bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of the Interaction of Blood Platelets with the Coagulation System at the Site of Plug Formation In Vivo in Man - Effect of Low-Dose Aspirin
Authors: Kyrle P A , Westwick J , Scully M F , Kakkar V V , Lewis G P 
Published: July 2018

SummaryIn 7 healthy volunteers, formation of thrombin (represented by fibrinopeptide A (FPA) generation, α-granule release (represented by β-thromboglobulin [βTG] release) and the generation of thromboxane B2 (TxB2) were measured in vivo in blood emerging from a template bleeding time incision. At the site of plug formation, considerable platelet activation and thrombin generation were seen within the first minute, as indicated by a 110-fold, 50-fold and 30-fold increase of FPA, TxB2 and PTG over the corresponding plasma values. After a further increase of the markers in the subsequent 3 minutes, they reached a plateau during the fourth and fifth minute. A low-dose aspirin regimen (0.42 mg.kg-1.day-1 for 7 days) caused >90% inhibition of TxB2formation in both bleeding time blood and clotted blood. At the site of plug formation, a-granule release was substantially reduced within the first three minutes and thrombin generation was similarly inhibited. We conclude that (a) marked platelet activation and considerable thrombin generation occur in the early stages.of haemostasis, (b) α-granule release in vivo is partially dependent upon cyclo-oxygenase-controlled mechanisms and (c) thrombin generation at the site of plug formation is promoted by the activation of platelets.
Deficient t-PA Release and Elevated PA Inhibitor Levels in Patients with Spontaneous or Recurrent Deep Venous Thrombosis
Authors: Juhan-Vague I , Valadier J , Alessi M C , Aillaud M F , Ansaldi J , Philip-Joet C , Holvoet P , Serradimigni A , Collen D 
Published: July 2018

SummaryThe fibrinolytic system was investigated in 120 patients with spontaneous or recurrent deep vein thrombosis (DVT) without any known organic disease able to explain by itself the occurrence of a thrombosis and without any known defect of antithrombin III, Heparin Cofactor II, Protein C, or Protein S. The assays included: Euglobulin fibrinolytic activity (EFA), tissue-type plasminogen activator related antigen (t-PA-Ag) and plasminogen activator inhibitor activity (PA inhibitor), which were measured before and after 10 min of venous occlusion (V. O.). On the basis of the results, the patients could be classified in 3 groups:good responders with an at least two-fold increase of EFA after venous occlusion (n = 76), poor responders with a lesser increase of EFA due to deficient release of t-PA (n = 12), and poor responders with a normal t-PA release but an increased level of PA-Inhibitor (n = 32).The poor responders due to deficient t-PA release (10% of total) had a higher incidence of recurrence of deep vein thrombosis, than the other groups (p <0.01). An overall correlation was found between the level of PA-Inhibitor activity and the triglyceride level (r = 0.40, p <0.01), suggesting that these elevations may be due to a common cause, at least in some of the patients.It is concluded that a poor fibrinolytic response to venous occlusion occurs in 35 percent of DVT patients. Poor responders however fall into two categories, one fourth with deficient t-PA release who have a high risk for recurrent venous thrombosis, and three fourth with increased PA-Inhibitor levels which may be associated with underlying diseases also causing hypertriglyceridemia. Further elucidation of the correlation between recurrent venous thrombosis and deficient fibrinolysis is expected to result in more specific and adequate treatment and prevention of DVT.
Catalysis of Thrombin Inhibition Provides an Index for Estimating the Antithrombotic Potential of Glycosaminoglycans in Rabbits
Authors: Fernandez F A , Buchanan M R , Hirsh J , Fenton II J W , Ofosu F A 
Published: July 2018

