bluuebunny/crossref_metadata_2025 huggingface dataset:
SCHUMPETER’S ASSESSMENT OF ADAM SMITH AND THEWEALTH OF NATIONS: WHY HE GOT IT WRONG
Authors: Ortmann Andreas , Walraevens Benoît , Baranowski David
Published: September 2019

In his widely read and citedHistory of Economic Analysis(Schumpeter 1954), Joseph Alois Schumpeter dismissed Adam Smith’sNature and Causes of the Wealth of Nations(Smith 1976a) in a blunt and oftenad hominemmanner. In fact, he even questioned Smith’s intellectual mettle. We argue that Schumpeter’s assessment might have resulted from his failure to appreciate the rhetorical structure of Smith’s masterpiece (and the highly political character of its Book V), a failure possibly due to Schumpeter’s not having access to student notes of Smith’s lectures on rhetoric that surfaced only after Schumpeter’s death. We argue that Schumpeter’s failure to appreciate the rhetorical structure of Smith’s masterpiece is a prominent example of the consequences of not taking into account Smith’s rhetorical strategies and principles when trying to understand the man and his oeuvre.
Querying Knowledge via Multi-Hop English Questions
Authors: GAO TIANTIAN , FODOR PAUL , KIFER MICHAEL
Published: September 2019

The inherent difficulty of knowledge specification and the lack of trained specialists are some of the key obstacles on the way to making intelligent systems based on the knowledge representation and reasoning (KRR) paradigm commonplace.Knowledge and query authoringusing natural language, especiallycontrollednatural language (CNL), is one of the promising approaches that could enable domain experts, who are not trained logicians, to both create formal knowledge and query it. In previous work, we introduced theKALMsystem (Knowledge Authoring Logic Machine) that supports knowledge authoring (and simple querying) with very high accuracy that at present is unachievable via machine learning approaches. The present paper expands on the question answering aspect of KALM and introducesKALM-QA(KALM for Question Answering) that is capable of answering much more complex English questions. We show that KALM-QA achieves 100% accuracy on an extensive suite of movie-related questions, calledMetaQA, which contains almost 29,000 test questions and over 260,000 training questions. We contrast this with a published machine learning approach, which falls far short of this high mark.
Abstract Solvers for Computing Cautious Consequences of ASP programs
Authors: AMENDOLA GIOVANNI , DODARO CARMINE , MARATEA MARCO
Published: September 2019

Abstract solvers are a method to formally analyze algorithms that have been profitably used for describing, comparing and composing solving techniques in various fields such as Propositional Satisfiability (SAT), Quantified SAT, Satisfiability Modulo Theories, Answer Set Programming (ASP), and Constraint ASP.

In this paper, we design, implement and test novel abstract solutions for cautious reasoning tasks in ASP. We show how to improve the current abstract solvers for cautious reasoning in ASP with new techniques borrowed from backbone computation in SAT, in order to design new solving algorithms. By doing so, we also formally show that the algorithms for solving cautious reasoning tasks in ASP are strongly related to those for computing backbones of Boolean formulas. We implement some of the new solutions in the ASP solver wasp and show that their performance are comparable to state-of-the-art solutions on the benchmark problems from the past ASP Competitions.
Inconsistency Proofs for ASP: The ASP - DRUPE Format
Authors: ALVIANO MARIO , DODARO CARMINE , FICHTE JOHANNES K. , HECHER MARKUS , PHILIPP TOBIAS , RATH JAKOB
Published: September 2019

Answer Set Programming (ASP) solvers are highly-tuned and complex procedures that implicitly solve the consistency problem, i.e., deciding whether a logic program admits an answer set. Verifying whether a claimed answer set is formally a correct answer set of the program can be decided in polynomial time for (normal) programs. However, it is far from immediate to verify whether a program that is claimed to be inconsistent, indeed does not admit any answer sets. In this paper, we address this problem and develop the new proof format ASP-DRUPE for propositional, disjunctive logic programs, including weight and choice rules. ASP-DRUPE is based on the Reverse Unit Propagation (RUP) format designed for Boolean satisfiability. We establish correctness of ASP-DRUPE and discuss how to integrate it into modern ASP solvers. Later, we provide an implementation of ASP-DRUPE into the wasp solver for normal logic programs.
On the Equivalence Between Abstract Dialectical Frameworks and Logic Programs
Authors: ALCÂNTARA JOÃO , SÁ SAMY , ACOSTA-GUADARRAMA JUAN
Published: September 2019

Abstract Dialectical Frameworks (ADFs) are argumentation frameworks where each node is associated with an acceptance condition. This allows us to model different types of dependencies as supports and attacks. Previous studies provided a translation from Normal Logic Programs (NLPs) toADFs and proved the stable models semantics for a normal logic program has an equivalent semantics to that of the correspondingADF. However, these studies failed in identifying a semantics forADFs equivalent to a three-valued semantics (as partial stable models and well-founded models) forNLPs. In this work, we focus on a fragment ofADFs, called Attacking Dialectical Frameworks (ADF+s), and provide a translation fromNLPs toADF+s robust enough to guarantee the equivalence between partial stable models, well-founded models, regular models, stable models semantics forNLPs and respectively complete models, grounded models, preferred models, stable models forADFs. In addition, we define a new semantics forADF+s, calledL-stable, and show it is equivalent to theL-stable semantics forNLPs.
Using Answer Set Programming for Commonsense Reasoning in the Winograd Schema Challenge
Authors: SHARMA ARPIT
Published: September 2019

