bluuebunny/crossref_metadata_2025 huggingface dataset:
Superlubricity achieved with two-dimensional nano-additives to liquid lubricants
Authors: Wang Hongdong , Liu Yuhong
Published: July 2020

The topic of superlubricity is attracting considerable interest around the world while humanity is facing an energy crisis. Since various liquid superlubricity systems can be commonly achieved on the macroscale in ambient conditions, it is considered an effective solution to reduce unnecessary energy and material losses. However, certain practical problems such as low load-bearing pressure, dependence on hydrogen ions, and relatively long running-in processes still limit its widespread application. Two-dimensional (2D) nano-additives with ultrathin longitudinal dimensions can lower the shear resistance between sliding solid surfaces, and thus further optimize the applied conditions. In this review, the latest studies on 2D nano-additives with a combination of various water-based lubricants in the state of superlubricity are reported, typically including black phosphorus (BP), graphene oxide (GO), and layered double hydroxide. During the sliding process, composite lubricants effectively improved the load capacity (up to 600 MPa), reduced wear, and accelerated the running-in period (within 1,000 s) of the liquid superlubricity system. Both macromechanical experiments and microscopic tests are conducted to precisely analyze various interactions at the interfaces of the nano-additives and solid surfaces. These interactions can be described as tribochemical reactions, physical protection, and adsorption enhancement, and improved wear resistance. This review provides better guidance for applying 2D nanomaterials in liquid superlubricity systems.
Der Sozialraum und seine Bedeutung für die Qualität im Elementarbereich
Authors: Schelle Regine
Published: July 2020

In der Diskussion um Qualität im Elementarbereich ist empirisch noch nicht eindeutig geklärt, welche Faktoren letztlich für eine hohe Qualität entscheidend sind und wie diese miteinander interagieren. Der Artikel zielt daher darauf ab, einen Einblick in die Qualitätsdiskussion im Elementarbereich zu geben (Teil 2) und daran anschließend den Begriff des Sozialraums zu klären sowie dessen Bedeutung für die kindliche Entwicklung und Bildung – und damit für die pädagogische Arbeit – darzulegen (Teil 3). Im vierten Teil werden schließlich die Diskurse zusammengeführt und anhand empirischer Ergebnisse wird verdeutlicht, welche Bedeutung der Sozialraum im Qualitätsdiskurs im Elementarbereich einnimmt. Damit leistet der Artikel einen wichtigen Beitrag zum aktuellen Diskurs über die Qualitätsentwicklung im Elementarbereich.
Radical Cystectomy and Perioperative Sexual Function: A Cross-Sectional Analysis
Authors: Westerman Mary E. , Kokorovic Andrea , Wang Xin Shelly , Lim Amy , Garcia-Gonzalez Araceli , Seif Mohamed , Wang Run , Kamat Ashish M. , Dinney Colin P.N. , Navai Neema
Published: July 2020

Background

Cancer-related changes in sexual function (SF) negatively impact quality of life and intimate partner relationships. There is a lack of data regarding SF among patients who underwent radical cystectomy (RC).

Aim

To comparatively evaluate perioperative SF among patients who underwent RC.

Methods

A prospective cohort of 150 patients undergoing RC for bladder cancer and participating in an internal validation study at a single institution from 2016 to 2019 were eligible for analysis. The European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire–Bladder Cancer Muscle Invasive (EORTC QLQ–BLM 30) and Functional Assessment of Cancer Therapy–Bladder were administered; those completing the SF subscale of the EORTC QLQ–BLM 30 were included in final analysis. Analysis was performed using descriptive statistics and generalized linear modeling.

Outcomes

The primary outcome was interest or engagement in sexual activity within 4 weeks of survey completion, whereas the secondary outcome was a mean score on the EORTC QLQ–BLM 30 SF subscale.

Results

Overall, 132 of 150 (88%) of patients were eligible, of whom 82% were male, and the median age was 68.5 years. 53% reported at least a little interest in sexual activity, and 40% endorsed sexual activity within the last 4 weeks. The mean SF subscale score was 61.5 ± 25.2. Women had significantly worse mean scores of 72.9 ± 27.1 versus 59.1 ± 24.2 for men (P = .02). On multivariate analysis, both age and female gender were independently associated with higher SF domain scores.

Clinical Implications

A substantial portion of patients who underwent RC endorse being sexually active or express interest in sexually activity in the perioperative period. Given the recent increase in attention given to SF outcomes and quality of life, this work supports further efforts to explore this area and develop novel interventions to improve outcomes.

Strengths and Limitations

Strengths include rigorously collected, cross-sectional data using standardized methodology. Limitations include a relatively small sample size of female patients and unknown meaningful clinical difference.

