bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of blade rotation on the lightning stroke characteristic of a wind turbine
Authors: Wang Yu , Deng Yeqiang , Liu Yilu , Qu Lu , Wen Xishan , Lan Lei , Wang Jian
Published: April 2019

The blades of a wind turbine rotate during normal operation. To investigate the influence of blade rotation on the lightning‐attracting ability of a wind turbine, a discharge test platform is designed for scaled wind turbines. The 50% impulse voltages and flash probabilities of the scaled wind turbines with gap distances of 1 to 8 m in the static and rotary conditions are determined by using the discharge test and selective discharge test. The discharge test for a single wind turbine with a gap of 1 to 2 m indicates that the breakdown voltages of the gap between the scaled turbine and electrodes increases with an increase in the blade rotation speed. However, the discharge test with a gap distance of 4 to 8 m indicates that the breakdown voltage of the fan decreases with an increase in the blade rotation speed. The test results of the scaled dual wind turbines experiment have the same rules. To explain this phenomenon, the influence of wind speed on the space‐charge distribution and electrical field intensity of corona discharge is simulated in the background of a target thundercloud. The rotation of the fan reduces the space‐charge density near the area of the blade tip, which leads to an increase in the field strength near the blade tip of the wind turbine and a decrease in the field strength away from the blade tip. This influence varies in short and long air gap, resulting in opposite relationships between discharge voltage and distance from the tip of the turbine. The results can provide a reference for the lightning protection of wind turbines.
The simplified likelihood framework
Authors: Buckley Andy , Citron Matthew , Fichet Sylvain , Kraml Sabine , Waltenberger Wolfgang , Wardle Nicholas
Published: April 2019

Abstract

We discuss the simplified likelihood framework as a systematic approximation scheme for experimental likelihoods such as those originating from LHC experiments. We develop the simplified likelihood from the Central Limit Theorem keeping the next-to-leading term in the large N expansion to correctly account for asymmetries. Moreover, we present an efficient method to compute the parameters of the simplified likelihood from Monte Carlo simulations. The approach is validated using a realistic LHC-like analysis, and the limits of the approximation are explored. Finally, we discuss how the simplified likelihood data can be conveniently released in the HepData error source format and automatically built from it, making this framework a convenient tool to transmit realistic experimental likelihoods to the community.
‘Making space’: a study into the use of mindfulness for alternative school teachers
Authors: Preston Kim , Spooner-Lane Rebecca
Published: April 2019

As teachers seek to educate and transform lives, often with limited resources and time, they can experience varying levels of stress and emotional exhaustion, particularly if effective emotion regulation strategies are not employed. The experience of teacher stress may be heightened in alternative schools that provide educational opportunities for students who present with complex needs and are ‘at-risk’ of withdrawing from the conventional school system. This case study explored the perceived outcomes of a 6-week school-based mindfulness program to manage stress and support the emotion regulation of four teachers at a metropolitan Australian alternative school. The study took a mixed-methods approach to data collection, which included self-report questionnaires, interview responses and journal reflections. A number of limitations, such as small sample size and lack of experimental design, had an impact on the generalisability of the study’s findings. However, a range of beneficial outcomes emerged in association with the mindfulness program, revealing that participants experienced increased levels of both mindfulness and emotion regulation ability, in conjunction with decreased stress and emotional exhaustion levels.
PURE INDUCTIVE LOGIC WITH FUNCTIONS
Authors: HOWARTH ELIZABETH , PARIS JEFFREY B.
Published: April 2019

We consider the version of Pure Inductive Logic which obtains for the language with equality and a single unary function symbol giving a complete characterization of the probability functions on this language which satisfy Constant Exchangeability.
Preclassic Maya Houses and Rituals: Excavations at the Karinel Group, Ceibal
Authors: MacLellan Jessica
Published: April 2019

The site of Ceibal was founded around the beginning of sedentary life in the Maya lowlands. Excavations at the Karinel Group within the site reveal domestic structures and ritual deposits dating to the Middle Preclassic, Late Preclassic, and Terminal Preclassic periods (c. 1000 BC–AD 300). The results complement data from Ceibal's Central Plaza and publications on early households in other regions of the lowlands, inviting future investigations of temporal and geographic variation in Preclassic Maya domestic rituals.
Establishing the Rule of Law in Weak and War-torn States: Evidence from a Field Experiment with the Liberian National Police
Authors: BLAIR ROBERT A. , KARIM SABRINA M. , MORSE BENJAMIN S.
Published: April 2019

How to restore citizens’ trust and cooperation with the police in the wake of civil war? We report results from an experimental evaluation of the Liberian National Police’s (LNP) “Confidence Patrols” program, which deployed teams of newly retrained, better-equipped police officers on recurring patrols to rural communities across three Liberian counties over a period of 14 months. We find that the program increased knowledge of the police and Liberian law, enhanced security of property rights, and reduced the incidence of some types of crime, notably simple assault and domestic violence. The program did not, however, improve trust in the police, courts, or government more generally. We also observe higher rates of crime reporting in treatment communities, concentrated almost entirely among those who were disadvantaged under prevailing customary mechanisms of dispute resolution. We consider implications of these findings for post-conflict policing in Liberia and weak and war-torn states more generally.
Individual Life Horizon Influences Attitudes Toward Democracy
Authors: LECHLER MARIE , SUNDE UWE
Published: April 2019