The Winograd Schema Challenge (WSC) is a natural language understanding task proposed as an alternative to the Turing test in 2011. In this work we attempt to solve WSC problems by reasoning with additional knowledge. By using an approach built on top of graph-subgraph isomorphism encoded using Answer Set Programming (ASP) we were able to handle 240 out of 291 WSC problems. The ASP encoding allows us to add additional constraints in an elaboration tolerant manner. In the process we present a graph based representation of WSC problems as well as relevant commonsense knowledge.
Precomputing Datalog Evaluation Plans in Large-Scale Scenarios
Authors: FIORENTINO ALESSIO , LEONE NICOLA , MANNA MARCO , PERRI SIMONA , ZANGARI JESSICA
Published: September 2019

With the more and more growing demand for semantic Web services over large databases, an efficient evaluation of Datalog queries is arousing a renewed interest among researchers and industry experts. In this scenario, to reduce memory consumption and possibly optimize execution times, the paper proposes novel techniques to determine an optimal indexing schema for the underlying database together with suitable body-orderings for the Datalog rules. The new approach is compared with the standard execution plans implemented in DLV over widely used ontological benchmarks. The results confirm that the memory usage can be significantly reduced without paying any cost in efficiency.
Introduction to the 35th International Conference on Logic Programming Special Issue
Authors: ERDEM ESRA , FORMISANO ANDREA , VIDAL GERMÁN , YANG FANGKAI
Published: September 2019

This volume contains the regular papers of the 35th International Conference on Logic Programming (ICLP 2019), held in Las Cruces, New Mexico, USA, from September 20 to September 25, 2019.
Is there a limit to the size of the state? The scope conditions of Wagner's law
Authors: Karceski Steven M. , Kiser Edgar
Published: September 2019

We investigate the relationship between economic development and the growth of the state by testing Wagner's Law. We begin with a general test, and find it does not hold in all cases: it breaks down at higher levels of development and in more recent time periods. This suggests that Wagner's law has specific scope conditions, beyond which states do not continue to grow as economies grow. We use a series of models to explore the temporal scope of Wagner's law and the point at which state growth may hit a ceiling. We conclude limits on the growth of the state are set by limits on the capacity of states to increase taxation. States can avoid this problem temporarily by running budget deficits, but eventually accumulated debt forces them to cut expenditures. Spending is tied to tax revenue like a rubber band, it can stretch only so far before being pulled back.
Covering Climate with Power Plants, Scooters, and Philosophy
Authors:   AGU
Published: September 2019

What Earth and space science stories are we recommending this week?
TLR4 signaling drives mesenchymal stromal cells commitment to promote tumor microenvironment transformation in multiple myeloma
Authors: Giallongo Cesarina , Tibullo Daniele , Camiolo Giuseppina , Parrinello Nunziatina L. , Romano Alessandra , Puglisi Fabrizio , Barbato Alessandro , Conticello Concetta , Lupo Gabriella , Anfuso Carmelina Daniela , Lazzarino Giacomo , Li Volti Giovanni , Palumbo Giuseppe Alberto , Di Raimondo Francesco
Published: September 2019

Inflammation represents a key feature and hallmark of tumor microenvironment playing a major role in the interaction with mesenchymal stromal cells (MSC) in cancer progression. The aim of the present study was to investigate the crosstalk between MSCs and myeloma cells (MM) in the pro-inflammatory microenvironment promoting immune evasion and tumor growth. MSC were collected from patients with diagnosis of MGUS (n = 10), smoldering myeloma (n = 7), multiple myeloma at diagnosis (n = 16), relapse (n = 5) or refractory (n = 3), and from age-matched healthy controls (HC, n = 10) and cultured with peripheral blood mononucleated cells (PBMC) from healthy volunteer donors. Similarly to MM, we showed that MSC from smoldering multiple myeloma (SMM) patients activated neutrophils and conferred an immunosuppressive and pro-angiogenic phenotype. Furthermore, co-cultures of plasma cells (PC) and HC-MSC suggested that such activation is driven by MM cells through the switching into a pro-inflammatory phenotype mediated by toll-like receptor 4 (TLR4). These results were further confirmed using a zebrafish as an immunocompetent in vivo model, showing the role of MM–MSC in supporting PCs engraftment and Th2 response. Such effect was abolished following inhibition of TLR4 signaling in MM–MSC before co-injection with PC. Moreover, the addition of a TLR4 inhibitor in the co-culture of HC-MSC with MM cells prevented the activation of the pro-tumor activity in PC-educated MSC. In conclusion, our study provides evidence that TLR4 signaling plays a key role in MSC transformation by inducing a pro-tumor phenotype associated with a permissive microenvironment allowing immune escape and tumor growth.
Mesophilic microorganisms build terrestrial mats analogous to Precambrian microbial jungles
Authors: Finke N. , Simister R. L. , O’Neil A. H. , Nomosatryo S. , Henny C. , MacLean L. C. , Canfield D. E. , Konhauser K. , Lalonde S. V. , Fowle D. A. , Crowe S. A.
Published: September 2019

Development of Archean paleosols and patterns of Precambrian rock weathering suggest colonization of continents by subaerial microbial mats long before evolution of land plants in the Phanerozoic Eon. Modern analogues for such mats, however, have not been reported, and possible biogeochemical roles of these mats in the past remain largely conceptual. We show that photosynthetic, subaerial microbial mats from Indonesia grow on mafic bedrocks at ambient temperatures and form distinct layers with features similar to Precambrian mats and paleosols. Such subaerial mats could have supported a substantial aerobic biosphere, including nitrification and methanotrophy, and promoted methane emissions and oxidative weathering under ostensibly anoxic Precambrian atmospheres. High C-turnover rates and cell abundances would have made these mats prime locations for early microbial diversification. Growth of landmass in the late Archean to early Proterozoic Eons could have reorganized biogeochemical cycles between land and sea impacting atmospheric chemistry and climate.
Circular RNA CircFndc3b modulates cardiac repair after myocardial infarction via FUS/VEGF-A axis
Authors: Garikipati Venkata Naga Srikanth , Verma Suresh Kumar , Cheng Zhongjian , Liang Dongming , Truongcao May M. , Cimini Maria , Yue Yujia , Huang Grace , Wang Chunlin , Benedict Cindy , Tang Yan , Mallaredy Vandana , Ibetti Jessica , Grisanti Laurel , Schumacher Sarah M. , Gao Erhe , Rajan Sudarsan , Wilusz Jeremy E. , Goukassian David , Houser Steven R. , Koch Walter J. , Kishore Raj
Published: September 2019