SummaryPrevious studies have demonstrated that standard anticoagulant tests are poor indices of the antithrombotic potential of glycosaminoglycans which are weak catalysts of the thrombinantithrombin III reaction. In this study we investigated whether the catalysis of thrombin inhibition by plasma could serve as a reliable index for assessing the antithrombotic effectiveness of glycosaminoglycans. Equal volumes of 125I-thrombin and control or test plasma were incubated for up to 10 min at 37° C. Inactivation of thrombin was then determined after 7.9% SDS-polyacrylamide gel electrophoresis and subsequent autoradiography. Increasing concentrations of heparin (>0.066 μg/mL or 0.01 USP units/mL) and dermatan sulfate (>0.1 μg/mL) could be readily demonstrated in undiluted plasma by enhanced formation of complexes of thrombin with antithrombin III and heparin cofactor II respectively. However, the detection of any catalytic effect of the two glycosaminoglycans decreased significantly with increasing plasma dilutions. When ex vivo plasmas obtained from rabbits that had been injected with the minimum dose of any one of seven glycosaminoglycans required to achieve their optimal antithrombotic effect were assessed for their ability to catalyse thrombin inhibition, there was approximately a 2-fold increase in the amount of thrombin inactivated 30 s after the thrombin had been added to the plasma. The enhanced inhibition of thrombin was achieved by catalysis of antithrombin III and/or heparin cofactor II activities. These results suggest that measurement of the catalysis of thrombin inactivation in undiluted plasma is a sensitive and reliable index for estimating the antithrombotic potential of glycosaminoglycans in rabbits.
Increased Plasma Thrombomodulin in Cancer Patients
Authors: Lindahl Anne Karin , Boffa Marie-Claire , Abildgaard Ulrich 
Published: July 2018

SummaryPlasma samples from 35 patients with colorectal cancer, 16 patients with pancreatic cancer and 46 patients with various cancers in the terminal stage were analysed for soluble plasma thrombomodulin with an ELISA method. At time of diagnosis and before primary treatment, the patients with colorectal cancer had normal plasma TM levels. In the patients who developed disseminated disease, the mean plasma TM level increased significantly. In the patients with pancreatic cancer, the mean plasma TM level was increased already at time of primary treatment. The TM level increased further with progress of the pancreatic cancer. In the patients with various cancer types in the terminal stage, the mean TM was also significantly increased compared to healthy controls. Great individual variation in the plasma TM level was observed, as well as great variation of mean TM level between the various cancer types. There was no significant correlation between the TM levels and the levels of tissue factor pathway inhibitor, another endothelial coagulation inhibitor, which increased with progress of malignant disease. This may indicate different underlying mechanisms for the increased plasma levels.
ADP Receptor Induced Activation of Guanine Nucleotide Binding Proteins in Rat Platelet Membranes– An Effect Selectively Blocked by the Thienopyridine Clopidogrel
Authors: Gachet C , Savi P , Ohlmann P , Maffrand J-P , Jakobs K H , Cazenave J-P 
Published: July 2018

SummaryThe thienopyridine clopidogrel, a potent analog of ticlopidine, is a powerful inhibitor of ADP induced platelet aggregation and ADP induced inhibition of cyclic AMP accumulation in intact platelets but not of ADP induced shape change. We have recently demonstrated that ADP stimulates the binding of GTPγS to GTP binding proteins (G proteins) in human platelet membranes. We now studied the effects of clopidogrel, a specific inhibitor of ADP induced platelet aggregation on the stimulation of GTPγS binding to rat platelet membranes by ADP. Using the non hydrolyzable stable analog of ADP, 2MeSADP, we demonstrate that 2MeSADP stimulates the binding of [35S]GTPγS to rat platelet membranes in a concentration dependent manner, that this effect is inhibited by the specific ADP receptor antagonist Sp-ATPαS and that clopidogrel completely and selectively blocks the stimulation by 2MeSADP of [35S]GTPγS binding to platelet membranes of treated rats. We conclude that: i) rat platelet membranes possess an ADP receptor coupled to unidentified G protein(s) and ii) the thienopyridine clopidogrel impairs the interaction of the ADP receptor with its G protein by an irreversible modification the ADP receptor itself or its putative G protein.
The position of the verb in Gothic
Authors: Falluomini Carla 
Published: July 2018

AbstractThe aim of this paper is to offer a descriptive analysis of the position of the verb in the recently discovered Gothic fragment of Bologna (Gothica Bononiensia) – a text that seems to be independent of Greek or Latin models – in order to highlight analogies to and differences from other Gothic texts. The analysis shows that the position of the verb is relatively free, both in main and in subordinate clauses, with some exceptions (negatives,wh-questions and imperatives). The text exhibits the coexistence of competing grammatical constructions, used to satisfy pragmatic and stylistic requirements.
Gothic graffiti from the Mangup basilica
Authors: Vinogradov Andrey , Korobov Maksim 
Published: July 2018

