bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel multiscale scheme to accelerate atomistic simulations of bio-macromolecules by adaptively driving coarse-grained coordinates
Authors: Wu Kai , Xu Shun , Wan Biao , Xiu Peng , Zhou Xin
Published: March 2020

All-atom molecular dynamics (MD) simulations of bio-macromolecules can yield relatively accurate results while suffering from the limitation of insufficient conformational sampling. On the other hand, the coarse-grained (CG) MD simulations efficiently accelerate conformational changes in biomolecules but lose atomistic details and accuracy. Here, we propose a novel multiscale simulation method called the adaptively driving multiscale simulation (ADMS)—it efficiently accelerates biomolecular dynamics by adaptively driving virtual CG atoms on the fly while maintaining the atomistic details and focusing on important conformations of the original system with irrelevant conformations rarely sampled. Herein, the “adaptive driving” is based on the short-time-averaging response of the system (i.e., an approximate free energy surface of the original system), without requiring the construction of the CG force field. We apply the ADMS to two peptides (deca-alanine and Ace-GGPGGG-Nme) and one small protein (HP35) as illustrations. The simulations show that the ADMS not only efficiently captures important conformational states of biomolecules and drives fast interstate transitions but also yields, although it might be in part, reliable protein folding pathways. Remarkably, a ∼100-ns explicit-solvent ADMS trajectory of HP35 with three CG atoms realizes folding and unfolding repeatedly and captures the important states comparable to those from a 398-µs standard all-atom MD simulation.
Error modeling and analysis of optomechanical platform based on multi-system theory
Authors: Wang Dongxue , Li Zhanguo , Lin Jieqiong , Lu Mingming , Li Yingchun
Published: March 2020

The quality of camera imaging is of great significance in aerial photography and space target detection, especially in the fields of military reconnaissance and geographic resource telemetry. There are many factors that affect the imaging quality of a camera mounted on the ground. One such factor is the optomechanical platform, as well as other related factors such as system control accuracy and optomechanical platform processing accuracy, where the optical axis pointing error is especially important for measuring the accuracy of a camera’s optomechanical platform. In this paper, to study the influence of the optical axis pointing error on the accuracy of the optomechanical platform, error traceability of a self-developed complex optomechanical platform is established, and based on the multi-body system theory, the spatial geometric error model of the platform and the mapping relationship between the optical axis pointing error and the geometric errors of the optomechanical platform are established. By analyzing the optical axis pointing error model, the influence of vertical axis errors of the pitch axis, azimuth axis, and rotation axis of the optomechanical platform on its optical axis is found. The results show that with the influence of the azimuth axis perpendicularity error, the pointing error decreases as the pitch angle increases, with the influence of the pitch axis perpendicularity error, the pointing error increases as the pitch angle increases, and with the influence of the rotation axis perpendicularity error, in the case of a smaller rotation angle, the pointing error increases as the pitch angle increases.
Dynamical matrix propagator scheme for large-scale proton dynamics simulations
Authors: Dreßler Christian , Kabbe Gabriel , Brehm Martin , Sebastiani Daniel
Published: March 2020

We derive a matrix formalism for the simulation of long range proton dynamics for extended systems and timescales. On the basis of an ab initio molecular dynamics simulation, we construct a Markov chain, which allows us to store the entire proton dynamics in an M × M transition matrix (where M is the number of oxygen atoms). In this article, we start from common topology features of the hydrogen bond network of good proton conductors and utilize them as constituent constraints of our dynamic model. We present a thorough mathematical derivation of our approach and verify its uniqueness and correct asymptotic behavior. We propagate the proton distribution by means of transition matrices, which contain kinetic data from both ultra-short (sub-ps) and intermediate (ps) timescales. This concept allows us to keep the most relevant features from the microscopic level while effectively reaching larger time and length scales. We demonstrate the applicability of the transition matrices for the description of proton conduction trends in proton exchange membrane materials.
Complex eikonal methods applied to geodesic acoustic mode dynamics
Authors: Palermo F. , Poli E. , Bottino A.
Published: March 2020

Techniques developed in the domain of optical theory are applied to investigate the behavior of Geodesic Acoustic Modes (GAMs). In this context, we show that this approach represents a powerful basis for the description of many characteristics of radial propagation and spreading of GAMs. The most attractive feature of these techniques is represented by their universality and intuitive applicability. We present and apply two different complex-eikonal methods able to describe the spreading of GAMs in terms of local plane waves. The methods are “inhomogeneous wave tracking” and “paraxial WKB” theory. We demonstrate their applicability and efficacy to the GAM dynamics problem by means of a comparison with gyrokinetic simulations.
Ab initio relativistic potential energy surfaces of benzene–Xe complex with application to intermolecular vibrations
Authors: Shirkov Leonid , Sladek Vladimir , Makarewicz Jan
Published: March 2020

