bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CD8+ NK cell transcriptomic signature associated with clinical outcome in relapsing remitting multiple sclerosis
Authors: McKinney Eoin F. , Cuthbertson Iona , Harris Kristina M. , Smilek Dawn E. , Connor Christopher , Manferrari Giulia , Carr Edward J. , Zamvil Scott S. , Smith Kenneth G. C. 
Published: January 2021

AbstractMultiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with the majority of cases characterised by relapsing/remitting (RRMS) attacks of neurologic dysfunction followed by variable resolution. Improving clinical outcomes in RRMS requires both a better understanding of the immunological mechanisms driving recurrent demyelination and better means of predicting future disease course to facilitate early targeted therapy. Here, we apply hypothesis-generating network transcriptomics to CD8+ cells isolated from patients in RRMS, identifying a signature reflecting expansion of a subset of CD8+ natural killer cells (NK8+) associated with favourable outcome. NK8+ are capable of regulating CD4+ T cell activation and proliferation in vitro, with reduced expression of HLA-G binding inhibitory receptors and consequent reduced sensitivity to HLA-G-mediated suppression. We identify surrogate markers of the NK8+ signature in peripheral blood leucocytes and validate their association with clinical outcome in an independent cohort, suggesting their measurement may facilitate early, targeted therapy in RRMS.
Structures of the archaerhodopsin-3 transporter reveal that disordering of internal water networks underpins receptor sensitization
Authors: Bada Juarez Juan F. , Judge Peter J. , Adam Suliman , Axford Danny , Vinals Javier , Birch James , Kwan Tristan O. C. , Hoi Kin Kuan , Yen Hsin-Yung , Vial Anthony , Milhiet Pierre-Emmanuel , Robinson Carol V. , Schapiro Igor , Moraes Isabel , Watts Anthony 
Published: January 2021

AbstractMany transmembrane receptors have a desensitized state, in which they are unable to respond to external stimuli. The family of microbial rhodopsin proteins includes one such group of receptors, whose inactive or dark-adapted (DA) state is established in the prolonged absence of light. Here, we present high-resolution crystal structures of the ground (light-adapted) and DA states of Archaerhodopsin-3 (AR3), solved to 1.1 Å and 1.3 Å resolution respectively. We observe significant differences between the two states in the dynamics of water molecules that are coupled via H-bonds to the retinal Schiff Base. Supporting QM/MM calculations reveal how the DA state permits a thermodynamic equilibrium between retinal isomers to be established, and how this same change is prevented in the ground state in the absence of light. We suggest that the different arrangement of internal water networks in AR3 is responsible for the faster photocycle kinetics compared to homologs.
Integrating deep learning CT-scan model, biological and clinical variables to predict severity of COVID-19 patients
Authors: Lassau Nathalie , Ammari Samy , Chouzenoux Emilie , Gortais Hugo , Herent Paul , Devilder Matthieu , Soliman Samer , Meyrignac Olivier , Talabard Marie-Pauline , Lamarque Jean-Philippe , Dubois Remy , Loiseau Nicolas , Trichelair Paul , Bendjebbar Etienne , Garcia Gabriel , Balleyguier Corinne , Merad Mansouria , Stoclin Annabelle , Jegou Simon , Griscelli Franck , Tetelboum Nicolas , Li Yingping , Verma Sagar , Terris Matthieu , Dardouri Tasnim , Gupta Kavya , Neacsu Ana , Chemouni Frank , Sefta Meriem , Jehanno Paul , Bousaid Imad , Boursin Yannick , Planchet Emmanuel , Azoulay Mikael , Dachary Jocelyn , Brulport Fabien , Gonzalez Adrian , Dehaene Olivier , Schiratti Jean-Baptiste , Schutte Kathryn , Pesquet Jean-Christophe , Talbot Hugues , Pronier Elodie , Wainrib Gilles , Clozel Thomas , Barlesi Fabrice , Bellin Marie-France , Blum Michael G. B. 
Published: January 2021

