bluuebunny/crossref_metadata_2025 huggingface dataset:
Universal method for magnetic skyrmion bubble generation by controlling the stripe domain instability
Authors: Moon Kyoung-Woong , Yang Seungmo , Ju Tae-Seong , Kim Changsoo , Chun Byoung Sun , Park Sungkyun , Hwang Chanyong
Published: March 2021

Magnetic skyrmions, which are topological swirling spin textures, have drawn much attention in spintronics because of their use as an information carrier with distinct robustness rooted in their topological nature. Real-time generation of skyrmions is therefore imperative for realizing skyrmion-based spintronic devices. However, to date, experimental demonstration has been limited to exquisite works with well-tuned samples. Here, we report a method to generate skyrmions by driving the stripe instability via an in-plane magnetic field. We have demonstrated that the key parameter determining the stripe domain instability is the stripe width, regardless of other material parameters. This skyrmion generation method can be applicable to generic magnetic films with perpendicular magnetic anisotropy. Our work will facilitate the development of skyrmion-based devices by offering a general method for controlling a large skyrmion population.
Discovery of fungal surface NADases predominantly present in pathogenic species
Authors: Strømland Øyvind , Kallio Juha P. , Pschibul Annica , Skoge Renate H. , Harðardóttir Hulda M. , Sverkeli Lars J. , Heinekamp Thorsten , Kniemeyer Olaf , Migaud Marie , Makarov Mikhail V. , Gossmann Toni I. , Brakhage Axel A. , Ziegler Mathias
Published: March 2021

Nicotinamide adenine dinucleotide (NAD) is a key molecule in cellular bioenergetics and signalling. Various bacterial pathogens release NADase enzymes into the host cell that deplete the host’s NAD+ pool, thereby causing rapid cell death. Here, we report the identification of NADases on the surface of fungi such as the pathogen Aspergillus fumigatus and the saprophyte Neurospora crassa. The enzymes harbour a tuberculosis necrotizing toxin (TNT) domain and are predominately present in pathogenic species. The 1.6 Å X-ray structure of the homodimeric A. fumigatus protein reveals unique properties including N-linked glycosylation and a Ca2+-binding site whose occupancy regulates activity. The structure in complex with a substrate analogue suggests a catalytic mechanism that is distinct from those of known NADases, ADP-ribosyl cyclases and transferases. We propose that fungal NADases may convey advantages during interaction with the host or competing microorganisms.
Ultrafast multi-cycle terahertz measurements of the electrical conductivity in strongly excited solids
Authors: Chen Z. , Curry C. B. , Zhang R. , Treffert F. , Stojanovic N. , Toleikis S. , Pan R. , Gauthier M. , Zapolnova E. , Seipp L. E. , Weinmann A. , Mo M. Z. , Kim J. B. , Witte B. B. L. , Bajt S. , Usenko S. , Soufli R. , Pardini T. , Hau-Riege S. , Burcklen C. , Schein J. , Redmer R. , Tsui Y. Y. , Ofori-Okai B. K. , Glenzer S. H.
Published: March 2021

Key insights in materials at extreme temperatures and pressures can be gained by accurate measurements that determine the electrical conductivity. Free-electron laser pulses can ionize and excite matter out of equilibrium on femtosecond time scales, modifying the electronic and ionic structures and enhancing electronic scattering properties. The transient evolution of the conductivity manifests the energy coupling from high temperature electrons to low temperature ions. Here we combine accelerator-based, high-brightness multi-cycle terahertz radiation with a single-shot electro-optic sampling technique to probe the evolution of DC electrical conductivity using terahertz transmission measurements on sub-picosecond time scales with a multi-undulator free electron laser. Our results allow the direct determination of the electron-electron and electron-ion scattering frequencies that are the major contributors of the electrical resistivity.
Compensation-free high-dimensional free-space optical communication using turbulence-resilient vector beams
Authors: Zhu Ziyi , Janasik Molly , Fyffe Alexander , Hay Darrick , Zhou Yiyu , Kantor Brian , Winder Taylor , Boyd Robert W. , Leuchs Gerd , Shi Zhimin
Published: March 2021

Free-space optical communication is a promising means to establish versatile, secure and high-bandwidth communication between mobile nodes for many critical applications. While the spatial modes of light offer a degree of freedom to increase the information capacity of an optical link, atmospheric turbulence can introduce severe distortion to the spatial modes and lead to data degradation. Here, we demonstrate experimentally a vector-beam-based, turbulence-resilient communication protocol, namely spatial polarization differential phase shift keying (SPDPSK), that can reliably transmit high-dimensional information through a turbulent channel without the need of any adaptive optics for beam compensation. In a proof-of-principle experiment with a controllable turbulence cell, we measure a channel capacity of 4.84 bits per pulse using 34 vector modes through a turbulent channel with a scintillation index of 1.09, and 4.02 bits per pulse using 18 vector modes through even stronger turbulence corresponding to a scintillation index of 1.54.
Cell kinetics of auxin transport and activity in Arabidopsis root growth and skewing
Authors: Hu Yangjie , Omary Moutasem , Hu Yun , Doron Ohad , Hoermayer Lukas , Chen Qingguo , Megides Or , Chekli Ori , Ding Zhaojun , Friml Jiří , Zhao Yunde , Tsarfaty Ilan , Shani Eilon
Published: March 2021