Support for democracy in the population is considered critical for the emergence and stability of democracy. Macro-determinants and retrospective experiences have been shown to affect the support for democracy at the individual level. We investigate whether and how the individual life horizon, in terms of the prospective length of life and age, affects individual attitudes toward democracy. Combining information from period life tables with individual survey response data spanning more than 260,000 observations from 93 countries over the period 1994–2014, we find evidence that the expected remaining years of life influence the attitudes toward a democratic political regime. The statistical identification decomposes the influence of age from the influence of the expected proximity to death. The evidence shows that support for democracy increases with age but declines with expected proximity to death, implying that increasing longevity might help fostering the support for democracy. Increasing age while keeping the remaining years of life fixed as well as increasing remaining years of life for a given age group both contribute to the support for democracy.
The End of the Peloponnesian War
Authors: Munro J. A. R.
Published: April 2019

The traditional text of Thucydides, II. 1, dates the surprise of Plataea by the Thebans, which began the Peloponnesian war, έπì ΠυΘοδώρου ⋯τι δύο μ⋯νας ἄρχοντος Αθηναίοις. It has long been recognized that the two months are too short a time, and that the facts of the history demand four. The day cannot be precisely determined, but the narrative of Thucydides fixes it near the end of a lunar month, and the choice has lain between the new moons of March 8 and April 7, 431 B.C. Now that Meritt has shown that the year of Pythodorus was not intercalary and ended on July 2, the former must be accepted. Accordingly the Theban attack may be put on the night of, let us say, March 3, which by Attic reckoning would be the early hours of Anthesterion 27.
G-NETWORKS AND THE OPTIMIZATION OF SUPPLY CHAINS
Authors: Wang Yi
Published: April 2019

Supply chains are fundamental to the economy of the world and many supply chains focus on perishable items, such as food, or even clothing that is subject to a limited shelf life due to fashion and seasonable effects. G-networks have not been previously applied to this important area. Thus in this paper, we apply G-networks to supply chain systems and investigate an optimal order allocation problem for a N-node supply chain with perishable products that share the same order source of fresh products. The objective is to find an optimal order allocation strategy to minimize the purchase price per object from the perspective of the customers. An analytical solution based on G-networks with batch removal, together with optimization methods are shown to produce the desired results. The results are illustrated by a numerical example with realistic parameters.
Nonlinear eigenvalue problems for a class of ordinary differential equations
Authors: Elias Uri , Pinkus Allan
Published: April 2019

We consider the class of nonlinear eigenvalue problems

where yp* = |y|p sgn y, pi > 0 and p0p1 … pn−1 = r, with various boundary conditions. We prove the existence of eigenvalues and study the zero properties and structure of the corresponding eigenfunctions.
A NEW LINEAR AND CONSERVATIVE FINITE DIFFERENCE SCHEME FOR THE GROSS–PITAEVSKII EQUATION WITH ANGULAR MOMENTUM ROTATION
Authors: CUI JIN , CAI WENJUN , JIANG CHAOLONG , WANG YUSHUN
Published: April 2019

A new linear and conservative finite difference scheme which preserves discrete mass and energy is developed for the two-dimensional Gross–Pitaevskii equation with angular momentum rotation. In addition to the energy estimate method and mathematical induction, we use the lifting technique as well as some well-known inequalities to establish the optimal
$H^{1}$
-error estimate for the proposed scheme with no restrictions on the grid ratio. Unlike the existing numerical solutions which are of second-order accuracy at the most, the convergence rate of the numerical solution is proved to be of order
$O(h^{4}+\unicode[STIX]{x1D70F}^{2})$
with time step
$\unicode[STIX]{x1D70F}$
and mesh size
$h$
. Numerical experiments have been carried out to show the efficiency and accuracy of our new method.
Understanding the Role of α Particles in Oblique Heliospheric Shock Oscillations
Authors: Ofman L. , Koval A. , Wilson L. B. , Szabo A.
Published: April 2019

Recent observations by DSCOVR provide high temporal resolution (50 samples per second) magnetic vector field data that allows investigating the details of oblique heliospheric shock oscillations. It was found that some of these shocks exhibit magnetic oscillations, both downstream and upstream of the shock front. The DSCOVR/MAG magnetic field data are supplemented by an extensive database of low Mach number (M < 3) low‐β (<1) shock data observed by Wind albeit with lower temporal resolution. Motivated by the observations, we use the 2.5D hybrid model of the oblique shocks with α particles in addition to kinetic protons and electron fluid. We model the properties of the oblique shocks for a number of typical parameters found in observations and study the effects of the shock parameters and the relative α particle abundances on the properties of the shock magnetic field, density, and velocity oscillations. We find the α particles “surf” on the shock front and produce a wake of density oscillations. We examine the details of the phase space of the ions as well as the ion velocity distribution functions in various parts of the shock and study their nonthermal properties. We determine the effects of the α particle kinetic properties and abundances on the structure and dynamics of the shock downstream oscillations for a range of parameters relevant to low Mach number low‐β heliospheric shocks.
Variability in Trends and Indicators of CO2 Exchange Across Arctic Wetlands
Authors: Coffer Megan M. , Hestir Erin L.
Published: April 2019