AbstractThe SARS-COV-2 pandemic has put pressure on intensive care units, so that identifying predictors of disease severity is a priority. We collect 58 clinical and biological variables, and chest CT scan data, from 1003 coronavirus-infected patients from two French hospitals. We train a deep learning model based on CT scans to predict severity. We then construct the multimodal AI-severity score that includes 5 clinical and biological variables (age, sex, oxygenation, urea, platelet) in addition to the deep learning model. We show that neural network analysis of CT-scans brings unique prognosis information, although it is correlated with other markers of severity (oxygenation, LDH, and CRP) explaining the measurable but limited 0.03 increase of AUC obtained when adding CT-scan information to clinical variables. Here, we show that when comparing AI-severity with 11 existing severity scores, we find significantly improved prognosis performance; AI-severity can therefore rapidly become a reference scoring approach.
Homodyne-based quantum random number generator at 2.9 Gbps secure against quantum side-information
Authors: Gehring Tobias , Lupo Cosmo , Kordts Arne , Solar Nikolic Dino , Jain Nitin , Rydberg Tobias , Pedersen Thomas B. , Pirandola Stefano , Andersen Ulrik L. 
Published: January 2021

AbstractQuantum random number generators promise perfectly unpredictable random numbers. A popular approach to quantum random number generation is homodyne measurements of the vacuum state, the ground state of the electro-magnetic field. Here we experimentally implement such a quantum random number generator, and derive a security proof that considers quantum side-information instead of classical side-information only. Based on the assumptions of Gaussianity and stationarity of noise processes, our security analysis furthermore includes correlations between consecutive measurement outcomes due to finite detection bandwidth, as well as analog-to-digital converter imperfections. We characterize our experimental realization by bounding measured parameters of the stochastic model determining the min-entropy of the system’s measurement outcomes, and we demonstrate a real-time generation rate of 2.9 Gbit/s. Our generator follows a trusted, device-dependent, approach. By treating side-information quantum mechanically an important restriction on adversaries is removed, which usually was reserved to semi-device-independent and device-independent schemes.
Particle-resolved topological defects of smectic colloidal liquid crystals in extreme confinement
Authors: Wittmann René , Cortes Louis B. G. , Löwen Hartmut , Aarts Dirk G. A. L. 
Published: January 2021

AbstractConfined samples of liquid crystals are characterized by a variety of topological defects and can be exposed to external constraints such as extreme confinements with nontrivial topology. Here we explore the intrinsic structure of smectic colloidal layers dictated by the interplay between entropy and an imposed external topology. Considering an annular confinement as a basic example, a plethora of competing states is found with nontrivial defect structures ranging from laminar states to multiple smectic domains and arrays of edge dislocations, which we refer to as Shubnikov states in formal analogy to the characteristic of type-II superconductors. Our particle-resolved results, gained by a combination of real-space microscopy of thermal colloidal rods and fundamental-measure-based density functional theory of hard anisotropic bodies, agree on a quantitative level.
Treadmilling FtsZ polymers drive the directional movement of sPG-synthesis enzymes via a Brownian ratchet mechanism
Authors: McCausland Joshua W. , Yang Xinxing , Squyres Georgia R. , Lyu Zhixin , Bruce Kevin E. , Lamanna Melissa M. , Söderström Bill , Garner Ethan C. , Winkler Malcolm E. , Xiao Jie , Liu Jian 
Published: January 2021

AbstractThe FtsZ protein is a central component of the bacterial cell division machinery. It polymerizes at mid-cell and recruits more than 30 proteins to assemble into a macromolecular complex to direct cell wall constriction. FtsZ polymers exhibit treadmilling dynamics, driving the processive movement of enzymes that synthesize septal peptidoglycan (sPG). Here, we combine theoretical modelling with single-molecule imaging of live bacterial cells to show that FtsZ’s treadmilling drives the directional movement of sPG enzymes via a Brownian ratchet mechanism. The processivity of the directional movement depends on the binding potential between FtsZ and the sPG enzyme, and on a balance between the enzyme’s diffusion and FtsZ’s treadmilling speed. We propose that this interplay may provide a mechanism to control the spatiotemporal distribution of active sPG enzymes, explaining the distinct roles of FtsZ treadmilling in modulating cell wall constriction rate observed in different bacteria.
Shedding light on the nature of the catalytically active species in photocatalytic reactions using Bi2O3 semiconductor
Authors: Riente Paola , Fianchini Mauro , Llanes Patricia , Pericàs Miquel A. , Noël Timothy 
Published: January 2021

