bluuebunny/crossref_metadata_2025 huggingface dataset:
The dichotomous and incomplete adaptive immunity in COVID-19 patients with different disease severity
Authors: Gao Leiqiong , Zhou Jing , Yang Sen , Wang Lisha , Chen Xiangyu , Yang Yang , Li Ren , Pan Zhiwei , Zhao Jing , Li Zhirong , Huang Qizhao , Tang Jianfang , Hu Li , Liu Pinghuang , Zhang Guozhong , Chen Yaokai , Ye Lilin
Published: March 2021

The adaptive immunity that protects patients from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not well characterized. In particular, the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses, but the underlying mechanisms remain unknown; meanwhile, the protective immunity that guide the recovery of these asymptomatic patients is elusive. Here, we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 64 patients with other disease severity (mild, n = 10, moderate, n = 32, severe, n = 12) and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center (GC) B cell responses that result in robust and prolonged humoral immunity, assessed by GC response indicators including follicular helper T (TFH) cell and memory B cell responses as well as serum CXCL13 levels. Alternatively, these patients mounted potent virus-specific TH1 and CD8+ T cell responses. In sharp contrast, patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses; however, the virus-specific TH1 and CD8+ T cells were minimally induced in these patients. These results, therefore, uncovered the protective immunity in asymptomatic patients and also revealed the strikingly dichotomous and incomplete humoral and cellular immune responses in COVID-19 patients with different disease severity, providing important insights into rational design of effective COVID-19 vaccines.
How do established developmental risk-factors for schizophrenia change the way the brain develops?
Authors: Eyles Darryl W.
Published: March 2021

The recognition that schizophrenia is a disorder of neurodevelopment is widely accepted. The original hypothesis was coined more than 30 years ago and the wealth of supportive epidemiologically data continues to grow. A number of proposals have been put forward to suggest how adverse early exposures in utero alter the way the adult brain functions, eventually producing the symptoms of schizophrenia. This of course is extremely difficult to study in developing human brains, so the bulk of what we know comes from animal models of such exposures. In this review, I will summarise the more salient features of how the major epidemiologically validated exposures change the way the brain is formed leading to abnormal function in ways that are informative for schizophrenia symptomology. Surprisingly few studies have examined brain ontogeny from embryo to adult in such models. However, where there is longitudinal data, various convergent mechanisms are beginning to emerge involving stress and immune pathways. There is also a surprisingly consistent alteration in how very early dopamine neurons develop in these models. Understanding how disparate epidemiologically-validated exposures may produce similar developmental brain abnormalities may unlock convergent early disease-related pathways/processes.
Predicting the public health impact of a malaria transmission-blocking vaccine
Authors: Challenger Joseph D. , Olivera Mesa Daniela , Da Dari F. , Yerbanga R. Serge , Lefèvre Thierry , Cohuet Anna , Churcher Thomas S.
Published: March 2021

Transmission-blocking vaccines that interrupt malaria transmission from humans to mosquitoes are being tested in early clinical trials. The activity of such a vaccine is commonly evaluated using membrane-feeding assays. Understanding the field efficacy of such a vaccine requires knowledge of how heavily infected wild, naturally blood-fed mosquitoes are, as this indicates how difficult it will be to block transmission. Here we use data on naturally infected mosquitoes collected in Burkina Faso to translate the laboratory-estimated activity into an estimated activity in the field. A transmission dynamics model is then utilised to predict a transmission-blocking vaccine’s public health impact alongside existing interventions. The model suggests that school-aged children are an attractive population to target for vaccination. Benefits of vaccination are distributed across the population, averting the greatest number of cases in younger children. Utilising a transmission-blocking vaccine alongside existing interventions could have a substantial impact against malaria.
Real-time tracking and prediction of COVID-19 infection using digital proxies of population mobility and mixing
Authors: Leung Kathy , Wu Joseph T. , Leung Gabriel M.
Published: March 2021

Digital proxies of human mobility and physical mixing have been used to monitor viral transmissibility and effectiveness of social distancing interventions in the ongoing COVID-19 pandemic. We develop a new framework that parameterizes disease transmission models with age-specific digital mobility data. By fitting the model to case data in Hong Kong, we are able to accurately track the local effective reproduction number of COVID-19 in near real time (i.e., no longer constrained by the delay of around 9 days between infection and reporting of cases) which is essential for quick assessment of the effectiveness of interventions on reducing transmissibility. Our findings show that accurate nowcast and forecast of COVID-19 epidemics can be obtained by integrating valid digital proxies of physical mixing into conventional epidemic models.
Extrusion of subducted crust explains the emplacement of far-travelled ophiolites
Authors: Porkoláb Kristóf , Duretz Thibault , Yamato Philippe , Auzemery Antoine , Willingshofer Ernst
Published: March 2021