Conclusions

A substantial portion of patients report sexual interest and activity in the perioperative period; however, female gender is associated with worse SF domain scores. These findings support further inquiry into this topic.
How biometrics can save companies from ‘fire and forget’
Authors: Sinno Salvatore , Hawley Christopher
Published: July 2020

A few years ago, the media reported on the now notorious case of ‘Bob’, a star programmer who was earning a six-figure salary at an American infrastructure company. When the company commissioned a network-security audit, however, they belatedly discovered that Bob had outsourced his job to a Chinese software company for a fifth of his pay.
The effect of postcard reminders on vaccinations among the elderly: a block-randomized experiment
Authors: CHEN NUOLE , TRUMP KRIS-STELLA , HALL STACY , LE QUAN
Published: July 2020

Prior research in the behavioral sciences has demonstrated that reminders can be an effective tool for encouraging health-related behavior changes. This article extends that literature by reporting the outcome of a randomized controlled trial of mailed vaccination reminders. In addition to making a substantive contribution regarding the efficacy of mailed reminders, this article also makes a methodological contribution: it illustrates how researchers can study the causal impact of an intervention even when a pure parallel trial is not possible. In this study, the Louisiana Department of Health sent postcard reminders regarding four recommended vaccinations (influenza, tetanus, shingles and pneumonia) to 208,867 senior residents of Louisiana. We used block randomization and a stepped wedge design to assess the efficacy of the intervention. Individuals were blocked by their prior vaccine record and randomized to receive the postcard in one of four consecutive months (October–January). The reminder postcard had an overall positive effect on vaccination rates. The statistically significant and substantively small increase in overall vaccination rates was driven by participants who received the postcard reminder early in the intervention period.
Buying Power: Electoral Strategy before the Secret Vote
Authors: GINGERICH DANIEL W.
Published: July 2020

Research on clientelism emphasizes the use of brokers to mobilize voters. To utilize these agents efficiently, politicians must learn about brokers’ relative abilities and allocate scarce resources accordingly. Drawing upon a hand-coded dataset based on the archives of Gustavo Capanema, a powerful mid-twentieth-century congressman from Minas Gerais, Brazil, this paper offers the first direct evidence of such learning dynamics. The analysis concentrates on Brazil’s pre-secret ballot era, a time when measuring broker performance was particularly straightforward. Consistent with theories of political learning, the data demonstrate that resource flows to local machines were contingent on the deviation between actual and expected votes received in previous elections. Moreover, given politicians’ ability to discern mobilization capacity, payments to brokers were highly effective in bringing out the vote.
Fine lexical tuning in infant directed speech to typically developing children
Authors: ODIJK Lotte , GILLIS Steven
Published: July 2020

Do parents fine-tune the MLU of utterances with a particular word as the word is on the verge of appearing in the child's production? We analyzed a corpus of spontaneous interactions of 30 dyads. The children were in the initial stages of their lexical development, and the parents’ utterances containing the words the children eventually acquired were selected. The main finding is that the MLU of the parental utterances containing the target words gradually decreased up to the point of the children's first production of those words. This suggests that parents fine-tune their utterances to support the children's linguistic development.
Cognitive flexibility in critical CHD: a target for intervention
Authors: Cassidy Adam R.
Published: July 2020

Most children born with even the most critical forms of CHD are now surviving well into adulthood. However, with increased survival has come increased recognition of the diverse neurobehavioural and psychosocial challenges these children experience. Among these challenges are deficits in executive function skills, including inhibitory control, working memory, and cognitive flexibility. Over the past several years, whereas inhibitory control and working memory deficits have garnered particular attention among clinicians and interventionists, relatively less attention has been paid to cognitive flexibility. This is unfortunate given both the high prevalence of cognitive flexibility deficits observed in children and adolescents with critical CHD, and also the far-reaching relevance of cognitive flexibility in helping individuals achieve optimal quality of life across the lifespan. This paper reviews the construct of cognitive flexibility, including its definition, development, measurement, and neuroanatomical basis, provides a summary of how cognitive flexibility is affected by CHD, and offers evidence-based recommendations to systematically support the development of cognitive flexibility within the context of CHD.
THE POET AND THE EVANGELIST IN NONNUS’PARAPHRASE OF THE GOSPEL ACCORDING TO JOHN
Authors: Hadjittofi Fotini
Published: July 2020

Christian poetry, and biblical epic in particular, is intensely self-conscious. Both Greek and Latin Christian poets begin or end their compositions, paraphrases and centos with poetological reflections on the value and objectives of their works. The fifth-centuryParaphrase of the Gospel according to Johnis an anomaly in this tradition. While Nonnus’ mythological epic, theDionysiaca, is heavily self-conscious in that it includes a strong authorial voice as well as an extensiveprooemiumand an interlude, the ChristianParaphrasehas noprooemium, epilogue or interlude, and its narrator never identifies himself. This article examines two passages in theParaphrasewhere subtle, implicit poetological reflections may be detected, and then explores the reasons why Nonnus may have chosen to deny theParaphrasea clear (meta)literary identity. It argues that Nonnus’ poem presents itself astheGospel of John, and that its narrator ‘becomes’ John the Evangelist in a spiritual exercise which is indebted to Origen's views on that Gospel.
It Must have been Burnout: Prevalence and Related Factors among Spanish PhD Students
Authors: Sorrel Miguel A. , Martínez-Huertas José Ángel , Arconada María
Published: July 2020

Recent studies in different countries indicate that PhD students are more vulnerable to psychological disorders compared to the general population. No such data are available for the Spanish population. This study addresses this issue by studying prevalence rates and factors related to a common response to prolonged stress such as burnout syndrome. Burnout, emotional abilities, resilience, satisfaction with the dissertation advisor, and sociodemographic data were collected from 305 PhD students. The results indicated that the burnout rates are high in this group, especially for the emotional exhaustion dimension. Different linear regression models explained between 14% and 41% of the overall burnout scores variance and its dimensions. The psychological variables and the satisfaction with the dissertation advisor were the most relevant predictors. Consistent with what has been found in other countries, the evidence found indicates that the mental state of PhD students in Spain is alarming. The results of this study have important implications for the design and implementation of interventions to alleviate this problem.
A K‐Means Clustering Analysis of the Jovian and Terrestrial Magnetopauses: A Technique to Classify Global Magnetospheric Behavior
Authors: Collier Michael R. , Gruesbeck Jacob R. , Connerney John E. P. , Joy Steven P. , Hospodarsky George B. , Roberts Aaron , Sibeck David G. , Roelof Edmond C.
Published: July 2020

