bluuebunny/crossref_metadata_2025_split huggingface dataset:
Getting the measure of diabetes: the evolution of the National Diabetes Audit
Authors: Young Bob 
Published: December 2018

AbstractThe 2018 Arnold Bloom lecture reviewed the development of the National Diabetes Audit (NDA) and what its measurements tell us about contemporary diabetes care. From seeds sown by the St Vincent Declaration in 1988 a national system has been established for benchmarking diabetes care across primary care settings, among specialist services and between commissioning areas in England and Wales. Wherever possible the sources of the data are routinely recorded electronic records; this supports data quality and minimises participation burden. Some overall national improvements have been documented but so have areas of stagnation and deterioration. Most strikingly, however, has been the revelation of large differences between services and geographies. A variety of system changes (service re‐design) illustrate how appreciable improvements can be achieved. England and Wales now have a set of measurements of diabetes care that can focus change effort appropriately and support on‐going improvement. Arnold Bloom's old hospital provided a perfect example of NDA measurements that can quickly identify priorities for improvement at an individual service level. Copyright © 2018 John Wiley & Sons.
Anomalous point‐of‐care ketone reading following use of ethyl chloride spray as a topical anaesthetic during the treatment of a teenager with DKA
Authors: Young Adam , Hollowbread Andrew , Wayman Matthew 
Published: December 2018

AbstractWe present the case of an anomalous ketone reading in a 16‐year‐old female patient with type 1 diabetes following the administration of ethyl chloride spray as a topical anaesthetic. The patient presented in diabetic ketoacidosis (DKA) and was agitated, distressed and combative. Assistance was sought in the ongoing management of the patient from the on‐call anaesthetic and intensive care team. The choice was made to use ethyl chloride spray as a topical anaesthetic. This was done in order to decrease the discomfort of capillary blood tests in an attempt to ameliorate the patient's agitation and distress. It was noted that when this spray was applied prior to point‐of‐care ketone concentration testing, a ketone reading out of context of the clinical picture was obtained.There is no caution against using ethyl chloride spray in the product literature for the ketone meter used in our hospital, but there is guidance about cleaning the hands and test site with soap and warm water. This was briefly investigated by this team and anomalous ketone concentrations were reproduced in a healthy volunteer who had ketone levels checked pre‐ and post‐application of ethyl chloride spray. There is no current published literature regarding abnormal ketone results following application of topical anaesthetic agents. Therefore, based on this experience, caution would be advised in using topical anaesthetic agents prior to capillary blood sampling and emphasis placed on strict adherence to the manufacturer's guidance of cleansing the hands and test site with warm water and soap prior to capillary sampling. Copyright © 2018 John Wiley & Sons.
A Double‐Edged Sword: Complement Component 3 in Toxoplasma gondii Infection
Authors: Huang Wan‐Yi , Wang Ya‐Pei , Mahmmod Yasser S. , Wang Jun‐Jie , Liu Tang‐Hui , Zheng Yu‐Xiang , Zhou Xue , Zhang Xiu‐Xiang , Yuan Zi‐Guo 
Published: December 2018

AbstractSprague Dawley rats and Kunming (KM) mice are artificially infected with type II Toxoplasma gondii strain Prugniaud (Pru) to generate toxoplasmosis, which is a fatal disease mediated by T. gondii invasion of the central nervous system (CNS) by unknown mechanisms. The aim is to explore the mechanism of differential susceptibility of mice and rats to T. gondii infection. Therefore, a strategy of isobaric tags for relative and absolute quantitation (iTRAQ) is established to identify differentially expressed proteins (DEPs) in the rats’ and the mice's brains compared to the healthy groups. In KM mice, which is susceptible to T. gondii infection, complement component 3 (C3) is upregulated and the tight junction (TJ) pathway shows a disorder. It is presumed that T. gondii‐stimulated C3 disrupts the TJ of the blood–brain barrier in the CNS. This effect allows more T. gondii passing to the brain through the intercellular space.
Functional Study of Carboxylesterase 1 Protein Isoforms
Authors: Wang Xinwen , Shi Jian , Zhu Hao‐Jie 
Published: December 2018