The benzene–Xe (BXe) complex in its electronic ground state is studied using ab initio methods. Since this complex contains the heavy Xe atom, the relativistic effects cannot be neglected. We test two different approaches that describe the scalar relativistic effects in the framework of the coupled-cluster level of theory with single, double, and perturbative triple excitations, used for the interaction energy calculations. The first one is based on the small core pseudopotential (PP), and the second one is based on the explicit treatment of scalar relativistic effects using the Douglas–Kroll–Hess (DKH) Hamiltonian. A few basis sets are tested with the PP and DKH, and for each one, the analytical potential energy surface (PES) is constructed. It is shown that the difference between PESs determined with PP and DKH methods is small, if the orbitals of the 4d subshell in Xe are correlated. We select the most appropriate approach for the calculation of the potential energy surface of BXe, with respect to accuracy and computational cost. The optimal level of theory includes a small Dunning’s basis set for the benzene monomer and a larger PP basis set for Xe supplemented by midbond functions. The PES obtained using such an approach provides a reasonable accuracy when compared to the empirical one derived from the microwave spectra of BXe. The empirical and the theoretical values of intermolecular vibrational energies agree within 0.5 cm−1 up to second overtones. The vibrational energy level pattern of BXe is characterized by a distinct polyad structure.
Single-particle imaging by x-ray free-electron lasers—How many snapshots are needed?
Authors: Poudyal I. , Schmidt M. , Schwander P.
Published: March 2020

X-ray free-electron lasers (XFELs) open the possibility of obtaining diffraction information from a single biological macromolecule. This is because XFELs can generate extremely intense x-ray pulses that are so short that diffraction data can be collected before the sample is destroyed. By collecting a sufficient number of single-particle diffraction patterns, the three-dimensional electron density of a molecule can be reconstructed ab initio. The quality of the reconstruction depends largely on the number of patterns collected at the experiment. This paper provides an estimate of the number of diffraction patterns required to reconstruct the electron density at a targeted spatial resolution. This estimate is verified by simulations for realistic x-ray fluences, repetition rates, and experimental conditions available at modern XFELs. Employing the bacterial phytochrome as a model system, we demonstrate that sub-nanometer resolution is within reach.
Accurate electron affinity of Ga and fine structures of its anions
Authors: Tang Rulin , Fu Xiaoxi , Lu Yuzhu , Ning Chuangang
Published: March 2020

We report the high-resolution photoelectron spectra of negative gallium anions obtained via the slow-electron velocity-map imaging method. The electron affinity of Ga is determined to be 2429.07(12) cm−1 or 0.301 166(14) eV. The fine structures of Ga are well resolved: 187.31(22) cm−1 or 23.223(27) meV for 3P1 and 502.70(28) cm−1 or 62.327(35) meV for 3P2 above the ground state 3P0, respectively. The photoelectron angular distribution for photodetachment from Ga−(4s24p2 3P0) to Ga(4s25s 2S1/2) is measured. An unexpected perpendicular distribution instead of an isotropic distribution is observed, which is due to a resonance near 3.3780 eV.
Proper orthogonal decomposition and recurrence map for the identification of spatial–temporal patterns in a low-Re wake downstream of two cylinders
Authors: Zhang Meihua , Zheng Zhongquan Charlie , Wu Huixuan
Published: March 2020

Flow decomposition methods provide systematic ways to extract the flow modes, which can be regarded as the spatial distribution of a coherent structure. They have been successfully used in the study of wake, boundary layer, and mixing. However, real flow structures also possess complex temporal patterns that can hardly be captured using the spatial modes obtained in the decomposition. In order to analyze the temporal variation of coherent structures in a complex flow field, this paper studies the recurrence in phase space to identify the pattern and classify the evolution of the flow modes. The recurrence pattern depends on the time delay and initial condition. In some cases, the flow system will revisit a previous state regardless of the initial state, and in other cases, the system’s recurrence will depend on the initial state. These patterns are determined by the arrangement and interactions of coherent structures in the flow. The temporal order of the repetition pattern reflects the possible ways of flow evolution.
Photolithographic method used to control the formation of DNA hydrogels
Authors: Mandel Savannah
Published: March 2020

Method of controlling the shape of DNA hydrogels at a micrometer scale using light irradiation doesn’t require radical polymerization.
Arrays of fiber laser sensors can detect and locate cracks in a material
Authors: Bandari Anashe
Published: March 2020

The multiplexed sensors use arrival times of signals to determine the source location of acoustic emissions caused by structural changes.
Threshold for horseshoe chaos in fractional-order hysteretic nonlinear suspension system of vehicle
Authors: Chang Yujian , Chen Enli , Xing Wuce , Li Shaohua , Wang Meiqi
Published: March 2020

The chaotic behavior of a nonlinear vehicle suspension system with a fractional-order derivative is considered. A hysteretic nonlinear model of vehicle suspension with a fractional-order derivative term is established and the analytically necessary condition for heterotopic chaos is derived based on the Melnikov method. The largest Lyapunov exponents are compared. Then, the necessary condition is numerically verified by various simulation factors. The possibility of chaotic motion in vehicles should be higher for larger amplitude of road excitation. It is found that the coefficient and order of the fractional differential term, the stiffness coefficient, and the damping coefficient of the system all affect the necessary condition, and analysis on the effects of these parameters is presented individually. It has been shown that the larger the coefficient of the fractional differential term, or the stiffness and damping coefficients of the system, the lower the possibility of chaos in the system. Meanwhile, without considering the fractional order, the integer order suspension model obviously reduces the actual area where chaos may occur, so designing suspensions according to the fractional order model can avoid chaos more accurately than the integer order model.
Culturally safe and sustainable solution for Closing the Gap-registered patients discharging from a tertiary public hospital
Authors: Mitchell Scott , Michael Hayley , Highden-Smith Stephanie , Bryce Vivian , Grugan Sean , Yong Hua Bing , Renouf Sonia , Kitchener Tanya , Wang William Y. S.
Published: March 2020