Previous studies suggested that the Jovian magnetopause position is best characterized as a bimodal distribution indicative of a two‐state system. We applied a modified k‐means clustering analysis to observations of the Jovian and terrestrial magnetopause crossings. Clustering analysis using pre‐Juno data shows that the Jovian magnetopause is best described as a two‐state system, whereas the terrestrial magnetopause is best described by a single state, indicating that the behavior of the Jovian magnetopause is fundamentally different from that of the terrestrial magnetopause. We also analyzed magnetopause locations detected by the Juno spacecraft and conclude that their distribution is consistent with a two‐state system. The origin of the different number of Jovian and terrestrial magnetopause states may be due to the disparate source strengths supplying the two magnetospheres. The Jovian magnetosphere is supplied with about a metric ton of Iogenic heavy ions per second, whereas the terrestrial source, Earth's ionosphere, is two orders of magnitude weaker. A suggestive correlation between Io phase and magnetopause state may be consistent with this proposed link between an internal source and a two‐state magnetopause. The possible role of energetic magnetospheric events and Jovian current systems is discussed.
Shock Melting Curve of Iron: A Consensus on the Temperature at the Earth's Inner Core Boundary
Authors: Li Jun , Wu Qiang , Li Jiabo , Xue Tao , Tan Ye , Zhou Xianming , Zhang Youjun , Xiong Zhengwei , Gao Zhipeng , Sekine Toshimori
Published: July 2020

The Earth's core consists of iron as the major component. The melting point of iron at the inner core boundary constrains the thermal structure and solidification of the Earth's core. However, the current estimation of the melting temperature of iron under the core conditions has significant variations. Here, we measured the temperatures of iron shocked up to ~256 GPa using precise pyrometer and velocimeter diagnostics via a two‐stage light‐gas gun. Our results indicated that the melting temperatures of iron at the core‐mantle and inner core boundaries are 4300(250) and 5950(400) K, respectively. These temperatures are significantly lower than some previous shock experiments but are overall consistent with the recent results determined by fast X‐ray diffraction techniques, X‐ray absorption experiments in laser‐heated diamond anvil cells, and by ab initio computations. Our iron melting curve indicates a relatively small Clapeyron slope and supports thermal models for a young inner core.
Influences of the Interdecadal Pacific Oscillation on the Locally Amplified Ningaloo Niño
Authors: Tanuma Natsumi , Tozuka Tomoki
Published: July 2020

Using observation/reanalysis data, influences of the Interdecadal Pacific Oscillation (IPO) on the frequency of the locally amplified Ningaloo Niño (i.e., events with local air‐sea interactions playing an important role) and their mechanisms are investigated in this study. It is found that the ratio of the locally amplified Ningaloo Niño increases during the negative phase of the IPO. This is due to positive interdecadal sea surface temperature anomalies to the northwest of Australia that promote deep atmospheric convection and anomalous cyclone off the west coast of Australia through a Matsuno‐Gill response. Based on a mixed layer heat budget analysis using outputs from a regional ocean model, it is shown that an enhanced warming of anomalously thin mixed layer by the shortwave radiation contributes dominantly to the interdecadal sea surface temperature anomalies. The shallow mixed layer depth is suggested to be generated by anomalously weak winds associated with the negative IPO.
Coseismic Uplift of the 1999 Mw7.6 Chi‐Chi Earthquake and Implication to Topographic Change in Frontal Mountain Belts
Authors: Chuang R. Y. , Lu C. H. , Yang C. J. , Lin Y. S. , Lee T. Y.
Published: July 2020

Large dip‐slip earthquakes have a major contribution to mountain building while earthquake‐induced landslides lower mountains simultaneously. The amount of the coseismic uplift and landslides may dominate long‐term mountain evolution. However, how earthquakes contribute to mountain evolution through coseismic uplift and landslides is less constrained in real cases. We present the regional coseismic uplift of the 1999 Mw7.6 Chi‐Chi earthquake by using synthetic aperture radar (SAR) images and GPS. The coseismic uplift pattern is consistent with field observations showing increasing movement to the north with ~8 m of uplift toward the northern end. We estimated uplifted rock volume of 2.60 ± 1.09 km3, which is five times greater than the coseismic landslide volume. Intense erosion of the Taiwan orogen may erode elevated rocks rapidly, but the uplift and landslide distributions do not match and correlate more inversely, suggesting the frontal orogenic topography should be increased rather than annulled over earthquake cycles.
Electron‐Driven Magnetic Dip Embedded Within the Proton‐Driven Magnetic Dip and the Related Echoes of Butterfly Distribution of Relativistic Electrons
Authors: Zhu Hui , Chen Lunjin , Xia Zhiyang
Published: July 2020