Auxin is a key regulator of plant growth and development. Local auxin biosynthesis and intercellular transport generates regional gradients in the root that are instructive for processes such as specification of developmental zones that maintain root growth and tropic responses. Here we present a toolbox to study auxin-mediated root development that features: (i) the ability to control auxin synthesis with high spatio-temporal resolution and (ii) single-cell nucleus tracking and morphokinetic analysis infrastructure. Integration of these two features enables cutting-edge analysis of root development at single-cell resolution based on morphokinetic parameters under normal growth conditions and during cell-type-specific induction of auxin biosynthesis. We show directional auxin flow in the root and refine the contributions of key players in this process. In addition, we determine the quantitative kinetics of Arabidopsis root meristem skewing, which depends on local auxin gradients but does not require PIN2 and AUX1 auxin transporter activities. Beyond the mechanistic insights into root development, the tools developed here will enable biologists to study kinetics and morphology of various critical processes at the single cell-level in whole organisms.
Reversible hydrogen control of antiferromagnetic anisotropy in α-Fe2O3
Authors: Jani Hariom , Linghu Jiajun , Hooda Sonu , Chopdekar Rajesh V. , Li Changjian , Omar Ganesh Ji , Prakash Saurav , Du Yonghua , Yang Ping , Banas Agnieszka , Banas Krzysztof , Ghosh Siddhartha , Ojha Sunil , Umapathy G. R. , Kanjilal Dinakar , Ariando A. , Pennycook Stephen J. , Arenholz Elke , Radaelli Paolo G. , Coey J. M. D. , Feng Yuan Ping , Venkatesan T.
Published: March 2021

Antiferromagnetic insulators are a ubiquitous class of magnetic materials, holding the promise of low-dissipation spin-based computing devices that can display ultra-fast switching and are robust against stray fields. However, their imperviousness to magnetic fields also makes them difficult to control in a reversible and scalable manner. Here we demonstrate a novel proof-of-principle ionic approach to control the spin reorientation (Morin) transition reversibly in the common antiferromagnetic insulator α-Fe2O3 (haematite) – now an emerging spintronic material that hosts topological antiferromagnetic spin-textures and long magnon-diffusion lengths. We use a low-temperature catalytic-spillover process involving the post-growth incorporation or removal of hydrogen from α-Fe2O3 thin films. Hydrogenation drives pronounced changes in its magnetic anisotropy, Néel vector orientation and canted magnetism via electron injection and local distortions. We explain these effects with a detailed magnetic anisotropy model and first-principles calculations. Tailoring our work for future applications, we demonstrate reversible control of the room-temperature spin-state by doping/expelling hydrogen in Rh-substituted α-Fe2O3.
Pervasive cooperative mutational effects on multiple catalytic enzyme traits emerge via long-range conformational dynamics
Authors: Acevedo-Rocha Carlos G. , Li Aitao , D’Amore Lorenzo , Hoebenreich Sabrina , Sanchis Joaquin , Lubrano Paul , Ferla Matteo P. , Garcia-Borràs Marc , Osuna Sílvia , Reetz Manfred T.
Published: March 2021

Multidimensional fitness landscapes provide insights into the molecular basis of laboratory and natural evolution. To date, such efforts usually focus on limited protein families and a single enzyme trait, with little concern about the relationship between protein epistasis and conformational dynamics. Here, we report a multiparametric fitness landscape for a cytochrome P450 monooxygenase that was engineered for the regio- and stereoselective hydroxylation of a steroid. We develop a computational program to automatically quantify non-additive effects among all possible mutational pathways, finding pervasive cooperative signs and magnitude epistasis on multiple catalytic traits. By using quantum mechanics and molecular dynamics simulations, we show that these effects are modulated by long-range interactions in loops, helices and β-strands that gate the substrate access channel allowing for optimal catalysis. Our work highlights the importance of conformational dynamics on epistasis in an enzyme involved in secondary metabolism and offers insights for engineering P450s.
Impact of equatorial Atlantic variability on ENSO predictive skill
Authors: Exarchou Eleftheria , Ortega Pablo , Rodríguez-Fonseca Belén , Losada Teresa , Polo Irene , Prodhomme Chloé
Published: March 2021

El Niño-Southern Oscillation (ENSO) is a key mode of climate variability with worldwide climate impacts. Recent studies have highlighted the impact of other tropical oceans on its variability. In particular, observations have demonstrated that summer Atlantic Niños (Niñas) favor the development of Pacific Niñas (Niños) the following winter, but it is unclear how well climate models capture this teleconnection and its role in defining the seasonal predictive skill of ENSO. Here we use an ensemble of seasonal forecast systems to demonstrate that a better representation of equatorial Atlantic variability in summer and its lagged teleconnection mechanism with the Pacific relates to enhanced predictive capacity of autumn/winter ENSO. An additional sensitivity study further shows that correcting SST variability in equatorial Atlantic improves different aspects of forecast skill in the Tropical Pacific, boosting ENSO skill. This study thus emphasizes that new efforts to improve the representation of equatorial Atlantic variability, a region with long standing systematic model biases, can foster predictive skill in the region, the Tropical Pacific and beyond, through the global impacts of ENSO.
Bi-allelic MCM10 variants associated with immune dysfunction and cardiomyopathy cause telomere shortening
Authors: Baxley Ryan M. , Leung Wendy , Schmit Megan M. , Matson Jacob Peter , Yin Lulu , Oram Marissa K. , Wang Liangjun , Taylor John , Hedberg Jack , Rogers Colette B. , Harvey Adam J. , Basu Debashree , Taylor Jenny C. , Pagnamenta Alistair T. , Dreau Helene , Craft Jude , Ormondroyd Elizabeth , Watkins Hugh , Hendrickson Eric A. , Mace Emily M. , Orange Jordan S. , Aihara Hideki , Stewart Grant S. , Blair Edward , Cook Jeanette Gowen , Bielinsky Anja-Katrin
Published: March 2021