This case study describes the development, implementation and review of a sustainable and culturally sensitive procedure for a hospital-funded discharge medicine subsidy for Aboriginal and Torres Strait Islander patients registered with the Closing the Gap (CTG) program discharging from a public hospital. A 7-day fully subsidised medication supply was approved to be offered to Aboriginal and Torres Strait Islander patients admitted under cardiac care teams, including cardiology and cardiothoracic surgery patients. Patients were offered the option of a 7-day supply free of cost to them or a full Pharmaceutical Benefits Scheme (PBS) supply if preferred. A general practitioner (GP) appointment was organised within 7 days of discharge to ensure patients received ongoing supply of their medications as well as timely clinical review after discharge. Over a 34-month period from September 2015 to June 2018, 535 Aboriginal and Torres Strait Islander patients were admitted to the hospital under cardiac care teams. Of these patients, 296 received a subsidised discharge medication supply with a total cost of A$6314.56 to the hospital over the trial period, with a mean cost of A$21.26 per discharge. The provision of subsidised medications through the CTG program has improved the continuity of care for Aboriginal and Torres Strait Islander patients. The culturally sensitive approach is well received and has allowed smooth transition back to the community. This site-specific and state-based funding model was found to be financially sustainable at a public hospital.
What is known about the topic?The CTG PBS program is not applicable to discharge prescriptions from public hospitals. As such, patients are required to either leave the hospital with no medicines or leave the hospital with medicines for which they have to pay full PBS price. This creates a huge financial barrier to the care for CTG-registered patients in the acute care setting.
What does this paper add?A sustainable solution to the problem was found via a state-funded model while providing a supportive team to ensure GP follow-up and continuity of care after discharge.
What are the implications for practitioners?If similar approvals are granted and supported at other public hospital sites, practitioners will be afforded one less barrier to provide patient-centred care for Aboriginal and Torres Strait Islander patients.
Dissociable effects of visual crowding on the perception of color and motion
Authors: Greenwood John A. , Parsons Michael J.
Published: March 2020

Our ability to recognize objects in peripheral vision is fundamentally limited by crowding, the deleterious effect of clutter that disrupts the recognition of features ranging from orientation and color to motion and depth. Previous research is equivocal on whether this reflects a singular process that disrupts all features simultaneously or multiple processes that affect each independently. We examined crowding for motion and color, two features that allow a strong test of feature independence. “Cowhide” stimuli were presented 15° in peripheral vision, either in isolation or surrounded by flankers to give crowding. Observers reported either the target direction (clockwise/counterclockwise from upward) or its hue (blue/purple). We first established that both features show systematic crowded errors (biased predominantly toward the flanker identities) and selectivity for target–flanker similarity (with reduced crowding for dissimilar target/flanker elements). The multiplicity of crowding was then tested with observers identifying both features. Here, a singular object-selective mechanism predicts that when crowding is weak for one feature and strong for the other that crowding should be all-or-none for both. In contrast, when crowding was weak for color and strong for motion, errors were reduced for color but remained for motion, and vice versa with weak motion and strong color crowding. This double dissociation reveals that crowding disrupts certain combinations of visual features in a feature-specific manner, ruling out a singular object-selective mechanism. Thus, the ability to recognize one aspect of a cluttered scene, like color, offers no guarantees for the correct recognition of other aspects, like motion.
Bayesian inference of chromatin structure ensembles from population-averaged contact data
Authors: Carstens Simeon , Nilges Michael , Habeck Michael
Published: March 2020

Mounting experimental evidence suggests a role for the spatial organization of chromatin in crucial processes of the cell nucleus such as transcription regulation. Chromosome conformation capture techniques allow us to characterize chromatin structure by mapping contacts between chromosomal loci on a genome-wide scale. The most widespread modality is to measure contact frequencies averaged over a population of cells. Single-cell variants exist, but suffer from low contact numbers and have not yet gained the same resolution as population methods. While intriguing biological insights have already been garnered from ensemble-averaged data, information about three-dimensional (3D) genome organization in the underlying individual cells remains largely obscured because the contact maps show only an average over a huge population of cells. Moreover, computational methods for structure modeling of chromatin have mostly focused on fitting a single consensus structure, thereby ignoring any cell-to-cell variability in the model itself. Here, we propose a fully Bayesian method to infer ensembles of chromatin structures and to determine the optimal number of states in a principled, objective way. We illustrate our approach on simulated data and compute multistate models of chromatin from chromosome conformation capture carbon copy (5C) data. Comparison with independent data suggests that the inferred ensembles represent the underlying sample population faithfully. Harnessing the rich information contained in multistate models, we investigate cell-to-cell variability of chromatin organization into topologically associating domains, thus highlighting the ability of our approach to deliver insights into chromatin organization of great biological relevance.
Specific subfamilies of transposable elements contribute to different domains of T lymphocyte enhancers
Authors: Ye Mengliang , Goudot Christel , Hoyler Thomas , Lemoine Benjamin , Amigorena Sebastian , Zueva Elina
Published: March 2020

