bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional interplay among thiol-based redox signaling, metabolism, and ferroptosis unveiled by a genetic variant of
TP53
Authors: Leu Julia I-Ju , Murphy Maureen E. , George Donna L.
Published: October 2020

Significance

Thiol-mediated protein cysteine modifications represent important, but often overlooked, physiologic regulatory determinants. We previously reported that the codon 47 variants of
TP53
associate with differences in the intracellular abundance of low molecular weight (LMW) thiol metabolites, directly promoting enhanced resistance to the oxidative death process of ferroptosis in S47 cells. We now report that these polymorphic variants also associate with distinct metabolic profiles, including the redox-mediated, reversible reprogramming of glycolytic metabolism. The observed metabolic differences are mechanistically linked to changes in the activities of key physiologic regulatory proteins, including ATF4, GAPDH, and G6PD. The results support LMW thiol abundance as a critical factor in the regulation of adaptive, coordinated, metabolic signaling networks and oxidative stress response pathways.
Plasmonic probing of the adhesion strength of single microbial cells
Authors: Liu Yi-Nan , Lv Zhen-Ting , Lv Wen-Li , Liu Xian-Wei
Published: October 2020

Significance

Studying interfacial dynamics of a single biological entity (cell, virus, or organelle) is critical for understanding microbial biofilm formation processes, developing biosensors, and designing biomaterials. However, the ability to measure the binding force between a single biological entity and surface remains a great challenge due to the hydrated feature of biological entity. In this paper, we present an optical imaging method that is able to measure the adhesion strength of single microbial cells. Unlike the existing methods with limited throughput, this method determines the adhesion strength of multiple individual cells simultaneously. This approach has the potential to contribute to a better understanding of the adhesion process at the microscopic scale and probe the biointerfaces.
Photon-level broadband spectroscopy and interferometry with two frequency combs
Authors: Picqué Nathalie , Hänsch Theodor W.
Published: October 2020

Significance

Dual-comb spectroscopy has emerged a powerful technique of Fourier transform spectroscopy without moving parts. Broad spectra can be acquired with a single photodetector in any spectral range where laser frequency combs are available. Because the technique is multiplex, systematic effects are minimized and a great consistency of the spectra can be achieved. We show that dual-comb spectroscopy can be implemented with photon-counting instrumentation and work at power levels one-billion-fold weaker than those usually employed. Our demonstration opens many scenarios for applications of this powerful spectroscopic technique.
Classifying heuristic textual practices in academic discourse
Authors: Becker Maria , Bender Michael , Müller Marcus
Published: October 2020

In this paper, we investigate how deep learning techniques can be applied to discourse pragmatics. As a testcase we analyse heuristic textual practices, defined as linguistic implementations of decision routines in research processes in academic discourse. We develop a complex annotation scheme of pragmalinguistic categories on different levels of granularity and manually annotate a corpus of texts across various scientific disciplines. This is the basis for training recurrent neural networks to classify heuristic textual practices. Our experiments show that the annotation categories are robust enough to be recognised by our models which learn similarities of the sentence-surfaces represented as word embeddings. Our study aims at an iterative human-in-the-loop process in which manual-hermeneutic and algorithmic procedures mutually advance the insight process. It underlines the fact that the interaction between manual and automated methods opens up a promising field for further research, allowing interpretative analyses of complex pragmatic phenomena in large corpora.
National construction and popular erasure in Colombia
Authors: Lobo Gregory Joseph
Published: October 2020

This article analyses the diachronic symbolic struggle (1810–1991) waged in Colombia’s foundational documents over the
legitimation and delegitimation of social relations through the concepts “people” and “nation.” Following the introduction, the method and
theory are explained: concept analysis and language-based social ontology. The analysis of the foundational documents follows. These are
analysed as extended status function declarations that attempt to legitimate and delegitimate the concepts “people” and “nation”, in order
to authorize/deauthorize possible social relations. On the basis of the analysis, the conclusion briefly specifies the discourse of
nationism as the ontologisation and wielding of the idea of the nation against internal dissent/opposition, and points up the fundamental
importance of symbolic practice in the struggle to change social reality.
“Neur”al brain wave: Coordinating epithelial-to-neural stem cell transition in the fly optic lobe
Authors: Ambrosini Arnaud , Röper Katja
Published: October 2020

In the Drosophila larval optic lobe, the generation of neural stem cells involves an epithelial-to-mesenchymal–like transition of a continuous stripe of cells that sweeps across the neuroepithelium, but the dynamics at cell and tissue level were unknown until now. In this issue, Shard et al. (2020. J. Cell Biol.https://doi.org/10.1083/jcb.202005035) identify that Neuralized controls a partial epithelial-to-mesenchymal transition through regulation of the apical Crumbs complex and through the coordination of cell behaviors such as apical constriction and cell alignment.
Active Learning Approach to Optimization of Experimental Control*
Authors: Wu Yadong , Meng Zengming , Wen Kai , Mi Chengdong , Zhang Jing , Zhai Hui
Published: October 2020

