bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping of Epitopes on Human Tissue-Type Plasminogen Activator with Recombinant Deletion Mutant Proteins
Authors: Zonneveld Anton-Jan van , Veerman Harry , Brakenhoff Just P J , Aarden Lucien A , Cajot Jean-Francois , Pannekoek Hans 
Published: July 2018

SummaryAn antigen assay based on a monoclonal antibody directed against the light chain of tissue-type plasminogen activator (t-PA) was developed to quantify seven recombinant (r) t-PA deletion mutant proteins. These recombinant proteins were then employed to map different epitopes on t-PA which interact with a panel of twenty-three monoclonal anti-t-PA antibodies. Twenty were directed against domains on the heavy chain, two against the “finger” domain, three against the “epidermal growth factor-like” domain, five against the kringle 1 domain, and ten against the kringle 2 domain. Only three monoclonal anti-t-PA antibodies interact with the light chain. The finding that the epitopes of each of the monoclonals could be determined with the deletion mutant proteins supports the hypothesis of autonomous folding of structural domains and emphasizes the validity of the use of the recombinant t-PA-deletion mutant proteins for structure-function studies.
The Animal Models for Hemorrhage and Thrombosis in the Neonate
Authors: Kisker C Thomas 
Published: July 2018

SummaryAnimal models have added significantly to our understanding of adult hemorrhagic and thrombotic diseases. Few models, however, have been developed for studies of the hemostatic disorders in the fetus and newborn. This report reviews the current information on animal models of fetal and neonatal hemostasis. The requirements of a relevant model are addressed and previous studies using fetal and neonatal animal models are reviewed. A recommendation of a single animal for all studies of fetal and neonatal hemostasis is not possible. However, the lamb has been the most frequently studied and appears to provide relevant information regarding normal development and the factors which may adversely influence hemostasis in the fetus and newborn.
Metformin Decreases the High Plasminogen Activator Inhibition Capacity, Plasma Insulin and Triglyceride Levels in Non-Diabetic Obese Subjects
Authors: Vague Ph , Juhan-Vague I , Alessi M C , Badier C , Valadier J 
Published: July 2018

SummaryWe have previously observed a positive correlation between Plasminogen Activator Inhibition capacity (PA Inhibition), Body Mass Index (BMI) and plasma insulin levels in a population of non diabetic subjects. The anti diabetic biguanide Metformin which decreases insulin resistance has been reported to increase the blood fibrinolytic activity. Therefore we have studied the effect of Metformin on PA Inhibition levels in obese subjects with normal glucose tolerance. Eighteen obese women (O) (BMI: 31.4 ± 1.13, m ± S.E.M.) were compared to age matched controls (C) (BMI: 20.2 ± 0.8) and randomized to a 15 days treatment by Metformin (M) (1.7 g/day) or placebo (P) in a double blind study while on a weight maintaining diet. O compared to C had higher levels (m ± S.E.M.) of PA Inhibition (9 ± 1.8 IU/ml, versus 2.88 ± 0.29 p <0.01), lower euglobulin fibrinolytic activity (EFA) (4.95 ±1.17 mm versus 9 ± 0.29 p <0.05), higher plasma insulin (24.1 ±2.1. uU/ml), versus 12 ± 1 p <0.01) and triglyceride (1.32 ± 0.16 mmol/1, versus 0.8 ± 0.08 p <0.05). After 15 days of treatment, in group M a significant decrease in PA Inhibition (5.51 ± 1.4, versus 9.48 ±2.1 p <0.05) in plasma insulin (18.5 ±0.1, versus 24.5 ± 3.5, p <0.05) and plasma triglyceride (1.08 ± 0.1, versus 1.47 ± 0.3 p <0.05) and an increase in EFA (6.50 ± 0.28, versus 5.25 ± 0.35 p <0.05) were observed. No significant variation was observed in group P.
Using a Monoclonal Antibody to Identify Patients with Type I and Type II von Willebrand’s Disease
Authors: Hall Jeffrey D , Willis Dean W , Evatt Bruce L , Jackson Debra W 
Published: July 2018