Transposable elements (TEs) compose nearly half of mammalian genomes and provide building blocks for
cis
-regulatory elements. Using high-throughput sequencing, we show that 84 TE subfamilies are overrepresented, and distributed in a lineage-specific fashion in core and boundary domains of CD8
+
T cell enhancers. Endogenous retroviruses are most significantly enriched in core domains with accessible chromatin, and bear recognition motifs for immune-related transcription factors. In contrast, short interspersed elements (SINEs) are preferentially overrepresented in nucleosome-containing boundaries. A substantial proportion of these SINEs harbor a high density of the enhancer-specific histone mark H3K4me1 and carry sequences that match enhancer boundary nucleotide composition. Motifs with regulatory features are better preserved within enhancer-enriched TE copies compared to their subfamily equivalents located in gene deserts. TE-rich and TE-poor enhancers associate with both shared and unique gene groups and are enriched in overlapping functions related to lymphocyte and leukocyte biology. The majority of T cell enhancers are shared with other immune lineages and are accessible in common hematopoietic progenitors. A higher proportion of immune tissue-specific enhancers are TE-rich compared to enhancers specific to other tissues, correlating with higher TE occurrence in immune gene-associated genomic regions. Our results suggest that during evolution, TEs abundant in these regions and carrying motifs potentially beneficial for enhancer architecture and immune functions were particularly frequently incorporated by evolving enhancers. Their putative selection and regulatory cooption may have accelerated the evolution of immune regulatory networks.
Kinetics of the conformational cycle of Hsp70 reveals the importance of the dynamic and heterogeneous nature of Hsp70 for its function
Authors: Wu Si , Hong Liu , Wang Yuqing , Yu Jieqiong , Yang Jie , Yang Jie , Zhang Hong , Perrett Sarah
Published: March 2020

Hsp70 is a conserved molecular chaperone that plays an indispensable role in regulating protein folding, translocation, and degradation. The conformational dynamics of Hsp70 and its regulation by cochaperones are vital to its function. Using bulk and single-molecule fluorescence resonance energy transfer (smFRET) techniques, we studied the interdomain conformational distribution of human stress-inducible Hsp70A1 and the kinetics of conformational changes induced by nucleotide and the Hsp40 cochaperone Hdj1. We found that the conformations between and within the nucleotide- and substrate-binding domains show heterogeneity. The conformational distribution in the ATP-bound state can be induced by Hdj1 to form an “ADP-like” undocked conformation, which is an ATPase-stimulated state. Kinetic measurements indicate that Hdj1 binds to monomeric Hsp70 as the first step, then induces undocking of the two domains and closing of the substrate-binding cleft. Dimeric Hdj1 then facilitates dimerization of Hsp70 and formation of a heterotetrameric Hsp70–Hsp40 complex. Our results provide a kinetic view of the conformational cycle of Hsp70 and reveal the importance of the dynamic nature of Hsp70 for its function.
Virion-incorporated PSGL-1 and CD43 inhibit both cell-free infection and transinfection of HIV-1 by preventing virus–cell binding
Authors: Murakami Tomoyuki , Carmona Nancy , Ono Akira
Published: March 2020

Significance

No host-encoded restriction factor identified thus far inhibits the first step of HIV-1 infection: virus–cell attachment. Here we demonstrate that virion-incorporated host transmembrane proteins PSGL-1 and CD43 inhibit attachment of HIV-1 particles to target cells. This inhibition of virus attachment occurs regardless of molecules mediating virus–cell binding and leads to inhibition of both cell-free infection and bystander cell-mediated transinfection. We also show that coclustering of HIV-1 structural protein Gag with PSGL-1 and subsequent progeny virion release contribute to depletion of PSGL-1 from an infected cell surface. Our study reveals an anti–HIV-1 mechanism in which virion-incorporated host transmembrane proteins block virus attachment. In addition, we report a previously unidentified role for Gag in viral down-regulation of antiviral proteins.
The impact of long-range dispersal on gene surfing
Authors: Paulose Jayson , Hallatschek Oskar
Published: March 2020

Significance

The expansion of a population into a new area occurs frequently in nature. Examples include epidemic outbreaks, invasions by nonnative species, and colonization of regions rendered hospitable by climate change. Many expansions are driven by long-range migration of organisms or seeds borne by air, water, or traveling hosts. These events amplify the impact of random chance on genetic variation: A lucky individual which reaches unoccupied territory first can have more descendants than subsequent arrivals, even without advantageous mutations. We model the patterns of variation generated by random long-range migration events and study their effects on genetic diversity. Our results elucidate the evolutionary consequences of long-range dispersal and are important for correctly interpreting sources of variation in geographically structured genomic data.
Nonuniform growth and surface friction determine bacterial biofilm morphology on soft substrates
Authors: Fei Chenyi , Mao Sheng , Yan Jing , Alert Ricard , Stone Howard A. , Bassler Bonnie L. , Wingreen Ned S. , Košmrlj Andrej
Published: March 2020