We present a general machine learning based scheme to optimize experimental control. The method utilizes the neural network to learn the relation between the control parameters and the control goal, with which the optimal control parameters can be obtained. The main challenge of this approach is that the labeled data obtained from experiments are not abundant. The central idea of our scheme is to use the active learning to overcome this difficulty. As a demonstration example, we apply our method to control evaporative cooling experiments in cold atoms. We have first tested our method with simulated data and then applied our method to real experiments. It is demonstrated that our method can successfully reach the best performance within hundreds of experimental runs. Our method does not require knowledge of the experimental system as a prior and is universal for experimental control in different systems.
Coupling Stacking Orders with Interlayer Magnetism in Bilayer H-VSe2*
Authors: Li Aolin , Zhou Wenzhe , Pan Jiangling , Xia Qinglin , Long Mengqiu , Ouyang Fangping
Published: October 2020

Stacking-dependent magnetism in van der Waals materials has caught intense interests. Based on the first principle calculations, we investigate the coupling between stacking orders and interlayer magnetic orders in bilayer H-VSe2. It is found that there are two stable stacking orders in bilayer H-VSe2, named AB-stacking and A′B-stacking. Under standard DFT framework, the A′B-stacking prefers the interlayer AFM order and is semiconductive, whereas the AB-stacking prefers the FM order and is metallic. However, under the DFT+U framework both the stacking orders prefer the interlayer AFM order and are semiconductive. By detailedly analyzing this difference, we find that the interlayer magnetism originates from the competition between antiferromagnetic interlayer super-superexchange and ferromagnetic interlayer double exchange, in which both the interlayer Se-4pz
orbitals play a crucial role. In the DFT+U calculations, the double exchange is suppressed due to the opened bandgap, such that the interlayer magnetic orders are decoupled with the stacking orders. Based on this competition mechanism, we propose that a moderate hole doping can significantly enhance the interlayer double exchange, and can be used to switch the interlayer magnetic orders in bilayer VSe2. This method is also applicable to a wide range of semiconductive van der Waals magnets.
Superconductivity of Lanthanum Superhydride Investigated Using the Standard Four-Probe Configuration under High Pressures*
Authors: Hong Fang , Yang Liuxiang , Shan Pengfei , Yang Pengtao , Liu Ziyi , Sun Jianping , Yin Yunyu , Yu Xiaohui , Cheng Jinguang , Zhao Zhongxian
Published: October 2020

Recently, the theoretically predicted lanthanum superhydride, LaH10 ± δ
, with a clathrate-like structure was successfully synthesized and found to exhibit a record high superconducting transition temperature T
c ≈ 250 K at ∼ 170 GPa, opening a new route for room-temperature superconductivity. However, since in situ experiments at megabar pressures are very challenging, few groups have reported the ∼ 250 K superconducting transition in LaH10 ± δ
. Here, we establish a simpler sample-loading procedure that allows a relatively large sample size for synthesis and a standard four-probe configuration for resistance measurements. Following this procedure, we successfully synthesized LaH10 ± δ
with dimensions up to 10 × 20 μm2 by laser heating a thin La flake and ammonia borane at ∼ 1700 K in a symmetric diamond anvil cell under the pressure of 165 GPa. The superconducting transition at T
c ≈ 250 K was confirmed through resistance measurements under various magnetic fields. Our method will facilitate explorations of near-room-temperature superconductors among metal superhydrides.
Antimony Selenide Thin Film Solar Cells with an Electron Transport Layer of Alq3*
Authors: Shi Wen-Jian , Kan Ze-Ming , Cheng Chuan-Hui , Li Wen-Hui , Song Hang-Qi , Li Meng , Yu Dong-Qi , Du Xiu-Yun , Liu Wei-Feng , Jin Sheng-Ye , Cong Shu-Lin
Published: October 2020

We fabricated Sb2Se3 thin film solar cells using tris(8-hydroxy-quinolinato) aluminum (Alq3) as an electron transport layer by vacuum thermal evaporation. Another small organic molecule of N,N’-bis(naphthalen-1-yl)-N,N’-bis(phenyl)benzidine (NPB) was used as a hole transport layer. We took ITO/NPB/Sb2Se3/Alq3/Al as the device architecture. An open circuit voltage (V
oc) of 0.37 V, a short circuit current density (J
sc) of 21.2 mA/cm2, and a power conversion efficiency (PCE) of 3.79% were obtained on an optimized device. A maximum external quantum efficiency of 73% was achieved at 600 nm. The J
sc, V
oc, and PCE were dramatically enhanced after introducing an electron transport layer of Alq3. The results suggest that the interface state density at Sb2Se3/Al interface is decreased by inserting an Alq3 layer, and the charge recombination loss in the device is suppressed. This work provides a new electron transport material for Sb2Se3 thin film solar cells.
Interacting chiral electrons at the 2D Dirac points: a review
Authors: Hirata Michihiro , Kobayashi Akito , Berthier Claude , Kanoda Kazushi
Published: October 2020