AbstractCarboxylesterase 1 (CES1) is a primary human hepatic hydrolase involved in hydrolytic biotransformation of numerous medications. Considerable interindividual variability in CES1 expression and activity has been consistently reported. Four isoforms of the CES1 protein are produced by alternative splicing (AS). In the current study, the activity and expression of each CES1 isoform are examined using transfected cell lines, and CES1 isoform composition and its impact on CES1 activity in human livers are determined. In transfected cells, isoforms 3 and 4 show mRNA and protein expressions comparable to isoforms 1 and 2, but have significantly impaired activity when hydrolyzing enalapril and clopidogrel. In individual human liver samples, isoforms 1 and 2 are the major forms, contributing 73–90% of the total CES1 protein expression. In addition, the protein expression ratios of isoforms 1 and 2 to isoforms 3 and 4 are positively associated with CES1 activity in the liver, suggesting that CES1 isoform composition is a factor contributing to the variability in hepatic CES1 function. Further investigations of the regulation of CES1 AS would improve the understanding of CES1 variability and help develop a strategy to optimize the pharmacotherapy of many CES1 substrate medications.
Proteomics Analysis of Thermoplasma Quinone Droplets
Authors: Nagy István , Sun Na , Varga Sándor , Boicu Marius , Zinzula Luca , Kukolya József 
Published: December 2018

AbstractA novel type of lipid droplet/lipoprotein (LD/LP) particle from Thermoplasma acidophilum has been identified recently, and based on biochemical evidences, it was named Thermoplasma Quinone Droplet (TaQD). The major components of TaQDs are menaquinones, and to some extent polar lipids, and the 153 amino acid long Ta0547 vitellogenin‐N domain protein.In this paper, the aim is to identify TaQD proteome components with 1D‐SDS‐PAGE/LC–MS/MS and cross reference them with Edman degradation. TaQD samples isolated with three different purification methods—column chromatography, immunoprecipitation, and LD ultracentrifugation—are analyzed. Proteins Ta0093, Ta0182, Ta0337, Ta0437, Ta0438, Ta0547, and Ta1223a are identified as constituents of the TaQD proteome. The majority of these proteins is uncharacterized and has low molecular weight, and none of them is predicted to take part in lipid metabolism. Bioinformatics analyses does not predict any interaction between these proteins, however, there are indications of interactions with proteins taking part in lipid metabolism. Whether if TaQDs provide platform for lipid metabolism and the interactions between TaQD proteins and lipid metabolism proteins occur in the reality remain for further studies.
Hydroxyl‐terminated Polybutadiene Curing by 1,3‐dipolar Cycloaddition of Energetic Nitrile N‐Oxides: Room Temperature Curing Property, Kinetics, Thermodynamics, and Propellant Combustion Characteristics
Authors: Lei Yonglin , Fan Yaqin , Huo Jichuan 
Published: December 2018

Abstract5‐nitro‐1,3‐benzenedichloroaldehyde oxime was designed and synthesized to achieve room temperature curing of HTPB binders, and its structures were characterized. A new kind of 1,3‐dipolar cycloaddition reaction system was formed by HTPB as main resin, 5‐nitro‐1,3‐benzenedichloroaldehyde oxime and triethylamine as curing agent. The results revealed that the formation of isoxazoline ring in cured HTPB elastomers mainly derived form the reaction of Nitrile N‐Oxide with cis alkene of HTPB, and the cured HTPB elastomers underwent three stages decomposition. The kinetic parameters and thermodynamic parameters for the 14 % curing agent's sample were obtained from the DSC data. The activation energy was computed to be 204.75 kJ mol−1 and pre‐exponential factor was 1.38×1023 s−1.The burning rate of the propellant showed that the propellant with HTPB cured by containing −NO2 Nitrile N‐Oxides (100 % HTPB, 14 % Nitrile N‐Oxides, 2 % Aluminum and 77 % Ammonium perchlorate, Curing at 25 °C for 5 days ) had a higher burning rate and pressure exponent compared to conventional HTPB propellant (100 % HTPB, 14 % toluene diisocyanate, Nitrile N‐Oxides, 2 % Aluminum and 77 % Ammonium perchlorate, Curing at 60 °C for 5 days). Therefore, the containing −NO2 Nitrile N‐Oxides curing system could be used as a novel promising curing system for HTPB‐based solid composite propellants.
Disulfide bridge formation influences ligand recognition by the ATAD2 bromodomain
Authors: Gay Jamie C. , Eckenroth Brian E. , Evans Chiara M. , Langini Cassiano , Carlson Samuel , Lloyd Jonathan T. , Caflisch Amedeo , Glass Karen C. 
Published: December 2018