SummaryThree monoclonal antibodies produced against vWF:Ag by conventional hybridoma technique did not inhibit factor VIII coagulant activity (F.VIII:C) but did inhibit VIII ristocetin cofactor activity. The antibodies were used in an indirect competitive ELISA for quantifying von Willebrand’s antigen (vWF: Ag) and compared with values obtained by the Laurell technique using commercial antibody by means of a ratio: ELISA/Laurell. For one monoclonal BD2-CC9, vWF:Ag values obtained in the two assays were in good agreement for normal and hemophilia A plasmas (normal, n = 19, ratio = 1.13 ± .17, hemophilia A, n = 10, ratio = 0.91 ± .15). However, type II vWD patients had a disproportionately low value of vWF: Ag with the ELISA. Use of the ratio normalized the difference among individual plasma values and allowed a significant separation of type II vWD plasma (n = 9, ratio = 0.46 ± .19) from normal plasma (p = .0001) and type I vWD plasma (n = 8, ratio = 1.52 ± .34) from type II vWD plasma (p = .0003) using BD2-CC9. Although the sample size was small, the greater degree of discrimination among the vWD plasmas tested with BD2-CC9 (compared with the other two antibodies [CA3-AE4, CC6-BG10]) suggests that this antibody may recognize conformational epitopes that reflect the degree of multimeric polymerization of the vWF molecule rather than simply recognize a decreased number of antigenic sites in a basic subunit. BD2-CC9 may be valuable in investigating the various types of vWD and/or the process of polymerization of this complex protein.
Platelet Procoagulant Properties Studied with Snake Venom Prothrombin Activators
Authors: Speijer Han , Govers-Riemslag José W P , Zwaal Robert F A , Rosing Jan 
Published: July 2018

SummaryPurified snake venom prothrombin activators were used to probe the procoagulant properties of platelet membranes. Human platelets were able to stimulate prothrombin activation by the venom activators from Oxyuranus scutellatus and Notechis scutatus, while the prothrombin activator from Echis carinatus was not affected by the presence of platelets. The prothrombinconverting activity of platelets was further studied with the venom activator from Oxyuranus scutellatus and with the factor Xa-Va complex as prothrombin activating enzymes. Stimulation of platelets with collagen, collagen plus thrombin or with the Ca-ionophore A23187 resulted in a considerable increase of platelet prothrombin converting activity probed with the factor Xa-Va complex as well as with the prothrombin activator from Oxyuranus scutellatus. The stimulatory effect of activated platelets on the rates of prothrombin activation by Oxyuranus scutellatus was similar to that determined for factor Xa-Va-catalyzed prothrombin activation. Compared to non-stimulated platelets, platelets stimulated with thrombin plus collagen exposed 20-times more procoagulant sites for as well the factor Xa-Va complex, as for the venom activator from Oxyuranus scutellatus. The actual number of procoagulant sites per platelet determined with the factor Xa-Va complex was in close agreement with the number of sites determined with the venom activator. Also the time course of appearance of procoagulant activity during platelet stimulation by collagen plus thrombin was comparable for both activator complexes. Phospholipase A2 treatment of stimulated platelets resulted in an almost complete loss of their ability to stimulate prothrombin activation by the enzyme from Oxyuranus scutellatus or by factor Xa-Va complex. The findings presented in this paper suggest: a) that the factor Xa-Va complex and the prothrombin activator from Oxyuranus scutellatus recognize the same procoagulant sites on both stimulated and unstimulated platelets and b) that negatively-charged phospholipids are essential components of these procoagulant sites.
Vulvar Hemangioma: Case Report
Authors: Silva Janine Medeiros da , Calife Emily Ramos , Cabral João Victor de Sousa , Andrade Hildemárzio Pinheiro Falcão de , Gonçalves Ana Katherine 
Published: July 2018

AbstractHemangioma is a benign neoplasm that may affect the vulva, and it can cause functional or emotional disability. This article reports the case of a 52-year-old female patient with a history of a genital ulcer for the past 3 years and who had undergone various treatments with creams and ointments. The patient was biopsied and diagnosed with vulvar hemangioma and was subsequently submitted to surgical excision of the lesion. We emphasize the importance of following the steps of the differential diagnosis and proceeding with a surgical approach only if necessary.
Acute Otologic Infections in Pediatric Patients
Authors: Tipton Courtney , Honsinger Kristen , Harris Michael , Malhotra Prashant 
Published: July 2018

