bluuebunny/crossref_metadata_2025_split huggingface dataset:
Random and combinatorial mutagenesis for improved total production of secretory target protein in Escherichia coli
Authors: Gonzalez-Perez David , Ratcliffe James , Tan Shu Khan , Wong Mary Chen May , Yee Yi Pei , Nyabadza Natsai , Xu Jian-He , Wong Tuck Seng , Tee Kang Lan 
Published: March 2021

AbstractSignal peptides and secretory carrier proteins are commonly used to secrete heterologous recombinant protein in Gram-negative bacteria. The Escherichia coli osmotically-inducible protein Y (OsmY) is a carrier protein that secretes a target protein extracellularly, and we have previously applied it in the Bacterial Extracellular Protein Secretion System (BENNY) to accelerate directed evolution. In this study, we reported the first application of random and combinatorial mutagenesis on a carrier protein to enhance total secretory target protein production. After one round of random mutagenesis followed by combining the mutations found, OsmY(M3) (L6P, V43A, S154R, V191E) was identified as the best carrier protein. OsmY(M3) produced 3.1 ± 0.3 fold and 2.9 ± 0.8 fold more secretory Tfu0937 β-glucosidase than its wildtype counterpart in E. coli strains BL21(DE3) and C41(DE3), respectively. OsmY(M3) also produced more secretory Tfu0937 at different cultivation temperatures (37 °C, 30 °C and 25 °C) compared to the wildtype. Subcellular fractionation of the expressed protein confirmed the essential role of OsmY in protein secretion. Up to 80.8 ± 12.2% of total soluble protein was secreted after 15 h of cultivation. When fused to a red fluorescent protein or a lipase from Bacillus subtillis, OsmY(M3) also produced more secretory protein compared to the wildtype. In this study, OsmY(M3) variant improved the extracellular production of three proteins originating from diverse organisms and with diverse properties, clearly demonstrating its wide-ranging applications. The use of random and combinatorial mutagenesis on the carrier protein demonstrated in this work can also be further extended to evolve other signal peptides or carrier proteins for secretory protein production in E. coli.
Association of maternal gut microbiota and plasma metabolism with congenital heart disease in offspring: a multi-omic analysis
Authors: Wang Tingting , Chen Lizhang , Huang Peng , Yang Tubao , Zhang Senmao , Zhao Lijuan , Chen Letao , Ye Ziwei , Luo Liu , Qin Jiabi 
Published: March 2021

AbstractCongenital heart disease (CHD) is the most common congenital disorder diagnosed in newborns. Although lots of related studies have been published, yet the pathogenesis has not been fully elucidated. A growing body of evidence indicates perturbations of the gut microbiota may contribute in a significant way to the development of obesity and diabetes. Given that maternal obesity and diabetes are well-known risk factors for CHD, maternal gut microbiota may be considered as one of the environmental factors involved in the pathogenesis of CHD. The object of this study is to explore the association between maternal gut microbiota and risk of congenital heart disease (CHD) in offspring, as well as the possible mechanisms linking gut microbiota and disease risk. A case–control study was conducted in mothers of infants with CHD (n = 101) and mothers of infants without CHD (n = 95). By applying 16S rRNA gene sequencing and metabolic approaches to 196 stool and plasma samples, we determined microbiome and metabolome profiles in mothers of infants with CHD and controls, and their association with risk of CHD in offspring. The gut microbiome of mothers of infants with CHD was characterized with lower alpha-diversity and distinct overall microbial composition compared with mothers of infants without CHD. A distinct different metabolic profile was found between mothers of infants with CHD and controls. After controlling for the possible confounders, thirty-four bacterial genera and fifty-three plasma metabolites showed distinct abundances between the two groups. The results of the Spearman correlation analyses revealed a great number of significant correlations between the abundant bacterial genera and differentially expressed metabolites. In particular, the genusBifidobacteriumandStreptococcusshowed comparable moderate positive correlations with a range of metabolites that involved in lipid metabolism pathway. Our findings suggest that perturbations of maternal gut microbiota and plasma metabolites may be associated with risk of CHD in offspring, and co-variation between microbiota and metabolites may play a part in the linkage between gut microbiota and risk of CHD in offspring.
Investigation of the relationships between the alveograph parameters
Authors: Jødal Anne-Sophie Schou , Larsen Kim Lambertsen 
Published: March 2021