AbstractThe ATPase family, AAA domain‐containing protein 2 (ATAD2) has a C‐terminal bromodomain, which functions as a chromatin reader domain recognizing acetylated lysine on the histone tails within the nucleosome. ATAD2 is overexpressed in many cancers and its expression is correlated with poor patient outcomes, making it an attractive therapeutic target and potential biomarker. We solved the crystal structure of the ATAD2 bromodomain and found that it contains a disulfide bridge near the base of the acetyllysine binding pocket (Cys1057‐Cys1079). Site‐directed mutagenesis revealed that removal of a free C‐terminal cysteine (C1101) residue greatly improved the solubility of the ATAD2 bromodomain in vitro. Isothermal titration calorimetry experiments in combination with the Ellman's assay demonstrated that formation of an intramolecular disulfide bridge negatively impacts the ligand binding affinities and alters the thermodynamic parameters of the ATAD2 bromodomain interaction with a histone H4K5ac peptide as well as a small molecule bromodomain ligand. Molecular dynamics simulations indicate that the formation of the disulfide bridge in the ATAD2 bromodomain does not alter the structure of the folded state or flexibility of the acetyllysine binding pocket. However, consideration of this unique structural feature should be taken into account when examining ligand‐binding affinity, or in the design of new bromodomain inhibitor compounds that interact with this acetyllysine reader module.
Interplay of cysteine exposure and global protein dynamics in small‐molecule recognition by a regulator of G‐protein signaling protein
Authors: Mohammadi Mohammadjavad , Mohammadiarani Hossein , Shaw Vincent S. , Neubig Richard R. , Vashisth Harish 
Published: December 2018

AbstractRegulator of G protein signaling (RGS) proteins play a pivotal role in regulation of G protein‐coupled receptor (GPCR) signaling and are therefore becoming an increasingly important therapeutic target. Recently discovered thiadiazolidinone (TDZD) compounds that target cysteine residues have shown different levels of specificities and potencies for the RGS4 protein, thereby suggesting intrinsic differences in dynamics of this protein upon binding of these compounds. In this work, we investigated using atomistic molecular dynamics (MD) simulations the effect of binding of several small‐molecule inhibitors on perturbations and dynamical motions in RGS4. Specifically, we studied two conformational models of RGS4 in which a buried cysteine residue is solvent‐exposed due to side‐chain motions or due to flexibility in neighboring helices. We found that TDZD compounds with aromatic functional groups perturb the RGS4 structure more than compounds with aliphatic functional groups. Moreover, small‐molecules with aromatic functional groups but lacking sulfur atoms only transiently reside within the protein and spontaneously dissociate to the solvent. We further measured inhibitory effects of TDZD compounds using a protein–protein interaction assay on a single‐cysteine RGS4 protein showing trends in potencies of compounds consistent with our simulation studies. Thermodynamic analyses of RGS4 conformations in the apo‐state and on binding to TDZD compounds revealed links between both conformational models of RGS4. The exposure of cysteine side‐chains appears to facilitate initial binding of TDZD compounds followed by migration of the compound into a bundle of four helices, thereby causing allosteric perturbations in the RGS/Gα protein–protein interface.
Metyltetraprole, a novel putative complex III inhibitor, targets known QoI‐resistant strains of Zymoseptoria tritici and Pyrenophora teres
Authors: Suemoto Haruka , Matsuzaki Yuichi , Iwahashi Fukumatsu 
Published: December 2018