Circular RNAs are generated from many protein-coding genes, but their role in cardiovascular health and disease states remains unknown. Here we report identification of circRNA transcripts that are differentially expressed in post myocardial infarction (MI) mouse hearts including circFndc3b which is significantly down-regulated in the post-MI hearts. Notably, the human circFndc3b ortholog is also significantly down-regulated in cardiac tissues of ischemic cardiomyopathy patients. Overexpression of circFndc3b in cardiac endothelial cells increases vascular endothelial growth factor-A expression and enhances their angiogenic activity and reduces cardiomyocytes and endothelial cell apoptosis. Adeno-associated virus 9 -mediated cardiac overexpression of circFndc3b in post-MI hearts reduces cardiomyocyte apoptosis, enhances neovascularization and improves left ventricular functions. Mechanistically, circFndc3b interacts with the RNA binding protein Fused in Sarcoma to regulate VEGF expression and signaling. These findings highlight a physiological role for circRNAs in cardiac repair and indicate that modulation of circFndc3b expression may represent a potential strategy to promote cardiac function and remodeling after MI.
Ultra-long-acting tunable biodegradable and removable controlled release implants for drug delivery
Authors: Benhabbour S. Rahima , Kovarova Martina , Jones Clinton , Copeland Daijha J. , Shrivastava Roopali , Swanson Michael D. , Sykes Craig , Ho Phong T. , Cottrell Mackenzie L. , Sridharan Anush , Fix Samantha M. , Thayer Orrin , Long Julie M. , Hazuda Daria J. , Dayton Paul A. , Mumper Russell J. , Kashuba Angela D. M. , Victor Garcia J.
Published: September 2019

Here we report an ultra-long-acting tunable, biodegradable, and removable polymer-based delivery system that offers sustained drug delivery for up to one year for HIV treatment or prophylaxis. This robust formulation offers the ability to integrate multiple drugs in a single injection, which is particularly important to address the potential for drug resistance with monotherapy. Six antiretroviral drugs were selected based on their solubility inN-methyl-2-pyrrolidone and relevance as a combination therapy for HIV treatment or prevention. All drugs released with concentrations above their protein-adjusted inhibitory concentration and retained their physical and chemical properties within the formulation and upon release. The versatility of this formulation to integrate multiple drugs and provide sustained plasma concentrations from several weeks to up to one year, combined with its ability to be removed to terminate the treatment if necessary, makes it attractive as a drug delivery platform technology for a wide range of applications.
Linked-read sequencing of gametes allows efficient genome-wide analysis of meiotic recombination
Authors: Sun Hequan , Rowan Beth A. , Flood Pádraic J. , Brandt Ronny , Fuss Janina , Hancock Angela M. , Michelmore Richard W. , Huettel Bruno , Schneeberger Korbinian
Published: September 2019

Meiotic crossovers (COs) ensure proper chromosome segregation and redistribute the genetic variation that is transmitted to the next generation. Large populations and the demand for genome-wide, fine-scale resolution challenge existing methods for CO identification. Taking advantage of linked-read sequencing, we develop a highly efficient method for genome-wide identification of COs at kilobase resolution in pooled recombinants. We first test this method using a pool of Arabidopsis F2 recombinants, and recapitulate results obtained from the same plants using individual whole-genome sequencing. By applying this method to a pool of pollen DNA from an F1 plant, we establish a highly accurate CO landscape without generating or sequencing a single recombinant plant. The simplicity of this approach enables the simultaneous generation and analysis of multiple CO landscapes, accelerating the pace at which mechanisms for the regulation of recombination can be elucidated through efficient comparisons of genotypic and environmental effects on recombination.
A fungal pathogen deploys a small silencing RNA that attenuates mosquito immunity and facilitates infection
Authors: Cui Chunlai , Wang Yan , Liu Jingnan , Zhao Jing , Sun Peilu , Wang Sibao
Published: September 2019

Insecticidal fungi represent a promising alternative to chemical pesticides for disease vector control. Here, we show that the pathogenic fungus Beauveria bassiana exports a microRNA-like RNA (bba-milR1) that hijacks the host RNA-interference machinery in mosquito cells by binding to Argonaute 1 (AGO1). bba-milR1 is highly expressed during fungal penetration of the mosquito integument, and suppresses host immunity by silencing expression of the mosquito Toll receptor ligand Spätzle 4 (Spz4). Later, upon entering the hemocoel, bba-milR1 expression is decreased, which avoids induction of the host proteinase CLIPB9 that activates the melanization response. Thus, our results indicate that the pathogen deploys a cross-kingdom small-RNA effector that attenuates host immunity and facilitates infection.
Enhanced CRISPR-based DNA demethylation by Casilio-ME-mediated RNA-guided coupling of methylcytosine oxidation and DNA repair pathways
Authors: Taghbalout Aziz , Du Menghan , Jillette Nathaniel , Rosikiewicz Wojciech , Rath Abhijit , Heinen Christopher D. , Li Sheng , Cheng Albert W.
Published: September 2019

