bluuebunny/crossref_metadata_2025 huggingface dataset:
Droplet impact of Newtonian fluids and blood on simple fabrics: Effect of fabric pore size and underlying substrate
Authors: de Goede T. C. , Moqaddam A. M. , Limpens K. C. M. , Kooij S. A. , Derome D. , Carmeliet J. , Shahidzadeh N. , Bonn D.
Published: March 2021

When a droplet impacts a fabric mesh at a sufficiently high impact velocity, it not only spreads over the fabric but also penetrates its pores. To determine the influence of this liquid penetration of the fabric on droplet spreading on thin fabric meshes, we measured the droplet spreading ratio on fabric with and without an underlying substrate using a high-speed camera. For fabrics without a substrate, the droplet spreading ratio is reduced as the fabric penetration by the liquid reduces the droplet volume spreading on top of the fabric. Using entropic lattice Boltzmann simulations, we find that the lower droplet spreading ratio on fabrics, both with and without a substrate, is due to an increase in viscous losses inside the droplet during spreading. Comparing droplet impact of blood with its Newtonian counterpart, we show that for spreading on fabrics, just like on smooth surfaces, blood can be approximated as a Newtonian fluid.
Effective screening of medium-assisted van der Waals interactions between embedded particles
Authors: Fiedler Johannes , Walter Michael , Buhmann Stefan Yoshi
Published: March 2021

The effect of an implicit medium on dispersive interactions of particle pairs is discussed, and simple expressions for the correction relative to vacuum are derived. We show that a single point Gauss quadrature leads to the intuitive result that the vacuum van der Waals C6-coefficient is screened by the permittivity squared of the environment evaluated near to the resonance frequencies of the interacting particles. This approximation should be particularly relevant if the medium is transparent at these frequencies. In this manuscript, we provide simple models and sets of parameters for commonly used solvents, atoms, and small molecules.
The effect of interstitial-site nitrogen on structural, elastic, and magnetic properties of face-center cubic Co
Authors: Wu Binbin , Zhang Feng , Hu Qiwei , Tang Qiqi , Liu Shan , Xiang Xiaojun , Xia Yuanhua , Fang Leiming , Ohfuji Hiroaki , Irifune Tetsuo , Lei Li
Published: March 2021

Cobalt plays a crucial role in the systematic understanding of magnetic phenomena originating from 3d transition metals. Particularly, recent studies of Co systems doped with nitrogen (Co–N) have attracted a lot of attention for applications in spintronics and high-density magnetic data-storage devices. In this work, in order to understand the effect of interstitial incorporation of N atoms into a face-center cubic (fcc) Co lattice, we have studied the structure, elastic, and magnetic properties of spherical-like bulk CoNx (x = 0.06–0.07) samples. These samples were synthesized through a high-pressure solid-state metathesis reaction. We demonstrate that the use of a certain concentration of interstitial N atoms tends to stabilize the lattice of fcc Co at ambient conditions. Such a stabilizing effect is found to originate from the covalent bond between Co atoms and N atoms. High-pressure synchrotron x-ray diffraction indicates that the incorporation of N atoms into fcc Co has little effect on the elastic property up to 27.2 GPa with a bulk modulus (B0) of 200 GPa; the latter is found to be comparable to that of fcc and hcp Co. CoNx samples exhibited ferromagnetic behavior with saturation magnetization up to 153.55 emu/g and coercivity of 16.25 Oe. The introduction of small amounts of nitrogen in the cobalt matrix was found to induce a significant decrease in the coercive force parameter.
Low-carbon technology collaborative innovation in industrial cluster with social exclusion: An evolutionary game theory perspective
Authors: Zhou Ke , Ren Tianyu
Published: March 2021

As governments implement low-carbon economy widely, boosting low-carbon transformation in industrial clusters has become a challenge. This study establishes an evolutionary game model of low-carbon technology collaborative innovation based on spatial public goods game to solve the free-riding problem effectively in research and development. By introducing a social exclusion mechanism, we explore the requirements for the emergence of cooperation between enterprises, and we consider the heterogeneity and scale-free characteristics of industrial clusters comprehensively. Simulation results confirm that social exclusion can significantly promote cooperation as a form of cooperation with additional cost. When exclusion cost decreases and probability increases, an excluder can survive in a lower enhancement factor, which guarantees a stable exclusion mechanism. Furthermore, this mechanism is key to forming and maintaining cooperative behavior. When a cluster follows a scale-free distribution, the sparse network structure can avoid cooperation collapse. Moreover, heterogeneous investment is a robust alternative in the face of invading defectors. This study provides a new understanding to promote the collaborative innovation of enterprises in industrial clusters.
Absolute calibration of the Lyman-α measurement apparatus at DIII-D
Authors: Laggner F. M. , Bortolon A. , Rosenthal A. M. , Wilks T. M. , Hughes J. W. , Freeman C. , Golfinopoulos T. , Nagy A. , Mauzey D. , Shafer M. W. ,   the DIII-D Team
Published: March 2021