The pseudo-relativistic chiral electrons in 2D graphene and 3D topological semimetals, known as the massless Dirac or Weyl fermions, constitute various intriguing issues in modern condensed-matter physics. In particular, the issues linked to the Coulomb interaction between the chiral electrons attract great attentions due to their unusual features, namely, the interaction is not screened and has a long-ranged property near the charge-neutrality point, in clear contrast to its screened and short-ranged properties in the conventional correlated materials. In graphene, this long-range interaction induces an anomalous logarithmic renormalization of the Fermi velocity, which causes a nonlinear reshaping of its Dirac cone. In addition, for strong interactions, it even leads to the predictions of an excitonic condensation with a spontaneous mass generation. The interaction, however, would seem to be not that large in graphene, so that the latter phenomenon appears to have not yet been observed. Contrastingly, the interaction is probably large in the pressurized organic material α-(BEDT-TTF)2I3, where a 2D massless-Dirac-fermion phase emerges next to a correlated insulating phase. Therefore, an excellent testing ground would appear in this material for the studies of both the velocity renormalization and the mass generation, as well as for those of the short-range electronic correlations. In this review, we give an overview of the recent progress on the understanding of such interacting chiral electrons in 2D, by placing particular emphasis on the studies in graphene and α-(BEDT-TTF)2I3. In the first half, we briefly summarize our current experimental and theoretical knowledge about the interaction effects in graphene, then turn attentions to the understanding in α-(BEDT-TTF)2I3, and highlight its relevance to and difference from graphene. The second half of this review focusses on the studies linked to the nuclear magnetic resonance experiments and the associated model calculations in α-(BEDT-TTF)2I3. These studies allow us to discuss the anisotropic reshaping of a tilted Dirac cone together with various electronic correlations, and the precursor excitonic dynamics growing prior to a condensation. We see these provide unique opportunities to resolve the momentum dependence of the spin excitations and fluctuations that are strongly influenced by the long-range interaction near the Dirac points.
Comparing nonlinear optomechanical coupling in membrane-in-the-middle and single-cavity systems
Authors: Burgwal Roel , Pino Javier del , Verhagen Ewold
Published: October 2020

In cavity optomechanics, nonlinear interactions between an optical field and a mechanical resonator mode enable a variety of unique effects in classical and quantum measurement and information processing. Here, we describe nonlinear optomechanical coupling in the membrane-in-the-middle (MIM) system in a way that allows direct comparison to the intrinsic optomechanical nonlinearity in a standard, single-cavity optomechanical system. We find that the enhancement of nonlinear optomechanical coupling in the MIM system as predicted by Ludwig et al (2012 Phys. Rev. Lett. 109 063601) is limited to the degree of sideband resolution of the system. Moreover, we show that the selectivity of the MIM system of nonlinear over linear transduction has the same limit as in a single cavity system. These findings put constraints on the experiments in which it is advantageous to use an MIM system. We discuss dynamical backaction effects in this system and find that these effects per cavity photon are exactly as strong as in a single cavity system, while allowing for reduction of the required input power. We propose using the nonlinear enhancement and reduced input power in realistic MIM systems towards parametric squeezing and heralding of phonon pairs, and evaluate the limits to the magnitude of both effects.
Ground-state cooling based on a three-cavity optomechanical system in the unresolved-sideband regime*
Authors: Wang Jing
Published: October 2020

In the unresolved sideband regime, we propose a scheme for cooling mechanical resonator close to its ground state in a three-cavity optomechanical system, where the auxiliary cavities are indirectly connected with the mechanical resonator through standard optomechanical subsystem. The standard optomechanical subsystem is driven by a strong pump laser field. With the help of the auxiliary cavities, the heating process is suppressed and the cooling process of the mechanical resonator is enhanced. More importantly, the average phonon number is much less than 1 in a larger range. This means that the mechanical resonator can be cooled down to its ground state. All these interesting features will significantly promote the physical realization of quantum effects in multi-cavity optomechanical systems.
Beta-band modulation in the human hippocampus during a conflict response task
Authors: Chen Kuang-Hsuan , Gogia Angad S , Tang Austin M , Del Campo-Vera Roberto Martin , Sebastian Rinu , Nune George , Wong Janeline , Liu Charles Y , Kellis Spencer , Lee Brian
Published: October 2020

Objective. Identify the role of beta-band (13–30 Hz) power modulation in the human hippocampus during conflict processing. Approach. We investigated changes in the spectral power of the beta band (13–30 Hz) as measured by depth electrode leads in the hippocampus during a modified Stroop task in six patients with medically refractory epilepsy. Previous work done with direct electrophysiological recordings in humans has shown hippocampal theta-band (3–8 Hz) modulation during conflict processing. Local field potentials sampled at 2 k Hz were used for analysis and a non-parametric cluster-permutation t-test was used to identify the time period and frequency ranges of significant power change during cue processing (i.e. post-stimulus, pre-response). Main results. In five of the six patients, we observe a statistically significant increase in hippocampal beta-band power during successful conflict processing in the incongruent trial condition (cluster-based correction for multiple comparisons, p < 0.05). There was no significant beta-band power change observed during the cue-processing period of the congruent condition in the hippocampus of these patients. Significance. The beta-power changes during conflict processing represented here are consistent with previous studies suggesting that the hippocampus plays a role in conflict processing, but it is the first time that the beta band has been shown to be involved in humans with direct electrophysiological evidence. We propose that beta-band modulation plays a role in successful conflict detection and automatic response inhibition in the human hippocampus as studied during a conflict response task.
Assessment of ITER divertor performance during early operation phases
Authors: Park Jae-Sun , Bonnin Xavier , Pitts Richard
Published: October 2020