Continental subduction below oceanic plates and associated emplacement of ophiolite sheets remain enigmatic chapters in global plate tectonics. Numerous ophiolite belts on Earth exhibit a far-travelled ophiolite sheet that is separated from its oceanic root by tectonic windows exposing continental crust, which experienced subduction-related high pressure-low temperature metamorphism during obduction. However, the link between continental subduction-exhumation dynamics and far-travelled ophiolite emplacement remains poorly understood. Here we combine data collected from ophiolite belts worldwide with thermo-mechanical simulations of continental subduction dynamics to show the causal link between the extrusion of subducted continental crust and the emplacement of far-travelled ophiolites. Our results reveal that buoyancy-driven extrusion of subducted crust triggers necking and breaking of the overriding oceanic upper plate. The broken-off piece of oceanic lithosphere is then transported on top of the continent along a flat thrust segment and becomes a far-travelled ophiolite sheet separated from its root by the extruded continental crust. Our results indicate that the extrusion of the subducted continental crust and the emplacement of far-travelled ophiolite sheets are inseparable processes.
Modeled microgravity alters lipopolysaccharide and outer membrane vesicle production of the beneficial symbiont Vibrio fischeri
Authors: Vroom Madeline M. , Rodriguez-Ocasio Yaneli , Lynch Jonathan B. , Ruby Edward G. , Foster Jamie S.
Published: March 2021

Reduced gravity, or microgravity, can have a pronounced impact on the physiology of animals, but the effects on their associated microbiomes are not well understood. Here, the impact of modeled microgravity on the shedding of Gram-negative lipopolysaccharides (LPS) by the symbiotic bacterium Vibrio fischeri was examined using high-aspect ratio vessels. LPS from V. fischeri is known to induce developmental apoptosis within its symbiotic tissues, which is accelerated under modeled microgravity conditions. In this study, we provide evidence that exposure to modeled microgravity increases the amount of LPS released by the bacterial symbiont in vitro. The higher rates of shedding under modeled microgravity conditions are associated with increased production of outer-membrane vesicles (OMV), which has been previously correlated to flagellar motility. Mutants of V. fischeri defective in the production and rotation of their flagella show significant decreases in LPS shedding in all treatments, but levels of LPS are higher under modeled microgravity despite loss of motility. Modeled microgravity also appears to affect the outer-membrane integrity of V. fischeri, as cells incubated under modeled microgravity conditions are more susceptible to cell-membrane-disrupting agents. These results suggest that, like their animal hosts, the physiology of symbiotic microbes can be altered under microgravity-like conditions, which may have important implications for host health during spaceflight.
Dimensional transformation of chemical bonding during crystallization in a layered chalcogenide material
Authors: Saito Yuta , Hatayama Shogo , Shuang Yi , Fons Paul , Kolobov Alexander V. , Sutou Yuji
Published: March 2021

Two-dimensional (2D) van der Waals (vdW) materials possess a crystal structure in which a covalently-bonded few atomic-layer motif forms a single unit with individual motifs being weakly bound to each other by vdW forces. Cr2Ge2Te6 is known as a 2D vdW ferromagnetic insulator as well as a potential phase change material for non-volatile memory applications. Here, we provide evidence for a dimensional transformation in the chemical bonding from a randomly bonded three-dimensional (3D) disordered amorphous phase to a 2D bonded vdW crystalline phase. A counterintuitive metastable “quasi-layered” state during crystallization that exhibits both “long-range order and short-range disorder” with respect to atomic alignment clearly distinguishes the system from conventional materials. This unusual behavior is thought to originate from the 2D nature of the crystalline phase. These observations provide insight into the crystallization mechanism of layered materials in general, and consequently, will be useful for the realization of 2D vdW material-based functional nanoelectronic device applications.
Serotonin deficiency induced after brain maturation rescues consequences of early life adversity
Authors: Aboagye B. , Weber T. , Merdian H. L. , Bartsch D. , Lesch K. P. , Waider J.
Published: March 2021

Brain serotonin (5-HT) system dysfunction is implicated in depressive disorders and acute depletion of 5-HT precursor tryptophan has frequently been used to model the influence of 5-HT deficiency on emotion regulation. Tamoxifen (TAM)-induced Cre/loxP-mediated inactivation of the tryptophan hydroxylase-2 gene (Tph2) was used to investigate the effects of provoked 5-HT deficiency in adult mice (Tph2 icKO) previously subjected to maternal separation (MS). The efficiency of Tph2 inactivation was validated by immunohistochemistry and HPLC. The impact of Tph2 icKO in interaction with MS stress (Tph2 icKO × MS) on physiological parameters, emotional behavior and expression of 5-HT system-related marker genes were assessed. Tph2 icKO mice displayed a significant reduction in 5-HT immunoreactive cells and 5-HT concentrations in the rostral raphe region within four weeks following TAM treatment. Tph2 icKO and MS differentially affected food and water intake, locomotor activity as well as panic-like escape behavior. Tph2 icKO prevented the adverse effects of MS stress and altered the expression of the genes previously linked to stress and emotionality. In conclusion, an experimental model was established to study the behavioral and neurobiological consequences of 5-HT deficiency in adulthood in interaction with early-life adversity potentially affecting brain development and the pathogenesis of depressive disorders.
A first-passage approach to diffusion-influenced reversible binding and its insights into nanoscale signaling at the presynapse
Authors: Reva Maria , DiGregorio David A. , Grebenkov Denis S.
Published: March 2021