The LLAMA (Lyman-Alpha Measurement Apparatus) diagnostic was recently installed on the DIII-D tokamak [Rosenthal et al., Rev. Sci. Instrum. (submitted) (2020)]. LLAMA is a pinhole camera system with a narrow band Bragg mirror, a bandpass interference filter, and an absolute extreme ultraviolet photodiode detector array, which measures the Ly-α brightness in the toroidal direction on the inboard, high field side (HFS) and outboard, low field side (LFS). This contribution presents a setup and a procedure for an absolute calibration near the Ly-α line at 121.6 nm. The LLAMA in-vacuum components are designed as a compact, transferable setup that can be mounted in an ex situ vacuum enclosure that is equipped with an absolutely calibrated Ly-α source. The spectral purity and stability of the Ly-α source are characterized using a vacuum ultraviolet spectrometer, while the Ly-α source brightness is measured by a NIST-calibrated photodiode. The non-uniform nature of the Ly-α source emission was overcome by performing a calibration procedure that scans the Ly-α source position and employs a numerical optimization to determine the emission pattern. Nominal and measured calibration factors are determined and compared, showing agreement within their uncertainties. A first conversion of the measured signal obtained from DIII-D indicates that the Ly-α brightness on the HFS and LFS is on the order of 1020 Ph sr−1 m−2 s−1. The established calibration setup and procedure will be regularly used to re-calibrate the LLAMA during DIII-D vents to monitor possible degradation of optical components and detectors.
Structure and dynamics of water plastic crystals from computer simulations
Authors: Henao Andrés , Salazar-Rios Jorge Mario , Guardia Elvira , Pardo Luis C.
Published: March 2021

Water has a rich phase diagram with several crystals, as confirmed by experiments. High-pressure and high-temperature water is of interest for Earth’s mantle and exoplanetary investigations. It is in this region of the phase diagram of water that new plastic crystal phases of water have been revealed via computer simulations by both classical forcefields and ab initio calculations. However, these plastic phases still remain elusive in experiments. Here, we present a complete characterization of the structure, dynamics, and thermodynamics of the computational plastic crystal phases of water using molecular dynamics and the two-phase thermodynamic method and uncover the interplay between them. The relaxation times of different reorientational correlation functions are obtained for the hypothetical body-centered-cubic and face-centered-cubic plastic crystal phases of water at T = 440 K and P = 8 GPa. Results are compared to a high pressure liquid and ice VII phases to improve the understanding of the plastic crystal phases. Entropy results indicate that the fcc crystal is more stable compared to the bcc structure under the studied conditions.
Parameter extraction with reservoir computing: Nonlinear time series analysis and application to industrial maintenance
Authors: Thorne Braden , Jüngling Thomas , Small Michael , Hodkiewicz Melinda
Published: March 2021

We study the task of determining parameters of dynamical systems from their time series using variations of reservoir computing. Averages of reservoir activations yield a static set of random features that allows us to separate different parameter values. We study such random feature models in the time and frequency domain. For the Lorenz and Rössler systems throughout stable and chaotic regimes, we achieve accurate and robust parameter extraction. For vibration data of centrifugal pumps, we find a significant ability to recover the operating regime. While the time domain models achieve higher performance for the numerical systems, the frequency domain models are superior in the application context.
Unfolding bovine
α
-lactalbumin with T-jump: Characterizing disordered intermediates via time-resolved x-ray solution scattering and molecular dynamics simulations
Authors: Hsu Darren J. , Leshchev Denis , Kosheleva Irina , Kohlstedt Kevin L. , Chen Lin X.
Published: March 2021

The protein folding process often proceeds through partially folded transient states. Therefore, a structural understanding of these disordered states is crucial for developing mechanistic models of the folding process. Characterization of unfolded states remains challenging due to their disordered nature, and incorporating multiple methods is necessary. Combining the time-resolved x-ray solution scattering (TRXSS) signal with molecular dynamics (MD), we are able to characterize transient partially folded states of bovine α-lactalbumin, a model system widely used for investigation of molten globule states, during its unfolding triggered by a temperature jump. We track the unfolding process between 20 µs and 70 ms and demonstrate that it passes through three distinct kinetic states. The scattering signals associated with these transient species are then analyzed with TRXSS constrained MD simulations to produce protein structures that are compatible with the input signals. Without utilizing any experimentally extracted kinetic information, the constrained MD simulation successfully drove the protein to an intermediate molten globule state; signals for two later disordered states are refined to terminal unfolded states. From our examination of the structural characteristics of these disordered states, we discuss the implications disordered states have on the folding process, especially on the folding pathway. Finally, we discuss the potential applications and limitations of this method.
Steady radiating baroclinic vortices in vertically sheared flows
Authors: Sutyrin G. G. , Radko T. , Nycander J.
Published: March 2021

This paper examines baroclinic vortices embedded in a large-scale vertical shear. We describe a new class of steady propagating vortices that radiate Rossby waves but yet do not decay. This is possible since they can extract available potential energy from a large-scale vertically sheared flow, even though this flow is linearly stable. The vortices generate Rossby waves, which induce a meridional vortex drift and an associated heat flux explained by an analysis of pseudomomentum and pseudoenergy. An analytical steady solution is considered for the marginally stable flow in a two-layer model on the beta-plane, where the beta-effect is compensated by the potential vorticity gradient (PVG) associated with the meridional slope of the density interface. The compensation occurs in the upper layer for an upper layer westward flow (an easterly shear) and in the lower layer for an upper layer eastward flow (the westerly shear). The theory is confirmed by numerical simulations, indicating that for westward flows in subtropical oceans, the reduced PVG in the upper layer provides favorable conditions for eddy persistence and long-range propagation.
A temperature-controlled electric field sample environment for small-angle neutron scattering experiments
Authors: Hayward Dominic W. , Magro Germinal , Hörmann Anja , Prévost Sylvain , Schweins Ralf , Richardson Robert M. , Gradzielski Michael
Published: March 2021