During the ITER design phase, the focus of ITER boundary plasma modeling activities has been on divertor performance under baseline H-mode, fusion power operation (FPO) conditions. However, early ITER operation will be primarily with hydrogen fuel in L-mode, in the pre-fusion power operation 1 (PFPO-1) phase. Here, the SOLPS-ITER code is used to evaluate divertor performance during this non-active phase. To verify the assumptions used in the existing high power simulation database, gas throughput scans were performed for two types of divertor surface material (beryllium and tungsten) and two gas puff locations (divertor and main chamber). The adoption of beryllium target surfaces simulates the effect of main chamber material erosion and migration and, along with main chamber gas injection, is the current default for the high power database. Depending on the divertor surface material, the atom to molecule ratio of the recycled neutral particles varies. This modifies the momentum and power loss mechanisms arising from plasma–neutral interactions. However, since the effect of atomic and molecular reactions are compensatory, the ‘total’ power and momentum losses are relatively insensitive to the target surface material. Similarly, the impact of gas puff location on divertor plasma parameters is not significant, though main chamber injection provides an additional ionization source in the upstream scrape-off layer (SOL) and leads to moderate changes in the upstream density and far SOL parameters. However, these effects can be neglected within the available range of the gas puff and pump rates in ITER. Since beryllium and tungsten are materials at both extremes in terms of surface reflection properties, the conclusions may be applicable to other divertor surface materials. An important additional finding of the study is that the insensitivity of upstream density to divertor neutral pressure found in the FPO database is also recovered in these PFPO-1 simulations.
Preface
Authors: Gibson Brad K. , Kulikov Igor , Chernykh Igor
Published: October 2020

The fields of magnetohydrodynamics (MHD) and plasma physics might appear esoteric at first glance, but dig a little deeper, and one realizes that many of the most fundamental challenges facing mankind are underpinned by these processes. Examples range from the design of controlled thermonuclear fusion reactors as an ecologically-friendly approach to renewable energy, to tornado and vortex generation from a climate science perspective, and all the way to understanding the origin of the chemical elements within the hearts of dying stars. The breadth of these applications, the algorithm development required to model such processes, and the associated Big Data analysis tools, are inexorably linked and contribute to the philosophy of this year’s MHD and Plasma Physics Workshop. Our goal in organizing the 3rd in this series of Workshops has been to provide opportunities for these apparently disparate communities to both highlight their recent developments and discuss the future of algorithm co-design optimized for accuracy, scalability, and efficiency. This year, we have all worked and lived with the daily threat of Covid19; the need for social distancing and relative isolation has impacted upon the familiar and fundamental nature of conferences. Regardless, such interactions are the lifeblood of our respective communities, and so we made the decision to proceed with the Workshop, bring participants together from around the world through a digital platform.
Direct fluid flow simulation at pore scale with regularized hydrodynamic equations
Authors: Vladislav Balashov , Evgeny Savenkov
Published: October 2020

Laboratory analysis of rock samples (core material) is one of the main tools used in an analysis of oil and gas field development and methods to enhance oil recovery. A number of drawbacks are intrinsic to the laboratory techniques, among which we note the practical impossibility of carrying out parametric studies on one sample, the impossibility (and / or high cost) of taking into account reservoir conditions, and the impossibility of analyzing non-cemented rocks (sludge). With the development of computational capabilities and computed tomography methods, the “digital rock physics” technology, which consists in direct simulation of physical processes in a rock sample with resolved pore space geometry, is gaining popularity today. This technology complements the traditional laboratory studies and compensates for a number of their shortcomings. The presented work is devoted to the direct simulation of fluid flow within the scope of the digital rock physics. For simulation regularized (according to quasi-hydrodynamic technique) hydrodynamic equations are used. Both single-phase single-component flows and two-phase two-component flows, taking into account interfacial tension, are discussed. The results of simulations of fluid flows both in model domains and in domains corresponding to the pore space of real rocks are presented.
Optimized routines for event generators in QED-PIC codes
Authors: Volokitin V , Bastrakov S , Bashinov A , Efimenko E , Muraviev A , Gonoskov A , Meyerov I
Published: October 2020

