bluuebunny/crossref_metadata_2025 huggingface dataset:
Physicochemical and tribological properties of gemini-type halogen-free dicationic ionic liquids
Authors: Yu Qiangliang , Zhang Chaoyang , Dong Rui , Shi Yijun , Wang Yurong , Bai Yanyan , Zhang Jiaying , Cai Meirong , Zhou Feng , Liu Weimin
Published: July 2020

A series of new halogen-free dicationic ionic liquids (ILs) with different alkyl chain lengths were prepared, and the relationship between the alkyl chain length, physicochemical and tribological properties of ILs, and their role as neat lubricant for steel-steel friction pairs, was investigated. Evaluation of stability during hydrolysis and copper strip corrosion test results show that synthetic ILs are stable and not corrosive to metal contacts, due to the halogen-free anions. The friction and wear test results indicate that ILs with long alkyl chains have excellent friction-reducing and anti-wear properties, especially at high temperatures. Based on the surface three-dimensional (3D) profiles, electrical contact resistance, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and the X-ray photoelectron spectrometry (XPS) analysis of the worn surfaces of steel discs, we can conclude that the efficiency of ILs is due to the formation of high quality tribofilms that consist of both tribochemical reaction and ordered absorption films.
MOF-Derived Ni1−xCox@Carbon with Tunable Nano–Microstructure as Lightweight and Highly Efficient Electromagnetic Wave Absorber
Authors: Wang Lei , Huang Mengqiu , Yu Xuefeng , You Wenbin , Zhang Jie , Liu Xianhu , Wang Min , Che Renchao
Published: July 2020

Intrinsic electric-magnetic property and special nano-micro architecture of functional materials have a significant effect on its electromagnetic wave energy conversion, especially in the microwave absorption (MA) field. Herein, porous Ni1−xCox@Carbon composites derived from metal-organic framework (MOF) were successfully synthesized via solvothermal reaction and subsequent annealing treatments. Benefiting from the coordination, carbonized bimetallic Ni-Co-MOF maintained its initial skeleton and transformed into magnetic-carbon composites with tunable nano-micro structure. During the thermal decomposition, generated magnetic particles/clusters acted as a catalyst to promote the carbon sp2 arrangement, forming special core-shell architecture. Therefore, pure Ni@C microspheres displayed strong MA behaviors than other Ni1−xCox@Carbon composites. Surprisingly, magnetic-dielectric Ni@C composites possessed the strongest reflection loss value − 59.5 dB and the effective absorption frequency covered as wide as 4.7 GHz. Meanwhile, the MA capacity also can be boosted by adjusting the absorber content from 25% to 40%. Magnetic–dielectric synergy effect of MOF-derived Ni1−xCox@Carbon microspheres was confirmed by the off-axis electron holography technology making a thorough inquiry in the MA mechanism.
Self-Assembly Protein Superstructures as a Powerful Chemodynamic Therapy Nanoagent for Glioblastoma Treatment
Authors: Zheng Tao , Wang Wentao , Ashley Jon , Zhang Ming , Feng Xiaotong , Shen Jian , Sun Yi
Published: July 2020

Glioblastoma (GBM) remains a formidable challenge in oncology. Chemodynamic therapy (CDT) that triggers tumor cell death by reactive oxygen species (ROS) could open up a new door for GBM treatment. Herein, we report a novel CDT nanoagent. Hemoglobin (Hb) and glucose oxidase (GOx) were employed as powerful CDT catalysts. Instead of encapsulating the proteins in drug delivery nanocarriers, we formulate multimeric superstructures as self-delivery entities by crosslinking techniques. Red blood cell (RBC) membranes are camouflaged on the protein superstructures to promote the delivery across blood–brain barrier. The as-prepared RBC@Hb@GOx nanoparticles (NPs) offer superior biocompatibility, simplified structure, and high accumulation at the tumor site. We successfully demonstrated that the NPs could efficiently produce toxic ROS to kill U87MG cancer cells in vitro and inhibit the growth of GBM tumor in vivo, suggesting that the new CDT nanoagent holds great promise for treating GBM.
Sweet ceramics: how saccharide-based compounds have changed colloidal processing of ceramic materials
Authors: Wiecinska Paulina , Zurawska Agnieszka , Falkowski Pawel , Jeong Dae-Yong , Szafran Mikolaj
Published: July 2020

Herein, we present manifold possibilities of using saccharides and their derivatives in colloidal processing of ceramics. Sugar-based compounds are attractive alternatives for commonly used organic additives, because they are renewable materials, are non-toxic to human skin, and have a positive influence on the rheological behavior and stability of ceramic suspensions which is reflected in the properties of green and sintered bodies. The examined substances include sugar acids (galacturonic and lactobionic acid) as highly effective deflocculants for nanopowders; acryloyl derivatives of monosaccharides and sugar alcohols as organic monomers in gelcasting; polysaccharides as binders; and l-ascorbic acid as an activator of radical polymerization in gelcasting. The multifunctionality of the selected compounds as well as their thermal decomposition during sintering of ceramics is discussed. The study also reviews the related literature focusing on sugar-based compounds in ceramic processing.
The equilibrium states of large networks of Erlang queues
Authors: Martirosyan Davit , Robert Philippe
Published: July 2020