Synaptic transmission between neurons is governed by a cascade of stochastic calcium ion reaction–diffusion events within nerve terminals leading to vesicular release of neurotransmitter. Since experimental measurements of such systems are challenging due to their nanometer and sub-millisecond scale, numerical simulations remain the principal tool for studying calcium-dependent neurotransmitter release driven by electrical impulses, despite the limitations of time-consuming calculations. In this paper, we develop an analytical solution to rapidly explore dynamical stochastic reaction–diffusion problems based on first-passage times. This is the first analytical model that accounts simultaneously for relevant statistical features of calcium ion diffusion, buffering, and its binding/unbinding reaction with a calcium sensor for synaptic vesicle fusion. In particular, unbinding kinetics are shown to have a major impact on submillisecond sensor occupancy probability and therefore cannot be neglected. Using Monte Carlo simulations we validated our analytical solution for instantaneous calcium influx and that through voltage-gated calcium channels. We present a fast and rigorous analytical tool that permits a systematic exploration of the influence of various biophysical parameters on molecular interactions within cells, and which can serve as a building block for more general cell signaling simulators.
Homological scaffold via minimal homology bases
Authors: Guerra Marco , De Gregorio Alessandro , Fugacci Ulderico , Petri Giovanni , Vaccarino Francesco
Published: March 2021

The homological scaffold leverages persistent homology to construct a topologically sound summary of a weighted network. However, its crucial dependency on the choice of representative cycles hinders the ability to trace back global features onto individual network components, unless one provides a principled way to make such a choice. In this paper, we apply recent advances in the computation of minimal homology bases to introduce a quasi-canonical version of the scaffold, called minimal, and employ it to analyze data both real and in silico. At the same time, we verify that, statistically, the standard scaffold is a good proxy of the minimal one for sufficiently complex networks.
Direct evidence of microstructure dependence of magnetic flux trapping in niobium
Authors: Balachandran Shreyas , Polyanskii Anatolii , Chetri Santosh , Dhakal Pashupati , Su Yi-Feng , Sung Zu-Hawn , Lee Peter J.
Published: March 2021

Elemental type-II superconducting niobium is the material of choice for superconducting radiofrequency cavities used in modern particle accelerators, light sources, detectors, sensors, and quantum computing architecture. An essential challenge to increasing energy efficiency in rf applications is the power dissipation due to residual magnetic field that is trapped during the cool down process due to incomplete magnetic field expulsion. New SRF cavity processing recipes that use surface doping techniques have significantly increased their cryogenic efficiency. However, the performance of SRF Nb accelerators still shows vulnerability to a trapped magnetic field. In this manuscript, we report the observation of a direct link between flux trapping and incomplete flux expulsion with spatial variations in microstructure within the niobium. Fine-grain recrystallized microstructure with an average grain size of 10–50 µm leads to flux trapping even with a lack of dislocation structures in grain interiors. Larger grain sizes beyond 100–400 µm do not lead to preferential flux trapping, as observed directly by magneto-optical imaging. While local magnetic flux variations imaged by magneto-optics provide clarity on a microstructure level, bulk variations are also indicated by variations in pinning force curves with sequential heat treatment studies. The key results indicate that complete control of the niobium microstructure will help produce higher performance superconducting resonators with reduced rf losses1 related to the magnetic flux trapping.
The SUN2-nesprin-2 LINC complex and KIF20A function in the Golgi dispersal
Authors: Hieda Miki , Matsumoto Taizo , Isobe Mari , Kurono Sadamu , Yuka Kaneko , Kametaka Satoshi , Wang Jing-Ya , Chi Ya-Hui , Kameda Kenji , Kimura Hiroshi , Matsuura Nariaki , Matsuura Shuji
Published: March 2021

The morphology of the Golgi complex is influenced by the cellular context, which strictly correlates with nuclear functions; however, the mechanism underlying this association remains elusive. The inner nuclear membrane SUN proteins, SUN1 and SUN2, have diverse functions together with the outer nuclear membrane nesprin proteins, which comprise the LINC complex. We found that depletion of SUN1 leads to Golgi complex dispersion with maintenance of ministacks and retained function for vesicle transport through the Golgi complex. In addition, SUN2 associates with microtubule plus-end-directed motor KIF20A, possibly via nesprin-2. KIF20A plays a role in the Golgi dispersion in conjunction with the SUN2-nesprin-2 LINC complex in SUN1-depleted cells, suggesting that SUN1 suppresses the function of the SUN2-nesprin-2 LINC complex under a steady-state condition. Further, SUN1-knockout mice, which show impaired cerebellar development and cerebellar ataxia, presented altered Golgi morphology in Purkinje cells. These findings revealed a regulation of the Golgi organization by the LINC complex.
Thermodynamic mechanism evaluate the feasibility of oil shale pyrolysis by topochemical heat
Authors: Zhao Shuai , Lü Xiaoshu , Sun Youhong , Huang Jiandong
Published: March 2021