In recent years, the prospects of performing fundamental and applied studies at the next-generation high-intensity laser facilities have greatly stimulated the interest in performing large-scale simulations of laser interaction with matter with the account for quantum electrodynamics (QED) processes such as emission of high energy photons and decay of such photons into electron-positron pairs. These processes can be modelled via probabilistic routines that include frequent computation of synchrotron functions and can constitute significant computational demands within accordingly extended Particle-in-Cell (QED-PIC) algorithms. In this regard, the optimization of these routines is of great interest. In this paper, we propose and describe two modifications. First, we derive a more accurate upper-bound estimate for the rate of QED events and use it to arrange local sub-stepping of the global time step in a significantly more efficient way than done previously. Second, we present a new high-performance implementation of synchrotron functions. Our optimizations made it possible to speed up the computations by a factor of up to 13.7 depending on the problem. Our implementation is integrated into the PICADOR and Hi-Chi codes, the latter of which is distributed publicly (https://github.com/hi-chi/pyHiChi).
Numerical study of diamagnetic regime in open magnetic trap
Authors: Boronina M A , Dudnikova G I , Efimova A A , Genrikh E A , Vshivkov V A , Chernoshtanov I S
Published: October 2020

The article presents a two-dimensional axially symmetric numerical model of a diamagnetic plasma confinement regime in a linear magnetic system as applied to laboratory experiments at the BINP SB RAS, Novosibirsk. The model is based on the kinetic approximation for the ion components of the background plasma and the injected beam. The MHD approximation is used for the electron component, taking into account the mechanisms of energy dissipation due to conductivity and thermal conductivity. The particle-in-cell method is used to solve the Vlasov equation. The dependences of the magnetic field profile and plasma density on the current of the ion beam and its energy are found.
Beam characterization at NSRL for radiobiological experiments—phase 1
Authors: Burigo L. , Gehrke T. , Jäkel O. , Sivertz M. , Olsen T. , Rusek A. , Obcemea C. , Greilich S.
Published: October 2020

An experimental campaign was carried out at the NASA Space Radiation Laboratory to perform an additional, independent dosimetric characterization of the beams of protons, helium and carbon ions for radiobiological experiments. The campaign was undertaken by the request and with the support from the National Cancer Institute, U.S. In this initial phase, the goals were to obtain a first assessment of the dosimetric reproducibility of the beam control system, including analysis of spatial homogeneity and evaluation of ion beam contamination. They should facilitate the design of further experimental campaigns for beam characterization for radiobiological experiments. Measurements included reference dosimetry with comparison of in-house and external ionization chambers and electrometers, lateral-dose profile measurements in air, depth-dose profile in a water tank, evaluation of water equivalent thickness of a HDPE binary range shifter and estimation of impurities of the investigated helium-ion beam. The experiments and results are presented.
Evidence map: topics, trends, and policy in the energy transitions literature
Authors: Lu Jiaqi , Nemet Gregory F
Published: October 2020

We develop an evidence map of the academic research on energy transitions (ETs) with a focus on what that literature says about public policy for addressing climate change. In this article, the questions we ask are: What trends do we see in the topics that occur in journal articles on the energy transition? And to what extent has public policy been a focus? Where do we need or see energy transitions happening? Our approach involves: (1) using two literature databases to identify 4875 relevant ET articles over the period 1970–2018; (2) identifying important topics within ET using topic modeling via latent Dirichlet allocation on the abstracts of the articles; and (3) conducting a robustness check on the topics and analysis on the policy-relevant topics. This study contributes to the ETs research by providing the first systematic overview of peer-reviewed articles on ETs. We find that the number of academic articles covering ETs has increased by nearly a factor of 50 since 2008, 67% of them are policy related. Research on governance is pervasive in the literature and contains multiple topics differentiated by substantive foci. Some topics on the social-technical, social-behavioral, and political aspects of transition governance are becoming increasingly popular. Network analysis shows transition governance, energy economics and climate implications, and energy technologies comprise the three largest clusters of topics, but we observe a lack of connectedness between governance topics and technology topics. In the policy-relevant literature, we see a growing number of articles on technological and institutional innovation, and examples from leader countries, especially in Europe. We find only a quarter of articles discussed ETs in developing countries, which is not aligned with a recurring theme, their importance to the global ET.
Modulating extraordinary terahertz transmissions in multilayer plasmonic metasurfaces
Authors: Banerjee Sabyasachi , Lok Abhishikth Naka , Karmakar Subhajit , Kumar Deepak , Rane Shreeya , Goel Sanket , Azad Abul K , Roy Chowdhury Dibakar
Published: October 2020

Manipulations of light–matter interaction via sub-wavelength plasmonic structures have opened up many new research opportunities in photonics from microwave to the visible spectrum, including the relatively underdeveloped but technologically important terahertz regime. Here, we have studied manipulation of terahertz transmission through a bilayer metasurface consisting of a metallic hole array and a complimentary patch array separated by an ultra-thin dielectric spacer. The terahertz transmission spectra through our studied metasurfaces exhibit characteristic resonances due to the surface plasmon induced extraordinary transmission peak. Our study reveals a counterintuitive blue shift of the transmission peak with increasing spacer thickness, which is explained by reduced Coulomb interaction between two plasmonic layers. The measured quality factor exhibits a strong dependence on the spacer thickness, and the maximum quality factor is observed for a spacer thickness of around λ/30, indicating strong electric-field confinement inside the dielectric spacer. These bilayer plasmonic structures will aid in realizing next-generation terahertz plasmonic devices such as ultrasensitive thin-film sensors, modulators, narrow-band filters, and other nonlinear components.
Developing a culture of safety in biomedical research training
Authors: Bond Michelle R. , Gammie Alison E. , Lorsch Jon R.
Published: October 2020