The equilibrium properties of allocation algorithms for networks with a large number of nodes with finite capacity are investigated. Every node receives a flow of requests. When a request arrives at a saturated node, i.e. a node whose capacity is fully utilized, an allocation algorithm may attempt to reallocate the request to a non-saturated node. For the algorithms considered, the reallocation comes at a price: either extra capacity is required in the system, or the processing time of a reallocated request is increased. The paper analyzes the properties of the equilibrium points of the associated asymptotic dynamical system when the number of nodes gets large. At this occasion the classical model of Gibbens, Hunt, and Kelly (1990) in this domain is revisited. The absence of known Lyapunov functions for the corresponding dynamical system significantly complicates the analysis. Several techniques are used. Analytic and scaling methods are used to identify the equilibrium points. We identify the subset of parameters for which the limiting stochastic model of these networks has multiple equilibrium points. Probabilistic approaches are used to prove the stability of some of them. A criterion of exponential stability with the spectral gap of the associated linear operator of equilibrium points is also obtained.
Failure rate properties of parallel systems
Authors: Arab Idir , Hadjikyriakou Milto , Oliveira Paulo Eduardo
Published: July 2020

We study failure rate monotonicity and generalised convex transform stochastic ordering properties of random variables, with an emphasis on applications. We are especially interested in the effect of a tail-weight iteration procedure to define distributions, which is equivalent to the characterisation of moments of the residual lifetime at a given instant. For the monotonicity properties, we are mainly concerned with hereditary properties with respect to the iteration procedure providing counterexamples showing either that the hereditary property does not hold or that inverse implications are not true. For the stochastic ordering, we introduce a new criterion, based on the analysis of the sign variation of a suitable function. This criterion is then applied to prove ageing properties of parallel systems formed with components that have exponentially distributed lifetimes.
Stability and moment bounds under utility-maximising service allocations: Finite and infinite networks
Authors: Shneer Seva , Stolyar Alexander
Published: July 2020

We study networks of interacting queues governed by utility-maximising service-rate allocations in both discrete and continuous time. For finite networks we establish stability and some steady-state moment bounds under natural conditions and rather weak assumptions on utility functions. These results are obtained using direct applications of Lyapunov–Foster-type criteria, and apply to a wide class of systems, including those for which fluid-limit-based approaches are not applicable. We then establish stability and some steady-state moment bounds for two classes of infinite networks, with single-hop and multi-hop message routes. These results are proved by considering the infinite systems as limits of their truncated finite versions. The uniform moment bounds for the finite networks play a key role in these limit transitions.
EQUATIONAL THEORIES OF FIELDS
Authors: MARTIN-PIZARRO AMADOR , ZIEGLER MARTIN
Published: July 2020

A first-order theory is equational if every definable set is a Boolean combination of instances of equations, that is, of formulae such that the family of finite intersections of instances has the descending chain condition. Equationality is a strengthening of stability. We show the equationality of the theory of proper extensions of algebraically closed fields and of the theory of separably closed fields of arbitrary imperfection degree.
The MeerKAT telescope as a pulsar facility: System verification and early science results from MeerTime
Authors: Bailes M. , Jameson A. , Abbate F. , Barr E. D. , Bhat N. D. R. , Bondonneau L. , Burgay M. , Buchner S. J. , Camilo F. , Champion D. J. , Cognard I. , Demorest P. B. , Freire P. C. C. , Gautam T. , Geyer M. , Griessmeier J.-M. , Guillemot L. , Hu H. , Jankowski F. , Johnston S. , Karastergiou A. , Karuppusamy R. , Kaur D. , Keith M. J. , Kramer M. , van Leeuwen J. , Lower M. E. , Maan Y. , McLaughlin M. A. , Meyers B. W. , Osłowski S. , Oswald L. S. , Parthasarathy A. , Pennucci T. , Posselt B. , Possenti A. , Ransom S. M. , Reardon D. J. , Ridolfi A. , Schollar C. T. G. , Serylak M. , Shaifullah G. , Shamohammadi M. , Shannon R. M. , Sobey C. , Song X. , Spiewak R. , Stairs I. H. , Stappers B. W. , van Straten W. , Szary A. , Theureau G. , Venkatraman Krishnan V. , Weltevrede P. , Wex N. , Abbott T. D. , Adams G. B. , Burger J. P. , Gamatham R. R. G. , Gouws M. , Horn D. M. , Hugo B. , Joubert A. F. , Manley J. R. , McAlpine K. , Passmoor S. S. , Peens-Hough A. , Ramudzuli Z. R , Rust A. , Salie S. , Schwardt L. C. , Siebrits R. , Van Tonder G. , Van Tonder V. , Welz M. G.
Published: July 2020

We describe system verification tests and early science results from the pulsar processor (PTUSE) developed for the newly commissioned 64-dish SARAO MeerKAT radio telescope in South Africa. MeerKAT is a high-gain (${\sim}2.8\,\mbox{K Jy}^{-1}$) low-system temperature (${\sim}18\,\mbox{K at }20\,\mbox{cm}$) radio array that currently operates at 580–1 670 MHz and can produce tied-array beams suitable for pulsar observations. This paper presents results from the MeerTime Large Survey Project and commissioning tests with PTUSE. Highlights include observations of the double pulsar$\mbox{J}0737{-}3039\mbox{A}$, pulse profiles from 34 millisecond pulsars (MSPs) from a single 2.5-h observation of the Globular cluster Terzan 5, the rotation measure of Ter5O, a 420-sigma giant pulse from the Large Magellanic Cloud pulsar PSR$\mbox{J}0540{-}6919$, and nulling identified in the slow pulsar PSR J0633–2015. One of the key design specifications for MeerKAT was absolute timing errors of less than 5 ns using their novel precise time system. Our timing of two bright MSPs confirm that MeerKAT delivers exceptional timing. PSR$\mbox{J}2241{-}5236$exhibits a jitter limit of$<4\,\mbox{ns h}^{-1}$whilst timing of PSR$\mbox{J}1909{-}3744$over almost 11 months yields an rms residual of 66 ns with only 4 min integrations. Our results confirm that the MeerKAT is an exceptional pulsar telescope. The array can be split into four separate sub-arrays to time over 1 000 pulsars per day and the future deployment of S-band (1 750–3 500 MHz) receivers will further enhance its capabilities.
The genetic structure of the marine flatwormStylochoplana pusilla(Rhabditophora: Polycladida) and its use of intertidal snails
Authors: Yamazaki Daishi , Aota Tomoki , Chiba Satoshi
Published: July 2020