Here we develop a methylation editing toolbox, Casilio-ME, that enables not only RNA-guided methylcytosine editing by targeting TET1 to genomic sites, but also by co-delivering TET1 and protein factors that couple methylcytosine oxidation to DNA repair activities, and/or promote TET1 to achieve enhanced activation of methylation-silenced genes. Delivery of TET1 activity by Casilio-ME1 robustly alters the CpG methylation landscape of promoter regions and activates methylation-silenced genes. We augment Casilio-ME1 to simultaneously deliver the TET1-catalytic domain and GADD45A (Casilio-ME2) or NEIL2 (Casilio-ME3) to streamline removal of oxidized cytosine intermediates to enhance activation of targeted genes. Using two-in-one effectors or modular effectors, Casilio-ME2 and Casilio-ME3 remarkably boost gene activation and methylcytosine demethylation of targeted loci. We expand the toolbox to enable a stable and expression-inducible system for broader application of the Casilio-ME platforms. This work establishes a platform for editing DNA methylation to enable research investigations interrogating DNA methylomes.
Inactivation of NF-κB2 (p52) restrains hepatic glucagon response via preserving PDE4B induction
Authors: Zhang Wen-Song , Pan An , Zhang Xu , Ying Ang , Ma Gaoxiang , Liu Bao-Lin , Qi Lian-Wen , Liu Qun , Li Ping
Published: September 2019

Glucagon promotes hepatic gluconeogenesis and maintains whole-body glucose levels during fasting. The regulatory factors that are involved in fasting glucagon response are not well understood. Here we report a role of p52, a key activator of the noncanonical nuclear factor-kappaB signaling, in hepatic glucagon response. We show that p52 is activated in livers of HFD-fed and glucagon-challenged mice. Knockdown of p52 lowers glucagon-stimulated hyperglycemia, while p52 overexpression augments glucagon response. Mechanistically, p52 binds to phosphodiesterase 4B promoter to inhibit its transcription and promotes cAMP accumulation, thus augmenting the glucagon response through cAMP/PKA signaling. The anti-diabetic drug metformin and ginsenoside Rb1 lower blood glucose at least in part by inhibiting p52 activation. Our findings reveal that p52 mediates glucagon-triggered hepatic gluconeogenesis and suggests that pharmacological intervention to prevent p52 processing is a potential therapeutic strategy for diabetes.
Mechanistic Insights into β-Lactamase-Catalysed Carbapenem Degradation Through Product Characterisation
Authors: Lohans Christopher T. , Freeman Emily I. , Groesen Emma van , Tooke Catherine L. , Hinchliffe Philip , Spencer James , Brem Jürgen , Schofield Christopher J.
Published: September 2019

β-Lactamases are a major threat to the clinical use of carbapenems, which are often antibiotics of last resort. Despite this, the reaction outcomes and mechanisms by which β-lactamases degrade carbapenems are still not fully understood. The carbapenem bicyclic core consists of a β-lactam ring fused to a pyrroline ring. Following β-lactamase-mediated opening of the β-lactam, the pyrroline may interconvert between an enamine (2-pyrroline) form and two epimeric imine (1-pyrroline) forms; previous crystallographic and spectroscopic studies have reported all three of these forms in the contexts of hydrolysis by different β-lactamases. As we show by NMR spectroscopy, the serine β-lactamases (KPC-2, SFC-1, CMY-10, OXA-23, and OXA-48) and metallo-β-lactamases (NDM-1, VIM-1, BcII, CphA, and L1) tested all degrade carbapenems to preferentially give the Δ2 (enamine) and/or (R)-Δ1 (imine) products. Rapid non-enzymatic tautomerisation of the Δ2 product to the (R)-Δ1 product prevents assignment of the nascent enzymatic product by NMR. The observed stereoselectivity implies that carbapenemases control the form of their pyrroline ring intermediate(s)/product(s), thereby preventing pyrroline tautomerisation from inhibiting catalysis.
Subtractive inhibition assay for the detection of Campylobacter jejuni in chicken samples using surface plasmon resonance
Authors: Masdor Noor Azlina , Altintas Zeynep , Shukor Mohd. Yunus , Tothill Ibtisam E.
Published: September 2019

In this work, a subtractive inhibition assay (SIA) based on surface plasmon resonance (SPR) for the rapid detection of Campylobacter jejuni was developed. For this, rabbit polyclonal antibody with specificity to C. jejuni was first mixed with C. jejuni cells and unbound antibody was subsequently separated using a sequential process of centrifugation and then detected using an immobilized goat anti-rabbit IgG polyclonal antibody on the SPR sensor chip. This SIA-SPR method showed excellent sensitivity for C. jejuni with a limit of detection (LOD) of 131 ± 4 CFU mL−1 and a 95% confidence interval from 122 to 140 CFU mL−1. The method has also high specificity. The developed method showed low cross-reactivity to bacterial pathogens such as Salmonellaenterica serovar Typhimurium (7.8%), Listeria monocytogenes (3.88%) and Escherichia coli (1.56%). The SIA-SPR method together with the culturing (plating) method was able to detect C. jejuni in the real chicken sample at less than 500 CFU mL−1, the minimum infectious dose for C. jejuni while a commercial ELISA kit was unable to detect the bacterium. Since the currently available detection tools rely on culturing methods, which take more than 48 hours to detect the bacterium, the developed method in this work has the potential to be a rapid and sensitive detection method for C. jejuni.
High-performance flat-type InGaN-based light-emitting diodes with local breakdown conductive channel
Authors: Baek Seung-Hye , Lee Hyun-Jin , Lee Sung-Nam
Published: September 2019