AbstractBACKGROUNDMetyltetraprole is a new fungicide with a unique tetrazolinone‐moiety and a similar side chain to a known quinone outside inhibitor (QoI), pyraclostrobin. In this study we describe a unique bioactivity of metyltetraprole on QoI‐resistant strains of Zymoseptoria tritici and Pyrenophora teres.RESULTSMetyltetraprole exhibited potent antifungal activity against Ascomycetes; it was especially effective against Z. tritici and P. teres in seedling pot tests. Metyltetraprole was also effective in field tests with QoI‐resistant mutants. Antifungal activity tests using field strains of Z. tritici and P. teres showed that the performance of metyltetraprole was unaltered by QoI, succinate dehydrogenase inhibitor (SDHI), and sterol 14α‐demethylation inhibitor (DMI) resistance. However, the mitochondrial activity test indicated that the compound inhibits the respiratory chain via complex III.CONCLUSIONMetyltetraprole is a novel fungicide that is highly effective against a wide range of fungal diseases, including important cereal diseases. Although metyltetraprole most likely inhibits the respiratory chain via complex III, it remains effective against QoI resistant strains. Therefore, metyltetraprole is considered as a novel fungicidal agent for controlling diseases affecting cereal crops and overcoming pathogen resistance to existing fungicides. © 2018 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Analysing sustainability changes in seaports: Experiences from the Gävle Port Authority
Authors: Lozano Rodrigo , Fobbe Lea , Carpenter Angela , Sammalisto Kaisu 
Published: December 2018

AbstractPorts are under increasing pressure to become more sustainable. Although some ports have been including sustainability into their operations, this has been mainly done from economic and environmental perspectives and technological or policy‐related approaches, while there has been little research on organisational change management for sustainability. This paper analyses organisational change efforts for sustainability at the Port of Gävle, Sweden. Twenty‐three face‐to‐face interviews were conducted with various stakeholders. The findings show that there were differences in perception of sustainability; but similarities in the drivers for and the barriers to sustainability (with some key differences between the internal and external stakeholders). This research shows that, in their journey towards becoming more sustainable, ports have to take a holistic approach encompassing the four dimensions of sustainability (economic, environmental, social, and time); their stakeholders (internal and external); and legislative, technological, financial, cultural/social, voluntary initiatives, and organisational change management approaches.
Inequality and sustainable development: Insights from an analysis of the human development index
Authors: Castells‐Quintana David , Royuela Vicente , Thiel Fabian 
Published: December 2018

AbstractIn this paper, we connect two lines of research in the development economics literature: the analysis of the effect and transmission channels of inequality on economic development and the discussion about the necessity for a broader measure for development. We estimate the association between income inequality and the Human Development Index and its components in a panel of 117 countries over the period of 1970 to 2010. In doing so, we find evidence for (a) a negative long‐run association between inequality and human development and (b) different short‐run associations between inequality and different dimensions of human development: a positive one with economic development but a negative one with educational outcomes, hinting at particular transmission channels. In addition, we detect (c) that those associations can be even more pronounced in countries with low levels of development, reconciling seemingly conflicting findings in the literature.
Core outcome set for research studies evaluating treatments for twin–twin transfusion syndrome
Authors: Perry H. , Duffy J. M. N. , Reed K. , Baschat A. , Deprest J. , Hecher K. , Lewi L. , Lopriore E. , Oepkes D. , Khalil A. ,   the International Collaboration to Harmonise Outcomes for Twin–Twin Transfusion Syndrome (CHOOSE)
Published: December 2018