Arctic wetlands store nearly half of the world's soil organic carbon and are crucial to the global carbon cycle. However, most Earth system models fail to account for wetlands given heterogeneity and uncertainty surrounding the response of different wetland types to climate change. We analyzed summer (June–August) carbon dioxide (CO2) exchange, meteorological conditions, and ecological conditions at four Arctic wetlands. Micrometeorological flux tower data were used to assess CO2 exchange and meteorological conditions across 7 to 9 years of data. Climate data were used to assess meteorological conditions across 30 years of data. Satellite data described ecological conditions. Each site acted as a CO2 sink, but strength varied, ranging from −49 to −93 g C/m2 per summer. A trend analysis was used to investigate how CO2 balance and surrounding conditions may have changed. CO2 exchange significantly changed at one site, becoming a stronger sink. Changes in meteorological conditions were variable across sites with the exception of air temperature which, when considering significant trends, unanimously increased across sites. Ecological conditions suggested increased vegetation cover regardless of statistical significance at all sites. A conditional random forest algorithm was used to evaluate drivers of CO2 exchange. Cumulative precipitation and evapotranspiration were the main drivers of net ecosystem exchange and gross primary productivity, while ecosystem respiration was primarily driven by air temperature, suggesting that projected changes in temperature and precipitation patterns will influence the carbon balance of Arctic wetlands. Variability across sites emphasizes the need for long‐term observations across wetland types and climatic gradients.
A Regime Shift From Low to High Sediment Concentrations in a Tide‐Dominated Estuary
Authors: Dijkstra Yoeri M. , Schuttelaars Henk. M. , Schramkowski George P.
Published: April 2019

Many estuaries are strongly deepened to improve navigation, with sometimes large and poorly understood consequences to suspended sediment dynamics. To improve understanding of such large changes, we study the Ems River Estuary, where a regime shift from low to high sediment concentrations was observed after deepening. The aim of this study is to improve understanding of the development of the sediment concentration regime over time and estimate the associated time scale. Using the idealized width‐averaged iFlow model, we identify the coexistence of two distinct stable equilibrium regimes representing low and high sediment concentrations, qualitatively matching the regimes observed in the Ems. Depending on the river discharge, a critical depth profile is identified at which the regime shifts. By combining the model results and long‐term observations of the tidal range, first indications of the regime shift are observed around 1989, taking approximately 6–7 years to develop.
Advancements in Hurricane Prediction With NOAA's Next‐Generation Forecast System
Authors: Chen Jan‐Huey , Lin Shian‐Jiann , Magnusson Linus , Bender Morris , Chen Xi , Zhou Linjiong , Xiang Baoqiang , Rees Shannon , Morin Matthew , Harris Lucas
Published: April 2019

We use the fvGFS model developed at the Geophysical Fluid Dynamics Laboratory to demonstrate the potential of the upcoming United States Next‐Generation Global Prediction System for hurricane prediction. The fvGFS retrospective forecasts initialized with the European Centre for Medium‐Range Weather Forecasts (ECMWF) data showed much‐improved track forecasts for the 2017 Atlantic hurricane season compared to the best‐performing ECMWF operational model. The fvGFS greatly improved the ECMWF's poor track forecast for Hurricane Maria (2017). For Hurricane Irma (2017), a well‐predicted case by the ECMWF model, the fvGFS produced even lower five‐day track forecast errors. The fvGFS also showed better intensity prediction than both the United States and the ECMWF operational models, indicating the robustness of its numerical algorithms.
Cortisol administration after extinction in a fear-conditioning paradigm with traumatic film clips prevents return of fear
Authors: Brueckner Alexandra H. , Lass-Hennemann Johanna , Wilhelm Frank H. , Ferreira de Sá Diana S. , Michael Tanja
Published: April 2019

Cortisol is a stress hormone and potent modulator of learning and memory processes. If administered after learning, cortisol can enhance memory consolidation. Yet it is unknown whether cortisol administration after fear extinction learning strengthens extinction memory. Extinction is a crucial mechanism underlying psychotherapy of posttraumatic stress disorder (PTSD). The present study examined whether extinction can be enhanced by administering cortisol after extinction training. In a registered, randomized, double-blind and placebo controlled trial, 50 healthy participants were exposed to a differential fear-conditioning paradigm with neutral faces as conditioned stimuli (CS) and traumatic film clips as unconditioned stimuli (US). They received either cortisol (n = 25) or placebo (n = 25) immediately after extinction. The cortisol group showed less fear during a return of fear manipulation (reinstatement) evidenced by attenuated fear potentiated startle responses and US-expectancy ratings than the placebo group. Results indicate that cortisol administration after fear extinction strengthens extinction memory and suggest that it might be advantageous to administer cortisol subsequent to successful exposure treatment sessions.
Overexpression of microRNA-301b accelerates hippocampal microglia activation and cognitive impairment in mice with depressive-like behavior through the NF-κB signaling pathway
Authors: Tang Chao-Zhi , Zhang Dong-Fang , Yang Jun-Tang , Liu Qing-Hui , Wang Ya-Ru , Wang Wen-Sheng
Published: April 2019