Although marine phylogeographers have accumulated knowledge of the evolutionary history of various invertebrates, there is a large bias among the taxa regarding genetic data. The order Polycladida is a typical example for which little genetic information at population level is available. Here, we focused on the polyclad flatwormStylochoplana pusilla, distributed in the Japanese Pacific coastal area.Stylochoplana pusillais known to have commensal relationships with certain intertidal snails, using snails (mainlyMonodonta confusa) as a refugee house. During low tide,S. pusillahides in the mantle cavity of snails to protect themselves from desiccation and predation. Here, we investigated the genetic structure ofS. pusillausing a mitochondrial Cytochrome Oxidase I marker and the species diversity of snails used by it. We found thatS. pusillahas high genetic diversity of its populations. WhileS. pusillashowed a significant genetic differentiation among populations, it was relatively low. In addition, we also showed thatS. pusillaused several intertidal snail species which inhabit various coastal environments. The present study suggestsS. pusillahas sufficient dispersal ability to connect among its local populations. Also, the range of available snails forS. pusillamay help the connectivity among local populations. We provide important knowledge about this invertebrate taxon with a unique ecology, which has been insufficiently studied.
HOUSING MARKETS, EXPECTATION FORMATION AND INTEREST RATES
Authors: Martin Carolin , Schmitt Noemi , Westerhoff Frank
Published: July 2020

Based on a behavioral stock-flow housing market model in which the expectation formation behavior of boundedly rational and heterogeneous investors may generate endogenous boom-bust cycles, we explore whether central banks can stabilize housing markets via the interest rate. Using a mix of analytical and numerical tools, we find that the ability of central banks to tame housing markets by increasing the base (target) interest rate, thereby softening the demand pressure on house prices, is rather limited. However, central banks can greatly improve the stability of housing markets by dynamically adjusting the interest rate with respect to mispricing in the housing market.
In the Shadow of 1881: The Death of Sultan Jamalul Alam and its Impact on Colonial Transition in Sulu, Philippines from 1881–1904
Authors: Suva Cesar Andres-Miguel
Published: July 2020

In 1881, the southern Philippine archipelago of Sulu was plunged into an extended contest for the succession to its sultanate. With only a tentative peace established by 1894, tensions remained volatile between the districts of Patikul, Parang, Luuk, and Maimbung on the main island of Jolo. These tensions straddled coincided with the transition of the colonial regimes from the Spanish to the US regime in 1899. Therefore, the events of the early years of American rule, most often understood in the context of the American arrival and Spanish departure, were in fact intertwined with the prevailing conflict and rivalry between local candidates vying for the sultanate
Quantification of Uncertainty in Projections of Extreme Daily Precipitation
Authors: Kim Seokhyeon , Eghdamirad Sajjad , Sharma Ashish , Kim Joong Hoon
Published: July 2020

Projections of extreme precipitation are of considerable interest in a range of design and management applications. These projections, however, can exhibit uncertainty that requires quantification to provide confidence to any application they are used in. This study assesses the uncertainty in projected extreme daily precipitation, separated into model, scenario, and ensemble components using the square root error variance (SREV) rationale. For this, 45 projections of daily precipitation from the Coupled Model Intercomparison Project Phase 5 (CMIP5) are used, consisting of multiple global circulation models and their ensemble members, for a range of Representative Concentration Pathways, allowing assessment across land‐covered areas worldwide. It is found that the uncertainty in dry regions is significantly higher compared to wet regions, raising concerns regarding infrastructure design for the future in arid parts of the world. It is also found that the climate scenarios and initialization contribute significantly to the overall uncertainty, compared to contributions for more nonextreme precipitation simulations. This finding has implications in how design precipitation extremes ought to be projected into the future, with greater attention being paid on a broader selection of emission scenarios and initializations than is the case with projections of nonextreme precipitations.
Particle Trapping in Axisymmetric Electron Holes
Authors: Hutchinson I. H.
Published: July 2020

Electron orbits are calculated in solitary two‐dimensional axisymmetric electrostatic potential structures, typical of plasma electron holes, in order to establish the conditions for the particles to remain trapped. Analytic calculations of the evolution of the parallel energy caused by the perturbing radial electric field (breaking magnetic moment invariance) are shown to agree well with full numerical orbit integration Poincaré plots. The predominant mechanism of detrapping is resonance between the gyrofrequency in the parallel magnetic field and harmonics of the parallel bounce frequency. A region of phase space adjacent to the trapped‐passing boundary in parallel energy is generally stochastic because of island overlap of different harmonics, but except for very strong radial electric field perturbation, more deeply trapped orbits have well‐defined islands and are permanently confined. A simple universal quantitative algorithm is given, and its results plotted as a function of magnetic field strength and hole radial scale length, determining the phase space volume available to sustain the electron hole by depression of the permanently trapped distribution function.
Quiet Time Ionopheric Irregularities Over the African Equatorial Ionization Anomaly Region
Authors: Amaechi Paul O. , Oyeyemi Elijah O. , Akala Andrew O. , Falayi Elijah O. , Kaab Mohamed , Benkhaldoun Zouhair , Mazaudier Christine‐Amory
Published: July 2020