During development, organisms acquire three-dimensional (3D) shapes with important physiological consequences. While basic mechanisms underlying morphogenesis are known in eukaryotes, it is often difficult to manipulate them in vivo. To circumvent this issue, here we present a study of developingVibrio choleraebiofilms grown on agar substrates in which the spatiotemporal morphological patterns were altered by varying the agar concentration. Expanding biofilms are initially flat but later undergo a mechanical instability and become wrinkled. To gain mechanistic insights into this dynamic pattern-formation process, we developed a model that considers diffusion of nutrients and their uptake by bacteria, bacterial growth/biofilm matrix production, mechanical deformation of both the biofilm and the substrate, and the friction between them. Our model shows quantitative agreement with experimental measurements of biofilm expansion dynamics, and it accurately predicts two distinct spatiotemporal patterns observed in the experiments—the wrinkles initially appear either in the peripheral region and propagate inward (soft substrate/low friction) or in the central region and propagate outward (stiff substrate/high friction). Our results, which establish that nonuniform growth and friction are fundamental determinants of stress anisotropy and hence biofilm morphology, are broadly applicable to bacterial biofilms with similar morphologies and also provide insight into how other bacterial biofilms form distinct wrinkle patterns. We discuss the implications of forming undulated biofilm morphologies, which may enhance the availability of nutrients and signaling molecules and serve as a “bet hedging” strategy.
Turkish translations ofLolita
Authors: Denissova Nilüfer
Published: March 2020

This paper presents the results of research on translations of Nabokov’sLolitainto Turkish. Two of the translations were published under different names, but a closer look reveals that these target texts are identical, except for a difference in the character Lolita’s age; she is shown to be twelve in one translation and fourteen in the other. Apart from this, images of body and sex in the text are, to a certain degree, expurgated. Based on the data, I discuss the issues of authorship and (self) censorship in translation, as well as traditional cultural norms and the position of translator when she chooses to adapt to those norms or to question them.
Who wants to be a self-driving car?
Authors: Lee Joey , Groß Benedikt , Reimann Raphael
Published: March 2020

Self-driving cars and autonomous transportation systems are projected to create radical societal changes, yet public
understanding and trust of self-driving cars and autonomous systems is limited. The authors present a new mixed-reality experience designed
to provide its users with insights into the ways that self-driving cars operate. A single-person vehicle equipped with sensors provides its
users with data driven visual feedback in a virtual reality headset to navigate in physical space. The authors explore how immersive
experiences might provide ‘conceptual affordances’ that lower the entry barrier for diverse audiences to discuss complex topics.
Pragmatic evaluation of The BMJ’s visual abstracts
Authors: Stahl-Timmins Will , Black Jonathan , Simpson Paul
Published: March 2020

The British Medical Journal has recently started making visual abstracts to summarise published research studies. These 1024 × 1024 px images give a quick overview of a trial’s participants, design, and key findings. These visual abstracts are designed to help busy health professionals and researchers get a quick overview of newly published research. The present article describes simple pragmatic evaluations of these visual abstracts: analysis of social media stats and an opportunistic reader survey. Our goals were to identify how useful our readers found this new visual format, and whether there were any improvements we could make. The social media stats were initially very promising. Longer term performance over several visual abstracts, however, was not as strong, suggesting a possible halo effect provided by the novelty of a new presentation format. The survey proved to be a quick and valuable way of getting feedback on the design of the initial template, and resulted in several design adjustments.
Finding evidence for a changing society
Authors: Ratia Maura
Published: March 2020

This chapter examines, with the help of collocation analysis, how
patients were viewed in medical texts from 1500 to 1800. Previous studies have suggested
that this period witnessed considerable changes in society. The field of medicine also
underwent major developments during this time, but linguistic analyses have been
lacking. Two corpora were used in the study: the Corpus of Early Modern English
Medical Texts and the Corpus of Late Modern English Medical
Texts, together totaling over 4.2 million words. The results indicate a
development from the patient as an object of various treatments and cures in the early
modern period to patient as experiencer in the late modern period. The
growing importance of hospitals and public health in the latter era also emerges from
the results.
Analyzing change in the American English amplifier system in the fiction
genre
Authors: Schweinberger Martin
Published: March 2020

This study examines the diachronic development of amplification of
adjectives in American English (AmE), specifically in the fiction section of the
Corpus of Historical American English (COHA). The results show that
amplifier use in attributive contexts remains stable, while, in predicative contexts,
so has increased significantly since the 1980s and has replaced
very as the dominant amplifier. This development contrasts with
ongoing change in other regional varieties of English where really,
rather than so, has become the dominant amplifier of adjectives during
the latter half of the 20th century. The results show that so and
very are semantically highly similar and that the increase in
so is mostly based on its co-occurrence with
good.
Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid
Authors: Lehmann Guillermo L. , Hanke-Gogokhia Christin , Hu Yang , Bareja Rohan , Salfati Zelda , Ginsberg Michael , Nolan Daniel J. , Mendez-Huergo Santiago P. , Dalotto-Moreno Tomas , Wojcinski Alexandre , Ochoa Francisca , Zeng Shemin , Cerliani Juan P. , Panagis Lampros , Zager Patrick J. , Mullins Robert F. , Ogura Shuntaro , Lutty Gerard A. , Bang Jakyung , Zippin Jonathan H. , Romano Carmelo , Rabinovich Gabriel A. , Elemento Olivier , Joyner Alexandra L. , Rafii Shahin , Rodriguez-Boulan Enrique , Benedicto Ignacio
Published: March 2020