AbstractAlveograph analysis is an established method for flour characterisation, and several alveograph parameters have been introduced over the years. Typically, ten parameters are found for every analysis from the air pressure curve in the modern versions of the alveograph, but the relationships between the parameters and their potential redundancy are not well described in the literature. In this work, an overview of the parameters is provided, including how they are found and what they may represent, and the integral relationship between the parameters was investigated using Pearson correlation analysis of the parameters from 532 pressure curves. The parameters G (swelling index), Dmax (maximum of first derivative), SH (strain hardening index) and K (strength coefficient) exhibited very strong correlations with other alveograph parameters (r > 0.97), and these parameters do therefore not provide additional information. The parameters P (maximum overpressure), L (abscissa at rupture), W (deformation energy), P/L (configuration ratio), Ie (elasticity index) and Dmin (minimum of first derivative) on the other hand, represent a relatively basic set of parameters that uniquely characterises various parts of the pressure curves and thus the dough rheology/physics during dough inflation. Nevertheless, even between this basic set of parameters relatively strong correlations were found, signifying that they are interrelated, as they all are affected by changes in the dough constituents.
Predictive and prognostic transcriptomic biomarkers in soft tissue sarcomas
Authors: Merry Eve , Thway Khin , Jones Robin L. , Huang Paul H. 
Published: March 2021

AbstractSoft tissue sarcomas (STS) are rare and heterogeneous tumours comprising over 80 different histological subtypes. Treatment options remain limited in advanced STS with high rates of recurrence following resection of localised disease. Prognostication in clinical practice relies predominantly on histological grading systems as well as sarcoma nomograms. Rapid developments in gene expression profiling technologies presented opportunities for applications in sarcoma. Molecular profiling of sarcomas has improved our understanding of the cancer biology of these rare cancers and identified potential novel therapeutic targets. In particular, transcriptomic signatures could play a role in risk classification in sarcoma to aid prognostication. Unlike other solid and haematological malignancies, transcriptomic signatures have not yet reached routine clinical use in sarcomas. Herein, we evaluate early developments in gene expression profiling in sarcomas that laid the foundations for transcriptomic signature development. We discuss the development and clinical evaluation of key transcriptomic biomarker signatures in sarcomas, including Complexity INdex in SARComas (CINSARC), Genomic Grade Index, and hypoxia-associated signatures. Prospective validation of these transcriptomic signatures is required, and prospective trials are in progress to evaluate reliability for clinical application. We anticipate that integration of these gene expression signatures alongside existing prognosticators and other Omics methodologies, including proteomics and DNA methylation analysis, could improve the identification of ‘high-risk’ patients who would benefit from more aggressive or selective treatment strategies. Moving forward, the incorporation of these transcriptomic prognostication signatures in clinical practice will undoubtedly advance precision medicine in the routine clinical management of sarcoma patients.
The effects of pre-equilibrium emission and secondary decay on the determination of freeze-out volume at intermediate energies *
Authors: Duan Hui-Xiao , Zhang Dong-Hai , Zhang Fan , Wu Hai-Shun 
Published: March 2021

Abstract
The effects of pre-equilibrium emission and secondary decay on the determination of the freeze-out volume are investigated using the isospin-dependent quantum molecular dynamics model accompanied by the statistical decay model GEMINI. Small-mass projectiles and large-mass targets with central collisions are studied at intermediate energies. It is revealed that the proton yields of pre-equilibrium emission are smaller than those of secondary decay. However, the determination of the freeze-out volume from the proton yields is more easily affected by pre-equilibrium emission. Moreover, the percentage of proton yields in the freeze-out stage is found to be approximately 50%.
Application of microbial huff and puff technology in enhancing oil recovery in Weixing oilfield
Authors: Yuting Gao 
Published: March 2021

