bluuebunny/crossref_metadata_2025 huggingface dataset:
Managerial Risk-Taking Incentive and Firm Innovation: Evidence from FAS 123R
Authors: Mao Connie X. , Zhang Chi
Published: March 2018

We investigate how chief executive officers’ (CEOs) risk incentive (VEGA) affects firm innovation. To establish causality, we exploit compensation changes instigated by the FAS 123R accounting regulation in 2005 that mandated stock option expensing at fair values. Our identification tests indicate a positive and causal effect of CEOs’ VEGA on innovation activities. Furthermore, dampened managerial risk-taking incentive after the implementation of FAS 123R leads to a significant reduction in innovation related to firms’ core business and explorative inventions. It implies that managers diversify their innovation portfolios and decrease explorative inventions to curtail business risk when their risk-taking incentive is reduced.
Gradient assimilation in French cross-word /n/+velar stop sequences
Authors: Steele Jeffrey , Colantoni Laura , Kochetov Alexei
Published: March 2018

Articulatory studies have revealed cross-linguistic variation in the realization of cross-word nasal+stop sequences. Whereas languages such as Italian and Spanish show largely categorical regressive place assimilation (Kochetov & Colantoni 2011, Celata et al. 2013), English and German alveolar nasals are often characterized by gradient assimilation, modulated by the degree of overlap with the following gesture (Barry 1991, Ellis & Hardcastle 2002, Jaeger & Hoole 2011). The lack of comparable instrumental studies for French may be due to the common assumption that the language lacks nasal place assimilation in general. We investigate here the production of French /n/+/kɡ/ sequences via electropalatography. Four female speakers of European and Quebecois French wearing custom 62-electrode acrylic palates read the sentencesC'est une bonne casquette‘That's a good cap’ andC'est une bonne galette‘That's a good tart/cookie’ alongside comparable control sentences involving /n/+/t d/ sequences. For each sequence, assimilation type was determined both qualitatively via visual inspection of the linguopalatal profiles and quantitatively using two contact indices. None of the /n/-tokens exhibited either categorical assimilation (i.e. [ŋk]) or lack of assimilation (i.e. [n(ə)k]). Rather, an intermediate pattern was attested with the nasal involving overlapped coronal and velar gestures ([nn͡ŋ]) and continuous retraction of the constriction. The degree of overlap varied among speakers, extending up to half of the nasal interval. Overall, these French patterns are strikingly different from the categorical processes reported for other Romance languages, yet similar to the gradient assimilation attested in Germanic languages. We conclude by discussing possible sources of these differences.
DNA barcoding of ancient parasites
Authors: WOOD JAMIE R.
Published: March 2018

Ancient samples present a number of technical challenges for DNA barcoding, including damaged DNA with low endogenous copy number and short fragment lengths. Nevertheless, techniques are available to overcome these issues, and DNA barcoding has now been used to successfully recover parasite DNA from a wide variety of ancient substrates, including coprolites, cesspit sediment, mummified tissues, burial sediments and permafrost soils. The study of parasite DNA from ancient samples can provide a number of unique scientific insights, for example: (1) into the parasite communities and health of prehistoric human populations; (2) the ability to reconstruct the natural parasite faunas of rare or extinct host species, which has implications for conservation management and de-extinction; and (3) the ability to view in ‘real-time’ processes that may operate over century- or millenial-timescales, such as how parasites responded to past climate change events or how they co-evolved alongside their hosts. The application of DNA metabarcoding and high-throughput sequencing to ancient specimens has so far been limited, but in future promises great potential for gaining empirical data on poorly understood processes such as parasite co-extinction.
The first multilocus genotype analysis of Giardia intestinalis in humans in the Czech Republic
Authors: Lecová L. , Weisz F. , Tůmová P. , Tolarová V. , Nohýnková E.
Published: March 2018

To date, genotyping data on giardiasis have not been available in the Czech Republic. In this study, we characterized 47 human isolates of Giardia intestinalis from symptomatic as well as asymptomatic giardiasis cases. Genomic DNA from trophozoites was tested by PCR-sequence analysis at three loci (β-giardin, glutamate dehydrogenase and triose phosphate isomerase). Sequence analysis showed assemblages A and B in 41 (87.2%) and six (12.8%) isolates, respectively. Two of the 41 assemblage A samples were genotyped as sub-assemblage AI, and 39 were genotyped as sub-assemblage AII. Four previously identified multilocus genotypes (MLGs: AI-1, AII-1, AII-4 and AII-9) and six likely novel variations of MLGs were found. In agreement with previous studies, sequences from assemblage B isolates were characterized by a large genetic variability and by the presence of heterogeneous positions, which prevent the definition of MLGs. This study also investigated whether there was a relationship between the assemblage and clinical data (including drug resistance). However, due to the large number of genotypes and the relatively small number of samples, no significant associations with the clinical data were found.
Forgiveness then satisfaction: why the order matters for a theory of the atonement
Authors: KINTZ JAMES S.
Published: March 2018

Central to a theory of the atonement is one's position on forgiveness and satisfaction. These two issues are interrelated, but it is unclear whether one takes precedence over the other. Specifically, must one make satisfaction to remove the guilt incurred by sin prior to forgiveness, or can a victim forgive a wrongdoer independently of any work of satisfaction? Richard Swinburne argues that satisfaction must precede forgiveness, but I defend the view that forgiveness is a manifestation of love, and as such satisfaction is not required prior to forgiveness. Instead, I argue that forgiveness can and should precede satisfaction, and I highlight important implications of this view for a theory of the atonement.
Between conformity and innovation: China’s and India’s quest for status as responsible nuclear powers
Authors: Leveringhaus Nicola , de Estrada Kate Sullivan
Published: March 2018