In this study, a magnetic dip event in which a small‐scale magnetic dip is embedded within a large‐scale magnetic dip is analyzed based on the observations of the Van Allen Probes. The small‐scale dip is contributed by a sharp electron injection at the energy range of 1 to 10 keV, but the large‐scale dip is contributed by a smooth proton injection at the energy range higher than 10 keV. The formation of dip caused by the suprathermal electrons is supported by the self‐consistent magnetic model. Moreover, the echoes of butterfly distributions of relativistic electrons at the energy range of 0.5 to 3.4 MeV is observed. The time separations of the neighboring butterfly distributions are comparable to the drift periods of the electrons at the different energies. We suggest that the potential nonadiabatic processes in response to the magnetic dips possibly account for the butterfly distribution echoes.
Estimating of the Global Ionosphere Maps Using Hybrid Data Assimilation Method and Their Background Influence Analysis
Authors: Wang Sicheng , Huang Sixun , Fang Hanxian
Published: July 2020

The increasing amount of the Global Navigation Satellite System (GNSS) ground receivers provides extremely abundant data resource to ionospheric community. In present paper, a hybrid data assimilation method is proposed to derive the global ionosphere maps (GIM) using the GNSS measurements. This method can balance the weights of background information from the International Reference Ionosphere model (IRI‐2016) and actual observations to reach a reasonable estimation, and its background error covariance (BEC) is a weighted linear combination of climatological static BEC and ensemble‐based flow‐dependent BEC. The results show that this method is capable of improving the background outputs significantly. To evaluate the quantitative contribution of background information on the estimated GIM, the background influence analysis is performed. The background information contributes less in the data‐rich areas and more in the data‐sparse areas. The mean background influence is up to 0.93 for the reconstructed GIM; that is, about 93% of the contribution is due to the background information, and the complementary 7% is the influence of the assimilated observations.
Porites Coral on a Remote Reef Reveal Marine Phosphorus Biogeochemical Cycling Following Artificial Disturbance
Authors: Jiang Wei , Yang Haodan , Yu Kefu , Song Yinxian , Zhao Jian‐xin , Feng Yue‐xing , Han Tao , Wu Xingyuan , Ning Zhiming , Xu Shendong , Wang Yinghui
Published: July 2020

Excess anthropogenic phosphorus (P) supplied to marine systems, which may subsequently jeopardize ecosystem structure and function, has altered the P balance and quadrupled its flow. However, due to the diversity of P sources, the unpredictability and variability of human activities, and the absence of long‐term records, it remains uncertain how long the effects of excess P persist in aquatic ecosystems, and whether it stimulates gross primary productivity. In this study, we utilized geochemical proxies in coral skeletons from an atoll in the Xisha Islands of the South China Sea to reconstruct historical patterns of P in surface seawater. This atoll has remained in a natural state for an extended period of time, except for a short period of unambiguously documented guano extraction. Analyses of coral skeletons dating back to 1851 CE distinctly show that the P concentration in surface seawater increased abnormally in the 1960s. We deduced that guano extraction at that time led to an abrupt increase in the long‐term equilibrium of seawater P concentration. Subsequent P addition appeared to have continued for at least ~30 years after phosphorite exploitation ceased, and P showed a decay period that was longer than that of other elements. Similar temporal trends of coral P/Ca and δ13C indicated that elevated marine primary productivity was associated with increased P. Large inputs within a short period, as well as the continued influence of P over the long term, can serve as a natural ecological analog for coral reefs subject to nutrient contamination.
A Heavy Precipitation Event in the Yangtze River Basin Led by an Eastward Moving Tibetan Plateau Cloud System in the Summer of 2016
Authors: Chen Yilun , Zhang Aoqi , Zhang Yuheng , Cui Chunguang , Wan Rong , Wang Bin , Fu Yunfei
Published: July 2020

From 29 June to 6 July 2016, China's Yangtze River Basin experienced heavy precipitation, causing more than 200 deaths and affecting tens of millions of people. Using ERA5 reanalysis, soundings, and satellite observations from FY‐2 and Global Precipitation Measurement (GPM), we reviewed this heavy rainfall event from the perspective of its meteorological triggers and the cloud microphysics. As the cloud system moved eastward from the Tibetan Plateau, precipitation particles got larger and denser, and the enhancement of stratiform precipitation contributed the most precipitation. The riming and aggregation processes, the dominant growth modes of particles, were significantly enhanced between 5.5 and 7 km. The increase in the echo‐top height had a considerable positive effect on the near‐surface particle size (from ~1.0 mm at 4 km to ~1.5 mm at 10 km), but this feature was not significant over the Tibetan Plateau. We suggest that the microphysics of this event was dominated by the combination of the eastward moving cloud system, which acted as continuous “seeder” cloud, and the increase in water vapor associated with the low‐level vortex and jet, which generated enhancing “feeder” cloud. The particles from the “seeder” cloud grew by the lower “feeder” cloud, thus increasing the particle size to enhance the precipitation. Overall, the generation and movement of such a cloud system is an important atmospheric disturbance for the generation of heavy precipitation downstream, and could be an early warning signal in the forecasting of heavy rainfall in China during the Meiyu period.
Relativistic Electron Flux Prediction at Geosynchronous Orbit Based on the Neural Network and the Quantile Regression Method
Authors: Zhang Hui , Fu Suiyan , Xie Lun , Zhao Duo , Yue Chao , Pu Zuyin , Xiong Ying , Wu Tong , Zhao Shaojie , Sun Yixin , Cui Bo , Luo Zhekai
Published: July 2020