The activity and survival of retinal photoreceptors depend on support functions performed by the retinal pigment epithelium (RPE) and on oxygen and nutrients delivered by blood vessels in the underlying choroid. By combining single-cell and bulk RNA sequencing, we categorized mouse RPE/choroid cell types and characterized the tissue-specific transcriptomic features of choroidal endothelial cells. We found that choroidal endothelium adjacent to the RPE expresses high levels of Indian Hedgehog and identified its downstream target as stromal GLI1+ mesenchymal stem cell–like cells. In vivo genetic impairment of Hedgehog signaling induced significant loss of choroidal mast cells, as well as an altered inflammatory response and exacerbated visual function defects after retinal damage. Our studies reveal the cellular and molecular landscape of adult RPE/choroid and uncover a Hedgehog-regulated choroidal immunomodulatory signaling circuit. These results open new avenues for the study and treatment of retinal vascular diseases and choroid-related inflammatory blinding disorders.
Enhancing diastolic function by strain-dependent detachment of cardiac myosin crossbridges
Authors: Palmer Bradley M. , Swank Douglas M. , Miller Mark S. , Tanner Bertrand C.W. , Meyer Markus , LeWinter Martin M.
Published: March 2020

The force response of cardiac muscle undergoing a quick stretch is conventionally interpreted to represent stretching of attached myosin crossbridges (phase 1) and detachment of these stretched crossbridges at an exponential rate (phase 2), followed by crossbridges reattaching in increased numbers due to an enhanced activation of the thin filament (phases 3 and 4). We propose that, at least in mammalian cardiac muscle, phase 2 instead represents an enhanced detachment rate of myosin crossbridges due to stretch, phase 3 represents the reattachment of those same crossbridges, and phase 4 is a passive-like viscoelastic response with power-law relaxation. To test this idea, we developed a two-state model of crossbridge attachment and detachment. Unitary force was assigned when a crossbridge was attached, and an elastic force was generated when an attached crossbridge was displaced. Attachment rate, f(x), was spatially distributed with a total magnitude f0. Detachment rate was modeled as g(x) = g0+ g1x, where g0 is a constant and g1 indicates sensitivity to displacement. The analytical solution suggested that the exponential decay rate of phase 2 represents (f0 + g0) and the exponential rise rate of phase 3 represents g0. The depth of the nadir between phases 2 and 3 is proportional to g1. We prepared skinned mouse myocardium and applied a 1% stretch under varying concentrations of inorganic phosphate (Pi). The resulting force responses fitted the analytical solution well. The interpretations of phases 2 and 3 were consistent with lower f0 and higher g0 with increasing Pi. This novel scheme of interpreting the force response to a quick stretch does not require enhanced thin-filament activation and suggests that the myosin detachment rate is sensitive to stretch. Furthermore, the enhanced detachment rate is likely not due to the typical detachment mechanism following MgATP binding, but rather before MgADP release, and may involve reversal of the myosin power stroke.
New developments in the simulation of Rutherford backscattering spectrometry in channeling mode using arbitrary atom structures
Authors: Jin Xin , Crocombette Jean-Paul , Djurabekova Flyura , Zhang Shuo , Nordlund Kai , Garrido Frédérico , Debelle Aurélien
Published: March 2020

As Rutherford backscattering spectrometry in channeling mode (RBS/C) is an efficient technique for characterizing crystallographic defects, its computational simulation has drawn attention over the past several decades. Recently, a RBS/C simulation code based on the binary collision approximation called Rutherford backscattering simulation in arbitrary defective crystals has been suggested and successfully applied to predict the RBS/C spectra from different damaged materials, whose structures were generated in high-dose ion irradiation atomistic simulations. In the present paper, we introduce new developments improving the flexibility of the developed software and its applicability to different types of materials. More precisely, we modified the algorithm describing the slowdown process of backscattered ions, added fitting parameters in the collision partner search routine, modified the routine taking into account target atom thermal vibrations and provided new descriptions of the ion beam divergence. As an example, the effect of the modifications on simulated RBS/C spectra is shown for an 〈011〉-oriented UO2 crystal analyzed with a 3.085 MeV He2+ ion beam. Some of these changes proved necessary to achieve satisfying agreement between simulations and experimental data. Similar observation was made for 〈001〉-oriented Si and 〈001〉-oriented GaAs crystals analyzed with a 1.4 MeV He+ ion beam. In these simulations, the modifications have also resulted in good agreement with experiment.
Blow-up profiles in quasilinear fully parabolic Keller–Segel systems
Authors: Fuest Mario
Published: March 2020

We examine finite-time blow-up solutions

to

in a ball

,

, where D and S generalize the functions

with

. We show that if

as well as

and

is a nonnegative, radially symmetric classical solution to (

) blowing up at

, then there exists a so-called blow-up profile

satisfying

Moreover, for all

with

we can find

such that

for all

.
Dynamics and topology of non-Hermitian elastic lattices with non-local feedback control interactions
Authors: Rosa Matheus I N , Ruzzene Massimo
Published: March 2020