The National Institute of General Medical Sciences (NIGMS) at the U.S. National Institutes of Health (NIH) is committed to supporting the safety of the nation’s biomedical research and training environments. Institutional training grants affect many trainees and can have a broad influence across their parent institutions, making them good starting points for our initial efforts to promote the development and maintenance of robust cultures of safety at U.S. academic institutions. In this Perspective, we focus on laboratory safety, although many of the strategies we describe for improving laboratory safety are also applicable to other forms of safety including the prevention of harassment, intimidation, and discrimination. We frame the problem of laboratory safety using a number of recent examples of tragic accidents, highlight some of the lessons that have been learned from these and other events, discuss what NIGMS is doing to address problems related to laboratory safety, and outline steps that institutions can take to improve their safety cultures.
Ciliate behavior: blueprints for dynamic cell biology and microscale robotics
Authors: Coyle Scott M.
Published: October 2020

Place a drop of pond water under the microscope, and you will likely find an ocean of extraordinary and diverse single-celled organisms called ciliates. This remarkable group of single-celled organisms wield microtubules, active systems, electrical signaling, and chemical sensors to build intricate geometrical structures and perform complex behaviors that can appear indistinguishable from those of macroscopic animals. Advances in computer vision and machine learning are making it possible to completely digitize and track the dynamics of complex ciliates and mine these data for the hidden structure, patterns, and motifs that are responsible for their behaviors. By deconstructing the diversity of ciliate behaviors in the natural world, themes for organizing and controlling matter at the microscale are beginning to take hold, suggesting new modular approaches for the design of autonomous molecular machines that emulate nature’s finest examples.
Pedagogy of the Black academic
Authors: Simmons Glenn E.
Published: October 2020

I am just starting my career as a cancer biologist, but I have always been a Black man in America. This means that I have always inhabited a world that generally disregarded my existence in some form or another. It is June 17th, 2020 and protests have been happening for weeks since the killing of George Floyd in Minneapolis. The current state of America may be uneasy for some, but for many Americans, the looming threat of exclusion and violence has been an unwelcome companion since birth. This letter is not about a single person, but the Black academic’s experience of race inside and outside of the academy during a time of social upheaval. I have trained in a variety of institutions, big and small, and all the while acutely aware of the impact of my Blackness on my science. The intent of the following is to provoke the reader to reflect on how we as a nation can move toward radically positive change and not incremental adjustments to the status quo. The views expressed are my own and are the result of years of personal experience observing the anti-Black standard in America.
Implementation of a pharmacy-focused morbidity, mortality, and improvement conference
Authors: Odinet Johlee S , Vest Mary-Haston , Murphy Kristin , Pappas Ashley L , Stivers Andrew P
Published: October 2020

Purpose

Review lessons learned during the development and implementation of a pharmacy-focused Morbidity, Mortality, and Improvement conference at an academic medical center.

Since the early 1900s, Morbidity and Mortality conferences have provided a forum for clinicians to discuss medical errors and adverse outcomes. Many institutions have now added “improvement” to the conference title to emphasize the goal of approaching these conferences in a systems-oriented manner. To date, a gap remains in the literature evaluating the impact of a pharmacy-focused Morbidity, Mortality, and Improvement (MM&I) conference. The primary goal in establishing this pharmacy-focused conference was to foster and strengthen the culture of medication safety within our department. In establishing our program, we identified an opportunity to leverage pharmacy residents similar to a medical resident–facilitated conference. After gaining leadership buy-in, a core planning team was formed to identify events and create conference materials. Primary metrics to gauge the success of implementation included event reporting trends and medication-safety strategic initiative tracking. The first year of MM&I conferences provided forward momentum for our department’s safety culture. Safety event reporting by pharmacy staff increased by 150% over the fiscal year, and more frontline staff expressed a personal interest in becoming involved in safety projects and initiatives outside of their normal shift responsibilities.

Conclusion

We have learned several important lessons that may be helpful to others, the primary of which is that improving a culture of safety takes time.
Haecceitism in the Tractatus: A refutation of Ishiguro’s view on Tractarian names
Authors: Nakano Anderson
Published: October 2020