Minichromosome maintenance protein 10 (MCM10) is essential for eukaryotic DNA replication. Here, we describe compound heterozygous MCM10 variants in patients with distinctive, but overlapping, clinical phenotypes: natural killer (NK) cell deficiency (NKD) and restrictive cardiomyopathy (RCM) with hypoplasia of the spleen and thymus. To understand the mechanism of MCM10-associated disease, we modeled these variants in human cell lines. MCM10 deficiency causes chronic replication stress that reduces cell viability due to increased genomic instability and telomere erosion. Our data suggest that loss of MCM10 function constrains telomerase activity by accumulating abnormal replication fork structures enriched with single-stranded DNA. Terminally-arrested replication forks in MCM10-deficient cells require endonucleolytic processing by MUS81, as MCM10:MUS81 double mutants display decreased viability and accelerated telomere shortening. We propose that these bi-allelic variants in MCM10 predispose specific cardiac and immune cell lineages to prematurely arrest during differentiation, causing the clinical phenotypes observed in both NKD and RCM patients.
Single-cell transcriptional changes associated with drug tolerance and response to combination therapies in cancer
Authors: Aissa Alexandre F. , Islam Abul B. M. M. K. , Ariss Majd M. , Go Cammille C. , Rader Alexandra E. , Conrardy Ryan D. , Gajda Alexa M. , Rubio-Perez Carlota , Valyi-Nagy Klara , Pasquinelli Mary , Feldman Lawrence E. , Green Stefan J. , Lopez-Bigas Nuria , Frolov Maxim V. , Benevolenskaya Elizaveta V.
Published: March 2021

Tyrosine kinase inhibitors were found to be clinically effective for treatment of patients with certain subsets of cancers carrying somatic mutations in receptor tyrosine kinases. However, the duration of clinical response is often limited, and patients ultimately develop drug resistance. Here, we use single-cell RNA sequencing to demonstrate the existence of multiple cancer cell subpopulations within cell lines, xenograft tumors and patient tumors. These subpopulations exhibit epigenetic changes and differential therapeutic sensitivity. Recurrently overrepresented ontologies in genes that are differentially expressed between drug tolerant cell populations and drug sensitive cells include epithelial-to-mesenchymal transition, epithelium development, vesicle mediated transport, drug metabolism and cholesterol homeostasis. We show analysis of identified markers using the LINCS database to predict and functionally validate small molecules that target selected drug tolerant cell populations. In combination with EGFR inhibitors, crizotinib inhibits the emergence of a defined subset of EGFR inhibitor-tolerant clones. In this study, we describe the spectrum of changes associated with drug tolerance and inhibition of specific tolerant cell subpopulations with combination agents.
Plasmodium vivax infection compromises reticulocyte stability
Authors: Clark Martha A. , Kanjee Usheer , Rangel Gabriel W. , Chery Laura , Mascarenhas Anjali , Gomes Edwin , Rathod Pradipsinh K. , Brugnara Carlo , Ferreira Marcelo U. , Duraisingh Manoj T.
Published: March 2021

The structural integrity of the host red blood cell (RBC) is crucial for propagation of Plasmodium spp. during the disease-causing blood stage of malaria infection. To assess the stability of Plasmodium vivax-infected reticulocytes, we developed a flow cytometry-based assay to measure osmotic stability within characteristically heterogeneous reticulocyte and P. vivax-infected samples. We find that erythroid osmotic stability decreases during erythropoiesis and reticulocyte maturation. Of enucleated RBCs, young reticulocytes which are preferentially infected by P. vivax, are the most osmotically stable. P. vivax infection however decreases reticulocyte stability to levels close to those of RBC disorders that cause hemolytic anemia, and to a significantly greater degree than P. falciparum destabilizes normocytes. Finally, we find that P. vivax new permeability pathways contribute to the decreased osmotic stability of infected-reticulocytes. These results reveal a vulnerability of P. vivax-infected reticulocytes that could be manipulated to allow in vitro culture and develop novel therapeutics.
Human-interpretable image features derived from densely mapped cancer pathology slides predict diverse molecular phenotypes
Authors: Diao James A. , Wang Jason K. , Chui Wan Fung , Mountain Victoria , Gullapally Sai Chowdary , Srinivasan Ramprakash , Mitchell Richard N. , Glass Benjamin , Hoffman Sara , Rao Sudha K. , Maheshwari Chirag , Lahiri Abhik , Prakash Aaditya , McLoughlin Ryan , Kerner Jennifer K. , Resnick Murray B. , Montalto Michael C. , Khosla Aditya , Wapinski Ilan N. , Beck Andrew H. , Elliott Hunter L. , Taylor-Weiner Amaro
Published: March 2021