This paper investigated variations of quiet time ionospheric irregularities over the African equatorial ionization anomaly using the rate of change of total electron content index. Irregularities were quantified in terms of percentage occurrence and examined along with parameter of the anomaly, mainly its strength and the asymmetry of the crests as well as equatorial electric field derived from the real‐time equatorial electric field model and meridional wind obtained from the horizontal wind model. Irregularities occurred from 19:30 to 03:00 LT with a time difference of 1 hr between both crests. The highest occurrences were registered in April: 91.67%, 75.00%, and 96.43% for the northern crest, trough, and southern crest, respectively. Seasonally, stronger anomaly (>20 total electron content unit) in addition to the highest equatorial electric field value in the dusk sector corresponded with the equinoctial higher occurrence rate in both hemispheres, while stronger meridional wind and farthest crests location accounted for the least occurrence in winter. The summer occurrence rate was favored by reduced meridional wind, smaller crests location, and late time of prereversal enhancement at the magnetic equator. There was a significant asymmetry in irregularities over the crests in both hemispheres with stronger and greater occurrence rate over the southern crest. Also, irregularities strength and occurrence rate were similar over the northern crest and trough in summer. In addition to dusk‐sector activity, irregularities occurred during postmidnight in summer. Simultaneous variations of irregularities at the crests and trough also highlighted the contribution of nonequatorial processes to their formation at the crests.
Deciphering the star codings: astrocyte manipulation alters mouse behavior
Authors: Park Keebum , Lee Sung Joong
Published: July 2020

Astrocytes occupy a vast area within the central nervous system (CNS). Despite their abundance, the functional role of astrocytes in vivo has only begun to be uncovered. Astrocytes were typically thought to be involved in pathophysiological states. However, recent studies have shown that astrocytes are actively involved in cell signaling in normal physiological states; manipulating various aspects of astrocytic cell signaling in vivo has revealed that astrocytes are key players in controlling healthy behavior in the absence of pathophysiology. Unfortunately, the study of astrocyte function is often limited by the number of approaches available due to our lack of understanding of cell physiology. This review summarizes recent studies in which altered astrocyte signaling capacity resulted in dramatic changes in behavior. We not only discuss the methodologies available to manipulate astrocytes but also provide insights into the behavioral roles of astrocytes in the CNS.
Apoptotic cell therapy for cytokine storm associated with acute severe sepsis
Authors: Karbian Netanel , Abutbul Avraham , el-Amore Raja , Eliaz Ran , Beeri Ronen , Reicher Barak , Mevorach Dror
Published: July 2020

Sepsis has no proven pharmacologic treatment other than appropriate antibiotic agents, fluids, vasopressors as needed, and possibly corticosteroids. It is generally initiated mainly by the simultaneous recognition by various components of the innate immune system of either pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). In the current study, we employed the murine cecal ligation and puncture (CLP) model for sepsis to evaluate the effect of post-CLP infusion of apoptotic cells (Allocetra-OTS) on a CLP severe sepsis model. Cardiovascular evaluation, acute kidney injury (AKI), acute liver injury (ALI), and hematological and metabolic function were evaluated. Cytokine and chemokine profiles were measured by Multiplex ELISA and mitochondrial function, and glycolysis by Seahorse. The Murine Sepsis Score (MSS) was used for disease severity definition. CLP mice had low blood pressure, poor cardiac output, and lung dysfunction, as well as AKI, ALI, and thrombocytopenia, which correlated with the MSS and corresponded to a cytokine/chemokine storm. Apoptotic cell administration markedly improved the cytokine and chemokine storm and restored the impaired mitochondrial and glycolytic function in white blood cells leading to increased survival, from 6 to 60% (P < 0.0001), together with a significant improvement in organ dysfunction. We conclude that the deleterious immune response in CLP-induced sepsis can be successfully modified by apoptotic cell infusion.
Author Correction: Enhancing materials property prediction by leveraging computational and experimental data using deep transfer learning
Authors: Jha Dipendra , Choudhary Kamal , Tavazza Francesca , Liao Wei-keng , Choudhary Alok , Campbell Carelyn , Agrawal Ankit
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Tumor response and endogenous immune reactivity after administration of HER2 CAR T cells in a child with metastatic rhabdomyosarcoma
Authors: Hegde Meenakshi , Joseph Sujith K. , Pashankar Farzana , DeRenzo Christopher , Sanber Khaled , Navai Shoba , Byrd Tiara T. , Hicks John , Xu Mina L. , Gerken Claudia , Kalra Mamta , Robertson Catherine , Zhang Huimin , Shree Ankita , Mehta Birju , Dakhova Olga , Salsman Vita S. , Grilley Bambi , Gee Adrian , Dotti Gianpietro , Heslop Helen E. , Brenner Malcolm K. , Wels Winfried S. , Gottschalk Stephen , Ahmed Nabil
Published: July 2020

Refractory metastatic rhabdomyosarcoma is largely incurable. Here we analyze the response of a child with refractory bone marrow metastatic rhabdomyosarcoma to autologous HER2 CAR T cells. Three cycles of HER2 CAR T cells given after lymphodepleting chemotherapy induces remission which is consolidated with four more CAR T-cell infusions without lymphodepletion. Longitudinal immune-monitoring reveals remodeling of the T-cell receptor repertoire with immunodominant clones and serum autoantibodies reactive to oncogenic signaling pathway proteins. The disease relapses in the bone marrow at six months off-therapy. A second remission is achieved after one cycle of lymphodepletion and HER2 CAR T cells. Response consolidation with additional CAR T-cell infusions includes pembrolizumab to improve their efficacy. The patient described here is a participant in an ongoing phase I trial (NCT00902044; active, not recruiting), and is 20 months off T-cell infusions with no detectable disease at the time of this report.
Large-scale DNA-based phenotypic recording and deep learning enable highly accurate sequence-function mapping
Authors: Höllerer Simon , Papaxanthos Laetitia , Gumpinger Anja Cathrin , Fischer Katrin , Beisel Christian , Borgwardt Karsten , Benenson Yaakov , Jeschek Markus
Published: July 2020