We investigate non-Hermitian elastic lattices characterized by non-local feedback interactions. In one-dimensional lattices, proportional feedback produces non-reciprocity associated with complex dispersion relations characterized by gain and loss in opposite propagation directions. For non-local controls, such non-reciprocity occurs over multiple frequency bands characterized by opposite non-reciprocal behavior. The dispersion topology is investigated with focus on winding numbers and non-Hermitian skin effect, which manifests itself through bulk modes localized at the boundaries of finite lattices. In two-dimensional lattices, non-reciprocity is associated with directional wave amplification. Moreover, the combination of skin effect in two directions produces modes that are localized at the corners of finite two-dimensional lattices. Our results describe fundamental properties of non-Hermitian elastic lattices, and suggest new possibilities for the design of meta materials with novel functionalities related to selective wave filtering, amplification and localization. The considered non-local lattices also provide a platform for the investigation of topological phases of non-Hermitian systems.
Small-signal modeling and parameter extraction method for a multigate GaAs pHEMT switch
Authors: Luo Lin , Liu Jun , Wang Guofang , Wu Yuxing
Published: March 2020

This paper presents an accurate small-signal model for multi-gate GaAs pHEMTs in switching-mode. The extraction method for the proposed model is developed. A 2-gate switch structure is fabricated on a commercial 0.5 μm AlGaAs/GaAs pHEMT technology to verify the proposed model. Excellent agreement has been obtained between the measured and simulated results over a wide frequency range.
High performance GaN-based hybrid white micro-LEDs integrated with quantum-dots
Authors: Xu Feifan , Cen Xu , Liu Bin , Wang Danbei , Tao Tao , Zhi Ting , Wang Qi , Xie Zili , Zhou Yugang , Zheng Youdou , Zhang Rong
Published: March 2020

Hybrid white micro-pillar structure light emitting diodes (LEDs) have been manufacture utilizing blue micro-LEDs arrays integrated with 580 nm CIS ((CuInS2-ZnS)/ZnS) core/shell quantum dots. The fabricated hybrid white micro-LEDs have good electrical properties, which are manifested in relatively low turn-on voltage and reverse leakage current. High-quality hybrid white light emission has been demonstrated by the hybrid white micro-LEDs after a systemic optimization, in which the corresponding color coordinates are calculated to be (0.3303, 0.3501) and the calculated color temperature is 5596 K. This result indicates an effective way to achieve high-performance white LEDs and shows great promise in a large range of applications in the future including micro-displays, bioinstrumentation and visible light communication.
35 km amplifier-less four-level pulse amplitude modulation signals enabled by a 23 GHz ultrabroadband directly modulated laser
Authors: Xiao Yaoping , Liu Yu , Zhang Yiming , Bao Haotian , Zhu Ninghua
Published: March 2020

The 4-level pulse amplitude modulation (PAM4) based on an 23 GHz ultrabroadband directly modulated laser (DML) was proposed. We have experimentally demonstrated that based on intensity modulation and direct detection (IMDD) 56 Gbps per wavelength PAM4 signals transferred over 35 km standard single mode fiber (SSMF) without any optical amplification and we have achieved the bit error rate (BER) of the PAM4 transmission was under 2.9 × 10−4 by using feed forward equalization (FFE).
Warmer climate projections in EC-Earth3-Veg: the role of changes in the greenhouse gas concentrations from CMIP5 to CMIP6
Authors: Wyser Klaus , Kjellström Erik , Koenigk Torben , Martins Helena , Döscher Ralf
Published: March 2020

Climate projections for the 21st century for CMIP6 are warmer than those for CMIP5 despite nominally identical instantaneous radiative forcing. Many climate modeling groups attribute the stronger warming in the CMIP6 projections to the higher climate sensitivity of the new generation of climate models, but here we demonstrate that also changes in the forcing datasets can play an important role, in particular the prescribed concentrations of greenhouse gases (GHG) that are used to force the models. In the EC-Earth3-Veg model the effective radiative forcing (ERF) is reduced by 1.4 W m−2 when the GHG concentrations from SSP5-8.5 (used in CMIP6) are replaced by the GHG concentrations from RCP8.5 (used in CMIP5), and similar yet smaller reductions are seen for the SSP2-4.5/RCP4.5 and SSP1-2.6/RCP2.6 scenario pairs. From the reduced ERF we can estimate the temperature at the end of the century in a full climate simulation with the CMIP6 version of the EC-Earth model but using CMIP5 GHG concentrations instead. For the new SSP5-8.5 and SSP2-4.5 scenarios we find that 50% or more of the temperature increase from CMIP5 to CMIP6 at the end of the century is due to changes in the prescribed GHG concentrations. The implication is that CMIP5 and CMIP6 projections for the 21st century are difficult to compare with each other not only as models differ but also as the forcing conditions are not equal. Therefore, the communication of CMIP6 results to the impact, mitigation and adaptation communities has to be carefully formulated, taking into account the role of the updated GHG concentrations when interpreting the warmer climate projections for the 21st century.
Facile transdermal delivery of upconversion nanoparticle by iontophoresis-responsive magneto-upconversion oleogel
Authors: Dhal Soumyashree , Gavara Roja Ramani , Pal Kunal , Banerjee Indranil , Mishra Monalisa , Giri Supratim
Published: March 2020