Computational methods have made substantial progress in improving the accuracy and throughput of pathology workflows for diagnostic, prognostic, and genomic prediction. Still, lack of interpretability remains a significant barrier to clinical integration. We present an approach for predicting clinically-relevant molecular phenotypes from whole-slide histopathology images using human-interpretable image features (HIFs). Our method leverages >1.6 million annotations from board-certified pathologists across >5700 samples to train deep learning models for cell and tissue classification that can exhaustively map whole-slide images at two and four micron-resolution. Cell- and tissue-type model outputs are combined into 607 HIFs that quantify specific and biologically-relevant characteristics across five cancer types. We demonstrate that these HIFs correlate with well-known markers of the tumor microenvironment and can predict diverse molecular signatures (AUROC 0.601–0.864), including expression of four immune checkpoint proteins and homologous recombination deficiency, with performance comparable to ‘black-box’ methods. Our HIF-based approach provides a comprehensive, quantitative, and interpretable window into the composition and spatial architecture of the tumor microenvironment.
Model-based evaluation of school- and non-school-related measures to control the COVID-19 pandemic
Authors: Rozhnova Ganna , van Dorp Christiaan H. , Bruijning-Verhagen Patricia , Bootsma Martin C. J. , van de Wijgert Janneke H. H. M. , Bonten Marc J. M. , Kretzschmar Mirjam E.
Published: March 2021

The role of school-based contacts in the epidemiology of SARS-CoV-2 is incompletely understood. We use an age-structured transmission model fitted to age-specific seroprevalence and hospital admission data to assess the effects of school-based measures at different time points during the COVID-19 pandemic in the Netherlands. Our analyses suggest that the impact of measures reducing school-based contacts depends on the remaining opportunities to reduce non-school-based contacts. If opportunities to reduce the effective reproduction number (Re) with non-school-based measures are exhausted or undesired and Re is still close to 1, the additional benefit of school-based measures may be considerable, particularly among older school children. As two examples, we demonstrate that keeping schools closed after the summer holidays in 2020, in the absence of other measures, would not have prevented the second pandemic wave in autumn 2020 but closing schools in November 2020 could have reduced Re below 1, with unchanged non-school-based contacts.
Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase
Authors: Chen Bingyi , Luo Siting , Zhang Songxuan , Ju Yingchen , Gu Qiong , Xu Jun , Yang Xiang-Lei , Zhou Huihao
Published: March 2021

The polyketide natural product reveromycin A (RM-A) exhibits antifungal, anticancer, anti-bone metastasis, anti-periodontitis and anti-osteoporosis activities by selectively inhibiting eukaryotic cytoplasmic isoleucyl-tRNA synthetase (IleRS). Herein, a co-crystal structure suggests that the RM-A molecule occupies the substrate tRNAIle binding site of Saccharomyces cerevisiae IleRS (ScIleRS), by partially mimicking the binding of tRNAIle. RM-A binding is facilitated by the copurified intermediate product isoleucyl-adenylate (Ile-AMP). The binding assays confirm that RM-A competes with tRNAIle while binding synergistically with l-isoleucine or intermediate analogue Ile-AMS to the aminoacylation pocket of ScIleRS. This study highlights that the vast tRNA binding site of the Rossmann-fold catalytic domain of class I aminoacyl-tRNA synthetases could be targeted by a small molecule. This finding will inform future rational drug design.
On-surface preparation of coordinated lanthanide-transition-metal clusters
Authors: Liu Jing , Li Jie , Xu Zhen , Zhou Xiong , Xue Qiang , Wu Tianhao , Zhong Mingjun , Li Ruoning , Sun Rong , Shen Ziyong , Tang Hao , Gao Song , Wang Bingwu , Hou Shimin , Wang Yongfeng
Published: March 2021

The study of lanthanide (Ln)-transition-metal (TM) heterometallic clusters which play key roles in various high-tech applications is a rapid growing field of research. Despite the achievement of numerous Ln-TM cluster compounds comprising one Ln atom, the synthesis of Ln-TM clusters containing multiple Ln atoms remains challenging. Here, we present the preparation and self-assembly of a series of Au-bridged heterometallic clusters containing multiple cerium (Ce) atoms via on-surface coordination. By employing different pyridine and nitrile ligands, the ordered coordination assemblies of clusters containing 2, 3 and 4 Ce atoms bridged by Au adatoms are achieved on Au(111) and Au(100), as revealed by scanning tunneling microscopy. Density functional theory calculations uncover the indispensable role of the bridging Au adatoms in constructing the multi-Ce-containing clusters by connecting the Ce atoms via unsupported Ce-Au bonds. These findings demonstrate on-surface coordination as an efficient strategy for preparation and organization of the multi-Ln-containing heterometallic clusters.
Cryo-EM structure of amyloid fibrils formed by the entire low complexity domain of TDP-43
Authors: Li Qiuye , Babinchak W. Michael , Surewicz Witold K.
Published: March 2021

Amyotrophic lateral sclerosis and several other neurodegenerative diseases are associated with brain deposits of amyloid-like aggregates formed by the C-terminal fragments of TDP-43 that contain the low complexity domain of the protein. Here, we report the cryo-EM structure of amyloid formed from the entire TDP-43 low complexity domain in vitro at pH 4. This structure reveals single protofilament fibrils containing a large (139-residue), tightly packed core. While the C-terminal part of this core region is largely planar and characterized by a small proportion of hydrophobic amino acids, the N-terminal region contains numerous hydrophobic residues and has a non-planar backbone conformation, resulting in rugged surfaces of fibril ends. The structural features found in these fibrils differ from those previously found for fibrils generated from short protein fragments. The present atomic model for TDP-43 LCD fibrils provides insight into potential structural perturbations caused by phosphorylation and disease-related mutations.
Iron control of erythroid microtubule cytoskeleton as a potential target in treatment of iron-restricted anemia
Authors: Goldfarb Adam N. , Freeman Katie C. , Sahu Ranjit K. , Elagib Kamaleldin E. , Holy Maja , Arneja Abhinav , Polanowska-Grabowska Renata , Gru Alejandro A. , White Zollie , Khalil Shadi , Kerins Michael J. , Ooi Aikseng , Leitinger Norbert , Luckey Chance John , Delehanty Lorrie L.
Published: March 2021