A new sample environment is introduced for the study of soft matter samples in electric fields using small-angle neutron scattering instruments. The sample environment is temperature controlled and features external electrodes, allowing standard quartz cuvettes to be used and conducting samples or samples containing ions to be investigated without the risk of electrochemical reactions occurring at the electrodes. For standard 12.5 mm quartz cuvettes, the maximum applied field is 8 kV/cm, and the applied field may be static or alternating (up to 10 kHz for 8 kV/cm and up to 60 kHz for 4 kV/cm). The electric fields within the sample are calculated and simulated under a number of different conditions, and the capabilities of the setup are demonstrated using a variety of liquid crystalline samples. Measurements were performed as a function of temperature and time spent in the electric field. Finally, the advantages, drawbacks, and potential optimization of the sample environment are discussed with reference to applications in the fields of complex soft matter, biology, and electrorheology.
Simulations of the IR and Raman spectra of water confined in amorphous silica slit pores
Authors: Senanayake Hasini S. , Greathouse Jeffery A. , Ilgen Anastasia G. , Thompson Ward H.
Published: March 2021

Water in nano-scale confining environments is a key element in many biological, material, and geological systems. The structure and dynamics of the liquid can be dramatically modified under these conditions. Probing these changes can be challenging, but vibrational spectroscopy has emerged as a powerful tool for investigating their behavior. A critical, evolving component of this approach is a detailed understanding of the connection between spectroscopic features and molecular-level details. In this paper, this issue is addressed by using molecular dynamics simulations to simulate the linear infrared (IR) and Raman spectra for isotopically dilute HOD in D2O confined in hydroxylated amorphous silica slit pores. The effect of slit-pore width and hydroxyl density on the silica surface on the vibrational spectra is also investigated. The primary effect of confinement is a blueshift in the frequency of OH groups donating a hydrogen bond to the silica surface. This appears as a slight shift in the total (measurable) spectra but is clearly seen in the distance-based IR and Raman spectra. Analysis indicates that these changes upon confinement are associated with the weaker hydrogen-bond accepting properties of silica oxygens compared to water molecules.
Direct numerical simulation of the turbulent flow generated during a violent expiratory event
Authors: Fabregat Alexandre , Gisbert Ferran , Vernet Anton , Dutta Som , Mittal Ketan , Pallarès Jordi
Published: March 2021

A main route for SARS-CoV-2 (severe acute respiratory syndrome coronavirus) transmission involves airborne droplets and aerosols generated when a person talks, coughs, or sneezes. The residence time and spatial extent of these virus-laden aerosols are mainly controlled by their size and the ability of the background flow to disperse them. Therefore, a better understanding of the role played by the flow driven by respiratory events is key in estimating the ability of pathogen-laden particles to spread the infection. Here, we numerically investigate the hydrodynamics produced by a violent expiratory event resembling a mild cough. Coughs can be split into an initial jet stage during which air is expelled through mouth and a dissipative phase over which turbulence intensity decays as the puff penetrates the environment. Time-varying exhaled velocity and buoyancy due to temperature differences between the cough and the ambient air affect the overall flow dynamics. The direct numerical simulation (DNS) of an idealized isolated cough is used to characterize the jet/puff dynamics using the trajectory of the leading turbulent vortex ring and extract its topology by fitting an ellipsoid to the exhaled fluid contour. The three-dimensional structure of the simulated cough shows that the assumption of a spheroidal puff front fails to capture the observed ellipsoidal shape. Numerical results suggest that, although analytical models provide reasonable estimates of the distance traveled by the puff, trajectory predictions exhibit larger deviations from the DNS. The fully resolved hydrodynamics presented here can be used to inform new analytical models, leading to improved prediction of cough-induced pathogen-laden aerosol dispersion.
Localized high concentration electrolytes decomposition under electron-rich environments
Authors: Zheng Yu , Balbuena Perla B.
Published: March 2021

Localized high concentration electrolytes have been proposed as an effective route to construct stable solid-electrolyte interphase (SEI) layers near Li-metal anodes. However, there is still a limited understanding of the decomposition mechanisms of electrolyte components during SEI formation. In this work, we investigate reactivities of lithium bis(fluorosulfonyl)imide (LiFSI, salt), 1,2-dimethoxyethane (DME, solvent), and tris(2,2,2-trifluoroethyl)orthoformate (TFEO, diluent) species in DME + TFEO mixed solvents and 1M LiFSI/DME/TFEO solutions. By supplying an excess of electrons into the simulation cell, LiFSI is initially reduced via a four-electron charge transfer reaction yielding F− and N(SO2)23−. The local solvation environment has little effect on the subsequent TFEO reaction, which typically requires 6 |e| to decompose into F−, HCOO−, CH2CF−, and −OCH2CF3. Besides, the TFEO dehydrogenation reaction mechanism under an attack of anions is also identified. Unlike salt and diluent, DME shows good stability with any excess of electrons. The energetics of most relevant reactions are characterized. Most reactions are thermodynamically favorable with low activation barriers.
Development of a forward model for Bayesian analysis of a single crystal dispersion interferometer
Authors: Lee Jae-seok , Lee Dong-Geun , Lee K. C. , Juhn J.-W. , Ghim Y.-c.
Published: March 2021