The effective application of upconversion nanoparticle (UCNP) as a photo-medicine in skin cancers critically depends on a facile transdermal delivery process through topical route. Herein, combining two non-invasive techniques, i.e. skin permeation enhancement and alternating current (AC) induced iontophoresis, we report a controlled transdermal delivery of UCNP with a time advantage. We have synthesized a series of soybean oil-based oleogels termed as magneto-upconversion (MU) gels by incorporating a fixed amount of UCNP and different proportions of magnetic nanoparticle (MNP) using stearic acid-based gelator as a skin permeation enhancing agent. The microstructures of the synthesized MU gels were characterized by microscopy, X-Ray diffraction and vibrational spectroscopy. A detailed analysis of the electrical properties revealed a gradual increase in the electrical conductance in the MU gel series with increasing proportion of MNP. Such trend of conductance imparted proportional iontophoretic response within the respective MU gels, validated through the release of ciprofloxacin hydrochloride as a model drug preloaded within the oleogels. Through a series of skin permeation experiment using pig ear skin as animal model, we established that the UCNP was able to permeate the whole thickness of the skin within as little as 3 h, only when the two conditions, i.e. the presence of skin permeation enhancer and iontophoresis were met. Within the same time, UCNP permeation was enhanced by the presence of MNP in the MU gels upto 2 folds. Our study developed a rational method for the transdermal delivery of any electrically non-conducting nanoparticle in a faster and tunable way.
Effects of an intervention to reduce fear of falling and increase physical activity during hip and pelvic fracture rehabilitation
Authors: Pfeiffer Klaus , Kampe Karin , Klenk Jochen , Rapp Kilian , Kohler Michaela , Albrecht Diana , Büchele Gisela , Hautzinger Martin , Taraldsen Kristin , Becker Clemens
Published: March 2020

Background

fear of falling and reduced fall-related self-efficacy are frequent consequences of falls and associated with poorer rehabilitation outcomes. To address these psychological consequences, geriatric inpatient rehabilitation was augmented with a cognitive behavioural intervention (“Step by Step”) and evaluated in a RCT.

Methods

one hundred fifteen hip and pelvic fracture patients (age = 82.5 years, 70% female) admitted to geriatric inpatient rehabilitation were randomly allocated to the intervention or control group. The intervention consisted of eight additional individual sessions during inpatient rehabilitation, one home visit and four telephone calls delivered over 2 months after discharge. Both groups received geriatric inpatient rehabilitation. Primary outcomes were fall-related self-efficacy (short falls efficacy scale-international) and physical activity as measured by daily walking duration (activPAL3™ sensor) after admission to rehabilitation, before discharge and 1-month post-intervention.

Results

in covariance analyses, patients in the intervention group showed a significant improvement in fall-related self-efficacy (P = 0.025, d = −0.42), but no difference in total daily walking duration (P = 0.688, d = 0.07) 1-month post-intervention compared to the control condition. Further significant effects in favour of the intervention group were found in the secondary outcomes “perceived ability to manage falls” (P = 0.031, d = 0.41), “physical performance” (short physical performance battery) (P = 0.002, d = 0.58) and a lower “number of falls” (P = 0.029, d = −0.45).

Conclusions

the intervention improved psychological and physical performance measures but did not increase daily walking duration. For the inpatient part of the intervention further research on the required minimum intensity needed to be effective is of interest. Duration and components used to improve physical activity after discharge should be reconsidered.
Mediation of Firearm Violence and Preterm Birth by Pregnancy Complications and Health Behaviors: Addressing Structural and Postexposure Confounding
Authors: Goin Dana E , Rudolph Kara E , Gomez Anu Manchikanti , Ahern Jennifer
Published: March 2020

Firearm violence may indirectly affect health among pregnant women living in neighborhoods where it is endemic. We used birth, death, emergency department, and hospitalization data from California from 2007–2011 to estimate the association between living in a neighborhood with high firearm violence and preterm delivery, and assessed whether there was mediation by diagnoses of pregnancy complications and health behaviors during pregnancy. We used an ensemble machine learning algorithm to predict the propensity for neighborhoods to be classified as having a high level of firearm violence. Risk differences for the total effect and stochastic direct and indirect effects were estimated using targeted maximum likelihood. Residence in high-violence neighborhoods was associated with higher prevalence of preterm birth (risk difference (RD) = 0.46, 95% confidence interval (CI): 0.13, 0.80), infections (RD = 1.34, 95% CI: −0.17, 2.86), asthma (RD = 0.76, 95% CI: 0.03, 1.48), and substance use (RD = 0.74, 95% CI: 0.00, 1.47). The largest indirect effects for the association between violence and preterm birth were observed for infection (stochastic indirect effect = 0.04, 95% CI: 0.00, 0.08) and substance use (stochastic indirect effect = 0.04, 95% CI: 0.01, 0.06). Firearm violence was associated with risk of preterm delivery, and this association was partially mediated by infection and substance use.