Abstract
For more than a millennium there have been reports testifying to the presence of Goths in the Crimea. However, until a few years ago, the
only evidence of a Gothic or Germanic idiom spoken in the peninsula stems from the list of words recorded between 1560 and 1562 by Ogier de
Busbecq. Significant new evidence, however, has become available through the recent discovery of five Gothic graffiti scratched on two
reused fragments of a cornice belonging to the early Byzantine basilica at Mangup-Qale in the Crimea. The graffiti, datable to between about
850 and the end of the 10th century, exhibit words in Gothic known from Wulfila’s Bible translation, the script used being an archaic
variant of Wulfila’s alphabet and the only specimen of this alphabet attested outside Pannonia and Italy. There would seem to be evidence
for assuming that, among educated Crimean Goths, Gothic served as a spoken vernacular in a triglossic situation along with a purely literary
type of Gothic and with Greek in the second half of the 9th century.
The Spanish quotative según across written genres
Authors: Llopis Cardona Ana 
Published: July 2018

Abstract
This research aims to provide an insight into characterization of quotative markers from a specific and prototypical Spanish one, según. The analysis is corpus-based, specifically the data comes from four different genres (academic articles, essays, news and novels). Our study examines the linguistic features, the source of information, the combination with reporting verbs, and the frequency in relation to genres. Thus, it underlines that, in contrast to the counterpart in other languages, the evidential function of según is fulfilled by means of a prepositional phrase or a clause bringing a reporting verb. Also, it demonstrates the modification of the prototypical specific source (3d person) causes a reduction of reliability as a pragmatic extension, and it shows the evidential function is the most frequent across written genres and has increased significantly in news.
Positioning through address practice in Finland-Swedish and Sweden-Swedish service encounters
Authors: Norrby Catrin , Wide Camilla , Nilsson Jenny , Lindström Jan K. 
Published: July 2018

Abstract
This chapter investigates social positioning through the use (or non-use) of address pronouns in Finland-Swedish and Sweden-Swedish service encounters recorded at theatre and event booking venues in Finland and Sweden. The results demonstrate some compelling variation in address practices which can be attributed to participant roles (customer or staff), national variety (Finland-Swedish or Sweden-Swedish), age (younger or older speaker and addressee) and situational circumstances, such as type of venue and type of transaction, as well as micro-situational aspects which occur during the course of the interaction (complications, problems or topics treated as sensitive). The study highlights that different forms of address cannot be associated a priori with a certain level of formality, but should be interpreted in their micro and macro contexts in order to understand existing cultural norms for appropriate address.
Closeness at a distance
Authors: Debray Carolin , Reissner-Roubicek Sophie 
Published: July 2018

Abstract
Social relationships are argued to have a special importance in Brazilian workplaces, as in Brazil generally (Amado and Brasil 1991; Fonseca and Castor 2005; Tanure and Duarte 2005), but scarce attention has been paid to the way such relationships are indexed through language. This research explores the way employees position themselves and others in emails to shape and influence relationships, highlighting how features that are specific to the medium index workplace identities. The analysis of 77 emails from a range of workplaces focuses on phatic aspects occurring frequently in our sample, greetings and closings. Employees used these strategically to emphasise closeness or distance, and with different degrees of formality, fulfilling diverse positioning functions including contesting power, enhancing relationships, or emphasising others’ independence. In addition, the relatively high frequency of greetings and closings compared to findings from other settings appears to confirm the importance claimed for relating at work in Brazil.
Direct speech, subjectivity and speaker positioning in London English and Paris French
Authors: Secova Maria 
Published: July 2018

Abstract
This paper examines functional similarities and differences in the use of pragmatic features – in particular quotatives and general extenders – on the right and left periphery of direct quotations. This comparative study, based on the analysis of a contemporary corpus of London English and Paris French (MLE – MPF),1 finds that the form and frequency of these particles tend to vary not only with respect to social factors such as speakers’ age and gender, but also with respect to the different pragmatic functions they come to perform in different interactional settings. The contemporary data is analysed both qualitatively and quantitatively to show how different variants position the speaker in relation to: (i) the content of the quote, (ii) the interlocutors, (iii) the presumed author of the quote. The paper aims to contribute to a better understanding of pragmatic universals and variability in the use of direct speech.
Constellation of indexicalities and social meaning
Authors: Ghezzi Chiara 
Published: July 2018