Geosynchronous satellites are exposed to the relativistic electrons, which may cause irreparable damage to the satellites. The prediction of the relativistic electron flux is therefore important for the safety of the satellites. Unlike previous works focusing on the single‐value prediction of relativistic electron flux, we predict the relativistic electron flux in a probabilistic approach by using the neural network and the quantile regression method. In this study, a feedforward neural network is first designed to predict average daily flux of relativistic electrons (>2 MeV), or the expectation of the flux from the probabilistic perspective, at geosynchronous orbit 1 day in advance. The neural network performs well, with the average root mean squared error, the average prediction efficiency, and the average linear correlation coefficient between observations and predictions reaching 0.305, 0.832, and 0.916, respectively, during the periods of 2011–2017. We then combine the quantile regression method with the feedforward neural network to predict the quantiles of relativistic electron flux by applying a special loss function to the neural network. We use the multiple‐quantiles prediction model to predict flux ranges of the relativistic electrons and the corresponding probabilities, which is an advantage over the single‐value prediction. Moreover, it appears to be for the first time that the approximate shape of the probability density function of relativistic electron flux is predicted.
Nedd4l downregulation of NRG1 in the mPFC induces depression-like behaviour in CSDS mice
Authors: Xu Jia , Guo Cuiping , Liu Yi , Wu Gang , Ke Dan , Wang Qun , Mao Jing , Wang Jian-Zhi , Liu Rong , Wang Xiaochuan
Published: July 2020

The occurrence of major depressive disorders has been closely related to the vulnerability of stress. The medial prefrontal cortex (mPFC) is involved in regulating pathological reactivity to stress, changes in affective behaviour and cognitive functions by distress. Increasing evidence indicates that neuregulin 1 (NRG1) plays an important role in psychiatric illnesses, including depression, schizophrenia and bipolar disorder. However, whether NRG1 in the mPFC is related to stress vulnerability remains unclear. We here assessed the regulation of NRG1 by the E3 ubiquitin ligase Nedd4l (neural precursor cell expressed developmentally downregulated 4-like) and investigated whether NRG1 changes in the mPFC might lead to vulnerability to depression-like behaviours. We’ve identified a deficiency of NRG1 in the mPFC as a key factor that contributes to the regulation of stress susceptibility in mice, as further suggested by the finding that overexpression of NRG1 attenuated depression-like behaviours in the animal model of chronic social defeat stress (CSDS). Interestingly, RNA sequencing in the mPFC brain region showed no differences in NRG1 mRNA levels between control animals and stress-susceptible (SS) or resilient mice (RES) following CSDS. However, mRNA and protein levels of Nedd4l were markedly increased in SS mice, but not in RES mice compared to controls. Furthermore, ubiquitination of NRG1 was increased in SS mice. Remarkably, overexpression of Nedd4l in mouse mPFC induced a decrease in NRG1 level and caused vulnerability to stress by subthreshold social defeat stress (SSDS), while downregulation of Nedd4l expression in the mPFC rescued the vulnerability to stress-induced social avoidance and anhedonia. Our data strongly indicate that the Nedd4l-mediated downregulation of NRG1 acts as a critical role in depression-like phenotypes of mice in CSDS.
Analyzing kinetic signaling data for G-protein-coupled receptors
Authors: Hoare Sam R. J. , Tewson Paul H. , Quinn Anne Marie , Hughes Thomas E. , Bridge Lloyd J.
Published: July 2020

In classical pharmacology, bioassay data are fit to general equations (e.g. the dose response equation) to determine empirical drug parameters (e.g. EC50and Emax), which are then used to calculate chemical parameters such as affinity and efficacy. Here we used a similar approach for kinetic, time course signaling data, to allow empirical and chemical definition of signaling by G-protein-coupled receptors in kinetic terms. Experimental data are analyzed using general time course equations (model-free approach) and mechanistic model equations (mechanistic approach) in the commonly-used curve-fitting program, GraphPad Prism. A literature survey indicated signaling time course data usually conform to one of four curve shapes: the straight line, association exponential curve, rise-and-fall to zero curve, and rise-and-fall to steady-state curve. In the model-free approach, the initial rate of signaling is quantified and this is done by curve-fitting to the whole time course, avoiding the need to select the linear part of the curve. It is shown that the four shapes are consistent with a mechanistic model of signaling, based on enzyme kinetics, with the shape defined by the regulation of signaling mechanisms (e.g. receptor desensitization, signal degradation). Signaling efficacy is the initial rate of signaling by agonist-occupied receptor (kτ), simply the rate of signal generation before it becomes affected by regulation mechanisms, measurable using the model-free analysis. Regulation of signaling parameters such as the receptor desensitization rate constant can be estimated if the mechanism is known. This study extends the empirical and mechanistic approach used in classical pharmacology to kinetic signaling data, facilitating optimization of new therapeutics in kinetic terms.
Laser spectroscopy of indium Rydberg atom bunches by electric field ionization
Authors: Vernon A. R. , Ricketts C. M. , Billowes J. , Cocolios T. E. , Cooper B. S. , Flanagan K. T. , Garcia Ruiz R. F. , Gustafsson F. P. , Neyens G. , Perrett H. A. , Sahoo B. K. , Wang Q. , Waso F. J. , Yang X. F.
Published: July 2020