Depression is a condition with a complex etiological pattern, whose effective treatments are highly limited. MicroRNAs (miRNAs) have been investigated in intensive studies owing to their involvement in pathophysiology of mood disorders. The current study aimed to elucidate the role of miR-301b in hippocampus in mouse models of depressive-like behavior. Microarray-based prediction identified the differentially expressed gene neuronal pentraxin II (NPTX2) related to mental depression. Next, the putative miR-301b binding sites on the 3′UTR of NPTX2 were verified. Then the effect of miR-301b on cognitive function of mice with depressive-like behavior was analyzed using the Morris water maze test. In addition, the regulation of miR-301b to NPTX2 and activation of NF-κB signaling pathway was assessed. Following that, the microglia activation and inflammation in hippocampus were evaluated, with the expressions of inflammatory factors being examined. At last, microglia were flow cytometrically sorted and the inflammatory reaction was also assessed in vitro. The obtained findings revealed that miR-301b targeted and negatively regulated NPTX2. Moreover, overexpressed miR-301b activated the NF-κB signaling pathway, as reflected by increasing protein expressions of p-NF-κB. Upregulated miR-301b accelerated cognitive impairment in mice with depressive-like behavior. In addition, overexpression of miR-301b activated microglia and stimulated inflammation in hippocampus, accompanied by enhanced release of tumor necrosis factor-α (TNF-α), interleukin-Iβ (IL-Iβ) and cyclooxygenase-2(COX-2). Taken together, the evidence provided by the current study indicated that overexpression of miR-301b augmented hippocampal microglia activation, thus exacerbating cognitive impairment and inflammation in mice with depressive-like behavior by activating the NF-κB signaling pathway.
FASN activity is important for the initial stages of the induction of senescence
Authors: Fafián-Labora Juan , Carpintero-Fernández Paula , Jordan Samuel James Davison , Shikh-Bahaei Tamanna , Abdullah Sana Mohammad , Mahenthiran Midusa , Rodríguez-Navarro José Antonio , Niklison-Chirou Maria Victoria , O’Loghlen Ana
Published: April 2019

Senescent cells accumulate in several tissues during ageing and contribute to several pathological processes such as ageing and cancer. Senescence induction is a complex process not well defined yet and is characterized by a series of molecular changes acquired after an initial growth arrest. We found that fatty acid synthase (FASN) levels increase during the induction of senescence in mouse hepatic stellate cells and human primary fibroblasts. Importantly, we also observed a significant increase in FASN levels during ageing in mouse liver tissues. To probe the central role of FASN in senescence induction, we used a small-molecule inhibitor of FASN activity, C75. We found that C75 treatment prevented the induction of senescence in mouse and human senescent cells. Importantly, C75 also reduced the expression of the signature SASP factors interleukin 1α (IL-1α), IL-1β and IL-6, and suppressed the secretion of small extracellular vesicles. These findings were confirmed using a shRNA targeting FASN. In addition, we find that FASN inhibition induces metabolic changes in senescent cells. Our work underscores the importance of C75 as a pharmacological inhibitor for reducing the impact of senescent cell accumulation.
Melatonin as a master regulator of cell death and inflammation: molecular mechanisms and clinical implications for newborn care
Authors: Tarocco Anna , Caroccia Natascia , Morciano Giampaolo , Wieckowski Mariusz R. , Ancora Gina , Garani Giampaolo , Pinton Paolo
Published: April 2019

Melatonin, more commonly known as the sleep hormone, is mainly secreted by the pineal gland in dark conditions and regulates the circadian rhythm of the organism. Its intrinsic properties, including high cell permeability, the ability to easily cross both the blood–brain and placenta barriers, and its role as an endogenous reservoir of free radical scavengers (with indirect extra activities), confer it beneficial uses as an adjuvant in the biomedical field. Melatonin can exert its effects by acting through specific cellular receptors on the plasma membrane, similar to other hormones, or through receptor-independent mechanisms that involve complex molecular cross talk with other players. There is increasing evidence regarding the extraordinary beneficial effects of melatonin, also via exogenous administration. Here, we summarize molecular pathways in which melatonin is considered a master regulator, with attention to cell death and inflammation mechanisms from basic, translational and clinical points of view in the context of newborn care.
Breast cancer quantitative proteome and proteogenomic landscape
Authors: Johansson Henrik J. , Socciarelli Fabio , Vacanti Nathaniel M. , Haugen Mads H. , Zhu Yafeng , Siavelis Ioannis , Fernandez-Woodbridge Alejandro , Aure Miriam R. , Sennblad Bengt , Vesterlund Mattias , Branca Rui M. , Orre Lukas M. , Huss Mikael , Fredlund Erik , Beraki Elsa , Garred Øystein , Boekel Jorrit , Sauer Torill , Zhao Wei , Nord Silje , Höglander Elen K. , Jans Daniel C. , Brismar Hjalmar , Haukaas Tonje H. , Bathen Tone F. , Schlichting Ellen , Naume Bjørn ,   Consortia Oslo Breast Cancer Research Consortium (OSBREAC), Geisler Jürgen , Hofvind Solveig , Engebråten Olav , Geitvik Gry Aarum , Langerød Anita , Kåresen Rolf , Mælandsmo Gunhild Mari , Sørlie Therese , Skjerven Helle Kristine , Park Daehoon , Hartman-Johnsen Olaf-Johan , Luders Torben , Borgen Elin , Kristensen Vessela N. , Russnes Hege G. , Lingjærde Ole Christian , Mills Gordon B. , Sahlberg Kristine K. , Børresen-Dale Anne-Lise , Lehtiö Janne
Published: April 2019