Abstract
After a long term of water flooding, the near well area of Weixing oilfield was blocked by a large amount of colloids, asphaltenes and waxes, resulting in a decline in oil well production. It is urgent to explore new technologies to slow the decline of production and increase the production per well. The results of microbial reservoir adaptability evaluation show that the microbial huff and puff test is suitable for Weixing oilfield. 5 pilot test Wells were selected under the well selection principle, and the compatibility of bacillus subtilis SL-2 with native reservoir bacteria and the emulsifying effect on crude oil were evaluated. The corresponding huff and puff scheme is designed according to the production status, pay-zone thickness, treatment radius and porosity. After microbial huff and puff, the daily liquid production increased from 28.2 t/d to 63.4 t/d, the oil production increased from 9.7 t/d to 25.0 t/d. Throughput is valid for 240 days, the cumulative oil production of five wells was2048 t, and the economic benefit was good. After resuming production, the bacterial concentration of the produced liquid rose significantly to more than 107 cfu/mL, indicating that the injected microbial strain grew well in the target reservoir and had good oil-increasing potential.
Study of nitrogen (N) and phosphorus (P) in the land of mangrove sediments in ecotourism area Wonorejo Surabaya and coastal area of Jenu Tuban
Authors: Pradipta N , Alamsjah M A , Masithah E D 
Published: March 2021

Abstract
The mangrove forest is one of the wealth of natural resources in Indonesia. Based on data from the Ministry of Environment in 2006 that the Indonesian mangrove forest area reached 4.3 million hectares. Nutrient element N (nitrogen) and P (phosphorus) is an element that affect the growth of mangroves. The element nitrogen affect amount of photosynthesis that occurs in mangrove. Low uptake of phosphorus can cause plant tissue volume becomes smaller and the leaf color becomes darker. This study aims to measure the concentration of nitrogen and phosphorus in soil sediments obtained from the mangrove Ecotourism Wonorejo Surabaya and coastal Jenu Tuban. This research uses descriptive method through field surveys by sampling. Sampling was carried out at six points in each region. The results of this study showed that the highest nitrogen content was at the point A4 coastal areas Jenu Tuban is 40.86%, while the lowest nitrogen content is at the point B3 Ecotourism Mangrove Wonorejo Surabaya is 31.55%. Phosphorous levels are at their highest A6 coastal areas Jenu Tuban is 0.043 ppm, while the phosphorus content is in the lowest point of the region B3 Ecotourism Mangrove Wonorejo Surabaya is 0,021 ppm.
Visualizing UML’s Sequence and Class Diagrams Using Graph-Based Clusters
Authors: Sharma Nakul , Yalla Prasanth 
Published: March 2021

Abstract
The paper discusses the creation of UML diagram based recommendation system using java and class files as the input. The existing systems do not make use of techniques available in text-mining for creating UML diagrams. The overall methodology makes use of keyphrase extraction, contextual similarity calculation, and graph-based clusters in creating UML diagrams. The existing systems survey of state-of-art UML diagram generation techniques and keyphrase extraction survey is also provided. A comparative analysis of the existing tools for generating UML-diagrams is also provided. The recommendation system generated is useful to maintenance engineers and software developers.
Dielectric properties of solid solutions in a PFN-based system
Authors: Glazunova E V , Verbenko I A , Shilkina l A , Nagaenko A V , Reznichenko L A 
Published: March 2021

Abstract
The results of X-ray diffraction analysis of the solid solutions in the (1-x)Pb(Fe1/2Nb1/2)O3–xPb(Fe2/3W1/3)O3 systems with x = 0.0÷0.5, investigating their microstructure and measurements of dielectric characteristics are presented in this paper. The critical influence of Pb(Fe2/3Wy1/3)O3 on the crystallization of solid solutions and the nature of grain boundaries is established. A sintering mechanism of the solid solutions is defined. Correlations between the dynamics of the crystalline and grain structures and the dielectric properties of investigating solid solutions are established.
Reasons for discontinuing oral anticoagulation therapy for atrial fibrillation: a systematic review
Authors: Buck Jackie , Fromings Hill Julia , Martin Alison , Springate Cassandra , Ghosh Bikramaditya , Ashton Rachel , Lee Gerry , Orlowski Andrzei 
Published: March 2021

Abstract

Introduction
Atrial fibrillation (AF) is the most common cardiac arrhythmia and can lead to significant comorbidities and mortality. Persistence with oral anticoagulation (OAC) is crucial to prevent stroke but rates of discontinuation are high. This systematic review explored underlying reasons for OAC discontinuation.