This work reports on the application of a novel electric field-ionization setup for high-resolution laser spectroscopy measurements on bunched fast atomic beams in a collinear geometry. In combination with multi-step resonant excitation to Rydberg states using pulsed lasers, the field ionization technique demonstrates increased sensitivity for isotope separation and measurement of atomic parameters over previous non-resonant laser ionization methods. The setup was tested at the Collinear Resonance Ionization Spectroscopy experiment at ISOLDE-CERN to perform high-resolution measurements of transitions in the indium atom from the$$\text {5s}^2\text {5d}\,^2\text {D}_{5/2}$$5s25d2D5/2and$$\text {5s}^2\text {5d}\,^2\text {D}_{3/2}$$5s25d2D3/2states to$$\text {5s}^2n$$5s2np $$^2$$2P and$$\text {5s}^2n\text {f}\,^2$$5s2nf2F Rydberg states, up to a principal quantum number of$$n=72$$n=72. The extracted Rydberg level energies were used to re-evaluate the ionization potential of the indium atom to be$$46,670.107(4)\,\hbox {cm}^{-1}$$46,670.107(4)cm-1. The nuclear magnetic dipole and nuclear electric quadrupole hyperfine structure constants and level isotope shifts of the$$\text {5s}^2\text {5d}\,^2\text {D}_{5/2}$$5s25d2D5/2and$$\text {5s}^2\text {5d}\,^2\text {D}_{3/2}$$5s25d2D3/2states were determined for$$^{113,115}$$113,115In. The results are compared to calculations using relativistic coupled-cluster theory. A good agreement is found with the ionization potential and isotope shifts, while disagreement of hyperfine structure constants indicates an increased importance of electron correlations in these excited atomic states. With the aim of further increasing the detection sensitivity for measurements on exotic isotopes, a systematic study of the field-ionization arrangement implemented in the work was performed at the same time and an improved design was simulated and is presented. The improved design offers increased background suppression independent of the distance from field ionization to ion detection.
Author Correction: Human DC-SIGN and CD23 do not interact with human IgG
Authors: Temming A. Robin , Dekkers Gillian , van de Bovenkamp Fleur S. , Plomp H. Rosina , Bentlage Arthur E. H. , Szittner Zoltán , Derksen Ninotska I. L. , Wuhrer Manfred , Rispens Theo , Vidarsson Gestur
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Experimental kernel-based quantum machine learning in finite feature space
Authors: Bartkiewicz Karol , Gneiting Clemens , Černoch Antonín , Jiráková Kateřina , Lemr Karel , Nori Franco
Published: July 2020

We implement an all-optical setup demonstrating kernel-based quantum machine learning for two-dimensional classification problems. In this hybrid approach, kernel evaluations are outsourced to projective measurements on suitably designed quantum states encoding the training data, while the model training is processed on a classical computer. Our two-photon proposal encodes data points in a discrete, eight-dimensional feature Hilbert space. In order to maximize the application range of the deployable kernels, we optimize feature maps towards the resulting kernels’ ability to separate points, i.e., their “resolution,” under the constraint of finite, fixed Hilbert space dimension. Implementing these kernels, our setup delivers viable decision boundaries for standard nonlinear supervised classification tasks in feature space. We demonstrate such kernel-based quantum machine learning using specialized multiphoton quantum optical circuits. The deployed kernel exhibits exponentially better scaling in the required number of qubits than a direct generalization of kernels described in the literature.
Hydrogen gas inhalation improves delayed brain injury by alleviating early brain injury after experimental subarachnoid hemorrhage
Authors: Kumagai Kosuke , Toyooka Terushige , Takeuchi Satoru , Otani Naoki , Wada Kojiro , Tomiyama Arata , Mori Kentaro
Published: July 2020

Molecular hydrogen (H2) protect neurons against reactive oxygen species and ameliorates early brain injury (EBI) after subarachnoid hemorrhage (SAH). This study investigated the effect of H2 on delayed brain injury (DBI) using the rat SAH + unilateral common carotid artery occlusion (UCCAO) model with the endovascular perforation method. 1.3% H2 gas (1.3% hydrogen premixed with 30% oxygen and balanced nitrogen) inhalation was performed on days 0 and 1, starting from anesthesia induction and continuing for 2 h on day 0, and starting from anesthesia induction and continuing for 30 min on day 1. EBI was assessed on the basis of brain edema, expression of S100 calcium-binding protein B (S100B), and phosphorylation of C-Jun N-terminal kinase on day 2, and neurological deficits on day 3. Reactive astrogliosis and severity of cerebral vasospasm (CV) were assessed on days 3 and 7. DBI was assessed on the basis of neurological deficits and neuronal cell death on day 7. EBI, reactive astrogliosis, and DBI were ameliorated in the H2 group compared with the control group. CV showed no significant improvement between the control and H2 groups. This study demonstrated that H2 gas inhalation ameliorated DBI by reducing EBI without improving CV in the rat SAH + UCCAO model.
Investigating the pathogenic SNPs in BLM helicase and their biological consequences by computational approach
Authors: Alzahrani Faisal A. , Ahmed Firoz , Sharma Monika , Rehan Mohd , Mahfuz Maryam , Baeshen Mohammed N. , Hawsawi Yousef , Almatrafi Ahmed , Alsagaby Suliman Abdallah , Kamal Mohammad Azhar , Warsi Mohiuddin Khan , Choudhry Hani , Jamal Mohammad Sarwar
Published: July 2020