In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.
A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis
Authors: Zou Yilong , Palte Michael J. , Deik Amy A. , Li Haoxin , Eaton John K. , Wang Wenyu , Tseng Yuen-Yi , Deasy Rebecca , Kost-Alimova Maria , Dančík Vlado , Leshchiner Elizaveta S. , Viswanathan Vasanthi S. , Signoretti Sabina , Choueiri Toni K. , Boehm Jesse S. , Wagner Bridget K. , Doench John G. , Clish Clary B. , Clemons Paul A. , Schreiber Stuart L.
Published: April 2019

Clear-cell carcinomas (CCCs) are a histological group of highly aggressive malignancies commonly originating in the kidney and ovary. CCCs are distinguished by aberrant lipid and glycogen accumulation and are refractory to a broad range of anti-cancer therapies. Here we identify an intrinsic vulnerability to ferroptosis associated with the unique metabolic state in CCCs. This vulnerability transcends lineage and genetic landscape, and can be exploited by inhibiting glutathione peroxidase 4 (GPX4) with small-molecules. Using CRISPR screening and lipidomic profiling, we identify the hypoxia-inducible factor (HIF) pathway as a driver of this vulnerability. In renal CCCs, HIF-2α selectively enriches polyunsaturated lipids, the rate-limiting substrates for lipid peroxidation, by activating the expression of hypoxia-inducible, lipid droplet-associated protein (HILPDA). Our study suggests targeting GPX4 as a therapeutic opportunity in CCCs, and highlights that therapeutic approaches can be identified on the basis of cell states manifested by morphological and metabolic features in hard-to-treat cancers.
Nucleobase pairing and photodimerization in a biologically derived metal-organic framework nanoreactor
Authors: Anderson Samantha L. , Boyd Peter G. , Gładysiak Andrzej , Nguyen Tu N. , Palgrave Robert G. , Kubicki Dominik , Emsley Lyndon , Bradshaw Darren , Rosseinsky Matthew J. , Smit Berend , Stylianou Kyriakos C.
Published: April 2019

Biologically derived metal-organic frameworks (bio-MOFs) are of great importance as they can be used as models for bio-mimicking and in catalysis, allowing us to gain insights into how large biological molecules function. Through rational design, here we report the synthesis of a novel bio-MOF featuring unobstructed Watson-Crick faces of adenine (Ade) pointing towards the MOF cavities. We show, through a combined experimental and computational approach, that thymine (Thy) molecules diffuse through the pores of the MOF and become base-paired with Ade. The Ade-Thy pair binding at 40–45% loading reveals that Thy molecules are packed within the channels in a way that fulfill both the Woodward-Hoffmann and Schmidt rules, and upon UV irradiation, Thy molecules dimerize into Thy<>Thy. This study highlights the utility of accessible functional groups within the pores of MOFs, and their ability to ‘lock’ molecules in specific positions that can be subsequently dimerized upon light irradiation, extending the use of MOFs as nanoreactors for the synthesis of molecules that are otherwise challenging to isolate.
Specific inhibition of splicing factor activity by decoy RNA oligonucleotides
Authors: Denichenko Polina , Mogilevsky Maxim , Cléry Antoine , Welte Thomas , Biran Jakob , Shimshon Odelia , Barnabas Georgina D. , Danan-Gotthold Miri , Kumar Saran , Yavin Eylon , Levanon Erez Y. , Allain Frédéric H. , Geiger Tamar , Levkowitz Gil , Karni Rotem
Published: April 2019

Alternative splicing, a fundamental step in gene expression, is deregulated in many diseases. Splicing factors (SFs), which regulate this process, are up- or down regulated or mutated in several diseases including cancer. To date, there are no inhibitors that directly inhibit the activity of SFs. We designed decoy oligonucleotides, composed of several repeats of a RNA motif, which is recognized by a single SF. Here we show that decoy oligonucleotides targeting splicing factors RBFOX1/2, SRSF1 and PTBP1, can specifically bind to their respective SFs and inhibit their splicing and biological activities both in vitro and in vivo. These decoy oligonucleotides present an approach to specifically downregulate SF activity in conditions where SFs are either up-regulated or hyperactive.
Bad-metal relaxation dynamics in a Fermi lattice gas
Authors: Xu W. , McGehee W. R. , Morong W. N. , DeMarco B.
Published: April 2019