AbstractThis article summarizes significant acute infections involving the pediatric temporal bone. First, the management of acute otitis media (AOM) is discussed, including the medical and surgical management of invasive intracranial and extracranial complications associated with advanced disease. The clinical and radiographic findings, microbiology, and management of acute mastoiditis are discussed in greater detail, followed by the presentation and treatment of acute otitis externa (AOE). Finally, we discuss infectious considerations in auditory implants. The indications and use of both cochlear implants (CI) and bone conduction hearing implants have rapidly expanded in children, requiring greater understanding of managing infections in the context of these devices.
The use of face-threatening acts in the construction of in- and out-group identities in British parliamentary debates
Authors: Mollin Sandra 
Published: July 2018

Abstract
Identity construction is group membership construction in that humans bring their individual selves into being by declaring and performing their belonging to in-groups which are constructed in contrast to out-groups, as suggested in Tajfel’s theory of social identity. In parliamentary discourse, the establishment and reinforcement of in- and out-group identities is particularly important, since parliamentary discourse represents an institutionalized arguing game of ‘us’ versus ‘them’ (between political parties). One decisive way in which these group identities are construed and maintained is through the use of face-threatening acts (FTAs), analyzed here in British House of Commons debates on health policy. A taxonomy of FTAs in this context is developed, allowing for an analysis of addressers and addressees, and close interpretation of examples leads to the conclusion that FTAs are used to denigrate the out-group and strengthen in-group identification at the same time.
“And you know, Jeremy, my father came from a very poor background indeed”
Authors: Fetzer Anita 
Published: July 2018

Abstract
This chapter examines the discursive construction of identity in political discourse and considers collective identities as the default in that context. It utilises an integrated approach informed by interactional sociolinguistics and discourse pragmatics. Departing from the premise that discursive identities are co-constructed, reconstructed and – possibly – deconstructed in and through the process of communication, it focuses on those contexts in which political agents depart from the default by entextualising non-collective identities, e.g., private-domain-anchored family person or ordinary citizen. The ‘doing’ and ‘undoing’ of discursive identities in discourse is reflected in the importation of private-domain-anchored communicative styles and genres, such as colloquial expressions and small stories, contributing to the ongoing process of hybridisation of institutional discourse in general and political discourse in particular. The discursive construction, re- and deconstruction of identities in political discourse is a multifaceted endeavour which exploits the structural, pragmatic and cognitive constraints of a discourse genre as well as those of institution and society.
Nations as persons
Authors: Musolff Andreas 
Published: July 2018

Abstract
The paper analyses the construal of collective identities in the Middle East conflict, with special regard to the nation-as-person metaphor. This metaphor has been highlighted by proponents of Conceptual Metaphor Theory and Critical Metaphor Analysis as being instrumental in conceptualizing collective political entities as (pseudo-)personal identities. On the other hand, it has been critically argued that the nation-as-person metaphor should not be over-generalized and it has even been condemned as a fallacious theoretical construct. In view of the metaphor’s controversial status, the paper studies a corpus of ten speeches delivered by the Israeli and Palestinian political leaders B. Netanyahu and M. Abbas to the UN General assemblies in the period 2011–2015. Instances of emphatic use and enactment of the nation-as-person metaphor by the speakers are analysed in detail for their contextual implications and their function in collective identity-construction. The main finding is that whilst the nation-as-person metaphor is not ubiquitous in a statistical sense, it informs the fundamental pragmatic stance of the speakers as personifications of their nations’ collective identities vis-à-vis other nations. In conclusion, it is argued that such collective identity construction both expresses and shapes the progress of conflict communication.
MDPbiome: microbiome engineering through prescriptive perturbations
Authors: García-Jiménez Beatriz , de la Rosa Tomás , Wilkinson Mark D 
Published: July 2018

Abstract

Motivation
Recent microbiome dynamics studies highlight the current inability to predict the effects of external perturbations on complex microbial populations. To do so would be particularly advantageous in fields such as medicine, bioremediation or industrial scenarios.

