bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excessive Deposition of Fibrin, Platelets and Platelet Thrombi on Vascular Subendothelium During Contraceptive Drug Treatment
Authors: Inauen W , Baumgartner H R , Haeberli A , Straub P W 
Published: July 2018

SummaryWe investigated the effect of oral contraceptives on thrombogenesis induced by subendothelium of rabbit aorta (SE), exposed to flowing non-anticoagulated blood in an annular flow chamber. Six healthy women on sequential contraceptive drugs (0.05 mg aethinylestradiol/day, 0.125 mg desogestrel/day) were compared with 6 women without hormonal contraception and 6 men. On contraceptive drug treatment, blood values were significantly increased for fibrinogen (2.6±0.2vsl.9±0.1 g/1) and fibrinopeptide A (3.9 ± 0.9 vs 0.9 ± 0.1 ng/ml), whereas antithrombin III was decreased (81 ± 4 vs 97 ± 6%). Fibrin deposition on vascular subendothelium was more than four-fold increased when measured morphologically (63.4 ± 2.5 vs 14.6 ± 6.8% coverage of SE surface with fibrin) as well as immunologically (29.3 ± 2.2 vs 4.5 ± 1.9 pg fibrin/cm2 of SE). Thrombus volumes were more than two-fold increased in women with contraceptives (9.0 ± 1.4 vs 3.7 ± 1.0 μm3/μm2).Our study shows that during contraceptive drug treatment the exposure of flowing blood to vascular subendothelium leads to excessive deposition of fibrin and platelet thrombi. Measurement of blood interactions with subendothelium might be of predictive value in hypercoagulable states such as contraceptive treatment.
Hormonal Control of Haemostasis During Hypoglycaemia in Diabetes Mellitus
Authors: Grant P J , Stickland M H , Wiles P G , Davies J A , Wales J K , Prentice C R M 
Published: July 2018

SummaryFactor VIII (FVIII) and plasminogen activator activity (PAA) rise during hypoglycaemia, and this might contribute to the vascular complications of diabetes. Similar changes in haemostasis accompany raised plasma levels of vasopressin (aVP) and adrenaline. To investigate the effects of these hormones on haemostasis during hypoglycaemia and the role of plasma insulin concentrations, eight insulin-dependent diabetic patients underwent controlled hypoglycaemia for 20 min and 13 diabetic patients were investigated during hyperinsulinaemia with blood glucose maintained at 8.0 mmol/1. During hypoglycaemia, insulin levels increased to median values of 114 mU/1, aVP rose from 0.5 to 4.4 (p <0.005) pg/ml and adrenaline from 0.4 to 4.4 nmol/l (p <0.005). FVIII coagulant activity (FVIII :C) rose from 0.75 to 1.09 iU/ml (p <0.01) and the ristocetin co-factor (FVIIIR:Co) and von Willebrand factor antigen (vWF:Ag) showed similar responses. PAA increased from 156 to 745 units (p <0.005). During hyperinsulinaemia, insulin rose following infusion from 24 to 52 and 118 mU/l, maintained for an hour at each level. Despite this, plasma aVP, FVIII :C, FVIIIR:Co, vWF:Ag and PAA remained unchanged. This study indicates that the marked changes in FVIII, vWF and PAA concentrations which accompany hypoglycaemia depend on low blood glucose and not raised plasma insulin. The response in probably mediated by increases in adrenaline and aVP, which are part of the physiological response to hypoglycaemia.
Laryngeal and Tracheobronchial Infections of the Pediatric Airway
Authors: Ida Jonathan 
Published: July 2018

AbstractInfections of the pediatric airway result in partial obstruction of the airway and often require intervention to maintain the airway. Most airway infections are treated medically, but respiratory support or invasive airway protection may be required if the patient does not respond adequately to initial interventions. We review three major types of central airway infections, focusing on illustrative diagnostic and treatment dilemmas.
Judicious Use of Antibiotics and Radiologic Imaging in Diagnosis and Management of Pediatric Upper Respiratory Tract Infections
Authors: Jaggi Preeti 
Published: July 2018

AbstractA considerable amount of effort has been put into the reduction of the overuse of antibiotics and reduction in radiographic studies in the pediatric population. Infections within the ear, nose, and throat and in cervical regions are a frequent source of antibiotic use in children. Quality improvement projects creating clear care pathways have been important to delineate which imaging may be most helpful.
Indeterminate us and them: The complexities of referentiality, identity and group construction in a public online discussion
Authors: Kleinke Sonja , Bös Birte 
Published: July 2018

Abstract
This paper reinvestigates the polarizing effects of indeterminate first- and third-person plural pronouns and determiners (i.e. the we-set and the they-set) from a Digital Discourse perspective. Combining Critical Discourse Analysis and a cognitive-linguistic approach, it tackles the double-indexical nature of the use of the we-set and the they-set by the participants of the public discussion forum UK Debate. Our analysis of a sample thread considers both the referential and the propositional level and shows how users construct and negotiate potential in- and out-group referents at different degrees of specificity and as ranging between immediate discourse participants and external referents. Our analysis shows how major cognitive domains are triggered and how the specific selections of predications as cognitive access points form oscillating clusters of salient in- and out-group attributes. In this way, the analysis also aims to reveal manifestations of more permanent cultural and mental models.
Turn design and progression
Authors: Wu Ruey-Jiuan Regina 
Published: July 2018