Methods
A systematic review was undertaken to identify studies that reported factors influencing discontinuation of OAC in AF, in 11 databases, grey literature and backwards citations from eligible studies published between 2000 and 2019. Two reviewers independently screened titles, abstracts and papers against inclusion criteria and extracted data. Study quality was appraised using Gough’s weight of evidence framework. Data were synthesised narratively.

Results
Of 6,619 sources identified, 10 full studies and 2 abstracts met the inclusion criteria. Overall, these provided moderate appropriateness to answer the review question. Four reported clinical registry data, six were retrospective reviews of patients’ medical records and two studies reported interviews and surveys. Nine studies evaluated outcomes relating to dabigatran and/or warfarin and three included rivaroxaban (n = 3), apixaban (n = 3) and edoxaban (n = 1). Bleeding complications and gastrointestinal events were the most common factors associated with discontinuation, followed by frailty and risk of falling. Patients’ perspectives were seldom specifically assessed. Influence of family carers in decisions regarding OAC discontinuation was not examined.

Conclusion
The available evidence is derived from heterogeneous studies with few relevant data for the newer direct oral anticoagulants. Reasons underpinning decision-making to discontinue OAC from the perspective of patients, family carers and clinicians is poorly understood.
Epidemiology and Risk Factors for Healthcare-Associated Viral Infections in Children
Authors: Hanley Samantha , Odeniyi Folasade , Feemster Kristen , Coffin Susan E , Sammons Julia S 
Published: March 2021

Abstract

Background
Healthcare-associated viral infections (HA-VIs) are common in hospitalized children and are increasingly recognized as a cause of preventable harm; however, the epidemiology and modifiable risk factors for pediatric HA-VIs are poorly understood.

Methods
We performed a retrospective case-control study to identify risk factors and outcomes associated with pediatric HA-VIs at a quaternary care children’s hospital. HA-VI surveillance was performed hospital-wide using Centers for Disease Control and Prevention (CDC) definitions. We abstracted data from the electronic medical record and conducted semi-structured interviews with patient caregivers to identify potential exposures 4 days before the HA-VI onset.

Results
During the 20-month study period, we identified 143 eligible patients with HA-VIs and enrolled 64 matched case-control pairs. In total, 79 viruses were identified among 64 case patients. During the exposure period, case, as compared with control, patients were more frequently exposed to a sick visitor (odds ratio = 5.19; P = .05). During the 7 days after the HA-VI onset, case, as compared with control, patients had a greater length of antibacterial therapy per patient-days (mean 411 vs 159) as well as greater days of antibacterial therapy per patient-days (mean 665 vs 247).

Conclusions
The results of this study show that exposure to a sick visitor is a potentially modifiable risk factor for pediatric HA-VIs. Hospitalized children with HA-VIs also have increased exposure to antibacterial agents when compared with matched controls. Our findings suggest that hospital policies may need to be revised, with emphasis on visitor screening and partnership with families, to reduce the incidence of pediatric HA-VIs during hospitalization.
EU Competition Law and Economics
Authors: Geradin Damien , Layne-Farrar Anne , Petit Nicolas 
Published: March 2021

Abstract
This EU competition law treatise fully integrates economic reasoning in its treatment of the decisional practice of the European Commission and the case-law of the European Court of Justice. Since the European Commission's move to a “more economic approach” to competition law reasoning and decisional practice, the use of economic argument in competition law cases has become a stricter requirement. Many national competition authorities are also increasingly moving away from a legalistic analysis of a firm's conduct to an effect-based analysis of such conduct, indeed most competition cases today involve teams composed of lawyers and industrial organisation economists. Ensuring an integrated approach to legal and economic analysis, the book contains economic reasoning throughout in accessible form, and, more pertinently for practitioners, examines economics in the light of how it is used and put to effect in the courts and decision-making institutions of the EU. A general introductory section sets EU competition law in its historical context. The second chapter goes on to explore the economic foundations of EU competition law. What follows is an integrated treatment of each of the core substantive areas of EU competition law, including Article 101 TFEU, Article 102 TFEU, mergers, cartels and other horizontal agreements, vertical restraints, and technology transfer agreements.
Scope of Application of International Humanitarian Law
Authors: Fleck Dieter 
Published: March 2021