ABSTRACTObjectiveTo develop, using a Delphi procedure and a nominal group technique, a core outcome set (COS) for studies evaluating treatments for twin–twin transfusion syndrome (TTTS), which should assist in standardizing outcome selection, collection and reporting in future research studies.MethodsAn international steering group comprising healthcare professionals, researchers and patients with experience of TTTS guided the development of this COS. Potential core outcomes, identified through a comprehensive literature review and supplemented by outcomes suggested by the steering group, were entered into a three‐round Delphi survey. Healthcare professionals, researchers, and patients or relatives of patients who had experienced TTTS were invited to participate. Consensus was defined a priori using the 15%/70% definition of the Core Outcome Measures in Effectiveness Trials (COMET) initiative. The modified nominal group technique was used to evaluate the consensus outcomes in a face‐to‐face consultation meeting and identify the final COS.ResultsOne hundred and three participants, from 29 countries, participated in the three‐round Delphi survey. Of those, 88 completed all three rounds. Twenty‐two consensus outcomes were identified through the Delphi procedure and entered into the modified nominal group technique. The consensus meeting was attended by 11 healthcare professionals, two researchers and three patients; 12 core outcomes were prioritized for inclusion in the COS. Fetal core outcomes included live birth, pregnancy loss (including miscarriage, stillbirth, termination of pregnancy and neonatal mortality), subsequent death of a cotwin following single‐twin demise at the time of treatment, recurrence of TTTS, twin anemia–polycythemia sequence and amniotic band syndrome. Neonatal core outcomes included gestational age at delivery, birth weight, brain injury syndromes and ischemic limb injury. Maternal core outcomes included maternal mortality and admission to Level‐2 or ‐3 care setting. One aspirational outcome, neurodevelopment at 18–24 months of age, was also prioritized.ConclusionsImplementing the COS for TTTS within future research studies could make a substantial contribution to advancing the usefulness of research in TTTS. Standardized definitions and measurement instruments are now required for individual core outcomes. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
A framework for isogeometric‐analysis‐based optimization of wind turbine blade structures
Authors: Herrema Austin J. , Kiendl Josef , Hsu Ming‐Chen 
Published: December 2018

AbstractEarly‐stage wind turbine blade design usually relies heavily on low‐fidelity structural models; high‐fidelity, finite‐element‐based structural analyses are reserved for later design stages because of their complex workflows and high computational expense. Yet, high‐fidelity structural analyses often provide design‐governing feedback such as buckling load factors. Mitigation of the issues of workflow complexity and computational expense would allow designers to utilize high‐fidelity feedback earlier, more easily, and more often in the design process. Thus, a blade analysis framework that employs isogeometric analysis (IGA), a simulation method that overcomes many of the aforementioned drawbacks associated with traditional finite element analysis (FEA), is presented. IGA directly utilizes the mathematical models generated by computer‐aided design (CAD) software, requiring less user interaction and no conversion of parametric geometries to finite element meshes. Furthermore, IGA tends to have superior per‐degree‐of‐freedom accuracy compared with traditional FEA. Issues unique to IGA in the context of wind turbine blade design, such as coupling of thin‐shell components, are addressed, and a design approach that combines reduced‐order aeroelastic analysis with IGA is outlined. Aeroelastic analysis is used to efficiently provide dynamic kinematic data for a wide range of wind load cases, while IGA is used to perform buckling analysis. The value of incorporating high‐fidelity analysis feedback into blade design is demonstrated through optimization of the NREL/SNL 5 MW wind turbine blade. A variety of potential designs are produced with reduced blade mass and material cost, and IGA‐based buckling analysis is shown to provide design‐governing constraint information.
Global and regional climate in 2017
Authors: Kennedy John J. , Dunn Robert J. H. , Titchner Holly A. , Morice Colin P. , Killick Rachel E. , McCarthy Mark P. 
Published: December 2018

AbstractGlobally, 2017 was one of the three warmest years on record at the surface of the Earth, despite neutral or weak La Niña conditions. Warmth was widespread in the climate system, with ocean heat and atmospheric temperatures also among the top three years. Arctic and Antarctic sea ice extents were below the long‐term average, and a number of months had record low extents. In the UK and Europe there were a number of unusual weather events, and high spring and summer temperatures affected areas of Europe, North Africa and the Middle East.