In a seminal essay, Hidé Ishiguro argued that names in the Tractatus are ‘like dummy names’ and that a simple object is to be conceived of as ‘an instantiation of an irreducible predicate’. In this paper, I argue that Ishiguro’s view is incompatible with other claims made in the Tractatus and should be abandoned for this reason. To this end, I adopt a two-step strategy. First, I show that Ishiguro’s view implies the adoption of an anti-haecceitistic position. Then I show that the Tractatus allows for the possibility of there being haecceitistic differences between two complete descriptions of the world. Since anti-haecceitism will be characterized as the doctrine that haecceitistic differences are meaningless, this provides a refutation of Ishiguro’s view. In the final section, I make a few remarks on the relation between anti-haecceitism and the context principle.
High temperatures limit developmental resilience to high-elevation hypoxia in the snakeNatrix maura(Squamata: Colubridae)
Authors: Souchet Jérémie , Bossu Coralie , Darnet Elodie , Le Chevalier Hugo , Poignet Manon , Trochet Audrey , Bertrand Romain , Calvez Olivier , Martinez-Silvestre Albert , Mossoll-Torres Marc , Guillaume Olivier , Clobert Jean , Barthe Laurent , Pottier Gilles , Philippe Hervé , Gangloff Eric J , Aubret Fabien
Published: October 2020

Climate change is generating range shifts in many organisms, notably along the altitudinal gradient. However, moving up in altitude exposes organisms to lower oxygen availability, which may negatively affect development and fitness, especially at high temperatures. To test this possibility in a potentially upward-colonizing species, we artificially incubated developing embryos of the viperine snake Natrix maura Linnaeus 1758, using a split-clutch design, in conditions of extreme high elevation or low elevation at two ecologically-relevant incubation temperatures (24 and 32 °C). Embryos at low and extreme high elevations incubated at cool temperatures did not differ in development time, hatchling phenotype or locomotor performance. However, at the warmer incubation temperature and at extreme high elevation, hatching success was reduced. Further, embryonic heart rates were lower, incubation duration longer and juveniles born smaller. Nonetheless, snakes in this treatment were faster swimmers than siblings in other treatment groups, suggesting a developmental trade-off between size and performance. Constraints on development may be offset by the maintenance of important performance metrics, thus suggesting that early life-history stages will not prevent the successful colonization of high-elevation habitat even under the dual limitations of reduced oxygen and increased temperature.
The Evolutionary History of Common Genetic Variants Influencing Human Cortical Surface Area
Authors: Tilot Amanda K , Khramtsova Ekaterina A , Liang Dan , Grasby Katrina L , Jahanshad Neda , Painter Jodie , Colodro-Conde Lucía , Bralten Janita , Hibar Derrek P , Lind Penelope A , Liu Siyao , Brotman Sarah M , Thompson Paul M , Medland Sarah E , Macciardi Fabio , Stranger Barbara E , Davis Lea K , Fisher Simon E , Stein Jason L
Published: October 2020

Structural brain changes along the lineage leading to modern Homo sapiens contributed to our distinctive cognitive and social abilities. However, the evolutionarily relevant molecular variants impacting key aspects of neuroanatomy are largely unknown. Here, we integrate evolutionary annotations of the genome at diverse timescales with common variant associations from large-scale neuroimaging genetic screens. We find that alleles with evidence of recent positive polygenic selection over the past 2000–3000 years are associated with increased surface area (SA) of the entire cortex, as well as specific regions, including those involved in spoken language and visual processing. Therefore, polygenic selective pressures impact the structure of specific cortical areas even over relatively recent timescales. Moreover, common sequence variation within human gained enhancers active in the prenatal cortex is associated with postnatal global SA. We show that such variation modulates the function of a regulatory element of the developmentally relevant transcription factor HEY2 in human neural progenitor cells and is associated with structural changes in the inferior frontal cortex. These results indicate that non-coding genomic regions active during prenatal cortical development are involved in the evolution of human brain structure and identify novel regulatory elements and genes impacting modern human brain structure.
Epidemiology and Ecology of Severe Fever With Thrombocytopenia Syndrome in China, 2010‒2018
Authors: Miao Dong , Liu Ming-Jin , Wang Yi-Xing , Ren Xiang , Lu Qing-Bin , Zhao Guo-Ping , Dai Ke , Li Xin-Lou , Li Hao , Zhang Xiao-Ai , Shi Wen-Qiang , Wang Li-Ping , Yang Yang , Fang Li-Qun , Liu Wei
Published: October 2020

Background

The growing epidemics of severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne disease in East Asia, and its high case fatality rate have raised serious public health concerns.

Methods

Surveillance data on laboratory-confirmed SFTS cases in China were collected. The spatiotemporal dynamics and epidemiological features were explored. The socioeconomic and environmental drivers were identified for SFTS diffusion using survival analysis and for SFTS persistence using a two-stage generalized boosted regression tree model.

Results

During 2010‒2018, a total of 7721 laboratory-confirmed SFTS cases were reported in China, with an overall case fatality rate (CFR) of 10.5%. The average annual incidence increased >20 times and endemic areas expanded from 27 to 1574 townships, whereas the CFR declined from 19% to 10% during this period. Four geographical clusters—the Changbai Mountain area, the Jiaodong Peninsula, the Taishan Mountain area, and the Huaiyangshan Mountain area—were identified. Diffusion and persistence of the disease were both driven by elevation, high coverages of woods, crops, and shrubs, and the vicinity of habitats of migratory birds but had different meteorological drivers. Residents ≥60 years old in rural areas with crop fields and tea farms were at increased risk to SFTS.