The Single Crystal Dispersion Interferometer (SCDI) is a newly developed dispersion interferometer (DI) system installed on KSTAR and has obtained the first data successfully in January 2020. Unlike conventional heterodyne DI systems, which use two nonlinear crystals, only one nonlinear crystal is used to eliminate the difficulty in overlapping the first and second harmonic beams, aligning and focusing the beams to a small aperture of the second nonlinear crystal, and resolving a problem of significant efforts to maintain the beam alignment to the second nonlinear crystal after a long beam transmission. The second nonlinear crystal is replaced by a frequency doubler, a simple electronic component. To infer a line integrated electron density with its associated uncertainty consistent with the measured data, we develop a forward model of the KSTAR SCDI that can be used as a likelihood within a Bayesian-based data analysis routine. The forward model consists of two main parts, which are an optical system and an electronics system, and it takes into account noises by modeling the mechanical vibrations and the electronic noises as Gaussian distributions, while the photon noise is modeled with a Poisson distribution. The developed forward model can be used for designing and improving the SCDI system.
Rainbow scattering in rotationally inelastic collisions of HCl and H2
Authors: Morita Masato , Zuo Junxiang , Guo Hua , Balakrishnan Naduvalath
Published: March 2021

We examine rotational transitions of HCl in collisions with H2 by carrying out quantum mechanical close-coupling and quasi-classical trajectory (QCT) calculations on a recently developed globally accurate full-dimensional ab initio potential energy surface for the H3Cl system. Signatures of rainbow scattering in rotationally inelastic collisions are found in the state resolved integral and differential cross sections as functions of the impact parameter (initial orbital angular momentum) and final rotational quantum number. We show the coexistence of distinct dynamical regimes for the HCl rotational transition driven by the short-range repulsive and long-range attractive forces whose relative importance depends on the collision energy and final rotational state, suggesting that the classification of rainbow scattering into rotational and l-type rainbows is effective for H2 + HCl collisions. While the QCT method satisfactorily predicts the overall behavior of the rotationally inelastic cross sections, its capability to accurately describe signatures of rainbow scattering appears to be limited for the present system.
A phase diagram for energy flow-limited reactivity
Authors: Zhang Chenghao , Sibert Edwin L. , Gruebele Martin
Published: March 2021

Intramolecular energy flow (also known as intramolecular vibrational redistribution or IVR) is often assumed in Rice–Ramsperger–Kassel–Marcus, transition state, collisional energy transfer, and other rate calculations not to be an impediment to reaction. In contrast, experimental spectroscopy, computational results, and models based on Anderson localization have shown that ergodicity is achieved rather slowly during molecular energy flow. The statistical assumption in rate theories might easily fail due to quantum localization. Here, we develop a simple model for the interplay of IVR and energy transfer and simulate the model with near-exact quantum dynamics for a 10-degree of freedom system composed of two five-mode molecular fragments. The calculations are facilitated by applying the van Vleck transformation to local random matrix models of the vibrational Hamiltonian. We find that there is a rather sharp “phase transition” as a function of molecular anharmonicity “a” between a region of facile energy transfer and a region limited by IVR and incomplete accessibility of the state space (classically, the phase space). The very narrow transition range of the order parameter a happens to lie right in the middle of the range expected for molecular torsion, bending, and stretching vibrations, thus demonstrating that reactive energy transfer dynamics several kBT above the thermal energy occurs not far from the localization boundary, with implications for controllability of reactions.
Electron attachment to representative cations composing ionic liquids
Authors: Anusiewicz Iwona , Freza Sylwia , Bobrowski Maciej , Skurski Piotr
Published: March 2021

Using ab initio electronic structure methods with flexible atomic orbital basis sets, we investigated the electronic structure and stability of reduction products of selected representative cations (C+) constituting ionic liquids. We found that an electron attachment to such cations leads to the neutral radicals, whereas a subsequent attachment of another (i.e., excess) electron leads to adiabatically stable anions only in two cases {[P(CH3)4]− and [MeMePyr]−}. The possibility of the formation of various dimers (such as CC+, CC, and CC−) was also considered, and the resulting systems were characterized by predicting their lowest energy structures, ionization potentials, electron affinities, and susceptibilities to the fragmentation process. Among the cations studied, only the [MeMePyr]+ was found to form a typical Rydberg radical (MeMePyr) and double-Rydberg anion ([MeMePyr]−), whereas the remaining cations were predicted to form neutral radicals of a primarily valence (MeMeIm and MePy) or mixed Rydberg-valence [P(CH3)4] character. Our calculations confirmed the stability of all CC+ and CC dimers against fragmentation yielding the corresponding monomers (the binding energies of 12.2–20.5 kcal/mol and 11.3–72.3 kcal/mol were estimated for CC+ and CC dimers, respectively). [(MeMePyr)2]− was identified as the only adiabatically stable CC− dimeric anion having its vertical electron detachment energy of 0.417 eV. We also found that in the [(MeMePyr)2]− anionic state, three outermost electrons are described by Rydberg orbitals, which results in the (σ)2(σ*)1 configuration.
Evolution of atomic structure and electronic transport properties in n-type Bi2Te3 films via Bi2 planar defects
Authors: Zhang Min , Liu Wei , Zhang Cheng , Xie Sen , Hua Fuqiang , Yan Fan , Cheng Rui , Luo Jiangfan , Wang Wei , Sang Hao , Ge Haoran , Wang Zhaohui , Tao Qirui , Bai Hui , Luo Hao , Wu Jinsong , Tang Xinfeng
Published: March 2021