Anemias of chronic disease and inflammation (ACDI) result from restricted iron delivery to erythroid progenitors. The current studies reveal an organellar response in erythroid iron restriction consisting of disassembly of the microtubule cytoskeleton and associated Golgi disruption. Isocitrate supplementation, known to abrogate the erythroid iron restriction response, induces reassembly of microtubules and Golgi in iron deprived progenitors. Ferritin, based on proteomic profiles, regulation by iron and isocitrate, and putative interaction with microtubules, is assessed as a candidate mediator. Knockdown of ferritin heavy chain (FTH1) in iron replete progenitors induces microtubule collapse and erythropoietic blockade; conversely, enforced ferritin expression rescues erythroid differentiation under conditions of iron restriction. Fumarate, a known ferritin inducer, synergizes with isocitrate in reversing molecular and cellular defects of iron restriction and in oral remediation of murine anemia. These findings identify a cytoskeletal component of erythroid iron restriction and demonstrate potential for its therapeutic targeting in ACDI.
Dual Ni/photoredox-catalyzed asymmetric cross-coupling to access chiral benzylic boronic esters
Authors: Zheng Purui , Zhou Pan , Wang Dong , Xu Wenhao , Wang Hepan , XU Tao
Published: March 2021

The flourishing Ni/photoredox-catalyzed asymmetric couplings typically rely on redox-neutral reactions. In this work, we report a reductive cross-coupling of aryl iodides and α-chloroboranes under a dual catalytic regime to further enrich the metallaphotoredox chemistry. This approach proceeds under mild conditions (visible light, ambient temperature, no strong base) to access the versatile benzylic boronic esters with good functional group tolerance and excellent enantioselectivities.
Anatomy of subcritical submarine flows with a lutocline and an intermediate destruction layer
Authors: Salinas Jorge S. , Balachandar S. , Shringarpure M. , Fedele J. , Hoyal D. , Zuñiga S. , Cantero M. I.
Published: March 2021

Turbidity currents are sediment-laden flows that travel over a sloping bed under a stagnant ambient fluid, driven by the density difference between the current and the ambient. Turbidity currents transport large amounts of carbon, nutrients and fresh water through oceans and play an important role in global geochemical cycling and seafloor ecosystems. Supercritical currents are observed in steeper slopes. Subcritical currents are observed in milder slopes, where the near-bed and interface layers are prevented from interacting across the velocity maximum. Past works show the existence of such a barrier to vertical momentum transfer is essential for the body of the subcritical current to extend over hundreds of kilometers in length without much increase in height. Here we observe the body of subcritical currents to have a three layer structure, where the turbulent near-bed layer and the non-turbulent interface layer are separated by an intermediate layer of negative turbulence production. We explain the mechanism by which this layer prevents the near-bed turbulent structures from penetrating into the interface layer by transferring energy back from turbulence to the mean flow.
A longitudinal, randomized experimental pilot study to investigate the effects of airborne ultrasound on human mental health, cognition, and brain structure
Authors: Ascone L. , Kling C. , Wieczorek J. , Koch C. , Kühn S.
Published: March 2021

Ultrasound-(US) emitting sources are highly present in modern human environments (e.g., movement sensors, electric transformers). US affecting humans or even posing a health hazard remains understudied. Hence, ultrasonic (22.4 kHz) vs. sham devices were installed in participants’ bedrooms, and active for 28 nights. Somatic and psychiatric symptoms, sound-sensitivity, sleep quality, executive function, and structural MRI were assessed pre-post. Somatization (possible nocebo) and phasic alertness increased significantly in sham, accuracy in a flexibility task decreased significantly in the verum condition (indicating hastier responses). Effects were not sustained after p-level adjustment. Exploratory voxel-based morphometry (VBM) revealed regional grey matter (rGMV) but no regional white matter volume changes in verum (relative to placebo). rGMV increased in bilateral cerebellum VIIb/Crus II and anterior cingulate (BA24). There were rGMV decreases in two bilateral frontal clusters: in the middle frontal gyri/opercular part of inferior frontal gyrus (BA46, 44), and the superior frontal gyri (BA4 ,6, 8). No brain-behavior-links were identified. Given the overall pattern of results, it is suggested that ultrasound may particularly induce regional gray matter decline in frontal areas, however with yet unclear behavioral consequences. Given the localization of clusters, candidate behavioral variables for follow-up investigation are complex motor control/coordination, stress regulation, speech processing, and inhibition tasks.