China and India, as rising powers, have been proactive in seeking status as nuclear responsibles. Since the 1990s they have sought to demonstrate conformity with intersubjectively accepted understandings of nuclear responsibility within the global nuclear order, and have also sought recognition on the basis of particularistic practices of nuclear restraint. This article addresses two puzzles. First, nuclear restraint is at the centre of the pursuit of global nuclear order, so why have China and India not received recognition from influential members of the nuclear order for the full spectrum of their restraint-based behaviours? Second, why do China and India nonetheless persist with these behaviours? We argue that the conferral of status as a nuclear responsible is a politicised process shaped by the interests, values, and perceptions of powerful stakeholder states in the global nuclear order. China’s and India’s innovations are not incorporated into the currently accepted set of responsible nuclear behaviours because, indirectly, they pose a strategic, political, and social challenge to these states. However, China’s and India’s innovations are significant as an insight into their identity-projection and preferred social roles as distinctive rising powers, and as a means of introducing new, if nascent, ideas into non-proliferation practice and governance.
Education and Attitudes toward Interpersonal and State-Sanctioned Violence
Authors: Schnabel Landon
Published: March 2018

The link between education and liberal attitudes is among the most consistent findings in public-opinion research, but the theoretical explanations for this relationship warrant additional attention. Previous work suggested that the relationship is due to education socializing students to the “official culture” of the United States. This study uses the World Values Survey and General Social Survey to examine Americans’ attitudes toward the justifiability of violence. I find that Americans with more education are less likely to say that interpersonal violence—against women, children, and other individuals—can be justifiable. However, they are more likely to say that state-sanctioned violence—war and police violence—can be justifiable. These patterns are consistent with a modified socialization model of education and social attitudes. I conclude that American education socializes people to establishment culture, identity, and interests, which differentiate between unacceptable interpersonal violence and ostensibly acceptable state-sanctioned violence.
Sweetened beverages, snacks and overweight: findings from the Young Lives cohort study in Peru
Authors: Alviso-Orellana Claudia , Estrada-Tejada Dayna , Carrillo-Larco Rodrigo M , Bernabé-Ortiz Antonio
Published: March 2018

Objective

To determine the association between consumption of snacks and sweetened beverages and risk of overweight among children.

Design

Secondary analysis of the Young Lives cohort study in Peru.

Setting

Twenty sentinel sites from a total of 1818 districts available in Peru.

Subjects

Children in the younger cohort of the Young Lives study in Peru, specifically those included in the third (2009) and the fourth (2013) rounds.

Results

A total of 1813 children were evaluated at baseline; 49·2 % girls and mean age 8·0 (sd0·3) years. At baseline, 3·3 (95 % CI 2·5, 4·2) % reported daily sweetened beverage consumption, while this proportion was 3·9 (95 % CI 3·1, 4·9) % for snacks. Baseline prevalence of overweight was 22·0 (95 % CI 20·1, 23·9) %. Only 1414 children were followed for 4·0 (sd0·1) years, with an overweight incidence of 3·6 (95 % CI 3·1, 4·1) per 100 person-years. In multivariable analysis, children who consumed sweetened beverages and snacks daily had an average weight increase of 2·29 (95 % CI 0·62, 3·96) and 2·04 (95 % CI 0·48, 3·60) kg more, respectively, than those who never consumed these products, in approximately 4 years of follow-up. Moreover, there was evidence of an association between daily consumption of sweetened beverages and risk of overweight (relative risk=2·12; 95 % CI 1·05, 4·28).

Conclusions

Daily consumption of sweetened beverages and snacks was associated with increased weight gainv. never consuming these products; and in the case of sweetened beverages, with higher risk of developing overweight.
Microarray analysis for delineating the gene expression in biopsies of gastrocnemius muscle of patients with chronic critical limb ischaemia compared with non-ischaemic controls
Authors: Freund Daniel , Brilloff Silke , Ghazy Tamer , Kirschner Stephan , Gäbel Gabor , Hinterseher Irene , Weiss Norbert , Mahlmann Adrian
Published: March 2018

Abstract. Background: Microarray analysis has been carried out in this pilot study to compare delineated gene expression profiles in the biopsies of skeletal muscle taken from patients with chronic critical limb ischaemia (CLI) and non-ischaemic control subjects. Patients and methods: Biopsy of gastrocnemius muscle was obtained from six patients with unreconstructed CLI referred for surgical major amputation. As control, biopsies of six patients undergoing elective knee arthroplasty without evidence of peripheral arterial occlusive disease were taken. The differences in gene expression associated with angiogenic processes in specimens obtained from ischaemic and non-ischaemic skeletal muscle were confirmed by quantitative real-time polymerase chain reaction (PCR) analysis. Results: Compared with non-ischaemic skeletal muscle biopsy of chronic-ischaemic skeletal muscle contained 55 significantly up-regulated and 45 down-regulated genes, out of which 64 genes had a known genetic product. Tissue samples of ischaemic muscle were characterized by increased expression of cell survival factors (e. g. tissue factor pathway inhibitor 2) in combination with reduced expression of cell proliferation effectors (e. g. microfibrillar-associated protein 5 and transferrin receptor). The expression of growth factors (e. g. early growth response 3 and chemokine receptor chemokine C-X-C motif ligand 4) which play a central role in arterial and angiogenic processes and anti-angiogenetic factors (e. g. pentraxin 3) were increased in chronic ischaemic skeletal muscle. An increased expression of extracellular matrix proteins (e. g. cysteine-rich angiogenic inducer 61) was also observed. Conclusions: Gene expression profiles in biopsies of gastrocnemius muscle in patients with chronic critical limb ischaemia showed an increase in pro-survival factors, extracellular matrix protein deposition, and impaired proliferation, compared with non-ischaemic controls. Further studies are required to analyse the endogenous repair mechanism.
Erratum: Dynamic contrast-enhanced magnetic resonance imaging for head and neck cancers
Authors:   Joint Head and Neck Radiotherapy-MRI Development Cooperative, Elhalawani Hesham , Ger Rachel B. , Mohamed Abdallah S.R. , Awan Musaddiq J. , Ding Yao , Li Kimberly , Fave Xenia J. , Beers Andrew L. , Driscoll Brandon , Hormuth II David A. , van Houdt Petra J. , He Renjie , Zhou Shouhao , Mathieu Kelsey B. , Li Heng , Coolens Catherine , Chung Caroline , Bankson James A. , Huang Wei , Wang Jihong , Sandulache Vlad C. , Lai Stephen Y. , Howell Rebecca M. , Stafford R. Jason , Yankeelov Thomas E. , van der Heide Uulke A. , Frank Steven J. , Barboriak Daniel P. , Hazle John D. , Court Laurence E. , Kalpathy-Cramer Jayashree , Fuller Clifton D.
Published: March 2018