Bi2Te3 films always exhibit n-type transport characteristics even under the Bi-rich condition, which, however, was not clarified clearly. Herein, by virtue of advanced techniques such as scanning tunneling microscopy, angle-resolved photoelectron spectroscopy, scanning transmission electron microscopy, and x-ray photoelectron spectroscopy, we are able to identify the structural evolution on the atomic scale for Bi-rich Bi2Te3 films. The excess of Bi content will lead to the formation of p-type BiTe antisite defects; however, there is a doping limit for the excess of Bi to form BiTe antisites. Beyond this limit, the excess of Bi will form the n-type Bi2 planar defects in the van der Waals gap, the excellent electron donors, which can enhance the electron density by over one order of magnitude and up to the 1021 cm−3 range for Bi-rich Bi2Te3 films. Benefiting from the remarkable increase in the electron density and the suppression of carrier intrinsic excitations, Bi2Te3 films with Bi2 planar defects possess a much improved thermoelectric power factor, with a maximum value of 1.4 mW m−1 K−2 at 450 K, showing about 130% enhancement compared to that of the film without Bi2 intercalations. The discovery opens a new avenue to improve the thermoelectric properties of Bi2Te3 films utilizing the Bi2 planar defects.
Brassinosteroid signaling integrates multiple pathways to release apical dominance in tomato
Authors: Xia Xiaojian , Dong Han , Yin Yanling , Song Xuewei , Gu Xiaohua , Sang Kangqi , Zhou Jie , Shi Kai , Zhou Yanhong , Foyer Christine H. , Yu Jingquan
Published: March 2021

Significance

For almost a century, auxin had been well-known as the master regulator of apical dominance. Recently, however, sugars were shown to be the initial regulator of apical dominance, while strigolactones (SLs) and cytokinins (CKs) act downstream of auxin to control bud outgrowth. However, the interactions of the different pathways have remained outstanding questions. Here, we report that brassinosteroids (BRs) are essential for the release of apical dominance in tomato. CK signaling relays information from auxin, SL, and sugars to promote the production of BRs, which activate the BZR1 transcription factor to suppress the expression of
BRANCHED1
, an inhibitor of bud outgrowth. These findings demonstrate that hormonal and metabolic pathways impinge on a common BR signaling for controlling shoot branching.
Type I interferon activation and endothelial dysfunction in caveolin-1 insufficiency-associated pulmonary arterial hypertension
Authors: Gairhe Salina , Awad Keytam S. , Dougherty Edward J. , Ferreyra Gabriela A. , Wang Shuibang , Yu Zu-Xi , Takeda Kazuyo , Demirkale Cumhur Y. , Torabi-Parizi Parizad , Austin Eric D. , Elinoff Jason M. , Danner Robert L.
Published: March 2021

Significance

Caveolin-1 (CAV1) loss-of-function mutations are a hereditary cause of pulmonary arterial hypertension (PAH), but wild-type CAV1 is also decreased in the vascular lesions of idiopathic and disease-associated PAH. Using human pulmonary artery endothelium, lung tissue, and serum from
Cav1

−/−

mice, as well as fibroblasts and serum from patients with
CAV1
mutations, CAV1 deficiency produced a dysfunctional, PAH-like endothelial phenotype driven by an interferon-biased inflammatory response with constitutive STAT and AKT activation. Inhibiting JAK/STAT and PI3K/AKT reversed the aberrant endothelial phenotype of CAV1 loss and may similarly ameliorate pathologic vascular remodeling in PAH. Exogenous interferon alone reduced CAV1 expression and activated these same signaling pathways, suggesting that CAV1 insufficiency may contribute to the development of autoimmune and autoinflammatory disease-associated PAH.
Decidual cell FKBP51–progesterone receptor binding mediates maternal stress–induced preterm birth
Authors: Guzeloglu-Kayisli Ozlem , Semerci Nihan , Guo Xiaofang , Larsen Kellie , Ozmen Asli , Arlier Sefa , Mutluay Duygu , Nwabuobi Chinedu , Sipe Bradley , Buhimschi Irina , Buhimschi Catalin , Schatz Frederick , Kayisli Umit A. , Lockwood Charles J.
Published: March 2021

Significance

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality. The genetics and molecular characteristics of PTB remain unclear. FKBP51 is an important mediator of the stress response and is implicated in the etiology of stress-related disorders. By combining studies in humans and
Fkbp5
−/−
mice, we show that maternal stress up-regulates FKBP51 levels and enhances binding of FKBP51 to progesterone receptors. FKBP51 binding to progesterone receptors reduces progesterone receptor activity by causing functional progesterone withdrawal that induces PTB. In contrast,
Fkbp5
−/−
mice are resistant to maternal stress–induced PTB and exhibit prolonged gestation. These findings provide molecular insights into stress-related PTB, indicating the importance of the potential use of inhibitor(s) against FKBP51 to treat PTB in future studies.
Focusing climate negotiations on a uniform common commitment can promote cooperation
Authors: Schmidt Klaus M. , Ockenfels Axel
Published: March 2021

Significance

Climate change and other threats to modern societies require international cooperation. Utilizing a laboratory experiment and game theoretical analysis, we find that the success of negotiations to promote cooperation strongly depends on the kind of commitment negotiated. In the context of international climate policy, our findings indicate that individual commitments (as negotiated in the Paris Agreement) and complex common commitments (as negotiated in the Kyoto Protocol) tend to have only limited success in promoting cooperation. Shifting the negotiation focus to a uniform common commitment, such as a minimum carbon price, may potentially foster more ambitious cooperation and thus help mitigating climate change.
β2-adrenoceptor ligand efficacy is tuned by a two-stage interaction with the Gαs C terminus
Authors: Kim Keehun , Paulekas Shayla , Sadler Fredrik , Gupte Tejas M. , Ritt Michael , Dysthe Matthew , Vaidehi Nagarajan , Sivaramakrishnan Sivaraj
Published: March 2021