AbstractThe importance of discovering the true catalytically active species involved in photocatalytic systems allows for a better and more general understanding of photocatalytic processes, which eventually may help to improve their efficiency. Bi2O3 has been used as a heterogeneous photocatalyst and is able to catalyze several synthetically important visible-light-driven organic transformations. However, insight into the operative catalyst involved in the photocatalytic process is hitherto missing. Herein, we show through a combination of theoretical and experimental studies that the perceived heterogeneous photocatalysis with Bi2O3 in the presence of alkyl bromides involves a homogeneous BinBrm species, which is the true photocatalyst operative in the reaction. Hence, Bi2O3 can be regarded as a precatalyst which is slowly converted in an active homogeneous photocatalyst. This work can also be of importance to mechanistic studies involving other semiconductor-based photocatalytic processes.
Lead-free hybrid perovskite N(CH3)4SnI3 with robust ferroelectricity induced by large and non-polar N(CH3)4+ molecular cation
Authors: Wei Hai , Yang Yali , Chen Shiyou , Xiang H. J. 
Published: January 2021

AbstractThe ferroelectricity in the hybrid perovskite CH3NH3PbI3 is under debate because it results from the polar molecular cation CH3NH3+ while the molecular orientation was reported to be random. Here we predict that a Pb-free hybrid perovskite N(CH3)4SnI3 with non-polar molecular cation N(CH3)4+ has strong ferroelectricity with a spontaneous polarization of 16.13 μC cm−2. The large polarization results from the distortion of SnI6 octahedron induced by the large N(CH3)4+ and is independent of the molecular orientation, so the ferroelectricity is robust. The ferroelectric R3m perovskite structure of N(CH3)4SnI3 can be synthesized as the ground state under a hydrostatic pressure over 3 GPa and remains stable under ambient pressure. Given the strong ferroelectricity, good stability and high visible-light absorption, N(CH3)4SnI3 may be an ideal light-absorber semiconductor for high-efficiency solar cells because its ferroelectric polarization can facilitate electron-hole separation and produce large bulk photovoltaic effect, making the design of homogeneous bulk photovoltaic devices possible.
The molecular dynamics of subdistal appendages in multi-ciliated cells
Authors: Ryu Hyunchul , Lee Haeryung , Lee Jiyeon , Noh Hyuna , Shin Miram , Kumar Vijay , Hong Sejeong , Kim Jaebong , Park Soochul 
Published: January 2021

AbstractThe motile cilia of ependymal cells coordinate their beats to facilitate a forceful and directed flow of cerebrospinal fluid (CSF). Each cilium originates from a basal body with a basal foot protruding from one side. A uniform alignment of these basal feet is crucial for the coordination of ciliary beating. The process by which the basal foot originates from subdistal appendages of the basal body, however, is unresolved. Here, we show FGFR1 Oncogene Partner (FOP) is a useful marker for delineating the transformation of a circular, unpolarized subdistal appendage into a polarized structure with a basal foot. Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A) interacts with FOP to assemble region I of the basal foot. Importantly, disruption of ANKS1A reduces the size of region I. This produces an unstable basal foot, which disrupts rotational polarity and the coordinated beating of cilia in young adult mice. ANKS1A deficiency also leads to severe degeneration of the basal foot in aged mice and the detachment of cilia from their basal bodies. This role of ANKS1A in the polarization of the basal foot is evolutionarily conserved in vertebrates. Thus, ANKS1A regulates FOP to build and maintain the polarity of subdistal appendages.
A synthetic BRET-based optogenetic device for pulsatile transgene expression enabling glucose homeostasis in mice
Authors: Li Ting , Chen Xianjun , Qian Yajie , Shao Jiawei , Li Xie , Liu Shuning , Zhu Linyong , Zhao Yuzheng , Ye Haifeng , Yang Yi 
Published: January 2021