Abstract
This chapter analyses the evolution of Italian cioè lit. ‘that is’ in recent diachrony. Cioè developed a social indexicality as in the 1980s it was associated with a young speech style. Through a corpus-based analysis of listeners’ phone-ins to a radio station, this study analyses the functions of cioè in the speech styles of different age-cohorts and its diachronic evolution over the last thirty years. The evolution of cioè shows that speakers employ it creatively, through a progressive bleaching of its original semantic and pragmatic values. The expansion of its functions and contexts of occurrence is so extensive that the expression became stigmatized as a ‘verbal tic’ characteristic of the language spoken by an age-cohort of speakers. These same social values are at the origin of the progressive decline of cioè in new generations of young speakers and in the community as a whole.
Representations of self and other in narratives of return migration
Authors: Nikolaou Alexander , Sclafani Jennifer 
Published: July 2018

Abstract
This paper examines self and other representations in interviews conducted with second-generation Greek return migrants, (in their majority Greek Americans) who relocated to their parents’ homeland as adults within a decade prior to the interviews. Through the analysis of stories of linguistic and cultural assimilation, conflict and transition, authenticity and hybridity, we explore how return migrants construct and negotiate identity positions vis-à-vis other members of their immigrant community, native Greeks, and the interviewer through the employment of indexical devices during the interview. Return migrants constitute an understudied group, especially from a sociolinguistic perspective, and we argue that understanding the complex positioning of identities among this group may provide unique insights into the broader ideologies that mediate hybrid and hyphenated identities in general.
DREAM-Yara: an exact read mapper for very large databases with short update time
Authors: Dadi Temesgen Hailemariam , Siragusa Enrico , Piro Vitor C , Andrusch Andreas , Seiler Enrico , Renard Bernhard Y , Reinert Knut 
Published: July 2018

Abstract

Motivation
Mapping-based approaches have become limited in their application to very large sets of references since computing an FM-index for very large databases (e.g. &gt;10 GB) has become a bottleneck. This affects many analyses that need such index as an essential step for approximate matching of the NGS reads to reference databases. For instance, in typical metagenomics analysis, the size of the reference sequences has become prohibitive to compute a single full-text index on standard machines. Even on large memory machines, computing such index takes about 1 day of computing time. As a result, updates of indices are rarely performed. Hence, it is desirable to create an alternative way of indexing while preserving fast search times.

Results
To solve the index construction and update problem we propose the DREAM (Dynamic seaRchablE pArallel coMpressed index) framework and provide an implementation. The main contributions are the introduction of an approximate search distributor via a novel use of Bloom filters. We combine several Bloom filters to form an interleaved Bloom filter and use this new data structure to quickly exclude reads for parts of the databases where they cannot match. This allows us to keep the databases in several indices which can be easily rebuilt if parts are updated while maintaining a fast search time. The second main contribution is an implementation of DREAM-Yara a distributed version of a fully sensitive read mapper under the DREAM framework.

Availability and implementation
https://gitlab.com/pirovc/dream_yara/
SPhyR: tumor phylogeny estimation from single-cell sequencing data under loss and error
Authors: El-Kebir Mohammed 
Published: July 2018

Abstract

Motivation
Cancer is characterized by intra-tumor heterogeneity, the presence of distinct cell populations with distinct complements of somatic mutations, which include single-nucleotide variants (SNVs) and copy-number aberrations (CNAs). Single-cell sequencing technology enables one to study these cell populations at single-cell resolution. Phylogeny estimation algorithms that employ appropriate evolutionary models are key to understanding the evolutionary mechanisms behind intra-tumor heterogeneity.

Results
We introduce Single-cell Phylogeny Reconstruction (SPhyR), a method for tumor phylogeny estimation from single-cell sequencing data. In light of frequent loss of SNVs due to CNAs in cancer, SPhyR employs the k-Dollo evolutionary model, where a mutation can only be gained once but lost k times. Underlying SPhyR is a novel combinatorial characterization of solutions as constrained integer matrix completions, based on a connection to the cladistic multi-state perfect phylogeny problem. SPhyR outperforms existing methods on simulated data and on a metastatic colorectal cancer.

Availability and implementation
SPhyR is available on https://github.com/elkebir-group/SPhyR.