Electrical current in conventional metals is carried by electrons that retain their individual character. Bad metals, such as the normal state of some high-temperature superconductors, violate this scenario, and the complete picture for their behavior remains unresolved. Here, we report phenomena consistent with bad-metal behaviour in an optical-lattice Hubbard model by measuring the transport lifetime for a mass current excited by stimulated Raman transitions. We demonstrate incompatibility with weak-scattering theory and key characteristics of bad metals: anomalous resistivity scaling consistent with T-linear behavior, the onset of incoherent transport, and the approach to the Mott–Ioffe–Regel limit. Our work demonstrates a direct method for determining the transport lifetime, which is critical to theory but difficult to measure in materials, and exposes minimal ingredients for bad-metal behavior.
Contactless measurements of photocarrier transport properties in perovskite single crystals
Authors: Gong Xiwen , Huang Ziru , Sabatini Randy , Tan Chih-Shan , Bappi Golam , Walters Grant , Proppe Andrew , Saidaminov Makhsud I. , Voznyy Oleksandr , Kelley Shana O. , Sargent Edward H.
Published: April 2019

The remarkable properties of metal halide perovskites arising from their impressive charge carrier diffusion lengths have led to rapid advances in solution-processed optoelectronics. Unfortunately, diffusion lengths reported in perovskite single crystals have ranged widely – from 3 μm to 3 mm – for ostensibly similar materials. Here we report a contactless method to measure the carrier mobility and further extract the diffusion length: our approach avoids both the effects of contact resistance and those of high electric field. We vary the density of quenchers – epitaxially included within perovskite single crystals – and report the dependence of excited state lifetime in the perovskite on inter-quencher spacing. Our results are repeatable and self-consistent (i.e. they agree on diffusion length for many different quencher concentrations) to within ± 6%. Using this method, we obtain a diffusion length in metal-halide perovskites of 2.6 μm ± 0.1 μm.
Muscle functions as a connective tissue and source of extracellular matrix in planarians
Authors: Cote Lauren E. , Simental Eric , Reddien Peter W.
Published: April 2019

Regeneration and tissue turnover require new cell production and positional information. Planarians are flatworms capable of regenerating all body parts using a population of stem cells called neoblasts. The positional information required for tissue patterning is primarily harbored by muscle cells, which also control body contraction. Here we produce an in silico planarian matrisome and use recent whole-animal single-cell-transcriptome data to determine that muscle is a major source of extracellular matrix (ECM). No other ECM-secreting, fibroblast-like cell type was detected. Instead, muscle cells express core ECM components, including all 19 collagen-encoding genes. Inhibition of muscle-expressed hemicentin-1 (hmcn-1), which encodes a highly conserved ECM glycoprotein, results in ectopic peripheral localization of cells, including neoblasts, outside of the muscle layer. ECM secretion and hmcn-1-dependent maintenance of tissue separation indicate that muscle functions as a planarian connective tissue, raising the possibility of broad roles for connective tissue in adult positional information.
RNA editing is abundant and correlates with task performance in a social bumblebee
Authors: Porath Hagit T. , Hazan Esther , Shpigler Hagai , Cohen Mira , Band Mark , Ben-Shahar Yehuda , Levanon Erez Y. , Eisenberg Eli , Bloch Guy
Published: April 2019

Colonies of the bumblebee Bombus terrestris are characterized by wide phenotypic variability among genetically similar full-sister workers, suggesting a major role for epigenetic processes. Here, we report a high level of ADAR-mediated RNA editing in the bumblebee, despite the lack of an ADAR1-homolog. We identify 1.15 million unique genomic sites, and 164 recoding sites residing in 100 protein coding genes, including ion channels, transporters, and receptors predicted to affect brain function and behavior. Some edited sites are similarly edited in other insects, cephalopods and even mammals. The global editing level of protein coding and non-coding transcripts weakly correlates with task performance (brood care vs. foraging), but not affected by dominance rank or juvenile hormone known to influence physiology and behavior. Taken together, our findings show that brain editing levels are high in naturally behaving bees, and may be regulated by relatively short-term effects associated with brood care or foraging activities.
Surface melt driven summer diurnal and winter multi-day stick-slip motion and till sedimentology
Authors: Hart Jane K. , Martinez Kirk , Basford Philip J. , Clayton Alexander I. , Robson Benjamin A. , Young David S.
Published: April 2019