Trial registration: The trial was registered at NIH www.clinicaltrials.gov, trial identifier: NCT03459183, trial name: SonicBrain01, full trial protocol available here: https://clinicaltrials.gov/ct2/show/NCT03459183.
Collective migration during a gap closure in a two-dimensional haptotactic model
Authors: Versaevel Marie , Alaimo Laura , Seveau Valentine , Luciano Marine , Mohammed Danahe , Bruyère Céline , Vercruysse Eléonore , Théodoly Olivier , Gabriele Sylvain
Published: March 2021

The ability of cells to respond to substrate-bound protein gradients is crucial for many physiological processes, such as immune response, neurogenesis and cancer cell migration. However, the difficulty to produce well-controlled protein gradients has long been a limitation to our understanding of collective cell migration in response to haptotaxis. Here we use a photopatterning technique to create circular, square and linear fibronectin (FN) gradients on two-dimensional (2D) culture substrates. We observed that epithelial cells spread preferentially on zones of higher FN density, creating rounded or elongated gaps within epithelial tissues over circular or linear FN gradients, respectively. Using time-lapse experiments, we demonstrated that the gap closure mechanism in a 2D haptotaxis model requires a significant increase of the leader cell area. In addition, we found that gap closures are slower on decreasing FN densities than on homogenous FN-coated substrate and that fresh closed gaps are characterized by a lower cell density. Interestingly, our results showed that cell proliferation increases in the closed gap region after maturation to restore the cell density, but that cell–cell adhesive junctions remain weaker in scarred epithelial zones. Taken together, our findings provide a better understanding of the wound healing process over protein gradients, which are reminiscent of haptotaxis.
Lowest nocturnal systolic blood pressure is related to heavy proteinuria and outcomes in elderly patients with chronic kidney disease
Authors: Guo Xinru , Liang Shuang , Wang Wenling , Zheng Ying , Zhang Chun , Chen Xiangmei , Cai Guangyan
Published: March 2021

Ambulatory blood pressure monitoring (ABPM) can produce many variables, of which the lowest nocturnal systolic blood pressure (LNSBP) currently used in calculating morning surge is occasionally overlooked in recent kidney studies compared with other ABPM parameters. We explored the clinical effects of LNSBP in elderly patients with chronic kidney disease (CKD) in a multicenter, observational cohort study. A total of 356 elderly patients with CKD from 19 clinics were included in this analysis. We used multiple logistic regression and survival analyses to assess the associations between the lowest nocturnal systolic blood pressure and heavy proteinuria and kidney disease outcomes, respectively. The median age was 66 years, and 66.6% were men. The median eGFR was 49.2 ml/min/1.73 m2. Multivariate logistic regression analysis demonstrated that LNSBP (OR 1.24; 95% CI 1.10–1.39; P < 0.001; per 10 mmHg) was associated with heavy proteinuria. During the median follow-up of 23 months, 70 patients (19.7%) had a composite outcome; of these, 25 initiated dialysis, 25 had 40% eGFR loss, and 20 died. Cox analysis showed that the renal risk of LNSBP for CKD outcomes remained significant even after adjusting for background factors, including age, sex, medical history of hypertension and diabetes, smoking status, eGFR, 24-h proteinuria, and etiology of CKD (HR 1.18; 95% CI 1.06–1.32; P = 0.002; per 10 mmHg). Concentrating on LNSBP could be valuable in guiding antihypertensive treatment to control heavy proteinuria and improve renal prognosis in elderly CKD patients.
Photooxidation-induced fluorescence amplification system for an ultra-sensitive enzyme-linked immunosorbent assay (ELISA)
Authors: Heo Youhee , Shin Kwanwoo , Park Min Cheol , Kang Ji Yoon
Published: March 2021

This report suggests a method of enhancing the sensitivity of chemifluorescence-based ELISA, using photooxidation-induced fluorescence amplification (PIFA). The PIFA utilized autocatalytic photooxidation of the chemifluorescent substrate, 10-acetyl 3,7-dihydroxyphenoxazine (ADHP, Amplex Red) to amplify the fluorescent product resorufin, initially oxidized by horse radish peroxidase (HRP). As the amplification rate is proportional to the initial level of resorufin, the level of antigen labeled by HRP is quantified by analyzing the profile of fluorescence intensity. The normalized profile was interpolated into an autocatalysis model, and the rate of increase at half-maximum time was quantified by the use of an amplification index (AI). The lower limit of detection, for resorufin or HRP, was less than one-tenth that of the plate reader. It requires only slight modification of the fluorescence reader and is fully compatible with conventional or commercial ELISA. When it is applied to a commercial ELISA kit for the detection of amyloid beta, it is verified that the PIFA assay enhanced the detection sensitivity by more than a factor of 10 and was compatible with a conventional 96-well ELISA assay kit. We anticipate this PIFA assay to be used in research for the detection of low levels of proteins and for the early diagnosis of various diseases with rare protein biomarkers, at ultra-low (pg/mL) concentrations.
Antibody design using LSTM based deep generative model from phage display library for affinity maturation
Authors: Saka Koichiro , Kakuzaki Taro , Metsugi Shoichi , Kashiwagi Daiki , Yoshida Kenji , Wada Manabu , Tsunoda Hiroyuki , Teramoto Reiji
Published: March 2021