Predicting effects of gene regulatory elements (GREs) is a longstanding challenge in biology. Machine learning may address this, but requires large datasets linking GREs to their quantitative function. However, experimental methods to generate such datasets are either application-specific or technically complex and error-prone. Here, we introduce DNA-based phenotypic recording as a widely applicable, practicable approach to generate large-scale sequence-function datasets. We use a site-specific recombinase to directly record a GRE’s effect in DNA, enabling readout of both sequence and quantitative function for extremely large GRE-sets via next-generation sequencing. We record translation kinetics of over 300,000 bacterial ribosome binding sites (RBSs) in >2.7 million sequence-function pairs in a single experiment. Further, we introduce a deep learning approach employing ensembling and uncertainty modelling that predicts RBS function with high accuracy, outperforming state-of-the-art methods. DNA-based phenotypic recording combined with deep learning represents a major advance in our ability to predict function from genetic sequence.
A STING-based biosensor affords broad cyclic dinucleotide detection within single living eukaryotic cells
Authors: Pollock Alex J. , Zaver Shivam A. , Woodward Joshua J.
Published: July 2020

Cyclic dinucleotides (CDNs) are second messengers conserved across all three domains of life. Within eukaryotes they mediate protective roles in innate immunity against malignant, viral, and bacterial disease, and exert pathological effects in autoimmune disorders. Despite their ubiquitous role in diverse biological contexts, CDN detection methods are limited. Here, using structure guided design of the murine STING CDN binding domain, we engineer a Förster resonance energy transfer (FRET) based biosensor deemed BioSTING. Recombinant BioSTING affords real-time detection of CDN synthase activity and inhibition. Expression of BioSTING in live human cells allows quantification of localized bacterial and eukaryotic CDN levels in single cells with low nanomolar sensitivity. These findings establish BioSTING as a powerful kinetic in vitro platform amenable to high throughput screens and as a broadly applicable cellular tool to interrogate the temporal and spatial dynamics of CDN signaling in a variety of infectious, malignant, and autoimmune contexts.
Cross-serotype protection against group A Streptococcal infections induced by immunization with SPy_2191
Authors: Sanduja Pooja , Gupta Manish , Somani Vikas Kumar , Yadav Vikas , Dua Meenakshi , Hanski Emanuel , Sharma Abhinay , Bhatnagar Rakesh , Johri Atul Kumar
Published: July 2020

Group A Streptococcus (GAS) infection causes a range of diseases, but vaccine development is hampered by the high number of serotypes. Here, using reverse vaccinology the authors identify SPy_2191 as a cross-protective vaccine candidate. From 18 initially identified surface proteins, only SPy_2191 is conserved, surface-exposed and inhibits both GAS adhesion and invasion. SPy_2191 immunization in mice generates bactericidal antibodies resulting in opsonophagocytic killing of prevalent and invasive GAS serotypes of different geographical regions, including M1 and M49 (India), M3.1 (Israel), M1 (UK) and M1 (USA). Resident splenocytes show higher interferon-γ and tumor necrosis factor-α secretion upon antigen re-stimulation, suggesting activation of cell-mediated immunity. SPy_2191 immunization significantly reduces streptococcal load in the organs and confers ~76-92% protection upon challenge with invasive GAS serotypes. Further, it significantly suppresses GAS pharyngeal colonization in mice mucosal infection model. Our findings suggest that SPy_2191 can act as a universal vaccine candidate against GAS infections.
RETRACTED ARTICLE: Ornithine-A urea cycle metabolite enhances autophagy and controls Mycobacterium tuberculosis infection
Authors: Sivangala Thandi Ramya , Radhakrishnan Rajesh Kumar , Tripathi Deepak , Paidipally Padmaja , Azad Abul K. , Schlesinger Larry S. , Samten Buka , Mulik Sachin , Vankayalapati Ramakrishna
Published: July 2020

Macrophages are professional phagocytes known to play a vital role in controllingMycobacterium tuberculosis(Mtb) infection and disease progression. Here we compareMtbgrowth in mouse alveolar (AMs), peritoneal (PMs), and liver (Kupffer cells; KCs) macrophages and in bone marrow-derived monocytes (BDMs). KCs restrictMtbgrowth more efficiently than all other macrophages and monocytes despite equivalent infections through enhanced autophagy. A metabolomics comparison ofMtb-infected macrophages indicates that ornithine and imidazole are two top-scoring metabolites inMtb-infected KCs and that acetylcholine is the top-scoring inMtb-infected AMs. Ornithine, imidazole and atropine (acetylcholine inhibitor) inhibitMtbgrowth in AMs. Ornithine enhances AMPK mediated autophagy whereas imidazole directly killsMtbby reducing cytochrome P450 activity. Intranasal delivery of ornithine or imidazole or the two together restrictsMtbgrowth. Our study demonstrates that the metabolic differences betweenMtb-infected AMs and KCs lead to differences in the restriction ofMtbgrowth.
Structurally divergent dynamic combinatorial chemistry on racemic mixtures
Authors: Gianga Tiberiu-M. , Pantoș G. Dan
Published: July 2020