Significance

An outstanding challenge in GPCR pharmacology is quantifying the system-independent functional effects of ligand-receptor interactions. Current efforts to measure ligand efficacy at the level of the receptor (i.e., molecular efficacy) are limited by the requirement of extensive purification of receptor and G proteins to homogeneity. In this study, we present an accessible, scalable technology for the single point measurement of the molecular efficacy of GPCR ligands. Integrating this technology with insights from molecular dynamics simulations, we reveal that the transition of the G protein from an intermediate to a fully coupled interaction with the GPCR is a structural determinant of ligand molecular efficacy.
Determining the nonequilibrium criticality of a Gardner transition via a hybrid study of molecular simulations and machine learning
Authors: Li Huaping , Jin Yuliang , Jiang Ying , Chen Jeff Z. Y.
Published: March 2021

Apparent critical phenomena, typically indicated by growing correlation lengths and dynamical slowing down, are ubiquitous in nonequilibrium systems such as supercooled liquids, amorphous solids, active matter, and spin glasses. It is often challenging to determine if such observations are related to a true second-order phase transition as in the equilibrium case or simply a crossover and even more so to measure the associated critical exponents. Here we show that the simulation results of a hard-sphere glass in three dimensions are consistent with the recent theoretical prediction of a Gardner transition, a continuous nonequilibrium phase transition. Using a hybrid molecular simulation–machine learning approach, we obtain scaling laws for both finite-size and aging effects and determine the critical exponents that traditional methods fail to estimate. Our study provides an approach that is useful to understand the nature of glass transitions and can be generalized to analyze other nonequilibrium phase transitions.
Interventions can shift the thermal optimum for parasitic disease transmission
Authors: Nguyen Karena H. , Boersch-Supan Philipp H. , Hartman Rachel B. , Mendiola Sandra Y. , Harwood Valerie J. , Civitello David J. , Rohr Jason R.
Published: March 2021

Significance

Temperature influences the transmission of many pathogens, but the effects of temperature variability on parasite and host traits and their interactive effects on transmission are poorly understood. We integrated an epidemiological model of schistosomiasis, an infectious disease that affects over 200 million people, with temperature-dependent traits of the causative parasite and its intermediate snail host. We show that simulated interventions targeting snails and parasite larvae increased the optimum temperature for transmission because intervention-related mortality overrode natural thermal constraints. We show that interventions are more effective at lower temperatures, climate change will increase schistosomiasis risk in regions where surface water temperatures move closer to the thermal optimum, and considering local climate conditions for disease control can maximize human health outcomes.
Acetylcholine ameliorates colitis by promoting IL-10 secretion of monocytic myeloid-derived suppressor cells through the nAChR/ERK pathway
Authors: Zheng Wanwei , Song Huan , Luo Zhongguang , Wu Hao , Chen Lin , Wang Yuedi , Cui Haoshu , Zhang Yufei , Wang Bangting , Li Wenshuai , Liu Yao , Zhang Jun , Chu Yiwei , Luo Feifei , Liu Jie
Published: March 2021

Significance

Inflammatory bowel diseases (IBDs) have been characterized by immune-mediated destruction of intestinal homeostasis. Until now, there have been no optimal therapies due to lack of a comprehensive understanding on pathophysiology during IBDs. The enteric nervous system (ENS) is emerging as a critical participant in intestinal immunomodulation, but the interaction between the ENS and intestinal immunity in IBDs remains unclear. Here, we discover the alteration of the ENS featured with reduced neurons and decreased acetylcholine (ACh) in IBDs. Moreover, ACh directly enhances the antiinflammatory activity of monocytic myeloid-derived suppressor cells by promoting interleukin-10 production through nicotinic ACh receptors, and thus ameliorates colitis. Our data highlight a neuroimmunomodulatory pathway and provide an alternative avenue by locally increasing ACh level for IBD therapy.
Structural and functional dissection of reovirus capsid folding and assembly by the prefoldin-TRiC/CCT chaperone network
Authors: Knowlton Jonathan J. , Gestaut Daniel , Ma Boxue , Taylor Gwen , Seven Alpay Burak , Leitner Alexander , Wilson Gregory J. , Shanker Sreejesh , Yates Nathan A. , Prasad B. V. Venkataram , Aebersold Ruedi , Chiu Wah , Frydman Judith , Dermody Terence S.
Published: March 2021

Significance

Protein folding and oligomeric complex assembly are essential for protein homeostasis. These processes are orchestrated by a network of host chaperones that interact with nascent and formed polypeptides. We investigated the mechanism by which a ubiquitous, essential, molecular chaperone, TRiC, folds an aggregation-prone protein subunit of a viral capsid. Structural studies, mass spectrometry, and in vitro folding and assembly experiments provided insights into the mechanism by which TRiC, in cooperation with a cochaperone, prefoldin, folds and assembles protein multimers. As the principles of protein folding and assembly are evolutionarily conserved, these findings likely point to common functions for TRiC and prefoldin in assembling a diversity of intracellular protein complexes.
A multicountry perspective on gender differences in time use during COVID-19
Authors: Giurge Laura M. , Whillans Ashley V. , Yemiscigil Ayse
Published: March 2021