Fluctuations in glacier motion are very common and are thought to be controlled by subglacial hydrology and till deformation. There are few instrumented studies that have monitored seasonal changes. We use the innovative Glacsweb subglacial in situ wireless probes, combined with dGPS and custom geophone data from an Icelandic soft-bedded temperate glacier, to show that there are two distinct seasonal styles of speed-up events. Relatively small diurnal events occur during the melt season, whilst during winter there are larger multi-day events related to positive degree days. These events are accompanied by a distinct pattern of till deformation and basal icequakes. We argue these reflect stick-slip motion which occurs when the glacier hydrological system is unable to accommodate the melt water flux generated by surface melt episodes. We show a rare fully instrumented coupled glacier/till record of contrasting summer and winter stick-slip motion and discuss its implication for till sedimentology.
Boosting the efficiency of organic persistent room-temperature phosphorescence by intramolecular triplet-triplet energy transfer
Authors: Zhao Weijun , Cheung Tsz Shing , Jiang Nan , Huang Wenbin , Lam Jacky W. Y. , Zhang Xuepeng , He Zikai , Tang Ben Zhong
Published: April 2019

Persistent luminescence is a fascinating phenomenon with exceptional applications. However, the development of organic materials capable of persistent luminescence, such as organic persistent room-temperature phosphorescence, lags behind for their normally low efficiency. Moreover, enhancing the phosphorescence efficiency of organic luminophores often results in short lifetime, which sets an irreconcilable obstacle. Here we report a strategy to boost the efficiency of phosphorescence by intramolecular triplet-triplet energy transfer. Incorpotation of (bromo)dibenzofuran or (bromo)dibenzothiophene to carbazole has boosted the intersystem crossing and provided an intramolecular triplet-state bridge to offer a near quantitative exothermic triplet–triplet energy transfer to repopulate the lowest triplet-state of carbazole. All these factors work together to contribute the efficient phosphorescence. The generation and transfer of triplet excitons within a single molecule is revealed by low-temperature spectra, energy level and lifetime investigations. The strategy developed here will enable the development of efficient phosphorescent materials for potential high-tech applications.
Cycles of external dependency drive evolution of avian carotenoid networks
Authors: Badyaev Alexander V. , Posner Alexander B. , Morrison Erin S. , Higginson Dawn M.
Published: April 2019

All organisms depend on input of exogenous compounds that cannot be internally produced. Gain and loss of such dependencies structure ecological communities and drive species’ evolution, yet the evolution of mechanisms that accommodate these variable dependencies remain elusive. Here, we show that historical cycles of gains and losses of external dependencies in avian carotenoid-producing networks are linked to their evolutionary diversification. This occurs because internalization of metabolic controls—produced when gains in redundancy of dietary inputs coincide with increased branching of their derived products—enables rapid and sustainable exploration of an existing network by shielding it from environmental fluctuations in inputs. Correspondingly, loss of internal controls constrains evolution to the rate of the gains and losses of dietary precursors. Because internalization of a network’s controls necessarily bridges diet-specific enzymatic modules within a network, it structurally links local adaptation and continuous evolution even for traits fully dependent on contingent external inputs.
Coordinated host-pathogen transcriptional dynamics revealed using sorted subpopulations and single macrophages infected with Candida albicans
Authors: Muñoz José F. , Delorey Toni , Ford Christopher B. , Li Bi Yu , Thompson Dawn A. , Rao Reeta P. , Cuomo Christina A.
Published: April 2019

The outcome of fungal infections depends on interactions with innate immune cells. Within a population of macrophages encountering Candida albicans, there are distinct host-pathogen trajectories; however, little is known about the molecular heterogeneity that governs these fates. Here we developed an experimental system to separate interaction stages and single macrophage cells infected with C. albicans from uninfected cells and assessed transcriptional variability in the host and fungus. Macrophages displayed an initial up-regulation of pathways involved in phagocytosis and proinflammatory response after C. albicans exposure that declined during later time points. Phagocytosed C. albicans shifted expression programs to survive the nutrient poor phagosome and remodeled the cell wall. The transcriptomes of single infected macrophages and phagocytosed C. albicans displayed a tightly coordinated shift in gene expression co-stages and revealed expression bimodality and differential splicing that may drive infection outcome. This work establishes an approach for studying host-pathogen trajectories to resolve heterogeneity in dynamic populations.
Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation
Authors: Zheng Jun , Fan Rong , Wu Huiqiong , Yao Honghui , Yan Yujie , Liu Jiamiao , Ran Lu , Sun Zhifang , Yi Lunzhao , Dang Li , Gan Pingping , Zheng Piao , Yang Tilong , Zhang Yi , Tang Tao , Wang Yang
Published: April 2019

Self-assembling natural drug hydrogels formed without structural modification and able to act as carriers are of interest for biomedical applications. A lack of knowledge about natural drug gels limits there current application. Here, we report on rhein, a herbal natural product, which is directly self-assembled into hydrogels through noncovalent interactions. This hydrogel shows excellent stability, sustained release and reversible stimuli-responses. The hydrogel consists of a three-dimensional nanofiber network that prevents premature degradation. Moreover, it easily enters cells and binds to toll-like receptor 4. This enables rhein hydrogels to significantly dephosphorylate IκBα, inhibiting the nuclear translocation of p65 at the NFκB signalling pathway in lipopolysaccharide-induced BV2 microglia. Subsequently, rhein hydrogels alleviate neuroinflammation with a long-lasting effect and little cytotoxicity compared to the equivalent free-drug in vitro. This study highlights a direct self-assembly hydrogel from natural small molecule as a promising neuroinflammatory therapy.
Hepatic arginase 2 (Arg2) is sufficient to convey the therapeutic metabolic effects of fasting
Authors: Zhang Yiming , Higgins Cassandra B. , Fortune Hannah M. , Chen Phillip , Stothard Alicyn I. , Mayer Allyson L. , Swarts Benjamin M. , DeBosch Brian J.
Published: April 2019