The BLM helicase protein plays a vital role in DNA replication and the maintenance of genomic integrity. Variation in the BLM helicase gene resulted in defects in the DNA repair mechanism and was reported to be associated with Bloom syndrome (BS) and cancer. Despite extensive investigation of helicase proteins in humans, no attempt has previously been made to comprehensively analyse the single nucleotide polymorphism (SNPs) of the BLM gene. In this study, a comprehensive analysis of SNPs on the BLM gene was performed to identify, characterize and validate the pathogenic SNPs using computational approaches. We obtained SNP data from the dbSNP database version 150 and mapped these data to the genomic coordinates of the “NM_000057.3” transcript expressing BLM helicase (P54132). There were 607 SNPs mapped to missense, 29 SNPs mapped to nonsense, and 19 SNPs mapped to 3′-UTR regions. Initially, we used many consensus tools of SIFT, PROVEAN, Condel, and PolyPhen-2, which together increased the accuracy of prediction and identified 18 highly pathogenic non-synonymous SNPs (nsSNPs) out of 607 SNPs. Subsequently, these 18 high-confidence pathogenic nsSNPs were analysed for BLM protein stability, structure–function relationships and disease associations using various bioinformatics tools. These 18 mutants of the BLM protein along with the native protein were further investigated using molecular dynamics simulations to examine the structural consequences of the mutations, which might reveal their malfunction and contribution to disease. In addition, 28 SNPs were predicted as “stop gained” nonsense SNPs and one SNP was predicted as “start lost”. Two SNPs in the 3′UTR were found to abolish miRNA binding and thus may enhance the expression of BLM. Interestingly, we found that BLM mRNA overexpression is associated with different types of cancers. Further investigation showed that the dysregulation of BLM is associated with poor overall survival (OS) for lung and gastric cancer patients and hence led to the conclusion that BLM has the potential to be used as an important prognostic marker for the detection of lung and gastric cancer.
Schistocephalus parasite infection alters sticklebacks’ movement ability and thereby shapes social interactions
Authors: Jolles Jolle W. , Mazué Geoffrey P. F. , Davidson Jacob , Behrmann-Godel Jasminca , Couzin Iain D.
Published: July 2020

Parasitism is ubiquitous in the animal kingdom. Although many fundamental aspects of host-parasite relationships have been unravelled, few studies have systematically investigated how parasites affect organismal movement. Here we combine behavioural experiments of Schistocephalus solidus infected sticklebacks with individual-based simulations to understand how parasitism affects individual movement ability and thereby shapes social interaction patterns. High-resolution tracking revealed that infected fish swam, accelerated, and turned more slowly than did non-infected fish, and tended to be more predictable in their movements. Importantly, the strength of these effects increased with increasing parasite load (proportion of body weight), with more heavily infected fish showing larger changes and impairments in behaviour. When grouped, pairs of infected fish moved more slowly, were less cohesive, less aligned, and less temporally coordinated than non-infected pairs, and mixed pairs were primarily led by the non-infected fish. These social patterns also emerged in simulations of self-organised groups composed of individuals differing similarly in speed and turning tendency, suggesting infection-induced changes in mobility and manoeuvrability may drive collective outcomes. Together, our results demonstrate how infection with a complex life-cycle parasite affects the movement ability of individuals and how this in turn shapes social interaction patterns, providing important mechanistic insights into the effects of parasites on host movement dynamics.
Exogenous abscisic acid induces the lipid and flavonoid metabolism of tea plants under drought stress
Authors: Gai Zhongshuai , Wang Yu , Ding Yiqian , Qian Wenjun , Qiu Chen , Xie Hui , Sun Litao , Jiang Zhongwu , Ma Qingping , Wang Linjun , Ding Zhaotang
Published: July 2020

Abscisic acid (ABA) is an important phytohormone responsible for activating drought resistance, but the regulation mechanism of exogenous ABA on tea plants under drought stress was rarely reported. Here, we analyzed the effects of exogenous ABA on genes and metabolites of tea leaves under drought stress using transcriptomic and metabolomic analysis. The results showed that the exogenous ABA significantly induced the metabolic pathways of tea leaves under drought stress, including energy metabolism, amino acid metabolism, lipid metabolism and flavonoids biosynthesis. In which, the exogenous ABA could clearly affect the expression of genes involved in lipid metabolism and flavonoid biosynthesis. Meanwhile, it also increased the contents of flavone, anthocyanins, flavonol, isoflavone of tea leaves under drought stress, including, kaempferitrin, sakuranetin, kaempferol, and decreased the contents of glycerophospholipids, glycerolipids and fatty acids of tea leaves under drought stress. The results suggested that the exogenous ABA could alleviate the damages of tea leaves under drought stress through inducing the expression of the genes and altering the contents of metabolites in response to drought stress. This study will be helpful to understand the mechanism of resilience to abiotic stress in tea plant and provide novel insights into enhancing drought tolerance in the future.
Transcriptomic comparison of human and mouse brain microvessels
Authors: Song Hannah W. , Foreman Koji L. , Gastfriend Benjamin D. , Kuo John S. , Palecek Sean P. , Shusta Eric V.
Published: July 2020