AbstractPulsing cellular dynamics in genetic circuits have been shown to provide critical capabilities to cells in stress response, signaling and development. Despite the fascinating discoveries made in the past few years, the mechanisms and functional capabilities of most pulsing systems remain unclear, and one of the critical challenges is the lack of a technology that allows pulsatile regulation of transgene expression both in vitro and in vivo. Here, we describe the development of a synthetic BRET-based transgene expression (LuminON) system based on a luminescent transcription factor, termed luminGAVPO, by fusing NanoLuc luciferase to the light-switchable transcription factor GAVPO. luminGAVPO allows pulsatile and quantitative activation of transgene expression via both chemogenetic and optogenetic approaches in mammalian cells and mice. Both the pulse amplitude and duration of transgene expression are highly tunable via adjustment of the amount of furimazine. We further demonstrated LuminON-mediated blood-glucose homeostasis in type 1 diabetic mice. We believe that the BRET-based LuminON system with the pulsatile dynamics of transgene expression provides a highly sensitive tool for precise manipulation in biological systems that has strong potential for application in diverse basic biological studies and gene- and cell-based precision therapies in the future.
Shadow enhanced self-charging power system for wave and solar energy harvesting from the ocean
Authors: Zhang Qian , Liang Qijie , Nandakumar Dilip Krishna , Qu Hao , Shi Qiongfeng , Alzakia Fuad Indra , Tay Darrell Jun Jie , Yang Lin , Zhang Xueping , Suresh Lakshmi , Lee Chengkuo , Wee Andrew Thye Shen , Tan Swee Ching 
Published: January 2021

AbstractHybrid energy-harvesting systems that capture both wave and solar energy from the oceans using triboelectric nanogenerators and photovoltaic cells are promising renewable energy solutions. However, ubiquitous shadows cast from moving objects in these systems are undesirable as they degrade the performance of the photovoltaic cells. Here we report a shadow-tribo-effect nanogenerator that hybrids tribo-effect and shadow-effect together to overcome this issue. Several fiber-supercapacitors are integrated with the shadow-tribo-effect nanogenerator to form a self-charging power system. To capture and store wave/solar energy from oceans, an energy ball based on the self-charging power system is demonstrated. By harnessing the shadow-effect, i.e. the shadow of the moving object in the energy ball, the charging time shortens to 253.3 s to charge the fiber-supercapacitors to the same voltage (0.3 V) as using pure tribo-effect. This cost-effective method to harvest and store the wave/solar energy from the oceans in this work is expected to inspire next-generation large-scale blue energy harvesting.
Subtraction-free and bisulfite-free specific sequencing of 5-methylcytosine and its oxidized derivatives at base resolution
Authors: Liu Yibin , Hu Zhiyuan , Cheng Jingfei , Siejka-Zielińska Paulina , Chen Jinfeng , Inoue Masato , Ahmed Ahmed Ashour , Song Chun-Xiao 
Published: January 2021

AbstractAlthough various methods have been developed for sequencing cytosine modifications, it is still challenging for specific and quantitative sequencing of individual modification at base-resolution. For example, to obtain both true 5-methylcytosine (5mC) and true 5-hydroxymethylcytosine (5hmC) information, the two major epigenetic modifications, it usually requires subtraction of two methods, which increases noise and requires high sequencing depth. Recently, we developed TET-assisted pyridine borane sequencing (TAPS) for bisulfite-free direct sequencing of 5mC and 5hmC. Here we demonstrate that two sister methods, TAPSβ and chemical-assisted pyridine borane sequencing (CAPS), can be effectively used for subtraction-free and specific whole-genome sequencing of 5mC and 5hmC, respectively. We also demonstrate pyridine borane sequencing (PS) for whole-genome profiling of 5-formylcytosine and 5-carboxylcytosine, the further oxidized derivatives of 5mC and 5hmC. This work completes the set of versatile borane reduction chemistry-based methods as a comprehensive toolkit for direct and quantitative sequencing of all four cytosine epigenetic modifications.
Human antibodies targeting a Mycobacterium transporter protein mediate protection against tuberculosis
Authors: Watson Avia , Li Hao , Ma Bingting , Weiss Ronen , Bendayan Daniele , Abramovitz Lilach , Ben-Shalom Noam , Mor Michael , Pinko Erica , Bar Oz Michal , Wang Zhenqi , Du Fengjiao , Lu Yu , Rybniker Jan , Dahan Rony , Huang Hairong , Barkan Daniel , Xiang Ye , Javid Babak , Freund Natalia T. 
Published: January 2021