Flat-type InGaN-based light-emitting diodes (LEDs) without an n-type contact electrode were developed by using a local breakdown conductive channel (LBCC), and the effect of the In content of the InGaN quantum wells (QWs) on the local breakdown phenomenon was investigated. Electroluminescence and X-ray analyses demonstrated that the homogeneity and crystallinity of the InGaN QWs deteriorated as the In content of the InGaN QWs increased, thereby increasing the reverse leakage current and decreasing the breakdown voltage. After reverse breakdown with a reverse current of several mA, an LBCC was formed on the GaN-based LEDs. The surface size and anisotropic shape of the LBCC increased as the indium content of the InGaN QWs in the LEDs increased. Moreover, a flat-type InGaN LED without an n-type electrode was developed by using the LBCC. Notably, the resistance of the LBCC decreased with increasing indium content in the InGaN QWs, leading to lower resistance and higher light emission of the flat-type InGaN-based LEDs without an n-type contact electrode.
L-arginine supplementation and thromboxane synthase inhibition increases cerebral blood flow in experimental cerebral malaria
Authors: Moreira Aline S. , Estato Vanessa , Malvar David C. , Sanches Guilherme S. , Gomes Fabiana , Tibirica Eduardo , Daniel-Ribeiro Cláudio Tadeu , Carvalho Leonardo J. M.
Published: September 2019

Cerebral malaria pathogenesis involves vascular dysfunction with low nitric oxide (NO) bioavailability, vasoconstriction and impaired vasodilation, leading to ischemia, tissue hypoxia and ultimately death. Cerebral blood flow (CBF) involves NO and other pathways, including arachidonic acid (AA)-derived metabolites. Here we show that mice with experimental cerebral malaria (ECM) by P. berghei ANKA showed marked decreases in CBF (as assessed by laser speckle contrast imaging - LSCI) and that administration of L-arginine supplementation (50 mg/kg) and/or of the thromboxane synthase inhibitor Ozagrel (100 mg/kg) induced immediate increases in CBF. L-arginine in combination with artesunate (32 mg/kg) induced immediate reversal of brain ischemia in the short-term (1 hour), but the effect subsided after 3 and 6 hours. Neither L-arginine nor Ozagrel reversed blood brain barrier breakdown. Mice with ECM showed brain levels of selected AA-derived metabolites with a vasoconstrictor profile, with increased levels of 8-isoprostanes, 20-HETE and 14,15-DHET, whereas mice infected with a non-ECM-inducing strain of P. berghei (NK65) showed a vasodilator profile, with normal levels of 20-HETE and 14,15-DHET and increased levels of PGE2. L-arginine is capable of partially reversing cerebral ischemia and AA metabolites may play a role in the cerebrovascular dysfunction in ECM.
Emerging recombination of the C2 sub-genotype of HFMD-associated CV-A4 is persistently and extensively circulating in China
Authors: Ji Tianjiao , Guo Yue , Lv Likun , Wang Jianxing , Shi Yong , Yu Qiuli , Zhang Fan , Tong Wenbin , Ma Jiangtao , Zeng Hanri , Zhao Hua , Zhang Yong , Han Taoli , Song Yang , Yan Dongmei , Yang Qian , Zhu Shuangli , Zhang Yan , Xu Wenbo
Published: September 2019

Sporadic outbreaks caused by coxsackievirus A4 (CV-A4) have been reported worldwide. To further elucidate the detailed genetic characteristics and evolutionary recombination events of CV-A4, virus samples from nationwide hand, foot and mouth disease (HFMD) surveillance, encompassing 27 out of the 31 provinces in China, were investigated. Comprehensive and systematic phylogenetic analyses were performed by using 29 complete genomes, 142 complete CV-A4 VP1 sequences. Four genotypes (A, B, C and D) and five sub-genotypes (C1-C5) were re-identified based on the complete VP1 sequences. C2 is the predominant sub-genotype of CV-A4 associated with HFMD and has evolved into 3 clusters. Cluster 1 is a major cluster that has been persistently and extensively circulating in China since 2006 and has been associated with all severe cases. All the sequences showed high homology with the CV-A4 prototype in the P1 region, while higher identities with CV-A5, CV-14 and CV-16 in the P2 and P3 regions. Recombination analysis revealed that C2 had two specific genetic recombination patterns with other EV-A prototypes in the 5′-UTR and 3D region compared with C5. These recombination patterns might be associated with the increased transmissibility of C2 viruses, which were obtained due to their persistent and extensive circulation in populations.
A mass spectrometry-based assay using metabolic labeling to rapidly monitor chromatin accessibility of modified histone proteins
Authors: Sidoli Simone , Lopes Mariana , Lund Peder J. , Goldman Naomi , Fasolino Maria , Coradin Mariel , Kulej Katarzyna , Bhanu Natarajan V. , Vahedi Golnaz , Garcia Benjamin A.
Published: September 2019

Histone post-translational modifications (PTMs) contribute to chromatin accessibility due to their chemical properties and their ability to recruit enzymes responsible for DNA readout and chromatin remodeling. To date, more than 400 different histone PTMs and thousands of combinations of PTMs have been identified, the vast majority with still unknown biological function. Identification and quantification of histone PTMs has become routine in mass spectrometry (MS) but, since raising antibodies for each PTM in a study can be prohibitive, lots of potential is lost from MS datasets when uncharacterized PTMs are found to be significantly regulated. We developed an assay that uses metabolic labeling and MS to associate chromatin accessibility with histone PTMs and their combinations. The labeling is achieved by spiking in the cell media a 5x concentration of stable isotope labeled arginine and allow cells to grow for at least one cell cycle. We quantified the labeling incorporation of about 200 histone peptides with a proteomics workflow, and we confirmed that peptides carrying PTMs with extensively characterized roles in active transcription or gene silencing were in highly or poorly labeled forms, respectively. Data were further validated using next-generation sequencing to assess the transcription rate of chromatin regions modified with five selected PTMs. Furthermore, we quantified the labeling rate of peptides carrying co-existing PTMs, proving that this method is suitable for combinatorial PTMs. We focus on the abundant bivalent mark H3K27me3K36me2, showing that H3K27me3 dominantly represses histone swapping rate even in the presence of the more permissive PTM H3K36me2. Together, we envision this method will help to generate hypotheses regarding histone PTM functions and, potentially, elucidate the role of combinatorial histone codes.
Formation of Pseudomonas aeruginosa Biofilms in Full-thickness Scald Burn Wounds in Rats
Authors: Brandenburg Kenneth S. , Weaver Alan J. , Karna S. L. Rajasekhar , You Tao , Chen Ping , Stryk Shaina Van , Qian Liwu , Pineda Uzziel , Abercrombie Johnathan J. , Leung Kai P.
Published: September 2019