Molecular evolution is an important step in the development of therapeutic antibodies. However, the current method of affinity maturation is overly costly and labor-intensive because of the repetitive mutation experiments needed to adequately explore sequence space. Here, we employed a long short term memory network (LSTM)—a widely used deep generative model—based sequence generation and prioritization procedure to efficiently discover antibody sequences with higher affinity. We applied our method to the affinity maturation of antibodies against kynurenine, which is a metabolite related to the niacin synthesis pathway. Kynurenine binding sequences were enriched through phage display panning using a kynurenine-binding oriented human synthetic Fab library. We defined binding antibodies using a sequence repertoire from the NGS data to train the LSTM model. We confirmed that likelihood of generated sequences from a trained LSTM correlated well with binding affinity. The affinity of generated sequences are over 1800-fold higher than that of the parental clone. Moreover, compared to frequency based screening using the same dataset, our machine learning approach generated sequences with greater affinity.
Nutrient-driven genome evolution revealed by comparative genomics of chrysomonad flagellates
Authors: Majda Stephan , Beisser Daniela , Boenigk Jens
Published: March 2021

Phototrophic eukaryotes have evolved mainly by the primary or secondary uptake of photosynthetic organisms. A return to heterotrophy occurred multiple times in various protistan groups such as Chrysophyceae, despite the expected advantage of autotrophy. It is assumed that the evolutionary shift to mixotrophy and further to heterotrophy is triggered by a differential importance of nutrient and carbon limitation. We sequenced the genomes of 16 chrysophyte strains and compared them in terms of size, function, and sequence characteristics in relation to photo-, mixo- and heterotrophic nutrition. All strains were sequenced with Illumina and partly with PacBio. Heterotrophic taxa have reduced genomes and a higher GC content of up to 59% as compared to phototrophic taxa. Heterotrophs have a large pan genome, but a small core genome, indicating a differential specialization of the distinct lineages. The pan genome of mixotrophs and heterotrophs taken together but not the pan genome of the mixotrophs alone covers the complete functionality of the phototrophic strains indicating a random reduction of genes. The observed ploidy ranges from di- to tetraploidy and was found to be independent of taxonomy or trophic mode. Our results substantiate an evolution driven by nutrient and carbon limitation.
Population genomic and historical analysis suggests a global invasion by bridgehead processes in Mimulus guttatus
Authors: Vallejo-Marín Mario , Friedman Jannice , Twyford Alex D. , Lepais Olivier , Ickert-Bond Stefanie M. , Streisfeld Matthew A. , Yant Levi , van Kleunen Mark , Rotter Michael C. , Puzey Joshua R.
Published: March 2021

Imperfect historical records and complex demographic histories present challenges for reconstructing the history of biological invasions. Here, we combine historical records, extensive worldwide and genome-wide sampling, and demographic analyses to investigate the global invasion of Mimulus guttatus from North America to Europe and the Southwest Pacific. By sampling 521 plants from 158 native and introduced populations genotyped at >44,000 loci, we determined that invasive M. guttatus was first likely introduced to the British Isles from the Aleutian Islands (Alaska), followed by admixture from multiple parts of the native range. We hypothesise that populations in the British Isles then served as a bridgehead for vanguard invasions worldwide. Our results emphasise the highly admixed nature of introduced M. guttatus and demonstrate the potential of introduced populations to serve as sources of secondary admixture, producing novel hybrids. Unravelling the history of biological invasions provides a starting point to understand how invasive populations adapt to novel environments.
Transition from perovskite to misfit-layered structure materials: a highly oxygen deficient and stable oxygen electrode catalyst
Authors: Saqib Muhammad , Choi In-Gyu , Bae Hohan , Park Kwangho , Shin Ji-Seop , Kim You-Dong , Lee John-In , Jo Minkyeong , Kim Yeong-Cehol , Lee Kug-Seung , Song Sun-Ju , Wachsman Eric D. , Park Jun-Young
Published: March 2021

Despite the recent substantial progress in reversible protonic ceramic cells (RPCCs) it remains essential to further develop oxygen electrode materials that show superior activity and stability for oxygen reduction and evolution reactions due to the intrinsically sluggish kinetics of oxygen electrode reactions at lower temperature (<700 °C).
Efficient polysulfide trapping in lithium–sulfur batteries using ultrathin and flexible BaTiO3/graphene oxide/carbon nanotube layers
Authors: Wang Jing , Shi Zhe , Luo Yufeng , Wang Datao , Wu Hengcai , Li Qunqing , Fan Shoushan , Li Ju , Wang Jiaping
Published: March 2021

Ultrathin and flexible layers containing BaTiO3 (BTO) nanoparticles, graphene oxide (GO) sheets, and carbon nanotube (CNT) films (BTO/GO@CNT) are used to trap solvated polysulfides and alleviate the shuttle effect in lithium–sulfur (Li–S) batteries.
Updating atomic charge parameters of aliphatic amino acids: a quest to improve the performance of molecular modeling via sequential molecular dynamics and DFT-GIAO-NMR calculations
Authors: Colherinhas Guilherme
Published: March 2021

The update of the CHARMM36 atomic charge of amino acids changes the dipole moment, and the new description modifies the lifetime of HBs providing a better description of the magnetic signature of these compounds in water.
P-type transparent conducting characteristics of delafossite Ca doped CuScO2 prepared by hydrothermal synthesis
Authors: Gao Han , Zeng Xianwei , Guo Qiang , Yang Zhi , Deng Yanwen , Li Hong , Xiong Dehua
Published: March 2021

The thicknesses of Ca doped CSO sheets decreased with increasing Ca dopant due to Ca2+ substitution on Cu+ sites in CSO nanocrystals.
Edible and highly biocompatible nanodots from natural plants for the treatment of stress gastric ulcers
Authors: Lu Fang , Ma Yurong , Huang Hui , Zhang Yue , Kong Hui , Zhao Yan , Qu Huihua , Wang Qingguo , Liu Yang , Kang Zhenhui
Published: March 2021