Abstract
This chapter addresses the scope of application of international humanitarian law. International humanitarian law regulates, and as a rule applies in times of, armed conflicts. Accordingly, it is also referred to as the law of armed conflict or jus in bello. The three interchangeable terms denote the only branch of public international law that is specifically designed to strike a balance during armed conflicts between preserving humanitarian values, on the one hand, and considerations of military necessity, on the other by protecting those who do not or no longer directly participate in hostilities and by limiting the right of parties to the conflict to use armed force only to the amount necessary to achieve the aim of the conflict, which is to weaken the military potential of the enemy. While international humanitarian law specifically regulates situations of armed conflicts, it does not automatically supersede all other areas of public international law in the event of an armed conflict. The chapter then focuses on the law enforcement aspects, the continued relevance of rules of international law of peace during armed conflict, and the relevance of humanitarian law in peacetime and post-conflict military operations.
Starburst galaxies strike back: a multi-messenger analysis with Fermi-LAT and IceCube data
Authors: Ambrosone Antonio , Chianese Marco , Fiorillo Damiano F G , Marinelli Antonio , Miele Gennaro , Pisanti Ofelia 
Published: March 2021

ABSTRACT
Starburst galaxies, which are known as ‘reservoirs’ of high-energy cosmic-rays, can represent an important high-energy neutrino ‘factory’ contributing to the diffuse neutrino flux observed by IceCube. In this paper, we revisit the constraints affecting the neutrino and gamma-ray hadronuclear emissions from this class of astrophysical objects. In particular, we go beyond the standard prototype-based approach leading to a simple power-law neutrino flux, and investigate a more realistic model based on a data-driven blending of spectral indexes, thereby capturing the observed changes in the properties of individual emitters. We then perform a multi-messenger analysis considering the extragalactic gamma-ray background (EGB) measured by Fermi-LAT and different IceCube data samples: the 7.5-yr high-energy starting events (HESE) and the 6-yr high-energy cascade data. Along with starburst galaxies, we take into account the contributions from blazars and radio galaxies as well as the secondary gamma-rays from electromagnetic cascades. Remarkably, we find that, differently from the highly-constrained prototype scenario, the spectral index blending allows starburst galaxies to account for up to $40{{\ \rm per\ cent}}$ of the HESE events at $95.4{{\ \rm per\ cent}}$ CL, while satisfying the limit on the non-blazar EGB component. Moreover, values of $\mathcal {O}(100\, \mathrm{PeV})$ for the maximal energy of accelerated cosmic-rays by supernovae remnants inside the starburst are disfavoured in our scenario. In broad terms, our analysis points out that a better modelling of astrophysical sources could alleviate the tension between neutrino and gamma-ray data interpretation.
Synchrotron micro-X-ray fluorescence imaging of arsenic in frozen-hydrated sections of a root of Pteris vittata
Authors: Kashiwabara Teruhiko , Kitajima Nobuyuki , Onuma Ryoko , Fukuda Naoki , Endo Satoshi , Terada Yasuko , Abe Tomoko , Hokura Akiko , Nakai Izumi 
Published: March 2021

Abstract
We performed micro-X-ray fluorescence imaging of frozen-hydrated sections of a root of Pteris vittata for the first time, to the best of our knowledge, to reveal the mechanism of arsenic (As) uptake. The As distribution was successfully visualized in cross sections of different parts of the root, which showed that (i) the major pathway of As uptake changes from symplastic to apoplastic transport in the direction of root growth, and (ii) As and K have different mobilities around the stele before xylem loading, despite their similar distributions outside the stele in the cross sections. These data can reasonably explain As reduction, axially observed around the root tip in the direction of root growth and radially observed in the endodermis in the cross sections, as a consequence of the incorporation of As into the cells or symplast of the root. In addition, previous observations of As species in the midrib can be reconciled by ascribing a reduction capacity to the root cells, which implies that As reduction mechanisms at the cellular level may be an important control on the peculiar root-to-shoot transport of As in P. vittata.