Results
MDPbiome statistically models longitudinal metagenomics samples undergoing perturbations as a Markov Decision Process (MDP). Given a starting microbial composition, our MDPbiome system suggests the sequence of external perturbation(s) that will engineer that microbiome to a goal state, for example, a healthier or more performant composition. It also estimates intermediate microbiome states along the path, thus making it possible to avoid particularly undesirable/unhealthy states. We demonstrate MDPbiome performance over three real and distinct datasets, proving its flexibility, and the reliability and universality of its output ‘optimal perturbation policy’. For example, an MDP created using a vaginal microbiome time series, with a goal of recovering from bacterial vaginosis, suggested avoidance of perturbations such as lubricants or sex toys; while another MDP provided a quantitative explanation for why salmonella vaccine accelerates gut microbiome maturation in chicks. This novel analytical approach has clear applications in medicine, where it could suggest low-impact clinical interventions that will lead to achievement or maintenance of a healthy microbial population, or alternately, the sequence of interventions necessary to avoid strongly negative microbiome states.

Availability and implementation
Code (https://github.com/beatrizgj/MDPbiome) and result files (https://tomdelarosa.shinyapps.io/MDPbiome/) are available online.

Supplementary information
Supplementary data are available at Bioinformatics online.
Computational enhancement of single-cell sequences for inferring tumor evolution
Authors: Miura Sayaka , Huuki Louise A , Buturla Tiffany , Vu Tracy , Gomez Karen , Kumar Sudhir 
Published: July 2018

AbstractMotivationTumor sequencing has entered an exciting phase with the advent of single-cell techniques that are revolutionizing the assessment of single nucleotide variation (SNV) at the highest cellular resolution. However, state-of-the-art single-cell sequencing technologies produce data with many missing bases (MBs) and incorrect base designations that lead to false-positive (FP) and false-negative (FN) detection of somatic mutations. While computational methods are available to make biological inferences in the presence of these errors, the accuracy of the imputed MBs and corrected FPs and FNs remains unknown.ResultsUsing computer simulated datasets, we assessed the robustness performance of four existing methods (OncoNEM, SCG, SCITE and SiFit) and one new method (BEAM). BEAM is a Bayesian evolution-aware method that improves the quality of single-cell sequences by using the intrinsic evolutionary information in the single-cell data in a molecular phylogenetic framework. Overall, BEAM and SCITE performed the best. Most of the methods imputed MBs with high accuracy, but effective detection and correction of FPs and FNs is a challenge, especially for small datasets. Analysis of an empirical dataset shows that computational methods can improve both the quality of tumor single-cell sequences and their utility for biological inference. In conclusion, tumor cells descend from pre-existing cells, which creates evolutionary continuity in single-cell sequencing datasets. This information enables BEAM and other methods to correctly impute missing data and incorrect base assignments, but correction of FPs and FNs remains challenging when the number of SNVs sampled is small relative to the number of cells sequenced.Availability and implementationBEAM is available on the web at https://github.com/SayakaMiura/BEAM.
CNEFinder: finding conserved non-coding elements in genomes
Authors: Ayad Lorraine A K , Pissis Solon P , Polychronopoulos Dimitris 
Published: July 2018

Abstract

Motivation
Conserved non-coding elements (CNEs) represent an enigmatic class of genomic elements which, despite being extremely conserved across evolution, do not encode for proteins. Their functions are still largely unknown. Thus, there exists a need to systematically investigate their roles in genomes. Towards this direction, identifying sets of CNEs in a wide range of organisms is an important first step. Currently, there are no tools published in the literature for systematically identifying CNEs in genomes.

Results
We fill this gap by presenting CNEFinder; a tool for identifying CNEs between two given DNA sequences with user-defined criteria. The results presented here show the tool’s ability of identifying CNEs accurately and efficiently. CNEFinder is based on a k-mer technique for computing maximal exact matches. The tool thus does not require or compute whole-genome alignments or indexes, such as the suffix array or the Burrows Wheeler Transform (BWT), which makes it flexible to use on a wide scale.