Conclusions

Surveillance of SFTS and intervention programs need to be targeted at areas ecologically suitability for vector ticks and in the vicinity of migratory birds to curb the growing epidemic.
Clinical Characteristics and Outcomes of Coronavirus Disease 2019 Patients Who Received Compassionate-Use Leronlimab
Authors: Yang Bryant , Fulcher Jennifer A , Ahn Jenny , Berro Marlene , Goodman-Meza David , Dhody Kush , Sacha Jonah B , Naeim Arash , Yang Otto O
Published: October 2020

Background

Leronlimab, a monoclonal antibody blocker of C-C chemokine receptor type 5 originally developed to treat human immunodeficiency virus infection, was administered as an open-label compassionate-use therapeutic for coronavirus disease 2019 (COVID-19).

Methods

Twenty-three hospitalized severe/critical COVID-19 patients received 700 mg leronlimab subcutaneously, repeated after 7 days in 17 of 23 patients still hospitalized. Eighteen of 23 received other experimental treatments, including convalescent plasma, hydroxychloroquine, steroids, and/or tocilizumab. Five of 23 received leronlimab after blinded, placebo-controlled trials of remdesivir, sarilumab, selinexor, or tocilizumab. Outcomes and results were extracted from medical records.

Results

Mean age was 69.5 ± 14.9 years; 20 had significant comorbidities. At baseline, 22 were receiving supplemental oxygen (3 high flow, 7 mechanical ventilation). Blood showed markedly elevated inflammatory markers (ferritin, D-dimer, C-reactive protein) and an elevated neutrophil-to-lymphocyte ratio. By day 30 after initial dosing, 17 were recovered, 2 were still hospitalized, and 4 had died. Of the 7 intubated at baseline, 4 were fully recovered off oxygen, 2 were still hospitalized, and 1 had died.

Conclusions

Leronlimab appeared safe and well tolerated. The high recovery rate suggested benefit, and those with lower inflammatory markers had better outcomes. Some, but not all, patients appeared to have dramatic clinical responses, indicating that unknown factors may determine responsiveness to leronlimab. Routine inflammatory and cell prognostic markers did not markedly change immediately after treatment, although interleukin-6 tended to fall. In some persons, C-reactive protein clearly dropped only after the second leronlimab dose, suggesting that a higher loading dose might be more effective. Future controlled trials will be informative.
Estimating Total Excess Mortality During a Coronavirus Disease 2019 Outbreak in Stockholm, Sweden
Authors: Pimenoff Ville N , Elfström Miriam , Baussano Iacopo , Björnstedt Mikael , Dillner Joakim
Published: October 2020

Total excess mortality peaked during a coronavirus disease 2019 (COVID-19) outbreak in Stockholm, but 25% of these deaths were not recognized as COVID-19 related nor occurred in hospitals. Estimate of total excess mortality may give a more comprehensive picture of the total disease burden during a COVID-19 outbreak, and may facilitate managing future outbreaks.
A roadmap for optimizing chronic kidney disease patient care and patient-oriented research in the Eastern European nephrology community
Authors: Sever Mehmet Şükrü , Jager Kitty J , Vanholder Raymond , Stengel Benedicte , Harambat Jerome , Finne Patrik , Tesař Vladimir , Barbullushi Myftar , Bumblytė Inga A , Zakharova Elena , Spasovski Goce , Resic Halima , Wiecek Andrzej , Blankestijn Peter J , Bruchfeld Annette , Cozzolino Mario , Goumenos Dimitris , Soler Maria Jose , Rychlík Ivan , Stevens Kate I , Wanner Christoph , Zoccali Carmine , Massy Ziad A
Published: October 2020

Chronic kidney disease (CKD) is a major health problem because of its high prevalence, associated complications and high treatment costs. Several aspects of CKD differ significantly in the Eastern European nephrology community compared with Western Europe because of different geographic, socio-economic, infrastructure, cultural and educational features. The two most frequent aetiologies of CKD, DM and hypertension, and many other predisposing factors, are more frequent in the Eastern region, resulting in more prevalent CKD Stages 3–5. Interventions may minimize the potential drawbacks of the high prevalence of CKD in Eastern Europe, which include several options at various stages of the disease, such as raising public, medical personnel and healthcare authorities awareness; early detection by screening high-risk populations; preventing progression and CKD-related complications by training health professionals and patients; promoting transplantation or home dialysis as the preferred modality; disseminating and implementing guidelines and guided therapy and encouraging/supporting country-specific observational research as well as international collaborative projects. Specific ways to significantly impact CKD-related problems in every region of Europe through education, science and networking are collaboration with non-nephrology European societies who have a common interest in CKD and its associated complications, representation through an advisory role within nephrology via national nephrology societies, contributing to the training of local nephrologists and stimulating patient-oriented research. The latter is mandatory to identify country-specific kidney disease–related priorities. Active involvement of patients in this research via collaboration with the European Kidney Patient Federation or national patient federations is imperative to ensure that projects reflect specific patient needs.