estimate temporal discounting and the Horizon Task to quantify two strategies of explore-exploit behavior: directed exploration, where information drives exploration by choice, and random exploration, where behavioral variability drives exploration by chance. We find a clear correlation between temporal discounting and directed exploration, with more temporal discounting leading to less directed exploration. Conversely, we find no relationship between temporal discounting and random exploration. Unexpectedly, we find that the relationship with directed exploration appears to be driven by a correlation between temporal discounting and uncertainty seeking at short time horizons, rather than information seeking at long horizons. Taken together our results suggest a nuanced relationship between temporal discounting and explore-exploit behavior that may be mediated by multiple factors.
Publisher Correction: Two-dimensional Dirac particles in a Pöschl-Teller waveguide
Authors: Hartmann R. R. , Portnoi M. E.
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Lactation stage impacts the glycolytic function of bovine CD4+ T cells during ex vivo activation
Authors: Eder Jordan M. , Gorden Patrick J. , Lippolis John D. , Reinhardt Timothy A. , Sacco Randy E.
Published: March 2020

Dairy cattle undergo dynamic physiological changes over the course of a full lactation into the dry period, which impacts their immunocompetence. During activation, T cells undergo a characteristic rewiring to increase the uptake of glucose and metabolically reprogram to favor aerobic glycolysis over oxidative phosphorylation. To date it remains to be completely elucidated how the altered energetic demands associated with lactation in dairy cows impacts T cell metabolic reprogramming. Thus, in ourex vivostudies we have examined the influence of stage of lactation (early lactation into the dry period) on cellular metabolism in activated bovine CD4+T cells. Results showed higher rates of glycolytic function in activated CD4+T cells from late lactation and dry cows compared to cells from early and mid-lactation cows. Similarly, protein and mRNA expression of cytokines were higher in CD4+T cells from dry cows than CD4+T cells from lactating cows. The data suggest CD4+T cells from lactating cows have an altered metabolic responsiveness that could impact the immunocompetence of these animals, particularly those in early lactation, and increase their susceptibility to infection.