Semi-carbonized nanodots from charred Atractylodes macrocephala are demonstrated in detail for their strong anti-stress gastric ulcer effect with inhibition up to 90% and show extremely high biocompatibility and ultra-low toxicity.
Heterogeneous photocatalytic reversible deactivation radical polymerization
Authors: An Zixin , Zhu Shilong , An Zesheng
Published: March 2021

Photocatalytic reversible deactivation radical polymerization (RDRP) permits the use of sustainable solar light for spatiotemporal regulation of radical polymerization under mild conditions.
Structure evolution during phase separation in spin-coated ethylcellulose/hydroxypropylcellulose films
Authors: Carmona Pierre , Röding Magnus , Särkkä Aila , von Corswant Christian , Olsson Eva , Lorén Niklas
Published: March 2021

Porous phase-separated films made of ethylcellulose (EC) and hydroxypropylcellulose (HPC) for controlled drug release were made using spin-coating. The method optimization gave good control over the film thickness and the length scale.
Autonomous adaptive Q(U) control for distributed generation in weak medium‐voltage distribution grids
Authors: Ampofo Desmond Okwabi , Myrzik Johanna M. A.
Published: March 2021

This study seeks to exploit the reactive power capability of inverter‐based distributed generation (DG) to solve the voltageregulation challenges associated with weak medium‐voltage distribution networks in developing countries. Voltage‐dependent reactive power control, also known as the Q(U) control method, is widely used for voltage regulation. The challenge with this control mode, however, is determining its control parameters, which must be unique for each bus for optimal performance compared with implementing standardised or general parameters. This paper proposes an innovative approach to incorporate an adaptive functionality into the typical Q(U) control to enhance its performance in medium‐voltage grids. This concept, when implemented, achieved better performance than that of the Q(U) control with fixed parameters, which was unsatisfactory under certain conditions, and performance comparable to that of the centralised voltage scheme, which relies on communication facilities.
Inexact induced L2 observer‐based control of polytopic LPV systems: application to clutchless automated manual transmission of pure electric vehicles
Authors: Abbasghorbani Motahare , Hassan Asemani Mohammad , Vafamand Navid , Mobayen Saleh
Published: March 2021

A novel method for observer‐based control of disturbed polytopic linear parameter varying (LPV) systems with inexactly measured scheduling parameters is investigated in this study. Despite the imperfect scheduling parameters knowledge, the proposed control method ensures the closed‐loop induced L2‐norm performance criterion. Unlike the previous methods, the inexact scheduling parameters are not assumed to be proportional to the original scheduling parameters of the LPV system. Employing both cases of parameter‐dependent and parameter‐independent Lyapunov functions, sufficient design conditions in terms of linear matrix inequalities are provided using Finsler's lemma. Numerical examples are included to demonstrate the efficiency of the proposed method and its superiority over the previous techniques. Moreover, a practical case study, i.e. clutchless automated manual transmission system is considered and controlled by the developed approach numerically.
Design of a snubber circuit for low voltage DC solid‐state circuit breakers
Authors: Wang Zhongying , Sankara Narayanan Ekkanath Madathil
Published: March 2021

Solid‐state circuit breakers (SSCBs) are designed to interrupt fault currents typically several orders faster than its electromechanical counterparts. However, such an ultrafast switching operation would produce a dangerous overvoltage which might cause damages to SSCBs and other circuit elements in the system. This paper proposes a novel snubber circuit for suppressing the overvoltage. It takes the advantages of both resistor‐capacitor‐diode (RCD) snubbers and metal oxide varistors (MOVs). Its operating process is analysed before the proposed snubber circuit for 400V DC SSCBs is designed. Pspice simulator is employed for simulating the operating process and a prototype SSCB with the proposed snubber is built and tested in a lab‐scale DC system. The results of simulation and experiment validate the effectiveness of the proposed snubber.
Connection between the long secondary period and red giant evolution
Authors: Pawlak Michał
Published: March 2021

Aims.The mechanism behind the long secondary period (LSP) observed in pulsating red giants remains unknown. In this work, I investigate the connection between the red giant branch and the asymptotic giant branch evolution and the appearance of the LSP – a phenomenon that has been observed in a significant proportion of red giants.

Methods.For the purposes of this work, I used the OGLE-III sample of the OSARG variables in the Large Magellanic Cloud. I constructed density maps in the period-luminosity as well as color-magnitude planes for the stars showing an LSP and compared them to the remaining giants. I also fit the spectral energy distribution to test whether an additional source of reddening is present in the LSP stars.

Results.Here, I posit the hypothesis that the LSP phenomenon may be related to a transition between the different pulsation period-luminosity sequences. I also show that an overabundance of the stars showing LSP can be observed around the tip of the red giant branch, and much more prominently, at the upper part of the asymptotic giant branch. The main over-density region appears to be slightly fainter and redder than the bulk of the asymptotic giant branch. It also seems to correspond to the area of the Hertzsprung-Russell diagram where stable winds and high mass loss are present.

Conclusions.The LSP can possibly be shown to be a recurring phenomenon that appears and disappears at various points of the red giant evolution. The LSP stars appear to be more reddened than other giants, which suggests the intrinsic nature of the reddening is likely to be related to large dust emission. The analysis appears to confirm the hypothesis that there is a relation between the mass loss due to the presence of strong stellar wind and the appearance of an LSP.