Supplementary information
Supplementary data are available at Bioinformatics online.
Functional analysis of synovial fluid from osteoarthritic knee and carpometacarpal joints unravels different molecular profiles
Authors: Barreto Goncalo , Soliymani Rabah , Baumann Marc , Waris Eero , Eklund Kari K , Zenobi-Wong Marcy , Lalowski Maciej 
Published: July 2018

Abstract

Objective
In this work, we aimed to elucidate the molecular mechanisms driving primary OA. By studying the dynamics of protein expression in two different types of OA joints we searched for similarities and disparities to identify key molecular mechanisms driving OA.

Methods
For this purpose, human SF samples were obtained from CMC-I OA and knee joint of OA patients. SF samples were analysed by label-free quantitative liquid chromatography mass spectrometry. Disease-relevant proteins identified in proteomics studies, such as clusterin, paraoxonase/arylesterase 1 (PON1) and transthyretin were validated by enzyme-linked immunosorbent assays, and on the mRNA level by droplet digital PCR. Functional studies were performed in vitro using primary chondrocytes.

Results
Differential proteomic changes were observed in the concentration of 40 proteins including clusterin, PON1 and transthyretin. Immunoassay analyses of clusterin, PON1, transthyretin and other inflammatory cytokines confirmed significant differences in protein concentration in SF of CMC-I and knee OA patients, with primarily lower protein expression levels in CMC-I. Functional studies on chondrocytes unequivocally demonstrated that stimulation with SF obtained from knee OA, in contrast to CMC-I OA joint, caused a significant upregulation in pro-inflammatory response, cell death and hypertrophy.

Conclusion
This study demonstrates that differential expression of molecular players in SF from different OA joints evokes diverse effects on primary chondrocytes. The pathomolecular mechanisms of OA may significantly differ in various joints, a finding that brings a new dimension into the pathogenesis of primary OA.
Mycobacterium tuberculosis type III‐A CRISPR/Cas system crRNA and its maturation have atypical features
Authors: Wei Wenjing , Zhang Shuai , Fleming Joy , Chen Ying , Li Zihui , Fan Shanghua , Liu Yi , Wang Wei , Wang Ting , Liu Ying , Ren Baiguang , Wang Ming , Jiao Jianjian , Chen Yuanyuan , Zhou Ying , Zhou Yafeng , Gu Shoujin , Zhang Xiaoli , Wan Li , Chen Tao , Zhou Lin , Chen Yong , Zhang Xian-En , Li Chuanyou , Zhang Hongtai , Bi Lijun 
Published: July 2018

ABSTRACTClustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated protein (Cas) systems are prokaryotic adaptive immune systems against invading nucleic acids. CRISPR locus variability has been exploited in evolutionary and epidemiological studies of Mycobacterium tuberculosis, the causative agent of tuberculosis, for over 20 yr, yet the biological function of this type III‐A system is largely unexplored. Here, using cell biology and biochemical, mutagenic, and RNA‐seq approaches, we show it is active in invader defense and has features atypical of type III‐A systems: mature CRISPR RNA (crRNA) in its crRNA‐CRISPR/Cas protein complex are of uniform length (∼71 nt) and appear not to be subject to 3′‐end processing after Cas6 cleavage of repeat RNA 8 nt from its 3′ end. crRNAs generated resemble mature crRNA in type I systems, having both 5′ (8 nt) and 3′ (28 nt) repeat tags. Cas6 cleavage of repeat RNA is ion dependent, and accurate cleavage depends on the presence of a 3′ hairpin in the repeat RNA and the sequence of its stem base nucleotides. This study unveils further diversity among CRISPR/Cas systems and provides insight into the crRNA recognition mechanism in M. tuberculosis, providing a foundation for investigating the potential of a type III‐A–based genome editing system.—Wei, W., Zhang, S., Fleming, J., Chen, Y., Li, Z., Fan, S., Liu, Y., Wang, W., Wang, T., Liu, Y., Ren, B., Wang, M., Jiao, J., Chen, Y., Zhou, Y., Zhou, Y., Gu, S., Zhang, X., Wan, L., Chen, T., Zhou, L., Chen, Y., Zhang, X.‐E., Li, C., Zhang, H., Bi, L. Mycobacterium tuberculosis type III‐A CRISPR/Cas system crRNA and its maturation have atypical features. FASEB J. 33, 1496–1509 (2019). www.fasebj.org