Caloric restriction and intermittent fasting are emerging therapeutic strategies against obesity, insulin resistance and their complications. However, the effectors that drive this response are not completely defined. Here we identify arginase 2 (Arg2) as a fasting-induced hepatocyte factor that protects against hepatic and peripheral fat accumulation, hepatic inflammatory responses, and insulin and glucose intolerance in obese murine models. Arg2 is upregulated in fasting conditions and upon treatment with the hepatocyte glucose transporter inhibitor trehalose. Hepatocyte-specific Arg2 overexpression enhances basal thermogenesis, and protects from weight gain, insulin resistance, glucose intolerance, hepatic steatosis and hepatic inflammation in diabetic mouse models. Arg2 suppresses expression of the regulator of G-protein signalling (RGS) 16, and genetic RGS16 reconstitution reverses the effects of Arg2 overexpression. We conclude that hepatocyte Arg2 is a critical effector of the hepatic glucose fasting response and define a therapeutic target to mitigate the complications of obesity and non-alcoholic fatty liver disease.
Taming the stability of Pd active phases through a compartmentalizing strategy toward nanostructured catalyst supports
Authors: Yang Xinwei , Li Qing , Lu Erjun , Wang Zhiqiang , Gong Xueqing , Yu Zhiyang , Guo Yun , Wang Li , Guo Yanglong , Zhan Wangcheng , Zhang Jinshui , Dai Sheng
Published: April 2019

The design and synthesis of robust sintering-resistant nanocatalysts for high-temperature oxidation reactions is ubiquitous in many industrial catalytic processes and still a big challenge in implementing nanostructured metal catalyst systems. Herein, we demonstrate a strategy for designing robust nanocatalysts through a sintering-resistant support via compartmentalization. Ultrafine palladium active phases can be highly dispersed and thermally stabilized by nanosheet-assembled γ-Al2O3 (NA-Al2O3) architectures. The NA-Al2O3 architectures with unique flowerlike morphologies not only efficiently suppress the lamellar aggregation and irreversible phase transformation of γ-Al2O3 nanosheets at elevated temperatures to avoid the sintering and encapsulation of metal phases, but also exhibit significant structural advantages for heterogeneous reactions, such as fast mass transport and easy access to active sites. This is a facile stabilization strategy that can be further extended to improve the thermal stability of other Al2O3-supported nanocatalysts for industrial catalytic applications, in particular for those involving high-temperature reactions.
Ecological and geographical overlap drive plumage evolution and mimicry in woodpeckers
Authors: Miller Eliot T. , Leighton Gavin M. , Freeman Benjamin G. , Lees Alexander C. , Ligon Russell A.
Published: April 2019

Organismal appearances are shaped by selection from both biotic and abiotic drivers. For example, Gloger’s rule describes the pervasive pattern that more pigmented populations are found in more humid areas. However, species may also converge on nearly identical colours and patterns in sympatry, often to avoid predation by mimicking noxious species. Here we leverage a massive global citizen-science database to determine how biotic and abiotic factors act in concert to shape plumage in the world’s 230 species of woodpeckers. We find that habitat and climate profoundly influence woodpecker plumage, and we recover support for the generality of Gloger’s rule. However, many species exhibit remarkable convergence explained neither by these factors nor by shared ancestry. Instead, this convergence is associated with geographic overlap between species, suggesting occasional strong selection for interspecific mimicry.
The complexity of understanding others as the evolutionary origin of empathy and emotional contagion
Authors: Mafessoni Fabrizio , Lachmann Michael
Published: April 2019

Contagious yawning, emotional contagion and empathy are characterized by the activation of similar neurophysiological states or responses in an observed individual and an observer. For example, it is hard to keep one’s mouth closed when imagining someone yawning, or not feeling distressed while observing other individuals perceiving pain. The evolutionary origin of these widespread phenomena is unclear, since a direct benefit is not always apparent. We explore a game theoretical model for the evolution of mind-reading strategies, used to predict and respond to others’ behavior. In particular we explore the evolutionary scenarios favoring simulative strategies, which recruit overlapping neural circuits when performing as well as when observing a specific behavior. We show that these mechanisms are advantageous in complex environments, by allowing an observer to use information about its own behavior to interpret that of others. However, without inhibition of the recruited neural circuits, the observer would perform the corresponding downstream action, rather than produce the appropriate social response. We identify evolutionary trade-offs that could hinder this inhibition, leading to emotional contagion as a by-product of mind-reading. The interaction of this model with kinship is complex. We show that empathy likely evolved in a scenario where kin- and other indirect benefits co-opt strategies originally evolved for mind-reading, and that this model explains observed patterns of emotional contagion with kin or group members.