Structurally Divergent Reactions on Racemic Mixtures are atypical processes in Nature. The few examples reported in the literature take place in organic solvents and are driven by the reagents’ interaction with bulky chiral catalysts. Herein, we describe a dynamic combinatorial approach to generate structural divergence from racemic building blocks. The divergence is due to a stereospecific electron-donor – electron-acceptor interaction of diastereomeric macrocycles, leading to structurally distinct pseudorotaxanes. The equilibrated dynamic combinatorial library contains, amongst various macrocycles, two different types of [2]catenanes that are non-isomeric. The formation of these [2]catenanes is due to a spontaneous stereo and structurally divergent assembly of the building blocks.
Lactate released by inflammatory bone marrow neutrophils induces their mobilization via endothelial GPR81 signaling
Authors: Khatib-Massalha Eman , Bhattacharya Suditi , Massalha Hassan , Biram Adi , Golan Karin , Kollet Orit , Kumari Anju , Avemaria Francesca , Petrovich-Kopitman Ekaterina , Gur-Cohen Shiri , Itkin Tomer , Brandenburger Isabell , Spiegel Asaf , Shulman Ziv , Gerhart-Hines Zachary , Itzkovitz Shalev , Gunzer Matthias , Offermanns Stefan , Alon Ronen , Ariel Amiram , Lapidot Tsvee
Published: July 2020

Neutrophils provide first line of host defense against bacterial infections utilizing glycolysis for their effector functions. How glycolysis and its major byproduct lactate are triggered in bone marrow (BM) neutrophils and their contribution to neutrophil mobilization in acute inflammation is not clear. Here we report that bacterial lipopolysaccharides (LPS) orSalmonellaTyphimurium triggers lactate release by increasing glycolysis, NADPH-oxidase-mediated reactive oxygen species and HIF-1α levels in BM neutrophils. Increased release of BM lactate preferentially promotes neutrophil mobilization by reducing endothelial VE-Cadherin expression, increasing BM vascular permeability via endothelial lactate-receptor GPR81 signaling. GPR81−/−mice mobilize reduced levels of neutrophils in response to LPS, unless rescued by VE-Cadherin disrupting antibodies. Lactate administration also induces release of the BM neutrophil mobilizers G-CSF, CXCL1 and CXCL2, indicating that this metabolite drives neutrophil mobilization via multiple pathways. Our study reveals a metabolic crosstalk between lactate-producing neutrophils and BM endothelium, which controls neutrophil mobilization under bacterial infection.
Enhancing power factor of SnSe sheet with grain boundary by doping germanium or silicon
Authors: Sun Jie , Yu Jiabing , Guo Yaguang , Wang Qian
Published: July 2020

Grain boundaries (GBs) widely exist in two-dimensional (2D) and three-dimensional (3D) materials in experiment, which significantly affect the thermoelectric performance because of the scattering effect on the transport of both electron and phonon. Motivated by the research progress in 3D SnSe, we have systematically studied the GBs in a SnSe monolayer including their stable geometric configurations, the effect of GBs on power factor and Seebeck coefficient, and the strategies to improve the performance by using first principles calculations combined with semiclassical Boltzmann theory. We find that the GBs increase the potential energy barrier of carriers and decrease the valley degeneracy of the conducting bands, leading to the reduction of Seebeck coefficient, as compared to that of the pristine SnSe sheet. We further demonstrate that the trapping gap states are effectively eliminated or reduced by doping germanium or silicon, leading to the enhanced electrical conductivity, power factor, and Seebeck coefficient. These findings shed lights on developing practical strategies for modulating the thermoelectric performance of 2D polycrystalline sheets.
Publisher Correction: New international guidance on quality, safety and efficacy of DNA vaccines
Authors: Beasley David W. C.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
CerebrA, registration and manual label correction of Mindboggle-101 atlas for MNI-ICBM152 template
Authors: Manera Ana L. , Dadar Mahsa , Fonov Vladimir , Collins D. Louis
Published: July 2020

Accurate anatomical atlases are recognized as important tools in brain-imaging research. They are widely used to estimate disease-specific changes and therefore, are of great relevance in extracting regional information on volumetric variations in clinical cohorts in comparison to healthy populations. The use of high spatial resolution magnetic resonance imaging and the improvement in data preprocessing methods have enabled the study of structural volume changes on a wide range of disorders, particularly in neurodegenerative diseases where different brain morphometry analyses are being broadly used in an effort to improve diagnostic biomarkers. In the present dataset, we introduce the Cerebrum Atlas (CerebrA) along with the MNI-ICBM2009c average template. MNI-ICBM2009c is the most recent version of the MNI-ICBM152 brain average, providing a higher level of anatomical details. Cerebra is based on an accurate non-linear registration of cortical and subcortical labelling from Mindboggle 101 to the symmetric MNI-ICBM2009c atlas, followed by manual editing.
Factor structure of the Edinburgh Postnatal Depression Scale in the Japan Environment and Children’s Study
Authors: Matsumura Kenta , Hamazaki Kei , Tsuchida Akiko , Kasamatsu Haruka , Inadera Hidekuni ,   The Japan Environment and Children’s Study (JECS) Group, Kamijima Michihiro , Yamazaki Shin , Ohya Yukihiro , Kishi Reiko , Yaegashi Nobuo , Hashimoto Koichi , Mori Chisato , Ito Shuichi , Yamagata Zentaro , Nakayama Takeo , Iso Hiroyasu , Shima Masayuki , Kurozawa Youichi , Suganuma Narufumi , Kusuhara Koichi , Katoh Takahiko
Published: July 2020