Significance

We find pervasive gender differences in time use during COVID-19. Surveys of diverse samples with over 30,000 respondents reveal that women—especially mothers—spent more time on necessities such as childcare and chores. In turn, time spent completing household chores was linked to lower well-being. This research reveals persistent time-use differences between women and men in household responsibilities during the COVID-19 pandemic.
Thrombomodulin is essential for maintaining quiescence in vascular endothelial cells
Authors: Giri Hemant , Panicker Sumith R. , Cai Xiaofeng , Biswas Indranil , Weiler Hartmut , Rezaie Alireza R.
Published: March 2021

Significance

We demonstrate that deletion of thrombomodulin (TM) from endothelial cells confers inflammatory phenotype to TM-deficient (
TM

−/−

) cells. This is based on the loss of integrity of VE-cadherin at cellular junctions, disrupted basal barrier permeability, and increased expression of cell adhesion molecules in
TM

−/−

cells. Proinflammatory phenotype is rescued by reexpression of TM in
TM

−/−

cells; however, soluble TM lacked this effect. Interestingly, instead of storage in Weibel–Palade bodies, VWF was secreted in
TM

−/−

cells, thereby recruiting platelets to cell surfaces under flow conditions. Increased VWF and inflammatory foci were also observed in lungs of tamoxifen-treated ERcre-TM
f/f
mice. These results suggest cell-bound TM maintains a quiescent phenotype in vascular endothelial cells by regulating expression of procoagulant and proinflammatory molecules.
Nonlinear elasticity of biological basement membrane revealed by rapid inflation and deflation
Authors: Li Hui , Zheng Yue , Han Yu Long , Cai Shengqiang , Guo Ming
Published: March 2021

Significance

Basement membranes (BMs) are thin layers of extracellular matrix ubiquitously found in animals surrounding various tissues. As a physical barrier, their mechanical properties are important in maintaining structural integrity of tissues, and their permeabilities are essential for molecule exchange and internal cell activities. However, due to the lack of direct measurement methods, the physical properties of BMs remain largely unclear, limiting our understanding of BMs in various physiological and pathological processes such as tumor development. Here, we apply pressure-controlled inflation/deflation to measure the stress–strain behaviors of intact BM in situ and to determine the mechanical properties in a model-independent manner. We discover a strong strain-stiffening effect of intact BM, which is essential for preventing its snap-through instability.
Reevaluating the timing of Neanderthal disappearance in Northwest Europe
Authors: Devièse Thibaut , Abrams Grégory , Hajdinjak Mateja , Pirson Stéphane , De Groote Isabelle , Di Modica Kévin , Toussaint Michel , Fischer Valentin , Comeskey Dan , Spindler Luke , Meyer Matthias , Semal Patrick , Higham Tom
Published: March 2021

Significance

Understanding when Neanderthals disappeared is a hotly debated topic. When radiocarbon dating placed the Spy Neanderthals amongst the latest surviving in Northwest Europe, questions were raised regarding the reliability of the dates. Using a procedure more efficient in removing contamination and ancient genomic analysis, we show that previous dates produced on Neanderthal specimens from Spy are too young by up to 10,000 y. Our direct radiocarbon dates on the Neanderthals from Spy and those from Engis and Fonds-de-Forêt show a reduction of the uncertainty for the time window corresponding to Neanderthal disappearance in Northwest Europe. This population disappeared at 44,200 to 40,600 cal B.P. (at 95.4% probability). This is also earlier than previous suggestions based on dates on bulk collagen.
Therapeutic targeting of FOS in mutant
TERT
cancers through removing TERT suppression of apoptosis via regulating
survivin
and
TRAIL-R2
Authors: Liu Rengyun , Tan Jie , Shen Xiaopei , Jiang Ke , Wang Chaoqun , Zhu Guangwu , Xing Mingzhao
Published: March 2021

Significance

Given that oncogenic hotspot mutations in the promoter of the gene for telomerase reverse transcriptase (TERT) are common, it has been attractive to develop therapeutic strategies targeting TERT in mutant
TERT
human cancers. No direct TERT inhibitor is currently available, however, hindering this pursuit. By targeting FOS in the FOS/GABPB/(mutant)
TERT
cascade using a FOS inhibitor to inhibit mutant
TERT
cancer cells and tumors through induction of apoptosis by relieving TERT suppression, this study identifies a therapeutic strategy of targeting the TERT cascade for cancers. This study also uncovers a molecular mechanism in which TERT controls apoptosis by specifically regulating two key players among many in the apoptotic cascade, answering a long-time question of how TERT suppresses apoptosis.
Early fMRI responses to somatosensory and optogenetic stimulation reflect neural information flow
Authors: Jung Won Beom , Im Geun Ho , Jiang Haiyan , Kim Seong-Gi
Published: March 2021

Significance

fMRI has revolutionized how neuroscientists investigate human brain functions and networks. To further advance understanding of brain functions, identifying the direction of information flow, such as thalamocortical versus corticothalamic projections, is critical. Because the early hemodynamic response at microvessels near active neurons can be detected by ultrahigh field fMRI, we propose using the onset times of fMRI responses to discern the information flow. This approach was confirmed by observing the ultrahigh spatiotemporal resolution BOLD fMRI responses to bottom-up somatosensory stimulation and top-down optogenetic stimulation of the primary motor cortex in anesthetized mice. Because ultrahigh field MRI is increasingly available, ultrahigh spatiotemporal fMRI will significantly facilitate the investigation of functional circuits in humans.
Aryl hydrocarbon receptor is essential for the pathogenesis of pulmonary arterial hypertension
Authors: Masaki Takeshi , Okazawa Makoto , Asano Ryotaro , Inagaki Tadakatsu , Ishibashi Tomohiko , Yamagishi Akiko , Umeki-Mizushima Saori , Nishimura Manami , Manabe Yusuke , Ishibashi-Ueda Hatsue , Shirai Manabu , Tsuchimochi Hirotsugu , Pearson James T , Kumanogoh Atsushi , Sakata Yasushi , Ogo Takeshi , Kishimoto Tadamitsu , Nakaoka Yoshikazu
Published: March 2021