AbstractMycobacterium tuberculosis(Mtb) exposure drives antibody responses, but whether patients with active tuberculosis elicit protective antibodies, and against which antigens, is still unclear. Here we generate monoclonal antibodies from memory B cells of one patient to investigate the B cell responses during active infection. The antibodies, members of four distinct B cell clones, are directed against the Mtb phosphate transporter subunit PstS1. Antibodies p4-36 and p4-163 reduceMycobacterium bovis-BCG and Mtb levels in an ex vivo human whole blood growth inhibition assay in an FcR-dependent manner; meanwhile, germline versions of p4-36 and p4-163 do not bind Mtb. Crystal structures of p4-36 and p4-170, complexed to PstS1, are determined at 2.1 Å and 2.4 Å resolution, respectively, to reveal two distinctive PstS1 epitopes. Lastly, a prophylactic p4-36 and p4-163 treatment in Mtb-infected Balb/c mice reduces bacterial lung burden by 50%. Our study shows that inhibitory anti-PstS1 B cell responses arise during active tuberculosis.
Mechano-responsive hydrogen-bonding array of thermoplastic polyurethane elastomer captures both strength and self-healing
Authors: Eom Youngho , Kim Seon-Mi , Lee Minkyung , Jeon Hyeonyeol , Park Jaeduk , Lee Eun Seong , Hwang Sung Yeon , Park Jeyoung , Oh Dongyeop X. 
Published: January 2021

AbstractSelf-repairable materials strive to emulate curable and resilient biological tissue; however, their performance is currently insufficient for commercialization purposes because mending and toughening are mutually exclusive. Herein, we report a carbonate-type thermoplastic polyurethane elastomer that self-heals at 35 °C and exhibits a tensile strength of 43 MPa; this elastomer is as strong as the soles used in footwear. Distinctively, it has abundant carbonyl groups in soft-segments and is fully amorphous with negligible phase separation due to poor hard-segment stacking. It operates in dual mechano-responsive mode through a reversible disorder-to-order transition of its hydrogen-bonding array; it heals when static and toughens when dynamic. In static mode, non-crystalline hard segments promote the dynamic exchange of disordered carbonyl hydrogen-bonds for self-healing. The amorphous phase forms stiff crystals when stretched through a transition that orders inter-chain hydrogen bonding. The phase and strain fully return to the pre-stressed state after release to repeat the healing process.
Thermodynamic resources in continuous-variable quantum systems
Authors: Narasimhachar Varun , Assad Syed , Binder Felix C. , Thompson Jayne , Yadin Benjamin , Gu Mile 
Published: January 2021

AbstractThermodynamic resources, beyond their well-known usefulness in work extraction and other thermodynamic tasks, are often important also in tasks that are not evidently thermodynamic. Here we develop a framework for identifying such resources in diverse applications of bosonic continuous-variable systems. Introducing the class of bosonic linear thermal operations to model operationally feasible processes, we apply this model to identify uniquely quantum properties of bosonic states that refine classical notions of thermodynamic resourcefulness. Among these are (1) a suite of temperature-like quantities generalizing the equilibrium temperature to quantum, non-equilibrium scenarios; (2) signal-to-noise ratios quantifying a system’s capacity to carry information in phase-space displacement; and (3) well-established non-classicality measures quantifying the resolution in sensing and parameter estimation tasks.
LimeMap: a comprehensive map of lipid mediator metabolic pathways
Authors: Nishi Akinori , Ohbuchi Katsuya , Kaifuchi Noriko , Shimobori Chika , Kushida Hirotaka , Yamamoto Masahiro , Kita Yoshihiro , Tokuoka Suzumi M. , Yachie Ayako , Matsuoka Yukiko , Kitano Hiroaki 
Published: January 2021

AbstractLipid mediators are major factors in multiple biological functions and are strongly associated with disease. Recent lipidomics approaches have made it possible to analyze multiple metabolites and the associations of individual lipid mediators. Such systematic approaches have enabled us to identify key changes of biological relevance. Against this background, a knowledge-based pathway map of lipid mediators would be useful to visualize and understand the overall interactions of these factors. Here, we have built a precise map of lipid mediator metabolic pathways (LimeMap) to visualize the comprehensive profiles of lipid mediators that change dynamically in various disorders. We constructed the map by focusing on ω-3 and ω-6 fatty acid metabolites and their respective metabolic pathways, with manual curation of referenced information from public databases and relevant studies. Ultimately, LimeMap comprises 282 factors (222 mediators, and 60 enzymes, receptors, and ion channels) and 279 reactions derived from 102 related studies. Users will be able to modify the map and visualize measured data specific to their purposes using CellDesigner and VANTED software. We expect that LimeMap will contribute to elucidating the comprehensive functional relationships and pathways of lipid mediators.