Using Sprague-Dawley rats (350–450 g; n = 61) and the recently updated Walker-Mason rat scald burn model, we demonstrated that Pseudomonas aeruginosa readily formed biofilms within full-thickness burn wounds. Following the burn, wounds were surface-inoculated with P. aeruginosa in phosphate-buffered saline (PBS), while sterile PBS was used for controls. On post-burn days 1, 3, 7, and 11, animals were euthanized and samples collected for quantitative bacteriology, bacterial gene expression, complete blood cell counts, histology, and myeloperoxidase activity. Robust biofilm infections developed in the full-thickness burn wounds inoculated with 1 × 104 CFU of P. aeruginosa. Both histology and scanning electron microscopy showed the pathogen throughout the histologic cross-sections of burned skin. Quantigene analysis revealed significant upregulation of alginate and pellicle biofilm matrix genes of P. aeruginosa within the burn eschar. Additionally, expression of P. aeruginosa proteases and siderophores increased significantly in the burn wound environment. Interestingly, the host’s neutrophil response to the pathogen was not elevated in either the eschar or circulating blood when compared to the control burn. This new full-thickness burn biofilm infection model will be used to test new anti-biofilm therapies that may be deployed with soldiers in combat for immediate use at the site of burn injury on the battlefield.
Observation resolution critically influences movement-based foraging indices
Authors: Kalyuzhny Michael , Haran Tom , Hawlena Dror
Published: September 2019

Movement‐based indices such as moves per minute (MPM) and proportion time moving (PTM) are common methodologies to quantify foraging behavior. Hundreds of studies have reported these indices, many without specifying the temporal resolution of their original data, and others using varying resolutions. This was done despite the likelihood that observation resolution can affect MPM and PTM estimates. Our goal was to empirically determine the sensitivity of these foraging indices to changes in the temporal resolution of the observation. We used a high-speed camera to record movement sequences of 20 Acanthodactylus boskianus lizards. Then, we gradually decreased the resolution of the data and calculated the foraging indices at different temporal resolutions. When considering the range of temporal resolutions that are relevant for field observations with unassisted vision, we found 68% and 48% difference in MPM and PTM estimates, respectively. When using the highest resolution, our estimate of MPM was an order of magnitude higher than all prior reported values for lizards. Our results raise major concerns regarding the use of already published movement-based indices, and enable us to recommend how new foraging data should be collected.
A processive endoglucanase with multi-substrate specificity is characterized from porcine gut microbiota
Authors: Wang Weijun , Archbold Tania , Lam Joseph S. , Kimber Matthew S. , Fan Ming Z.
Published: September 2019

Cellulases play important roles in the dietary fibre digestion in pigs, and have multiple industrial applications. The porcine intestinal microbiota display a unique feature in rapid cellulose digestion. Herein, we have expressed a cellulase gene, p4818Cel5_2A, which singly encoded a catalytic domain belonging to glycoside hydrolase family 5 subfamily 2, and was previously identified from a metagenomic expression library constructed from porcine gut microbiome after feeding grower pigs with a cellulose-supplemented diet. The activity of purified p4818Cel5_2A was maximal at pH 6.0 and 50 °C and displayed resistance to trypsin digestion. This enzyme exhibited activities towards a wide variety of plant polysaccharides, including cellulosic substrates of avicel and solka-Floc®, and the hemicelluloses of β-(1 → 4)/(1 → 3)-glucans, xyloglucan, glucomannan and galactomannan. Viscosity, reducing sugar distribution and hydrolysis product analyses further revealed that this enzyme was a processive endo-β-(1 → 4)-glucanase capable of hydrolyzing cellulose into cellobiose and cellotriose as the primary end products. These catalytic features of p4818Cel5_2A were further explored in the context of a three-dimensional homology model. Altogether, results of this study report a microbial processive endoglucanase identified from the porcine gut microbiome, and it may be tailored as an efficient biocatalyst candidate for potential industrial applications.
Genetic lines respond uniquely within the chicken thymic transcriptome to acute heat stress and low dose lipopolysaccharide
Authors: Monson Melissa S. , Van Goor Angelica G. , Persia Michael E. , Rothschild Max F. , Schmidt Carl J. , Lamont Susan J.
Published: September 2019

Exposure to high temperatures is known to impair immune functions and disease resistance of poultry. Characterizing changes in the transcriptome can help identify mechanisms by which immune tissues, such as the thymus, respond to heat stress. In this study, 22-day-old chickens from two genetic lines (a relatively resistant Fayoumi line and a more susceptible broiler line) were exposed to acute heat stress (35 °C) and/or immune simulation with lipopolysaccharide (LPS; 100 µg/kg). Transcriptome responses in the thymus were identified by RNA-sequencing (RNA-seq). Expression of most genes was unaffected by heat and/or LPS in the Fayoumi line, whereas these treatments had more impact in the broiler line. Comparisons between the broiler and Fayoumi transcriptomes identified a large number of significant genes both at homeostasis and in response to treatment. Functional analyses predicted that gene expression changes impact immune responses, apoptosis, cell activation, migration, and adhesion. In broilers, acute heat stress changed thymic expression responses to LPS and could impact thymocyte survival and trafficking, and thereby contribute to the negative effects of high temperatures on immune responses. Identification of these genes and pathways provides a foundation for testing targets to improve disease resistance in heat-stressed chickens.
RNA-based qPCR as a tool to quantify and to characterize dual-species biofilms
Authors: Magalhães Andreia Patrícia , França Ângela , Pereira Maria Olívia , Cerca Nuno
Published: September 2019