Topochemical heat in-situ pyrolysis of oil shale is achieved by injecting high temperature nitrogen to promote oil shale pyrolysis and release heat, and then injecting air to trigger oil shale combustion in the early stage of oil shale pyrolysis, and then by injecting normal temperature air continuously to promote local oxidation of oil shale in the later stage. In order to verify the oil and gas recovery by topochemical heat method, Jilin University has chosen Fuyu City, Jilin Province, to carry out pilot project of oil shale in-situ pyrolysis by topochemical heat method. Besides, in order to infer the spontaneity, feasibility and difficulty of continuous pyrolysis of oil shale based on topochemical heat, this paper, the mechanism of solid-state pyrolysis and the thermodynamic analysis of transition state of oil shale in Fuyu area are discussed. Because the second stage of oil shale pyrolysis is the main stage of oil production. Therefore, the characteristics of Gibbs free energy, free enthalpy and free entropy of transition state in the main oil production stage of oil shale pyrolysis are obtained by calculation. The results show that in situ pyrolysis of oil shale topochemical heat can be carried out spontaneously and continuously, and the release characteristics of volatiles during pyrolysis of oil shale are described.
The in-vitro effect of famotidine on SARS-CoV-2 proteases and virus replication
Authors: Loffredo Madeline , Lucero Hector , Chen Da-Yuan , O’Connell Aoife , Bergqvist Simon , Munawar Ahmad , Bandara Asanga , De Graef Steff , Weeks Stephen D. , Douam Florian , Saeed Mohsan , Munawar Ali H.
Published: March 2021

The lack of coronavirus-specific antiviral drugs has instigated multiple drug repurposing studies to redirect previously approved medicines for the treatment of SARS-CoV-2, the coronavirus behind the ongoing COVID-19 pandemic. A recent, large-scale, retrospective clinical study showed that famotidine, when administered at a high dose to hospitalized COVID-19 patients, reduced the rates of intubation and mortality. A separate, patient-reported study associated famotidine use with improvements in mild to moderate symptoms such as cough and shortness of breath. While a prospective, multi-center clinical study is ongoing, two parallel in silico studies have proposed one of the two SARS-CoV-2 proteases, 3CLpro or PLpro, as potential molecular targets of famotidine activity; however, this remains to be experimentally validated. In this report, we systematically analyzed the effect of famotidine on viral proteases and virus replication. Leveraging a series of biophysical and enzymatic assays, we show that famotidine neither binds with nor inhibits the functions of 3CLpro and PLpro. Similarly, no direct antiviral activity of famotidine was observed at concentrations of up to 200 µM, when tested against SARS-CoV-2 in two different cell lines, including a human cell line originating from lungs, a primary target of COVID-19. These results rule out famotidine as a direct-acting inhibitor of SARS-CoV-2 replication and warrant further investigation of its molecular mechanism of action in the context of COVID-19.
Effect of surface carbonates on the cyclability of LiNbO3-coated NCM622 in all-solid-state batteries with lithium thiophosphate electrolytes
Authors: Kim A-Young , Strauss Florian , Bartsch Timo , Teo Jun Hao , Janek Jürgen , Brezesinski Torsten
Published: March 2021

While still premature as an energy storage technology, bulk solid-state batteries are attracting much attention in the academic and industrial communities lately. In particular, layered lithium metal oxides and lithium thiophosphates hold promise as cathode materials and superionic solid electrolytes, respectively. However, interfacial side reactions between the individual components during battery operation usually result in accelerated performance degradation. Hence, effective surface coatings are required to mitigate or ideally prevent detrimental reactions from occurring and having an impact on the cyclability. In the present work, we examine how surface carbonates incorporated into the sol–gel-derived LiNbO3 protective coating on NCM622 [Li1+x(Ni0.6Co0.2Mn0.2)1–xO2] cathode material affect the efficiency and rate capability of pellet-stack solid-state battery cells with β-Li3PS4 or argyrodite Li6PS5Cl solid electrolyte and a Li4Ti5O12 anode. Our research data indicate that a hybrid coating may in fact be beneficial to the kinetics and the cycling performance strongly depends on the solid electrolyte used.
Evaluation of the quality of lentic ecosystems in Romania by a GIS based WRASTIC model
Authors: Niculae Mihaita-Iulian , Avram Sorin , Corpade Ana-Maria , Dedu Silvia , Gheorghe Carmen Adriana , Pascu Ionut Silviu , Ontel Irina , Rodino Steliana
Published: March 2021

Globally, ecosystems are constantly degrading as a result of pressures derived from human activities and climate change. For working towards the restoration of the natural balance, it is necessary to evaluate the deviations induced in the ecosystems, to identify where the changes took place, to know what is their amplitude and to decide where it is possible to get involved. Many aquatic ecosystems are depreciated and their restoration is often difficult. Development of appropriate assessment methodologies will improve the decision-making process in public policies for environmental protection and conservation of biodiversity. This study presents an assessment of the degradation level of lentic ecosystems in Romania, performed through a multi-criteria analysis. An extension of the WRASTIC index (Wastewater-Recreational-Agricultural-Size-Transportations-Indutrial-Cover) was generated, namely WRASTIC-HI. The new index was obtained by including values derived from the Potential Pollutant Load index. The analysis showed that 13% of the evaluated lakes are natural, 56.5% are semi-degraded and 30.5% are degraded. The proposed methodology allows to determine the spatial distribution of the degradation sources and to calculate the corresponding indicators. The results obtained provide a useful tool for diagnostic step that can be used as a cornerstone to further identification of environmental conflicts and proposals for improvement of the ecological status of the lentic ecosystems.
Central rib and the nutritive value of leaves in forage grasses
Authors: Garcia Larissa Fernanda , Silva Guilherme Portes , Geremia Eliana Vera , Goulart Laura Beatriz Lima , Dias Carlos Tadeu dos Santos , da Silva Sila Carneiro
Published: March 2021