The Edinburgh Postnatal Depression Scale (EPDS) is frequently used to screen for postpartum depression. However, its factor structure exhibits noticeable inconsistencies between studies. We examined the EPDS at two postpartum time points using a large dataset from outside Western countries. Participants were 91,063 mothers in an ongoing birth cohort of the Japan Environment and Children’s Study. One-, two-, and three-factor structures of the EPDS at 1- and 6-months postpartum were extracted using exploratory factor analysis (EFA) with oblique rotation. Goodness-of-fit indices of extracted factor structures were compared with prior ones by conducting a confirmatory factor analysis (CFA). CFA revealed that a three-factor model extracted from the current EFA—anxiety (items 3, 4, 5, and 6), depression (items 7, 9, and 10), and anhedonia (items 1 and 2)—showed acceptably high goodness-of-fit and invariability across time. These three factors explained about 65% of the total variance with good reliability (all Cronbach’s αs ≥ 0.70). Most three-factor structures (vs. two-) showed higher goodness-of-fit indices. In conclusion, although we only examined the postpartum period, the EPDS likely comprises three dimensions: anxiety, depression, and anhedonia. Our findings raise questions about the one- or two-factor structure of the EPDS.

Trial registration: UMIN000030786.
Complete genome sequences of Streptococcus pyogenes type strain reveal 100%-match between PacBio-solo and Illumina-Oxford Nanopore hybrid assemblies
Authors: Salvà-Serra Francisco , Jaén-Luchoro Daniel , Jakobsson Hedvig E. , Gonzales-Siles Lucia , Karlsson Roger , Busquets Antonio , Gomila Margarita , Bennasar-Figueras Antoni , Russell Julie E. , Fazal Mohammed Abbas , Alexander Sarah , Moore Edward R. B.
Published: July 2020

We present the first complete, closed genome sequences of Streptococcus pyogenes strains NCTC 8198T and CCUG 4207T, the type strain of the type species of the genus Streptococcus and an important human pathogen that causes a wide range of infectious diseases. S. pyogenes NCTC 8198T and CCUG 4207T are derived from deposit of the same strain at two different culture collections. NCTC 8198T was sequenced, using a PacBio platform; the genome sequence was assembled de novo, using HGAP. CCUG 4207T was sequenced and a de novo hybrid assembly was generated, using SPAdes, combining Illumina and Oxford Nanopore sequence reads. Both strategies yielded closed genome sequences of 1,914,862 bp, identical in length and sequence identity. Combining short-read Illumina and long-read Oxford Nanopore sequence data circumvented the expected error rate of the nanopore sequencing technology, producing a genome sequence indistinguishable to the one determined with PacBio. Sequence analyses revealed five prophage regions, a CRISPR-Cas system, numerous virulence factors and no relevant antibiotic resistance genes. These two complete genome sequences of the type strain of S. pyogenes will effectively serve as valuable taxonomic and genomic references for infectious disease diagnostics, as well as references for future studies and applications within the genus Streptococcus.
The pharmaceutical solvent N-methyl-2-pyrollidone (NMP) attenuates inflammation through Krüppel-like factor 2 activation to reduce atherogenesis
Authors: Roche-Molina Marta , Hardwick Bryn , Sanchez-Ramos Cristina , Sanz-Rosa David , Gewert Dirk , Cruz Francisco M. , Gonzalez-Guerra Andres , Andres Vicente , Palma Joaquin A. , Ibanez Borja , Mckenzie Grahame , Bernal Juan A.
Published: July 2020

N-methyl-2-pyrrolidone (NMP) is a versatile water-miscible polar aprotic solvent. It is used as a drug solubilizer and penetration enhancer in human and animal, yet its bioactivity properties remain elusive. Here, we report that NMP is a bioactive anti-inflammatory compound well tolerated in vivo, that shows efficacy in reducing disease in a mouse model of atherosclerosis. Mechanistically, NMP increases the expression of the transcription factor Kruppel-like factor 2 (KLF2). Monocytes and endothelial cells treated with NMP express increased levels of KLF2, produce less pro-inflammatory cytokines and adhesion molecules. We found that NMP attenuates monocyte adhesion to endothelial cells inflamed with tumor necrosis factor alpha (TNF-α) by reducing expression of adhesion molecules. We further show using KLF2 shRNA that the inhibitory effect of NMP on endothelial inflammation and subsequent monocyte adhesion is KLF2 dependent. Enhancing KLF2 expression and activity improves endothelial function, controls multiple genes critical for inflammation, and prevents atherosclerosis. Our findings demonstrate a consistent effect of NMP upon KLF2 activation and inflammation, biological processes central to atherogenesis. Our data suggest that inclusion of bioactive solvent NMP in pharmaceutical compositions to treat inflammatory disorders might be beneficial and safe, in particular to treat diseases of the vascular system, such as atherosclerosis.
Valorization of Colombian fique (Furcraea bedinghausii) for production of cellulose nanofibers and its application in hydrogels
Authors: Guancha-Chalapud Marcelo A. , Gálvez Jaime , Serna-Cock Liliana , Aguilar Cristobal N.
Published: July 2020