Significance

Inflammatory signals are thought to be crucial for the pathogenesis of PAH; however, the underlying mechanism is still largely unknown. In this study, we demonstrate that AHR makes a causal contribution to the pathogenesis of PAH, activating a focal inflammatory response in the lungs and promoting infiltration of immune cells from the bone marrow. Furthermore, we found that PAH patients with higher AHR agonistic activity in sera are more susceptible to severe clinical events than those with lower activity. Because conventional therapy for pulmonary hypertension targeting pulmonary artery vasodilation has limited efficacy against severe PAH, the AHR-signaling pathway represents a promising therapeutic target for PAH. In addition, AHR agonistic activity in serum represents a biomarker for PAH.
Clutch mechanism of chemomechanical coupling in a DNA resecting motor nuclease
Authors: Unciuleac Mihaela-Carmen , Meir Aviv , Xue Chaoyou , Warren Garrett M. , Greene Eric C. , Shuman Stewart
Published: March 2021

Significance

Multisubunit motor nucleases such as RecBCD, AddAB, and AdnAB recognize, unwind, and resect DSB ends during homologous recombination in bacteria. Guided by recent cryo-EM structures of AdnAB bound to a forked duplex DNA, we conducted a thorough mutational analysis of the interface of the AdnB motor domain with the 3′ ssDNA tracking strand and the ssDNA–dsDNA junction. We thereby identified the tracking strand DNA contacts that, when severed, either completely decouple ATP hydrolysis from mechanical work or else markedly lower the efficiency of the helicase motor and hence its velocity during DSB resection. An analogy is drawn between the mechanism of chemomechanical coupling in AdnAB and that of an automobile clutch friction plate.
Spatial tuning of electrophysiological responses to multisensory stimuli reveals a primitive coding of the body boundaries in newborns
Authors: Ronga Irene , Galigani Mattia , Bruno Valentina , Noel Jean-Paul , Gazzin Andrea , Perathoner Cristina , Serino Andrea , Garbarini Francesca
Published: March 2021

The ability to identify our own body and its boundaries is crucial for survival. Ideally, the sooner we learn to discriminate external stimuli occurring close to our body from those occurring far from it, the better (and safer) we may interact with the sensory environment. However, when this mechanism emerges within ontogeny is unknown. Is it something acquired throughout infancy, or is it already present soon after birth? The presence of a spatial modulation of multisensory integration (MSI) is considered a hallmark of a functioning representation of the body position in space. Here, we investigated whether MSI is present and spatially organized in 18- to 92-h-old newborns. We compared electrophysiological responses to tactile stimulation when concurrent auditory events were delivered close to, as opposed to far from, the body in healthy newborns and in a control group of adult participants. In accordance with previous studies, adult controls showed a clear spatial modulation of MSI, with greater superadditive responses for multisensory stimuli close to the body. In newborns, we demonstrated the presence of a genuine electrophysiological pattern of MSI, with older newborns showing a larger MSI effect. Importantly, as for adults, multisensory superadditive responses were modulated by the proximity to the body. This finding may represent the electrophysiological mechanism responsible for a primitive coding of bodily self boundaries, thus suggesting that even just a few hours after birth, human newborns identify their own body as a distinct entity from the environment.
Unveiling the “invisible” druggable conformations of GDP-bound inactive Ras
Authors: Liu Dan , Mao Yunyun , Gu Xue , Zhou Yang , Long Dong
Published: March 2021

Significance

Recent progress in targeting Ras, an oncoprotein involved in approximately 30% of all human cancers, has been made with the identification of covalent and noncovalent inhibitors binding to druggable pockets that are not observed in the inhibitor-free protein structures. To understand the nature of these cryptic sites and to facilitate rational drug discovery, we constructed a conformational ensemble of inactive Ras by exploiting the rich information on protein intrinsic dynamics provided by NMR experimental and computational approaches. Our results unveil the transiently sampled conformations bearing preformed druggable pockets and demonstrate the utility of the Ras•GDP ensemble for computer-aided drug design.
A 4,565-My-old andesite from an extinct chondritic protoplanet
Authors: Barrat Jean-Alix , Chaussidon Marc , Yamaguchi Akira , Beck Pierre , Villeneuve Johan , Byrne David J. , Broadley Michael W. , Marty Bernard
Published: March 2021

Significance

The crusts of the oldest protoplanets are virtually unknown due to the scarcity of samples. Here, we describe the oldest known lava that crystallized ca. 4,565 Ma ago and formed by partial melting of a chondritic parent body.
26
Al-
26
Mg systematics suggest that the elapsed time between melting and crystallization was significant, on the order of several 10
5
y, probably due to the viscosity of the magma. Although the first protoplanetary crusts were frequently not basaltic, their remains are not detected in the asteroid belt because their parent bodies served as the building blocks for larger rocky bodies or were nearly totally destroyed.