In grasses, leaf expansion and central rib growth occur in a non-proportional manner, with potential implications to the nutritive value of leaves. The objective of this study was to evaluate the relationship among blade length, percentage of central rib, anatomical characteristics and the nutritive value along the length of leaf blades of different sizes and hierarchical order of insertion on the tiller axis of Napier elephant grass (Pennisetum purpureum Schum. cv. Napier). Two experiments were carried out with isolated growing plants during the summer of 2017 (January to March). Central rib mass increased linearly with the increase in leaf blade mass and its percentage relative to blade mass decreased from the base to the tip of the leaf. There were no significant variations in anatomical characteristics along the length of leaf blades when central rib was not taken into account. The central rib showed negative relationship with nutritive value. The apical portions of long leaves showed similar digestibility to short leaves. The multivariate analysis of Cluster and Principal Components grouped the response variables according to leaf hierarchical order, final blade length and percentage of structural tissues, highlighting the relationship between leaf size, structural tissues and nutritive value.
MRC5 cells engineered to express ACE2 serve as a model system for the discovery of antivirals targeting SARS-CoV-2
Authors: Uemura Kentaro , Sasaki Michihito , Sanaki Takao , Toba Shinsuke , Takahashi Yoshimasa , Orba Yasuko , Hall William W. , Maenaka Katsumi , Sawa Hirofumi , Sato Akihiko
Published: March 2021

Although the spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a worldwide pandemic, there are currently no virus-specific drugs that are fully effective against SARS-CoV-2. Only a limited number of human-derived cells are capable of supporting SARS-CoV-2 replication and the infectivity of SARS-CoV-2 in these cells remains poor. In contrast, monkey-derived Vero cells are highly susceptibility to infection with SARS-CoV-2, although they are not suitable for the study of antiviral effects by small molecules due to their limited capacity to metabolize drugs compared to human-derived cells. In this study, our goal was to generate a virus-susceptible human cell line that would be useful for the identification and testing of candidate drugs. Towards this end, we stably transfected human lung-derived MRC5 cells with a lentiviral vector encoding angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV-2. Our results revealed that SARS-CoV-2 replicates efficiently in MRC5/ACE2 cells. Furthermore, viral RNA replication and progeny virus production were significantly reduced in response to administration of the replication inhibitor, remdesivir, in MRC5/ACE2 cells compared with Vero cells. We conclude that the MRC5/ACE2 cells will be important in developing specific anti-viral therapeutics and will assist in vaccine development to combat SARS-CoV-2 infections.
Composition equivalents of stainless steels understood via gamma stabilizing efficiency
Authors: Zhang Shuqi , Wang Qing , Yang Rui , Dong Chuang
Published: March 2021

The phase-type of a stainless steel is generally predicted by equivalent equations in terms of a major austenitic (γ) or ferritic (α) stabilizer Ni or Cr. The present paper attempts to understand the equivalent methods in stainless steels via the slopes of the phase boundary lines separating γ and γ + α phase zones. The prevailing equivalent coefficients are well interpreted using the slope ratios of the alloying elements divided by that of Ni or Cr, after analyzing over one hundred common stainless steels. Different from traditional composition equivalents which evaluate γ stabilizers and α stabilizers separately; the new equivalent scheme provides a unified phase stabilizing parameter for all alloying elements in stainless steels. This parameter is defined as γ stabilizing efficiency. Its negative or positive sign indicates γ stabilizer or α stabilizer, and its value represents the stabilizing efficiency.
Programmable half-life and anti-tumour effects of bispecific T-cell engager-albumin fusions with tuned FcRn affinity
Authors: Mandrup Ole A. , Ong Sui Ching , Lykkemark Simon , Dinesen Anders , Rudnik-Jansen Imke , Dagnæs-Hansen Niels Frederik , Andersen Jan Terje , Alvarez-Vallina Luis , Howard Kenneth A.
Published: March 2021

Fc-less bispecific T-cell engagers have reached the immuno-oncology market but necessitate continual infusion due to rapid clearance from the circulation. This work introduces a programmable serum half-life extension platform based on fusion of human albumin sequences engineered with either null (NB), wild type (WT) or high binding (HB) FcRn affinity combined with a bispecific T-cell engager. We demonstrate in a humanised FcRn/albumin double transgenic mouse model (AlbuMus) the ability to tune half-life based on the albumin sequence fused with a BiTE-like bispecific (anti-EGFR nanobody x anti-CD3 scFv) light T-cell engager (LiTE) construct [(t½ 0.6 h (Fc-less LiTE), t½ 19 hours (Albu-LiTE-NB), t½ 26 hours (Albu-LiTE-WT), t½ 37 hours (Albu-LiTE-HB)]. We show in vitro cognate target engagement, T-cell activation and discrimination in cellular cytotoxicity dependent on EGFR expression levels. Furthermore, greater growth inhibition of EGFR-positive BRAF mutated tumours was measured following a single dose of Albu-LiTE-HB construct compared to the Fc-less LiTE format and a full-length anti-EGFR monoclonal antibody in a new AlbuMus RAG1 knockout model introduced in this work. Programmable half-life extension facilitated by this albumin platform potentially offers long-lasting effects, better patient compliance and a method to tailor pharmacokinetics to maximise therapeutic efficacy and safety of immuno-oncology targeted biologics.
Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster
Authors: Çoruh Orkun , Frank Anna , Tanaka Hideaki , Kawamoto Akihiro , El-Mohsnawy Eithar , Kato Takayuki , Namba Keiichi , Gerle Christoph , Nowaczyk Marc M. , Kurisu Genji
Published: March 2021