While considerable research has focused on studying individual-species, we now face the challenge of determining how interspecies interactions alter bacterial behaviours and pathogenesis. Pseudomonas aeruginosa and Staphylococcus aureus are often found to co-infect cystic-fibrosis patients. Curiously, their interaction is reported as competitive under laboratory conditions. Selecting appropriate methodologies is therefore critical to analyse multi-species communities. Herein, we demonstrated the major biases associated with qPCR quantification of bacterial populations and optimized a RNA-based qPCR able not only to quantify but also to characterize microbial interactions within dual-species biofilms composed by P. aeruginosa and S. aureus, as assessed by gene expression quantification. qPCR quantification was compared with flow-cytometry and culture-based quantification. Discrepancies between culture independent and culture dependent methods could be the result of the presence of viable but not-cultivable bacteria within the biofilm. Fluorescence microscopy confirmed this. A higher sensitivity to detect viable cells further highlights the potentialities of qPCR approach to quantify biofilm communities. By using bacterial RNA and an exogenous mRNA control, it was also possible to characterize bacterial transcriptomic profile, being this a major advantage of this method.
The Effect of Flavored E-cigarettes on Murine Allergic Airways Disease
Authors: Chapman David G. , Casey Dylan T. , Ather Jennifer L. , Aliyeva Minara , Daphtary Nirav , Lahue Karolyn G. , van der Velden Jos L. , Janssen-Heininger Yvonne M. W. , Irvin Charles G.
Published: September 2019

Flavored e-cigarettes are preferred by the majority of users yet their potential toxicity is unknown. Therefore our aim was to determine the effect of selected flavored e-cigarettes, with or without nicotine, on allergic airways disease in mice. Balb/c mice were challenged with PBS or house dust mite (HDM) (Days 0, 7, 14–18) and exposed to room air or e-cigarette aerosol for 30 min twice daily, 6 days/week from Days 0–18 (n = 8–12/group). Mice were exposed to Room Air, vehicle control (50%VG/%50PG), Black Licorice, Kola, Banana Pudding or Cinnacide without or with 12 mg/mL nicotine. Mice were assessed at 72 hours after the final HDM challenge. Compared to mice challenged with HDM and exposed to Room Air, nicotine-free Cinnacide reduced airway inflammation (p = 0.045) and increased peripheral airway hyperresponsiveness (p = 0.02), nicotine-free Banana Pudding increased soluble lung collagen (p = 0.049), with a trend towards increased airway inflammation with nicotine-free Black Licorice exposure (p = 0.089). In contrast, all e-cigarettes containing nicotine suppressed airway inflammation (p < 0.001 for all) but did not alter airway hyperresponsiveness or airway remodeling. Flavored e-cigarettes without nicotine had significant but heterogeneous effects on features of allergic airways disease. This suggests that some flavored e-cigarettes may alter asthma pathophysiology even when used without nicotine.
Neutrophils homing into the retina trigger pathology in early age-related macular degeneration
Authors: Ghosh Sayan , Padmanabhan Archana , Vaidya Tanuja , Watson Alan M. , Bhutto Imran A. , Hose Stacey , Shang Peng , Stepicheva Nadezda , Yazdankhah Meysam , Weiss Joseph , Das Manjula , Gopikrishna Santosh , Aishwarya  , Yadav Naresh , Berger Thorsten , Mak Tak W. , Xia Shuli , Qian Jiang , Lutty Gerard A. , Jayagopal Ashwath , Zigler J. Samuel , Sethu Swaminathan , Handa James T. , Watkins Simon C. , Ghosh Arkasubhra , Sinha Debasish
Published: September 2019

Age-related macular degeneration (AMD) is an expanding problem as longevity increases worldwide. While inflammation clearly contributes to vision loss in AMD, the mechanism remains controversial. Here we show that neutrophils are important in this inflammatory process. In the retinas of both early AMD patients and in a mouse model with an early AMD-like phenotype, we show neutrophil infiltration. Such infiltration was confirmed experimentally using ribbon-scanning confocal microscopy (RSCM) and IFNλ− activated dye labeled normal neutrophils. With neutrophils lacking lipocalin-2 (LCN-2), infiltration was greatly reduced. Further, increased levels of IFNλ in early AMD trigger neutrophil activation and LCN-2 upregulation. LCN-2 promotes inflammation by modulating integrin β1 levels to stimulate adhesion and transmigration of activated neutrophils into the retina. We show that in the mouse model, inhibiting AKT2 neutralizes IFNλ inflammatory signals, reduces LCN-2-mediated neutrophil infiltration, and reverses early AMD-like phenotype changes. Thus, AKT2 inhibitors may have therapeutic potential in early, dry AMD.
SERS-based immunoassay using gold-patterned array chips for rapid and sensitive detection of dual cardiac biomarkers
Authors: Cheng Ziyi , Wang Rui , Xing Yanlong , Zhao Linlu , Choo Jaebum , Yu Fabiao
Published: September 2019

A gold-patterned array platform has been developed for the ultrasensitive SERS-based detection of cTnI and CK-MB.
Selective synthesis of β-nitrated N-heterocycles and N-nitroso-2-alkoxyamine aldehydes from inactivated cyclic amines promoted by tBuONO and oxoammonium salt
Authors: He Yan , Zheng Zhi , Liu Yajie , Qiao Jiajie , Zhang Xinying , Fan Xuesen
Published: September 2019