The brain vasculature maintains brain homeostasis by tightly regulating ionic, molecular, and cellular transport between the blood and the brain parenchyma. These blood–brain barrier (BBB) properties are impediments to brain drug delivery, and brain vascular dysfunction accompanies many neurological disorders. The molecular constituents of brain microvascular endothelial cells (BMECs) and pericytes, which share a basement membrane and comprise the microvessel structure, remain incompletely characterized, particularly in humans. To improve the molecular database of these cell types, we performed RNA sequencing on brain microvessel preparations isolated from snap-frozen human and mouse tissues by laser capture microdissection (LCM). The resulting transcriptome datasets from LCM microvessels were enriched in known brain endothelial and pericyte markers, and global comparison identified previously unknown microvessel-enriched genes. We used these datasets to identify mouse-human species differences in microvessel-associated gene expression that may have relevance to BBB regulation and drug delivery. Further, by comparison of human LCM microvessel data with existing human BMEC transcriptomic datasets, we identified novel putative markers of human brain pericytes. Together, these data improve the molecular definition of BMECs and brain pericytes, and are a resource for rational development of new brain-penetrant therapeutics and for advancing understanding of brain vascular function and dysfunction.
17β-Estradiol supplementation changes gut microbiota diversity in intact and colorectal cancer-induced ICR male mice
Authors: Song Chin-Hee , Kim Nayoung , Nam Ryoung Hee , Choi Soo In , Lee Ha-Na , Surh Young-Joon
Published: July 2020

The composition of the gut microbiota is influenced by sex hormones and colorectal cancer (CRC). Previously, we reported that 17β-estradiol (E2) inhibits azoxymethane/dextran sulfate sodium (AOM/DSS)-induced tumorigenesis in male mice. Here, we investigated whether the composition of the gut microbiota is different between male and female, and is regulated by estrogen as a secondary outcome of previous studies. We established four groups of mice based on the sex and estrogen status [ovariectomized (OVX) female and E2-treated male]. Additionally, three groups of males were established by treating them with AOM/DSS, and E2, after subjecting them to AOM/DSS treatment. The mice were sacrificed at 21 weeks old. The composition of the gut microbiota was analyzed using 16S rRNA metagenomics sequencing. We observed a significant increase in the microbial diversity (Chao1 index) in females, males supplemented with E2, and males treated with AOM/DSS/E2 compared with normal males. In normal physiological condition, sex difference and E2 treatment did not affect the ratio of Firmicutes/Bacteroidetes (F/B). However, in AOM/DSS-treated male mice, E2 supplementation showed significantly lower level of the F/B ratio. The ratio of commensal bacteria to opportunistic pathogens was higher in females and E2-treated males compared to normal males and females subjected to OVX. Unexpectedly, this ratio was higher in the AOM/DSS group than that determined in other males and the AOM/DSS/E2 group. Our findings suggest that estrogen alters the gut microbiota in ICR (CrljOri:CD1) mice, particularly AOM/DSS-treated males, by decreasing the F/B ratio and changing Shannon and Simpson index by supply of estrogen. This highlights another possibility that estrogen could cause changes in the gut microbiota, thereby reducing the risk of developing CRC.
Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions
Authors: Mitchell Emma J. , Thomson David M. , Openshaw Rebecca L. , Bristow Greg C. , Dawson Neil , Pratt Judith A. , Morris Brian J.
Published: July 2020

There are no current treatments for autism, despite its high prevalence. Deletions of chromosome 16p11.2 dramatically increase risk for autism, suggesting that mice with an equivalent genetic rearrangement may offer a valuable model for the testing of novel classes of therapeutic drug. 16p11.2 deletion (16p11.2 DEL) mice and wild-type controls were assessed using an ethological approach, with 24 h monitoring of activity and social interaction of groups of mice in a home-cage environment. The ability of the excitation/inhibition modulator N-acetyl cysteine (NAC) and the 5-HT1B/1D/1F receptor agonist eletriptan to normalise the behavioural deficits observed was tested. 16p11.2 DEL mice exhibited largely normal behaviours, but, following the stress of an injection, showed hyperlocomotion, reduced sociability, and a strong anxiolytic phenotype. The hyperactivity and reduced sociability, but not the suppressed anxiety, were effectively attenuated by both NAC and eletriptan. The data suggest that 16p11.2 DEL mice show an autism-relevant phenotype that becomes overt after an acute stressor, emphasising the importance of gene-environmental interactions in phenotypic analysis. Further, they add to an emerging view that NAC, or 5-HT1B/1D/1F receptor agonist treatment, may be a promising strategy for further investigation as a future treatment.
Phosphate-dependent aggregation of [KL]n peptides affects their membranolytic activity
Authors: Strandberg Erik , Schweigardt Fabian , Wadhwani Parvesh , Bürck Jochen , Reichert Johannes , Cravo Haroldo L. P. , Burger Luisa , Ulrich Anne S.
Published: July 2020

In this study, we investigate how the length of amphiphilic β-sheet forming peptides affects their interaction with membranes. Four polycationic model peptides with lengths from 6 to 18 amino acids were constructed from simple Lys-Leu repeats, giving [KL]n=3,5,7,9. We found that (1) they exhibit a pronounced antimicrobial activity with an intriguing length dependent maximum for [KL]5 with 10 amino acids; (2) their hemolytic effect, on the other hand, increases steadily with peptide length. CD analysis (3) and TEM (4) show that all peptides-except for the short [KL]3-aggregate into amyloid-like fibrils in the presence of phosphate ions, which in turn has a critical effect on the results in (1) and (2). In fact, (5) vesicle leakage reveals an intrinsic membrane-perturbing activity (at constant peptide mass) of [KL]5 > [KL]9 > [KL]7 in phosphate buffer, which changes to [KL]5 ≈ [KL]7 ≈ [KL]9 in PIPES. A specific interaction with phosphate ions thus explains the subtle balance between two counteracting effects: phosphate-induced unproductive pre-aggregation in solution versus monomeric membrane binding and vigorous lipid perturbation due to self-assembly of the bound peptides within the bilayer. This knowledge can now be used to control and optimize the peptides in further applications.