Scientific Data 5:18008 doi: 10.1038/sdata.2018.8 (2018); Published 13 Feb 2018; Updated 20 March 2018. An additional word was erroneously inserted into the abstract of this Data Descriptor during typesetting. This has now been corrected in the HTML and PDF versions.
A genome-scale RNAi screen for genetic interactors of the dynein co-factor nud-2 in Caenorhabditis elegans
Authors: Rocha Helder , Maia André F. , Gassmann Reto
Published: March 2018

Cytoplasmic dynein 1 (dynein) is the predominant microtubule minus end-directed motor in animals and participates in a wide range of cellular processes, including membrane trafficking, nuclear migration, and cell division. Dynein's functional diversity depends on co-factors that regulate its subcellular localization, interaction with cargo, and motor activity. The ubiquitous co-factor nuclear distribution gene E (NudE) is implicated in many of dynein's functions, and mutations in NudE cause the brain developmental disease microcephaly. To identify genetic interactors of the Caenorhabditis elegans NudE homolog nud-2, we performed a genome-wide RNAi screen with the null allele nud-2(ok949), which compromises dynein function but leaves animals viable and fertile. Using bacterial feeding to deliver dsRNAs in a 96-well liquid format and a semi-automated fluorescence microscopy approach for counting parents and progeny, we screened 19762 bacterial clones and identified 38 genes whose inhibition caused enhanced lethality in nud-2(ok949) relative to the nud-2(+) control. Further study of these genes, many of which participate in cell division, promises to provide insight into the function and regulation of dynein.
Antibacterial mechanism of silver nanoparticles in Pseudomonas aeruginosa: proteomics approach
Authors: Yan Xueting , He Bin , Liu Lihong , Qu Guangbo , Shi Jianbo , Hu Ligang , Jiang Guibin
Published: March 2018

Silver nanoparticles (AgNPs) are the nanomaterials most widely used as antimicrobial agents in a range of consumer products, due to the environmental release of either the AgNPs themselves or silver ions.
Nanocluster superstructures or nanoparticles? The self-consuming scaffold decides
Authors: Suber Lorenza , Imperatori Patrizia , Pilloni Luciano , Caschera Daniela , Angelini Nicola , Mezzi Alessio , Kaciulis Saulius , Iadecola Antonella , Joseph Boby , Campi Gaetano
Published: March 2018

Formation of Ag thiolate nanocluster superstructure.
Evaluation of the toxic potential of arecoline toward the third instar larvae of transgenicDrosophila melanogaster (hsp70-lacZ) Bg9
Authors: Shakya Barkha , Siddique Yasir Hasan
Published: March 2018

Arecoline is the key component of areca nut and has been suggested as a carcinogenic agent.
BODIPY-based carbon dots as fluorescent nanoprobes for sensing and imaging of extreme acidity
Authors: Qiao Lihong , Wang Jingwen , Zheng Min , Xie Zhigang
Published: March 2018

Two kinds of novel water-soluble carbon dots (CD-A and CD-B) were synthesized from 4-bora-3a,4a-diaza-s-indacene (BODIPY) derivatives, and their abilities for sensing pH under extremely acidic conditions were studied.
Ultrasensitive and direct fluorescence detection of RDX explosive vapor via side-chain terminal functionalization of a polyfluorene probe
Authors: Peng Xin , Liu Huan , Liu Ao , Xu Wei , Fu Yanyan , He Qingguo , Cao Huimin , Cheng Jiangong
Published: March 2018

We have designed and synthesized a polyfluorene probe with side-chain terminals functionalized with Boc-NH– units (PF6-Boc) for ultrasensitive RDX explosive vapor detection.
Nanobiointerfaces: a themed collection
Authors: Benetti Edmondo M. , Textor Marcus , Duan Hongwei
Published: March 2018

The guest editors introduce this themed collection for Biomaterials Science on nanobiointerfaces.
Fate ofEnterococcus faecalisin stormwater matrices under ultraviolet-A (365 nm) irradiation
Authors: Kumar Amit , Ng Daphne , Cao Bin
Published: March 2018

Sunlight UVA (365 nm) irradiation induced a transition ofEnterococcus faecalisin stormwater to a viable but non-culturable (VBNC) state.
A new strategy for the synthesis of diverse benzo[a]carbazoles via a divergent catalytic Michael reaction
Authors: Kripalaya Ratheesh Arya , Sparkes Hazel A. , Prasad Karnam Jayarampillai Rajendra
Published: March 2018

A new type of divergent catalytic Michael addition reaction of α,α-dicyanomethylidene carbazoles afforded multifunctional benzo[a]carbazoles in good yields.
Ene cyclization reaction in heterocycle synthesis
Authors: Saha Pipas , Saikia Anil K.
Published: March 2018