Solvent-dependent-controlled selective synthesis of β-nitrated N-heterocycles and N-nitroso chain 2-alkoxyamine aldehydes has been successfully realized viatBuONO and oxoammonium salt promoted cascade reactions of inactivated cyclic amines.
Structural characterisation of amorphous solid dispersions via metropolis matrix factorisation of pair distribution function data
Authors: Geddes Harry S. , Blade Helen , McCabe James F. , Hughes Leslie P. , Goodwin Andrew L.
Published: September 2019

We use total scattering and non-negative matrix factorisation to characterise the structure of an amorphous pharmaceutical in a complex mixture.
Tailoring the structures and gas adsorption properties of copper–bent diisophthalate frameworks by a substituent-driven ligand conformation regulation strategy
Authors: He Minghui , Gao Xiaoxia , Xu Tingting , Jiang Zhenzhen , He Yabing
Published: September 2019

A substituent-induced ligand conformation regulation strategy was employed to tailor the structures and gas adsorption properties of copper-bent diisophthalate frameworks.
A series of flexible bis(pyridyl)bis(tetrazole)-modulated coordination polymers: construction, electrochemical properties, dye adsorption and magnetic properties
Authors: Liu Yu , Wang Xiuli , Zhao Jing , Lin Hongyan , Xu Na , Zhang Juwen , Yu Baoyi
Published: September 2019

Four new coordination polymers based on three bis(pyridyl)bis(tetrazole) ligands and 4,4′,4′′-benzene-1,3,5-triyltribenzoic acid were synthesized showing electrocatalytic, dye adsorption and antiferromagnetism properties.
Facile synthesized ZnO microcrystals for random microlasers and incandescent-type light sources
Authors: Ji Jiaolong , Jiang Mingming , Mao Wangqi , Wan Peng , Kan Caixia
Published: September 2019

Well-crystallized ZnO microcrystals (MCs) with a well-faceted, smooth surface were successfully synthesized and employed to construct ultraviolet microsized random lasers.
Strain analysis from M-edge resonant inelastic X-ray scattering of nickel oxide films
Authors: Miedema P. S. , Thielemann-Kühn N. , Calafell I. Alonso , Schüßler-Langeheine C. , Beye M.
Published: September 2019

3d-Metal M-edge RIXS quantitatively measures the electronic structure distortion due to strain with help of crystal field multiplet calculations.
The tetracapped truncated tetrahedron in 16-vertex tetrametallaborane structures: spherical aromaticity with an isocloso rather than a closo skeletal electron count
Authors: Attia Amr A. A. , Lupan Alexandru , King R. Bruce , Ghosh Sundargopal
Published: September 2019

DFT studies on the experimentally known Cp*3Rh3B12H12Rh(B4H9RhCp*) as well as two model compounds indicate low energy structures with central Rh4B12 tetracapped tetratruncated tetrahedra for these 32 Wadean skeletal electron systems.
β12-Borophene becomes a semiconductor and semimetal via a perpendicular electric field and dilute charged impurity
Authors: Le P. T. T. , Phong T. C. , Yarmohammadi M.
Published: September 2019

In this paper, the possible electronic phase transitions of β12-borophene crystal are examined using a five-band tight-binding calculation.
Topological flat band, Dirac fermions and quantum spin Hall phase in 2D Archimedean lattices
Authors: Crasto de Lima F. , Ferreira Gerson J. , Miwa R. H.
Published: September 2019

We've constructed a guide to the electronic properties and topological phases of Archimedean lattices. Within these lattices, a rich electronic structure emerges forming type-I and II Dirac fermions, topological flat bands and high-degeneracy points.
Structural transition induced by compression and stretching of puckered arsenene nanotubes
Authors: Quijano-Briones J. J. , Fernández-Escamilla H. N. , Guerrero-Sánchez J. , Martínez-Guerra E. , Takeuchi Noboru
Published: September 2019

The stretching and compression effects on puckered arsenene nanotubes (AsNTs) are investigated by using density functional calculations.
Understanding the intramolecular vibrational energy transfer and structural dynamics of anionic ligands in a photo-catalytic CO2reduction catalyst
Authors: Liu Qianchen , Zhang Yutong , Zhang Qi , Wei Qianshun , Zhou Dexia , Wu Guorong , Cai Kaicong , Yuan Kaijun , Bian Hongtao
Published: September 2019

The knowledge of intramolecular vibrational energy redistribution (IVR) and structural dynamics of rhenium photo-catalysts is essential for understanding the mechanism of the photo-catalytic process of CO2reduction.
Glycation by saccharides of different molecular sizes affected the allergenicity of shrimp tropomyosin via epitope loss and the generation of advanced glycation end products
Authors: Zhang Ziye , Xiao Hang , Zhou Peng
Published: September 2019

Greater epitope loss than AGE neoallergen generation resulted in weakened allergenicity, whereas less epitope loss than AGE neoallergen generation led to exacerbated allergenicity.
Fundamentals and new approaches to calibration in atomic spectrometry
Authors: Donati George L. , Amais Renata S.
Published: September 2019

Principles and applications of both traditional and some recently described calibration methods used in atomic spectrometry are critically discussed.
Hybrid negative enrichment of circulating tumor cells from whole blood in a 3D-printed monolithic device
Authors: Chu Chia-Heng , Liu Ruxiu , Ozkaya-Ahmadov Tevhide , Boya Mert , Swain Brandi E. , Owens Jacob M. , Burentugs Enerelt , Bilen Mehmet Asim , McDonald John F. , Sarioglu A. Fatih
Published: September 2019

A monolithic 3D-printed microfluidic device integrated with stacked layers of functionalized leukodepletion channels and microfiltration for the negative enrichment of circulating tumor cells directly from clinically relevant volumes of whole blood.