Availability and implementation
Free software under the terms of the GNU GPL (https://github.com/lorrainea/CNEFinder).
Ontology-based validation and identification of regulatory phenotypes
Authors: Kulmanov Maxat , Schofield Paul N , Gkoutos Georgios V , Hoehndorf Robert 
Published: July 2018

AbstractMotivationFunction annotations of gene products, and phenotype annotations of genotypes, provide valuable information about molecular mechanisms that can be utilized by computational methods to identify functional and phenotypic relatedness, improve our understanding of disease and pathobiology, and lead to discovery of drug targets. Identifying functions and phenotypes commonly requires experiments which are time-consuming and expensive to carry out; creating the annotations additionally requires a curator to make an assertion based on reported evidence. Support to validate the mutual consistency of functional and phenotype annotations as well as a computational method to predict phenotypes from function annotations, would greatly improve the utility of function annotations.ResultsWe developed a novel ontology-based method to validate the mutual consistency of function and phenotype annotations. We apply our method to mouse and human annotations, and identify several inconsistencies that can be resolved to improve overall annotation quality. We also apply our method to the rule-based prediction of regulatory phenotypes from functions and demonstrate that we can predict these phenotypes with Fmax of up to 0.647.Availability and implementationhttps://github.com/bio-ontology-research-group/phenogocon
The macroecology of passerine nest types, in the light of macroevolution
Authors: McEntee Jay P. , Zelazny Zoe , Burleigh J. Gordon 
Published: July 2018

AbstractPasserine birds build a diversity of nests to lay and incubate eggs, and to house nestlings. Open cup, dome, and hole (or cavity) nests have distinct advantages and/or disadvantages related to predation risk and thermoregulation. We used macroecological and macroevolutionary approaches to test contrasting predictions from considering these consequences. Patterns of prevalence across latitude and elevation for the roofed nest types (holes and domes) provide no evidence that their thermoregulation benefits promote colonization of colder environments. These patterns are more consistent with the role of predation in determining where dome-nesting species in particular occur. Macroevolutionary analyses suggest that diversity patterns for nest types along major ecological gradients mostly arise from how clades with conserved nest types have diversified across gradients, rather than arising from local adaptation. Lastly, we reveal a negative relationship between body mass and latitude in hole-nesting passerines, which runs counter to Bergmann’s rule.Statement of authorshipJPM and JGB designed the study. JPM and ZZ compiled data from the literature. JPM performed statistical analyses with input from JGB. JPM and JGB wrote the manuscript, and ZZ contributed to revisions.Data accessibility statementsData were obtained from existing sources in the literature, cited in the manuscript.
Causal relationships between blood lipids and depression phenotypes: A Mendelian randomization analysis
Authors: So Hon-Cheong , Chau Carlos Kwan-long , Cheng Yu-ying , Sham Pak C. 
Published: July 2018

AbstractBackgroundThe etiology of depression remains poorly understood. Changes in blood lipid levels were reported to be associated with depression and suicide, however study findings were mixed.MethodsWe performed a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between blood lipids and depression phenotypes, based on large-scale GWAS summary statistics (N=188,577/480,359 for lipid/depression traits respectively). Five depression-related phenotypes were included, namely major depressive disorder (MDD; from PGC), depressive symptoms (DS; from SSGAC), longest duration and number of episodes of low mood, and history of deliberate self-harm (DSH)/suicide (from UK Biobank). MR was conducted with inverse-variance weighted (MR-IVW), Egger and Generalized Summary-data-based MR(GSMR) methods.ResultsThere was consistent evidence that triglyceride (TG) is causally associated with DS (MR-IVW beta for one-SD increase in TG=0.0346, 95% CI=0.0114-0.0578), supported by MR-IVW and GSMR and multiple r2clumping thresholds. We also observed relatively consistent associations of TG with DSH/suicide (MR-Egger OR= 2.514, CI: 1.579-4.003). There was moderate evidence for positive associations of TG with MDD and the number of episodes of low mood. For HDL-c, we observed moderate evidence for causal associations with DS and MDD. LDL-c and TC did not show robust causal relationships with depression phenotypes, except for weak evidence that LDL-c is inversely related to DSH/suicide. We did not detect significant associations when depression phenotypes were treated as exposures.ConclusionsThis study provides evidence to a causal relationship between TG, and to a lesser extent, altered cholesterol levels with depression phenotypes. Further studies on its mechanistic basis and the effects of lipid-lowering therapies are warranted.