This review describes different types of ene cyclization reactions for the synthesis of various ring size heterocyclic compounds.
Up-conversion white emission and other luminescence properties of a YAG:Yb2O3·Tm2O3·Ho2O3@SiO2 glass-nanocomposite
Authors: Kłonkowski Andrzej M. , Kukliński Benedykt , Kubus Mariusz , Ryl Jacek , Szczodrowski Karol , Wileńska Dorota , Meyer H.-Jürgen
Published: March 2018

We present a glass-nanocomposite of the type YAG:YB3+, Tm3+, Ho3+@SiO2 as an alternative white phosphor based on up-conversion effect.
Boron-doped diamond nanowire array electrode with high mass transfer rates in flow-by operation
Authors: Lee Choong-Hyun , Lim Young-Kyun , Lee Eung-Seok , Lee Hyuk-Joo , Park Hee-Deung , Lim Dae-Soon
Published: March 2018

We fabricated a boron-doped diamond nanowire (BDDNW) array electrodevialithography and metal-assisted chemical etching (MACE) to provide a highly promoted surface area and increased mass transport during the electrochemical oxidation process.
Synergistic effects of boron-doped silicone resin and a layered double hydroxide modified with sodium dodecyl benzenesulfonate for enhancing the flame retardancy of polycarbonate
Authors: Jiang Yi , Hao Zhifeng , Luo Hongsheng , Shao Zehui , Yu Qian , Sun Ming , Ke Yong , Chen Yilong
Published: March 2018

Boron-doped silicone resin (BSR) combined with a layered double hydroxide (LDH) modified with sodium dodecyl benzenesulfonate (SDBS) to improve the flame retardancy of polycarbonate (PC).
Macromolecular diffusion in crowded media beyond the hard-sphere model
Authors: Blanco Pablo M. , Garcés Josep Lluís , Madurga Sergio , Mas Francesc
Published: March 2018

A novel model (Chain Entanglement Softened Potential) for polymer interaction is presented to consider macromolecular entanglementviaa soft potential.
Preparation of a photo- and thermo-responsive topological gel from anthracene-modified polyrotaxanes
Authors: Li Zhao , Su Shan , Yu Lin , Zheng Zhen , Wang Xinling
Published: March 2018

Anthracene functionalized PEG/α-CD based polyrotaxanes can undergo a sol–gel–sol reversible transition under the stimulation of UV and thermal treatment.
3D printing of Fe-based bulk metallic glasses and composites with large dimensions and enhanced toughness by thermal spraying
Authors: Zhang Cheng , Wang Wei , Li Yi-Cheng , Yang Yan-Ge , Wu Yue , Liu Lin
Published: March 2018

Large sized Fe-based bulk metallic glasses (BMGs) and BMG/stainless steel (SS) composites with excellent mechanical properties were successfully fabricated using a thermal spray three-dimensional (3D) printing (TS3DP) technique.
Enhanced pseudocapacitance contribution to outstanding Li-storage performance for a reduced graphene oxide-wrapped FeS composite anode
Authors: Huang Mingbao , Xu Anding , Duan Huanhuan , Wu Songping
Published: March 2018

A facile and eco-friendly one-pot approach was utilized to synthesize a rGO-wrapped FeS nanoflakes composite, delivering a reversible capacity of 325 mA h g−1 at a large rate of 5.0 A g−1 after 1000 cycles.
High efficiency ternary polymer solar cells based on a fused pentacyclic electron acceptor
Authors: Zhang Cai'e , Feng Shiyu , Liu Yahui , Ming Shouli , Lu Heng , Ma Danyang , Xu Xinjun , Wu Youzhi , Bo Zhishan
Published: March 2018

High-performance photovoltaic devices based on non-fullerene acceptors with fewer fused rings are realized via a ternary strategy.
Fabrication of (Ni,Co)0.85Se nanosheet arrays derived from layered double hydroxides toward largely enhanced overall water splitting
Authors: Xiao Kaiming , Zhou Lei , Shao Mingfei , Wei Min
Published: March 2018

A high-performance and durable bifunctional electrocatalyst based on (Ni,Co)0.85Se nanosheet arrays toward overall water splitting.
Core–shell protein clusters comprising haemoglobin and recombinant feline serum albumin as an artificial O2carrier for cats
Authors: Yokomaku Kyoko , Akiyama Motofusa , Morita Yoshitsugu , Kihira Kiyohito , Komatsu Teruyuki
Published: March 2018

Dual-protein clusters comprising haemoglobin and recombinant feline serum albumins as a red blood cell substitute for exclusive use in cats.
Liquid-ammonia synthesis of microporous Mg3N2showing intense red-light emission
Authors: Rein Viktor , Wenzel Olivia , Popescu Radian , Gerthsen Dagmar , Feldmann Claus
Published: March 2018

Magnesium nitride (Mg3N2) is preparedvialyotropic phases with liquid ammonia (lq-NH3). To avoid oxide contamination, the synthesis was performed in the absence of any oxygen source (e.g., solvents, starting materials and surfactants).
The conversion mechanism of amorphous silicon to stoichiometric WS2
Authors: Heyne Markus H. , de Marneffe Jean-François , Nuytten Thomas , Meersschaut Johan , Conard Thierry , Caymax Matty , Radu Iuliana , Delabie Annelies , Neyts Erik C. , De Gendt Stefan
Published: March 2018

Few-layer thin WS2 was deposited on large substrates by the gas phase precursors WF6/H2S and amorphous Si as solid precursor.
Wide-range non-contact fluorescence intensity ratio thermometer based on Yb3+/Nd3+co-doped La2O3microcrystals operating from 290 to 1230 K
Authors: Gao Guojun , Busko Dmitry , Kauffmann-Weiss Sandra , Turshatov Andrey , Howard Ian A. , Richards Bryce S.
Published: March 2018