Cellulose nanofibers were obtained from the Colombian fique (Furcraea bedinghausii) and Acrylic hydrogels (H) and reinforced acrylic hydrogels with fique nanofibres (HRFN) were synthesized, using the solution polymerization method. The extraction was carried out using a combined extraction method (chemical procedures and ultrasound radiation). The raw material (NAT-F), bleached fibers (B-F), hydrolyzed fibers and fibers treated with ultrasound (US-F) were characterized by infrared spectroscopy (FTIR) and thermal stability analysis; also, in order to have a comparison criterion, a commercial microcrystalline cellulose sample (CC) was analyzed, which demonstrated the extraction of fique cellulose. The surface morphology of the NAT-F and the B-F was determined by scanning electron microscopy and the average particle size of the nanofibers was made through transmission electron microscopy. In H y HRFN the strain percent and compression resistance (Rc) were measured. The fique nanofibers showed diameter and length averages of 25.2 ± 6.2 nm and 483.8 ± 283.2 nm respectively. Maximum degradation temperature was 317 °C. HRFN presented higher compression resistance (16.39 ± 4.30 kPa) and this resistance was 2.5 greater than the resistance of H (6.49 ± 2.48 kPa). The results indicate that fique lignocellulosic matrix has potential application for obtaining polymeric type composite materials.
Highly synergistic antimicrobial activity of magainin 2 and PGLa peptides is rooted in the formation of supramolecular complexes with lipids
Authors: Aisenbrey Christopher , Amaro Mariana , Pospíšil Petr , Hof Martin , Bechinger Burkhard
Published: July 2020

Magainin 2 and PGLa are cationic, amphipathic antimicrobial peptides which when added as equimolar mixture exhibit a pronounced synergism in both their antibacterial and pore-forming activities. Here we show for the first time that the peptides assemble into defined supramolecular structures along the membrane interface. The resulting mesophases are quantitatively described by state-of-the art fluorescence self-quenching and correlation spectroscopies. Notably, the synergistic behavior of magainin 2 and PGLa correlates with the formation of hetero-domains and an order-of-magnitude increased membrane affinity of both peptides. Enhanced membrane association of the peptide mixture is only observed in the presence of phophatidylethanolamines but not of phosphatidylcholines, lipids that dominate bacterial and eukaryotic membranes, respectively. Thereby the increased membrane-affinity of the peptide mixtures not only explains their synergistic antimicrobial activity, but at the same time provides a new concept to increase the therapeutic window of combinatorial drugs.
Winter-to-summer seasonal migration of microlithic human activities on the Qinghai-Tibet Plateau
Authors: Hou Guangliang , Gao Jingyi , Chen Youcheng , Xu Changjun , Lancuo Zhuoma , Xiao Yongming , Cai Linhai , He Yuanhong
Published: July 2020

The Qinghai-Tibet Plateau (QTP) has become a valuable site for investigation of adaptive regimes of prehistoric humans to extreme environments. At present most studies have focused solely on a single site. Using a more integrated approach that covers the complete scope of the plateau is needed to better understand the expansion logic of prehistoric humans moving towards the plateau. Here, we conducted accelerator mass spectrometry 14C dating of two microlithic sites. Canxiongashuo (CXGS) and Shalongka (SLK), which are located at the inner and marginal areas of the QTP, respectively. By using geographic information system, literature, and natural environmental factors, we constructed a model for the relationship between traveling distance and time, and we also used these factors to construct a plateau environmental index. The results indicated that the ages of the CXGS and SLK sites are 8.4–7.5 cal. ka BP and 8.4–6.2 cal. ka BP, respectively. Combining the archaeological evidence and literature, hunter-gatherers may have seasonal migration activities at low altitude in winter and high altitude in summer in order to make full use of natural resources. Our model of relationship between traveling distance and time shows that hunter-gatherers in CXGS site was active on the plateau all year-round at approximately 8.3 cal. ka BP. According to EI and archaeological remains, we propose that SLK site was a winter camp of prehistoric hunter-gatherers. Taken together, we determined 8.4–6.0 cal. ka BP as a transitional period from the Paleolithic to Neolithic Ages, and winter camps of hunter-gatherers evolved into settlements in the Neolithic Age.
Early modulation of macrophage ROS-PPARγ-NF-κB signalling by sonodynamic therapy attenuates neointimal hyperplasia in rabbits
Authors: Yao Jianting , Zhao Xuezhu , Tan Fancheng , Cao Xiaoru , Guo Shuyuan , Li Xiang , Huang Zhen , Diabakte Kamal , Wang Lu , Liu Mingyu , Shen Zhaoqian , Li Bicheng , Cao Zhengyu , Sheng Siqi , Lu Minqiao , Cao Yang , Jin Hong , Zhang Zhiguo , Tian Ye
Published: July 2020

Disruption of re-endothelialization and haemodynamic balance remains a critical side effect of drug-eluting stents (DES) for preventing intimal hyperplasia. Previously, we found that 5-aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) suppressed macrophage-mediated inflammation in atherosclerotic plaques. However, the effects on intimal hyperplasia and re-endothelialization remain unknown. In this study, 56 rabbits were randomly assigned to control, ultrasound, ALA and ALA-SDT groups, and each group was divided into two subgroups (n = 7) on day 3 after right femoral artery balloon denudation combined with a hypercholesterolemic diet. Histopathological analysis revealed that ALA-SDT enhanced macrophage apoptosis and ameliorated inflammation from day 1. ALA-SDT inhibited neointima formation without affecting re-endothelialization, increased blood perfusion, decreased the content of macrophages, proliferating smooth muscle cells (SMCs) and collagen but increased elastin by day 28. In vitro, ALA-SDT induced macrophage apoptosis and reduced TNF-α, IL-6 and IL-1β via the ROS-PPARγ-NF-κB signalling pathway, which indirectly inhibited human umbilical artery smooth muscle cell (HUASMC) proliferation, migration and IL-6 production. ALA-SDT effectively inhibits intimal hyperplasia without affecting re-endothelialization. Hence, its clinical application combined with bare-metal stent (BMS) implantation presents a potential strategy to decrease bleeding risk caused by prolonged dual-antiplatelet regimen after DES deployment.