A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI) from Thermosynechococcus elongatus was reported as the first atomic model of PSI almost 20 years ago. However, the monomeric PSI structure has not yet been reported despite long-standing interest in its structure and extensive spectroscopic characterization of the loss of red chlorophylls upon monomerization. Here, we describe the structure of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the trimer structure gave detailed insights into monomerization-induced changes in both the central trimerization domain and the peripheral regions of the complex. Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization of red chlorophylls and that lipids of the surrounding membrane present a major source of thermal energy for uphill excitation energy transfer from red chlorophylls to P700.
A solvent-free solid catalyst for the selective and color-indicating ambient-air removal of sulfur mustard
Authors: Collins-Wildman Daniel L. , Sullivan Kevin P. , Geletii Yurii V. , Snider Victoria G. , Gordon Wesley O. , Balboa Alex , Tian Yiyao , Slaugenhaupt Rachel M. , Kaledin Alexey L. , Karwacki Christopher J. , Frenkel Anatoly I. , Musaev Djamaladdin G. , Hill Craig L.
Published: March 2021

Bis(2-chloroethyl) sulfide or sulfur mustard (HD) is one of the highest-tonnage chemical warfare agents and one that is highly persistent in the environment. For decontamination, selective oxidation of HD to the substantially less toxic sulfoxide is crucial. We report here a solvent-free, solid, robust catalyst comprising hydrophobic salts of tribromide and nitrate, copper(II) nitrate hydrate, and a solid acid (NafionTM) for selective sulfoxidation using only ambient air at room temperature. This system rapidly removes HD as a neat liquid or a vapor. The mechanisms of these aerobic decontamination reactions are complex, and studies confirm reversible formation of a key intermediate, the bromosulfonium ion, and the role of Cu(II). The latter increases the rate four-fold by increasing the equilibrium concentration of bromosulfonium during turnover. Cu(II) also provides a colorimetric detection capability. Without HD, the solid is green, and with HD, it is brown. Bromine K-edge XANES and EXAFS studies confirm regeneration of tribromide under catalytic conditions. Diffuse reflectance infrared Fourier transform spectroscopy shows absorption of HD vapor and selective conversion to the desired sulfoxide, HDO, at the gas–solid interface.
A spectroscopic study of solvent effects on the formation of Cu(ii)–chloride complexes in aqueous solution
Authors: Zhang Ning , Tang Jianfeng , Ma Yuntian , Liang Minghui , Zeng Dewen , Hefter Glenn
Published: March 2021

A full understanding of the nature of complexes formed in concentrated electrolyte solutions requires explicit consideration of the role of the solvent water in the equilibria.
Fully spin-valley-polarized current induced by electric field in zigzag stanene and germanene nanoribbons
Authors: Ildarabadi Fereshte , Farghadan Rouhollah
Published: March 2021

Fully spin-valley-polarized current can be produced in zigzag stanene and germanene nanoribbons with large intrinsic spin–orbit coupling, considering the electron–electron interaction (U) and the external electric field (Ez) at room temperature.
The noncovalent conjugations of human serum albumin (HSA) with MS/AK and the effect on anti-oxidant capacity as well as anti-glycation activity of Monascus yellow pigments
Authors: Wu Shufen , Sun Yue , Chen Di , Liu Huanhuan , Li Zhenjing , Chen Mianhua , Wang Changlu , Cheng Lei , Guo Qingbin , Peng Xin
Published: March 2021

Monascus-fermented products rich in MS and AK show a great potential as food-based anti-glycation agents for their superior inhibitory effect on AGEs in model system of HSA-glucose.
Biodegradable Zn-ion battery with a lignin composite electrode and bio-ionic liquid based electrolyte: possible in situ energy generation by lignin electrocatalysis
Authors: Lahiri Abhishek , Yang Li , Höfft Oliver , Endres Frank
Published: March 2021

Biodegradable Zn ion batteries have been developed with lignin composite cathodes which can also generate in situ energy by lignin electrocatalytic reaction.
Biogenic selenium nanoparticles produced by Lactobacillus casei ATCC 393 inhibit colon cancer cell growth in vitro and in vivo
Authors: Spyridopoulou Katerina , Tryfonopoulou Eleni , Aindelis Georgios , Ypsilantis Petros , Sarafidis Charalampos , Kalogirou Orestis , Chlichlia Katerina
Published: March 2021

Biogenic selenium nanoparticles synthesized by the probiotic Lactobacillus casei inhibit colon cancer cell growth in vitro as well as in vivo when administered orally in mice.
A synergetic effect between a single Cu site and S vacancy on an MoS2basal plane for methanol synthesis from syngas
Authors: Su Hai-Yan , Ma Xiufang , Sun Chenghua , Sun Keju
Published: March 2021