Non-contact ratiometric thermometry has applications in areas such as industrial process monitoring.
Compact, wideband impedance tuner using a three‐line‐microstrip structure
Authors: Heredia J. , Ribó M. , Pradell L.
Published: March 2018

A novel three‐line‐microstrip compact impedance tuner is presented. It is based on a multimodal structure wherein six variable capacitances, implemented with two parallel‐connected varactors each, create multiple interactions among the three‐line‐microstrip modes in a reduced circuit area. Experimental results show better‐than‐70% coverage of the Smith chart in an 85% frequency bandwidth from 1.4 to 3.2 GHz.
Stochastic analysis of electric transportation charging impacts on power quality of distribution systems
Authors: Leou Rong‐Ceng , Teng Jen‐Hao , Lu Heng‐Jiu , Lan Bo‐Ren , Chen Hong‐Ting , Hsieh Ting‐Yen , Su Chun‐Lien
Published: March 2018

This work studies the power quality impacts of electric transportation charging including electric buses (EBs) and electric vehicles (EVs) on distribution systems. The stochastic harmonic models for EBs and EVs and the stochastic models for their usage scenarios are built utilising the measured charging data. Based on these models, a power quality analysis method considering the charging uncertainties of EBs and EVs is proposed in this study and then their impacts on distribution systems are investigated. The Monte Carlo simulation is integrated into the proposed method to study the under voltage, overcurrent, voltage unbalance, transformer overload, harmonic current, voltage etc. caused by the stochastic charging of EBs and EVs. An actual distribution system acquired from Taiwan Power Company is taken as an example to validate the practicability of the proposed method. The test results of the proposed stochastic model are compared with those of the conservative model.
Sparse patch‐based representation with combined information of atlas for multi‐atlas label fusion
Authors: Yan Meng , Liu Hong , Song Enmin , Qian Yuejing , Jin Lianghai , Hung Chih‐Cheng
Published: March 2018

To obtain a higher accuracy in the multi‐atlas patch‐based label fusion method, it is essential to have the accurate similarity measure of selected patches. In this study, the authors propose a new sparse patch‐based representation method using a local binary texture (LBT) in the atlas image and atlas label information for the multi‐atlas label fusion. In the proposed method, the intensity information in a patch is converted into a LBT which is then combined with the labels of corresponding patches from the atlas to form an atom of a dictionary. The initial labels of target images are estimated through a rough segmentation. The voxel in a patch to be labelled is also constructed as a vector similar to the atom. The voxel vector is then modelled as a sparse linear combination of the atoms in the dictionary. Experimental results on two MR brain data sets demonstrated that the proposed method is efficient in the segmentation which can achieve competitive performance compared with the state‐of‐the‐art methods.
Microgrid energy and reserve management incorporating prosumer behind‐the‐meter resources
Authors: Damisa Uyikumhe , Nwulu Nnamdi Ikechi , Sun Yanxia
Published: March 2018

The unpredictable nature of renewable power, coupled with the influx of prosumers has made accurate power forecasts in microgrids (MGs) more difficult to obtain. A direct consequence of this is the need for additional spinning reserve (SR) capacity to compensate for resulting power imbalances. Due to the economic and environmental concerns, increasing conventional generation to meet this additional SR capacity is undesirable. The aggregation of prosumer behind‐the‐meter resources for the provision of SR is proposed in this study, and a mathematical model for the proposed scheme is developed. This scheme is formulated as a constrained optimisation problem, whose solution maintains power supply and demand balance whilst reserving a virtual spinning capacity. The formulation is linearised and solved using the CPLEX 12.6.3 solver in the Advanced Interactive Multidimensional Modelling System environment. A 14‐bus MG test system is used to validate the proposed scheme, and results show the benefits of using prosumer behind‐the‐meter resources to provide ancillary services like SR.
Amiodarone-Induced Thyroid Dysfunction: A Clinical Update
Authors: Elnaggar Mohamed , Jbeili Kahtan , Nik-Hussin Nik , Kozhippally Mohandas , Pappachan Joseph
Published: March 2018

Amiodarone is one of the most commonly prescribed antiarrhythmic agents in clinical practice owing to its efficacy, even with high toxicity profile. The high iodine content and the prolonged biological half-life of the drug can result in thyroid dysfunction in a high proportion of patients treated with amiodarone even after cessation of amiodarone. Both hypothyroidism and hyperthyroidism are common side effects that mandate regular monitoring of patients with thyroid function tests. Amiodarone-induced hypothyroidism (AIH) is diagnosed and managed in the same way as a usual case of hypothyroidism. However, differential diagnosis and clinical management of amiodarone-induced thyrotoxicosis (AIT) subtypes can be challenging. With the aid of a case snippet, we update the current evidence for the diagnostic work up and management of patients with amiodarone-induced thyroid dysfunction in this article.
TAFI Meets the Sticky Ends
Authors: Booth Nuala
Published: March 2018

The coagulation and fibrinolytic system are often considered as separate entities, despite the obvious connection that one produces fibrin, the substrate for the other. A potent example of a more subtle and yet important connection lies in thrombin’s ability to generate an inhibitor of fibrinolysis. This exemplifies the pivotal role of thrombin in haemostasis, a consequence of its broad range of activities. Thrombin activates the zymogen form of a basic carboxypeptidase, generating an active enzyme called carboxypeptidase U, carboxypeptidase R, plasma carboxypeptidase B or TAFIa, thrombin activable fibrinolysis inhibitor (reviewed in 1-4; references from the reviews are not cited here). The activated carboxypeptidase removes C-terminal basic residues from fibrin. C-terminal Lys residues are key to binding t-PA and plasminogen, and thus to generating plasmin activity, a mechanism by which partially-lysed fibrin amplifies plasmin formation. The removal of these C-terminal Lys residues therefore decreases local fibrinolytic activity (Fig. 1). Several recent studies, two of which appear in this issue of Thrombosis and Haemostasis (5, 6), add to our knowledge of this activity and its potential role in thromboembolic disease.
Regulation of Fibrinolysis in Plasma by TAFI and Protein C Is Dependent on the Concentration of Thrombomodulin
Authors: Meijers Joost , Bouma Bonno , Mosnier Laurent
Published: March 2018

Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme, that after activation down regulates fibrinolysis. TAFI is activated by thrombin in the presence of the cofactor thrombomodulin (TM). By stimulation of TAFI activation TM down regulates fibrinolysis, however TM is also a cofactor in the activation of protein C. Activated protein C (APC) can up regulate fibrinolysis by limiting the activation of TAFI via the attenuation of thrombin production. We studied these counteracting fibrinolytic properties of TM in plasma by measuring the activation of TAFI during tissue factor induced coagulation. TAFI activation was stimulated at low concentrations of TM but decreased at higher concentrations of TM. Similarly, the clot lysis times increased at low concentrations of TM but decreased at higher concentrations of TM. The reduction of TAFI activation at high TM concentrations was found to be dependent on a functional protein C pathway. The concentration of TM is therefore an important factor in the regulation of TAFI activation and in the regulation of fibrinolysis. High concentrations of TM result in up regulation of fibrinolysis, whereas low concentrations of TM have a down regulatory effect on fibrinolysis. These results suggest that fibrinolysis might be differentially regulated by TM in different parts of the body depending on the local TM concentration in the vasculature.

Abbreviations: TAFI, thrombin activatable fibrinolysis inhibitor; TAFIa, activated TAFI; CPI, carboxypeptidase inhibitor from potato tubers; tPA, tissue-type plasminogen activator; TM, thrombo-modulin; TM4-6, Thrombomodulin fragment containing EGF domains 4 to 6; HMEC, human microvascular endothelial cell.
Immunological Assay for the Determination of Procarboxypeptidase U Antigen Levels in Human Plasma
Authors: Stromqvist Mats , Schatteman Katinka , Leurs Judith , Verkerk Robert , Andersson Jan-Olof , Johansson Thord , Scharpe Simon , Hendriks Dirk
Published: March 2018

The importance of carboxypeptidase U as a novel regulator of the fibrinolytic rate has attracted a lot of interest recently. In the present work, an ELISA was developed using polyclonal antibodies raised against recombinant proCPU, expressed in DON cells. The assay determines the antigen concentration of the zymogen of carboxypeptidase U, procarboxypeptidase U, in human citrated plasma or EDTA plasma. No interference is observed with plasma carboxypeptidase N. The assay is very reproducible (within-run: 4.6% CV, between-run: 6.8% CV). In a group of 479 healthy individuals the mean proCPU antigen concentration is 13.4 μg/ml (SD 2.5 μg/ml). A good correlation is found with the functional procarboxypeptidase U assay described earlier (r = 0.82, p <0.0001) (Schatteman K, Goossens F, Scharpé S, Neels H, Hendriks D Clin Chem 1999; 45: 807-813). The significant correlation between the proCPU antigen concentration and the 50% clot lysis time stresses its importance as a player in fibrinolysis control.

Abbreviations: CPU, carboxypeptidase U; proCPU, procarboxypeptidase U; TAFI, thrombin activatable fibrinolysis inhibitor; AP, alkaline phosphatase; EDTA, ethylenediamine tetra-acetic acid; Tris, tris-(hydroxyethyl)-aminomethane; PPACK, phenylalanyl-prolyl-chloromethyl ketone; SP, sulphopropyl; HEPES, N-2-hydroxyethylpiperazine-N’-ethanesulfonic acid
Circulating Procoagulant Microparticles in Women with Unexplained Pregnancy Loss: a New Insight
Authors: Laude I. , Rongières-Bertrand C. , Boyer-Neumann C. , Wolf M. , Mairovitz V. , Hugel B. , Freyssinet J. M. , Frydman R. , Eschwège V. , Meyer D.
Published: March 2018

One of the frequently proposed mechanisms for pregnancy losses refers to uteroplacental thrombosis. However the contribution of classical thrombotic risk factors remains questionable and, if real, does not account for a large number of pregnancy losses. The aim of this study was to investigate the presence of circulating procoagulant microparticles, a new marker of cell activation already associated with various prothrombotic clinical settings. Microparticles were assessed by an original prothrombinase assay on platelet depleted plasma obtained from 74 women with a history of pregnancy loss without apparent cause and 50 controls. Patients were studied at least 2 months after the last obstetrical event and were classified into 2 groups: 49 women with at least 3 consecutive spontaneous abortions at or before the 10th postmenstrual week and 25 with at least one fetal death beyond the 10th postmenstrual week. Among the 74 patients, 41 had increased levels of circulating microparticles, 29 belonging to the group of early pregnancy loss (59%) and 12 to the group of late pregnancy loss (48%). The high prevalence of increased levels of procoagulant microparticles in both groups makes this new marker very promising for the understanding, follow up and therapeutical handling of pregnancy loss.
Mechanism of the Immune Response to Human Factor VIII in Murine Hemophilia A
Authors: Wu Huiyun , Reding Mark , Qian Jiahua , Okita David , Parker Ernie , Lollar Pete , Hoyer Leon , Conti-Fine Bianca
Published: March 2018