Compared to MoS2(001), the synergetic effect between the single Cu site and S vacancy on Cu/MoS2(001) destabilizes O, which not only increases the CO hydrogenation rate by 5 orders of magnitude, but leads to the selectivity switch from CH4to CH3OH.
A power-triggered preparation strategy of nano-structured inorganics: sonosynthesis
Authors: Li Zhanfeng , Dong Jun , Wang Lun , Zhang Yongqiang , Zhuang Tingting , Wang Huiqi , Cui Xuejun , Wang Zonghua
Published: March 2021

Sonosynthesis widely emerges in the fabrication of nano-structured inorganicsviaultrasound-assisted approaches as a facile and short-time strategy.
Horeau amplification in the sequential acylative kinetic resolution of (±)-1,2-diols and (±)-1,3-diols in flow
Authors: Brandolese Arianna , Greenhalgh Mark D. , Desrues Titouan , Liu Xueyang , Qu Shen , Bressy Cyril , Smith Andrew D.
Published: March 2021

The sequential kinetic resolution of (±)-1,2-synand (±)-1,3-anti-diols in flow, using the polystyrene supported isothiourea, HyperBTM, gives highly enantioenriched products using the principles of Horeau amplification.
Metal–organic framework transistors for dopamine sensing
Authors: Song Jiajun , Zheng Jianzhong , Yang Anneng , Liu Hong , Zhao Zeyu , Wang Naixiang , Yan Feng
Published: March 2021

An n-type solution-gated MOF transistor (SGMT) is realized for the first time. The device is exploited as a low-voltage dopamine sensor, exhibiting high sensitivity and selectivity.
A self-boosting microwave plasma strategy tuned by air pressure for the highly efficient and controllable surface modification of carbon
Authors: Liu Yanjing , He Jiawei , Zhang Bing , Zhu Huacheng , Yang Yang , Wu Li , Zhang Wencong , Zhou Yanping , Huang Kama
Published: March 2021

Microwave enabled air plasma was boosted by a carbon fiber cloth (CFC) and used for the high-efficiency surface modification of the CFC, yielding CFCs with tunable contents of oxygen and each O-containing group.
Synthesis of gallotannin capped iron oxide nanoparticles and their broad spectrum biological applications
Authors: Ahmed Bilal , Syed Asad , Ali Khursheed , Elgorban Abdallah M. , Khan Afroz , Lee Jintae , AL-Shwaiman Hind A.
Published: March 2021

Broad-spectrum biological effects of gallo-tannin capped Fe2O3nanoparticles against planktonic bacteria, biofilm, fungi, and cancer cell line.
An attempt to synthesize a terthienyl-based analog of indacenedithiophene (IDT): unexpected synthesis of a naphtho[2,3-b]thiophene derivative
Authors: Anghel Cătălin C. , Stroia Ioan , Pop Alexandra , Bende Atilla , Grosu Ion , Hădade Niculina D. , Roncali Jean
Published: March 2021

Serendipitous synthesis of a novel naphtho[2,3-b]thiophene derivative. Detailed investigation of the structure and properties as well as a possible mechanism for its formation.
Two-dimensional SnO2 anchored biomass-derived carbon nanosheet anode for high-performance Li-ion capacitors
Authors: Liu Chang , He Zeyin , Niu Jianmin , Cheng Qiang , Zhao Zongchen , Li Haoran , Shi Jing , Wang Huanlei
Published: March 2021

In this work, we have fabricated lithium-ion capacitor using SnO2/PCN as anode and waste coffee grounds derived PCN as cathode, which delivers good combination of high energy and power characteristics.
Microbial electrosynthesis: is it sustainable for bioproduction of acetic acid?
Authors: Gadkari Siddharth , Mirza Beigi Behzad Haji , Aryal Nabin , Sadhukhan Jhuma
Published: March 2021

Detailed LCA study of acetic acid production using microbial electrosynthesis to explore scenarios when this process could become sustainable.
Searching for the 1 mHz variability in the flickering of V4743 Sgr: A cataclysmic variable accreting at a high rate
Authors: Dobrotka A. , Orio M. , Benka D. , Vanderburg A.
Published: March 2021

Aims. A few well studied cataclysmic variables (CVs) have shown discrete characteristic frequencies of fast variability; the most prominent ones are around log(f/Hz) ≃ −3. Because we still have only small number statistics, we obtained a new observation to test whether this is a general characteristic of CVs, especially if mass transfer occurs at a high rate typical for dwarf nova in outbursts, in the so called high state.

Methods. We analysed optical Kepler data of the quiescent nova and intermediate polar V4743 Sgr. This system hosts a white dwarf accreting through a disc in the high state. We calculated the power density spectra and searched for break or characteristic frequencies. Our goal is to assess whether the milihertz frequency of the flickering is a general characteristic.

Results. V4743 Sgr has a clear break frequency at log(f/Hz) ≃ −3. This detection increases the probability that the megahertz characteristic frequency is a general feature of CVs in the high state, from 69% to 91%. Furthermore, we propose the possibility that the variability is generated by a similar mechanism as in the nova-like system MV Lyr, which would make V4743 Sgr unique.
Radial velocity map of solar wind transients in the field of view of STEREO/HI1 on 3 and 4 April 2010
Authors: Li Xiaolei , Wang Yuming , Guo Jingnan , Liu Rui , Zhuang Bin
Published: March 2021

Context. The solar wind transients propagating out in the inner heliosphere can be observed in white-light images from Heliospheric Imager-1 (HI1), an instrument of the Sun Earth Connection Coronal and Heliospheric Investigation on board the Solar Terrestrial Relations Observatory (STEREO), from two perspectives. The spatial velocity distribution inside solar wind transients is key to understanding their dynamic evolution processes.

Aims. We generated a velocity map of transients in 3D space based on 2D white-light images and used it to estimate the expansion rate as well as some kinematic properties of solar wind transients.

Methods. Based on the recently developed correlation-aided reconstruction method in our previous work, which can recognize and locate 3D solar wind transients from STEREO/HI1 image data, we further developped a new technique for deriving the spatial distribution of the radial velocities of the most pronounced features inside solar wind transients.

Results. The technique was applied to events including a coronal mass ejection (CME) and three small-scale transients, so-called blobs, observed by HI1 on 3–4 April 2010 to reconstruct their radial velocity maps. The results match the forward-modeling results, simulations, and in situ observations at 1 AU fairly well. According to the obtained spatial distributions of height and radial velocity of the CME, we analyzed the self-similarity of the radial expansion of the CME ejecta. The dimensionless radial expansion rate of the northern and middle parts of the CME ejecta varies in the range of 0.7−1.0 at heliocentric distance between 25 R⊙ and 55 R⊙ and the rate of the southern part in the range of 0.3−0.5, suggesting that the CME structure was distorted and shaped by the ambient solar wind. The technique we developed is expected to be applied to more events.
Analysis of apsidal motion in eclipsing binaries using TESS data
Authors: Baroch D. , Giménez A. , Ribas I. , Morales J. C. , Anglada-Escudé G. , Claret A.
Published: March 2021

Context.The change in the argument of periastron of eclipsing binaries, that is, the apsidal motion caused by classical and relativistic effects, can be measured from variations in the difference between the time of minimum light of the primary and secondary eclipses. Poor apsidal motion rate determinations and large uncertainties in the classical term have hampered previous attempts to determine the general relativistic term with sufficient precision to test general relativity predictions.

Aims.As a product of the TESS mission, thousands of high-precision light curves from eclipsing binaries are now available. Using a selection of suitable well-studied eccentric eclipsing binary systems, we aim to determine their apsidal motion rates and place constraints on key gravitational parameters.

Methods.We compute the time of minimum light from the TESS light curves of 15 eclipsing binaries with precise absolute parameters and with an expected general relativistic contribution to the total apsidal motion rate of greater than 60%. We use the changing primary and secondary eclipse timing differences over time to compute the apsidal motion rate, when possible, or the difference between the linear periods as computed from primary and secondary eclipses. For a greater time baseline we carefully combine the high-precision TESS timings with archival reliable timings.

Results.We determine the apsidal motion rate of 9 eclipsing binaries, 5 of which are reported for the first time. From these, we are able to measure the general relativistic apsidal motion rate of 6 systems with sufficient precision to test general relativity for the first time using this method. This test explores a regime of gravitational forces and potentials that had not been probed before. We find perfect agreement with theoretical predictions, and we are able to set stringent constraints on two parameters of the parametrised post-Newtonian formalism.
Self-scattering on large, porous grains in protoplanetary disks with dust settling
Authors: Brunngräber R. , Wolf S.
Published: March 2021

Context. Observations of protoplanetary disks in the sub-millimetre wavelength range suggest that polarisation is caused by scattering of thermal re-emission radiation. Most of the dust models that are used to explain these observations have major drawbacks: they either use much smaller grain sizes than expected from dust evolution models, or result in polarisation degrees that are lower than observed.

Aims. We investigate the effect of dust grain porosity on the observable polarisation due to scattering at sub-millimetre wavelengths arising from grain size distributions up to millimetre sizes, as they are expected to be present close to the midplane of protoplanetary disks.

Methods. Using the effective medium theory, we calculated the optical properties of porous dust and used them to predict the behaviour of the observable polarisation degree due to scattering. Subsequently, Monte Carlo radiative transfer simulations for protoplanetary disks with porous dust grains were performed to analyse the additional effect of the optical depth structure, and thus the effect of multiple scattering events and inhomogeneous temperature distributions on the net observable polarisation degree.

Results. We find that porous dust grains with moderate filling factors of about 10% increase the degree of polarisation compared to compact grains. For higher grain porosities, that is, grains with a filling factor of 1% or lower, the extinction opacity decreases, as does the optical depth of a disk with constant mass. Consequently, the unpolarised direct radiation dominates the scattered flux, and the degree of polarisation drops rapidly. Even though the simulated polarisation degree is higher than in the case of compact grains, it is still below the typical observed values for face-on disks. However, the polarisation degree can be increased when crucial model assumptions derived from disk and dust evolution theories, for instance, dust settling and millimetre-sized dust grains, are dropped. In the case of inclined disks, however, our reference model is able to achieve polarisation degrees of about 1%, and using higher disk masses, even higher than this.