Mice genetically deficient in factor VIII (fVIII) are a model of hemophilia A. As a first step to reproduce in this mouse model what occurs over time in hemophilia A patients treated with human fVIII (hfVIII), we have investigated the time course and the characteristics of their immune response to hfVIII, after multiple intravenous injections. Anti-hfVIII antibodies appeared after four to five injections. They were IgG1 and to a lesser extent IgG2, indicating that they were induced by both Th2 and Th1 cells. Inhibitors appeared after six injections. CD4+ enriched splenocytes from hfVIII-treated mice proliferated in response to fVIII and secreted IL-10: in a few mice they secreted also IFN-γ and in one mouse IL-4, but never IL-2. A hfVIII-specific T cell line derived from hfVIII-treated mice secreted both IL-4 and IFN-γ, suggesting that it included both Th1 and Th2 cells. CD4+ enriched splenocytes of hfVIII-treated mice recognized all hfVIII domains. Thus, hemophilic mice develop an immune response to hfVIII administered intravenously similar to that of hemophilia A patients. Their anti-hfVIII antibodies can be inhibitors and belong to IgG subclasses homologous to those of inhibitors in hemophilic patients; their anti-hfVIII CD4+ cells recognize a complex repertoire and both Th1 and Th2 cytokines, and especially IL-10, may drive the antibody synthesis.

Abbreviations used: antibodies, Ab; antigen presenting cells, APC; Arbitrary Units, AU; enzyme-linked immunosorbant assay, ELISA; factor VIII, fVIII; human factor VIII, hf VIII; intravenous, i.v.; optical density, OD; polymerase chain reaction, PCR; phosphate buffered saline solution, PBS; PBS containing 3% bovine serum albumin, PBS/BSA; PBS containing 0.05% polyoxyethylene sorbitan monolaurate, PBS/Tween-20; phytohemoagglutinin, PHA; stimulation index, SI
Serum Prostaglandin D Synthase Level after Coronary Angioplasty May Predict Occurrence of Restenosis
Authors: Takayanagi Kan , Morooka Shigenori , Uehara Yoshio , Oda Hiroshi , Seiki Kousuke , Nakajima Hiroshi , Urade Yoshihiro , Inoue Teruo
Published: March 2018

Lipocalin-type prostaglandin D synthase (L-PGDS), which is responsible for the biosynthesis of PGD2, has recently been found to be present in the atherosclerotic plaque of the human coronary artery and also to be secreted in human serum. We measured the serum L-PGDS level and compared it with the expressions of the platelet membrane surface glycoprotein and neutrophil adhesion molecule in patients undergoing PTCA. The L-PGDS level significantly decreased (P < 0.01) and the platelet surface expression of CD62P (P-selectin) significantly increased (P < 0.01) immediately after PTCA in the coronary sinus blood. Both changes were inversely correlated (R = −0.72, P < 0.001). Although the L-PGDS level in the coronary sinus blood remained equivalent to the baseline level in patients who experienced restenosis, the level increased over the baseline level (P < 0.01) at 48 h after PTCA in patients without restenosis. Neutrophil surface expression of CD11b (a subunit of Mac-1) significantly increased at 24 h (P < 0.01) to 48 h (P < 0.001) after PTCA in the coronary sinus blood in patients with restenosis but the change showed less significant in patients without restenosis. The changes in the L-PGDS level and the CD11b expression at 48 h after PTCA were inversely correlated (R = −0.55, P < 0.05). An increased serum L-PGDS level at 48 h after PTCA possibly predicts the avoidance of late restenosis. It is suggested that reduction in PGD2 synthesis triggers platelet activation and that a subsequent increase in the PGD2 synthesis suppresses inflammatory reaction at the intervention site indicated by neutrophil activation and inhibits development of restenosis. Pharmacological or biological intervention that increases endogenous PGD2 synthesis should be tested as a new strategy to prevent restenosis.
Recombinant Factor IX Recovery and Inhibitor Safety: A Canadian Post-licensure Surveillance Study
Authors: Lillicrap David , Hensman Caroline , Card Robert , Scully Mary-Frances , Poon Man-Chiu ,   Members of Asso cia tion of Hemophilia Clinic Directors of Canada* and Canadian Association of Nurses in Hemophilia Care*
Published: March 2018

As part of the Canadian post-licensure surveillance on the safety of recombinant factor IX (rFIX, BeneFIX®), factor IX recovery and inhibitor development were studied. The recovery following rFIX infusion in 126 patients (mean = 0.77, median 0.72, range 0.36-1.85, 95% CI of mean 0.74-0.81, expressed as FIX activity increase in U/dL per IU FIX concentrate/kg body weight infused) was significantly lower than that following the last plasma-derived factor IX (pdFIX) infusion in 74 patients (mean 1.05, median 1.00, range 0.37-2.29, 95% CI of mean 0.99-0.97). The recovery for rFIX for patients aged ≤15 years (n = 41, mean recovery 0.64) and that for patients aged >15 years (n = 85, mean 0.84) was each significantly lower than that for pdFIX (aged ≤15 years: n = 21, mean recovery 0.91; aged >15 years: n = 53, mean recovery 1.10). For both rFIX and pdFIX concentrates, the recovery was lower in patients ≤15 years of age compared to those >15 years of age. Similar data and conclusions were obtained on 66 patients with paired recovery data from rFIX and pdFIX. Overall, our data are similar to those obtained in formal clinical trials. Two of 244 patients treated with rFIX for up to 5 years have developed de novo inhibitors associated with anaphylaxis, an incidence that is similar to that reported for pdFIX. No other serious adverse events, including thrombotic episodes, were reported. To the best of our knowledge, this is the first formal report of recovery and inhibitor formation on rFIX in a peer-reviewed manuscript form.
Plasminogen Has a Broad Extrahepatic Distribution
Authors: Seiffert Dietmar , Fowler Bruce , Jenkins George , Thinnes Therese , Loskutoff David , Parmer Robert , Miles Lindsey , Zhang Lu
Published: March 2018

Plasmin is the major enzyme that dissolves fibrin in the vasculature and the predominant source of its zymogen, plasminogen, is liver. However, plasmin has a broad substrate spectrum and, if present in other tissues, may perform additional functions. We tested the hypothesis that plasminogen is expressed broadly extrahepatically. A sensitive and specific isotopic quantitative RT-PCR assay was developed to detect plasminogen mRNA from total RNA isolated from C57BL/6J mice tissues. Plasminogen mRNA was detected in adrenal, kidney, brain, testis, heart, lung, uterus, spleen, thymus and gut. Of these tissues, adrenal had the highest plasminogen mRNA content. In situ hybridization was utilized to localize plasminogen mRNA expressing cell types. Besides hepatocytes, positive cells were identified in both adrenal and kidney medullae and cortexes. Plasminogen mRNA expression was detected in cerebral, hippocampal and cerebellar neurons. Plasminogen mRNA was detected in cells in early stages of spermatogenesis in testis, present in the cortex and medulla of the thymus and in splenic white and red pulps. Our results suggest that the plasminogen gene is expressed broadly in extrahepatic tissues. Thus, tissues separated by local anatomic barriers as well as tissues accessible to circulating plasminogen have the capacity to provide local sources of plasminogen.
Comparison of Venography and Ultrasound for the Diagnosis of Asymptomatic Deep Vein Thrombosis in the Upper Body in Children
Authors: Male Christoph , Chait Peter , Ginsberg Jeffrey , Hanna Kim , Andrew Maureen , Halton Jacqueline , Anderson Ron , McCusker Patricia , Wu John , Abshire Thomas , Cherrick Irene , Mahoney Donald , Mitchell Lesley
Published: March 2018

Deep vein thrombosis (DVT) in children occurs primarily in the upper body venous system. This prospective diagnostic study compared bilateral venography and ultrasound for detection of DVT in the upper venous system in 66 children with acute lymphoblastic leukemia. Results were interpreted by central blinded adjudication.

Deep venous thrombosis occurred in 29% (19/66) patients. While 15/19 DVT were detected by venography (sensitivity 79%), only 7/19 were detected by ultrasound (sensitivity 37%). The 12 DVT detected by venography but not by ultrasound were located in the subclavian vein or more central veins. Three of 4 DVT detected by ultrasound but not by venography were in the jugular vein. We conclude that ultrasound is insensitive for DVT in the central upper venous system but may be more sensitive than venography in the jugular veins. A combination of both venography and ultrasound is required for screening for DVT in the upper venous system.
Decreased Concentrations of Heparinoids Are Required to Inhibit Thrombin Generation in Plasma from Newborns and Children Compared to Plasma from Adults due to Reduced Thrombin Potential
Authors: Berry Leslie , Monagle Paul , Andrew Maureen , Chan Anthony
Published: March 2018

Thrombin generation is decreased and delayed in plasma from newborns and children compared to adults. We hypothesized that lower doses of heparinoid anticoagulants are required to give similar thrombin generation in newborn (umbilical cord) and child plasmas compared to that of adults. Thrombin generation was performed in either the absence or presence of unfractionated heparin (UFH), low molecular weight heparin (LMWH) or a covalent antithrombin-heparin complex (ATH). After contact activation and recalcification of each plasma, thrombin activity was measured by periodic sub-sampling into chromogenic substrate. UFH inhibited thrombin generation to a greater extent compared to LMWH in all plasmas. Cord plasma was more sensitive to inhibition and displayed a greater difference in the effectiveness of UFH compared to LMWH than other plasmas. Lower concentrations of UFH and LMWH were required to inhibit thrombin generation in cord and child plasmas compared to adult plasma. In comparison, ATH strongly inhibited thrombin generation in all 3 plasmas. Similar peak thrombin concentrations were observed at lower ATH concentrations (0.1 U/mL) compared to either UFH (0.25 U/mL) or LMWH (0.25 U/mL). As with UFH and LMWH, cord plasma was more sensitive to inhibition by ATH than the other plasmas and lower ATH concentrations inhibited thrombin generation in cord and child plasmas compared to adult plasma. Decreased thrombin generation with heparinoids in cord and child plasmas compared to adult plasma coincided with decreased rates of prothrombin consumption and increased proportion of thrombin- α2-macroglobulin inhibitor complexes. In summary, lower doses of UFH, LMWH or ATH result in similar peak thrombin generation in newborn and child plasmas compared to adult plasma. Cord plasma was the most sensitive to inhibition, with ATH being more effective than UFH or LMWH.
Internal Quality Control of PCR-based Genotyping Methods in Research Studies and Patient Diagnostics
Authors: Gram Jørgen , Jespersen Jørgen , de Maat Moniek , Bladbjerg Else-Marie
Published: March 2018

Genetic analyses are increasingly integrated in the clinical laboratory, and internal quality control programmes are needed. We have focused on quality control aspects of selected polymorphism analyses used in thrombosis research. DNA was isolated from EDTA-blood (n = 500) by ammonium acetate precipitation and analysed for 18 polymorphisms by polymerase chain reaction (PCR), i. e. restriction fragment length polymorphisms, allele specific amplification, or amplification of insertion/deletion fragments. We evaluated the following aspects in the analytical procedures: sample handling and DNA-isolation (pre-analytical factors), DNA-amplification, digestion with restriction enzymes, electrophoresis (analytical factors), result reading and entry into a database (post-analytical factors). Furthermore, we evaluated a procedure for result confirmation. Isolated DNA was of good quality (42 µ.g/ml blood, A260/A280 ratio >1.75, negative DNAsis tests), and the reagent blank was contaminated in <1% of the results. Occasionally, results were re-analysed because of positive reagent blanks (<1%) or because of problems with the controls (< 5%). On confirmation, we observed 4 genotyping discrepancies. Control of data handling revealed 0.1% reading mistakes and 0.5% entry mistakes. Based on our experiences we propose an internal quality control programme for widely used PCR-based haemostasis polymorphism analyses.