Abstract
The temporal character of talk is one fundamental feature of language
in situ. As interaction unfolds, participants
need to not only monitor the temporal progression of talk toward
completion, but also attend to how the current turn ties back to the
preceding turns. Whereas such dual-directional consideration is
often a latent aspect of turn construction, efforts to clear up
possible ambiguity are sometimes in order. This article introduces a
Mandarin practice, the aiyou-preface, which seems
to be used to just this end, and demonstrates an intimate
relationship between the prosodic design of
aiyou-preface and the displayed orientation to the
intended directionality of the talk. The analysis draws upon a
corpus of 35 hours of conversations collected in China.
Turn-initial voilà in closings in French
Authors: Mondada Lorenza 
Published: July 2018

Abstract
French has several ways of responding positively to a previous turn, such as oui, ouais, d’accord, tout à fait, exactement, bien sûr, voilà, etc. This chapter deals with voilà, offering a general overview of its uses in interaction before focusing on voilà in turn-initial position in closing environments. Analyses reveal that voilà is not equally used by all of the participants in social interaction, but rather by speakers whom the co-participants recognize as experts and/or responsible for the on-going activity. Stand-alone voilà achieves sequence closing in unproblematic ways and retrospectively asserts the speaker’s epistemic, organizational and moral authority over the sequence. By contrast, turn-initial voilà often occurs in a context where the co-participants disalign with the projected closing. The use of voilà addresses a possible emerging competition by further expanding the on-going action and thereby controlling possible next sequential slots. In these competitive contexts, stand-alone voilà and turn-initial voilà are used by speakers to re-affirm their authority over the sequence. Turn-initial voilà followed by a new turn constructional unit (TCU) orients to the possible progressivity of the activity, whereas turn-initial voilà with a continuation within the same TCU expands the on-going sequence and creates new opportunities for the co-participants to realign with it.
IRSOM, a reliable identifier of ncRNAs based on supervised self-organizing maps with rejection
Authors: Platon Ludovic , Zehraoui Farida , Bendahmane Abdelhafid , Tahi Fariza 
Published: July 2018

Abstract

Motivation
Non-coding RNAs (ncRNAs) play important roles in many biological processes and are involved in many diseases. Their identification is an important task, and many tools exist in the literature for this purpose. However, almost all of them are focused on the discrimination of coding and ncRNAs without giving more biological insight. In this paper, we propose a new reliable method called IRSOM, based on a supervised Self-Organizing Map (SOM) with a rejection option, that overcomes these limitations. The rejection option in IRSOM improves the accuracy of the method and also allows identifing the ambiguous transcripts. Furthermore, with the visualization of the SOM, we analyze the rejected predictions and highlight the ambiguity of the transcripts.

Results
IRSOM was tested on datasets of several species from different reigns, and shown better results compared to state-of-art. The accuracy of IRSOM is always greater than 0.95 for all the species with an average specificity of 0.98 and an average sensitivity of 0.99. Besides, IRSOM is fast (it takes around 254 s to analyze a dataset of 147 000 transcripts) and is able to handle very large datasets.

Availability and implementation
IRSOM is implemented in Python and C++. It is available on our software platform EvryRNA (http://EvryRNA.ibisc.univ-evry.fr).
Computational analysis of kinase inhibitor selectivity using structural knowledge
Authors: Lo Yu-Chen , Liu Tianyun , Morrissey Kari M , Kakiuchi-Kiyota Satoko , Johnson Adam R , Broccatelli Fabio , Zhong Yu , Joshi Amita , Altman Russ B 
Published: July 2018

Abstract

Motivation
Kinases play a significant role in diverse disease signaling pathways and understanding kinase inhibitor selectivity, the tendency of drugs to bind to off-targets, remains a top priority for kinase inhibitor design and clinical safety assessment. Traditional approaches for kinase selectivity analysis using biochemical activity and binding assays are useful but can be costly and are often limited by the kinases that are available. On the other hand, current computational kinase selectivity prediction methods are computational intensive and can rarely achieve sufficient accuracy for large-scale kinome wide inhibitor selectivity profiling.

Results
Here, we present a KinomeFEATURE database for kinase binding site similarity search by comparing protein microenvironments characterized using diverse physiochemical descriptors. Initial selectivity prediction of 15 known kinase inhibitors achieved an &gt;90% accuracy and demonstrated improved performance in comparison to commonly used kinase inhibitor selectivity prediction methods. Additional kinase ATP binding site similarity assessment (120 binding sites) identified 55 kinases with significant promiscuity and revealed unexpected inhibitor cross-activities between PKR and FGFR2 kinases. Kinome-wide selectivity profiling of 11 kinase drug candidates predicted novel as well as experimentally validated off-targets and suggested structural mechanisms of kinase cross-activities. Our study demonstrated potential utilities of our approach for large-scale kinase inhibitor selectivity profiling that could contribute to kinase drug development and safety assessment.

Availability and implementation
The KinomeFEATURE database and the associated scripts for performing kinase pocket similarity search can be downloaded from the Stanford SimTK website (https://simtk.org/projects/kdb).

Supplementary information
Supplementary data are available at Bioinformatics online.
Scalable and exhaustive screening of metabolic functions carried out by microbial consortia
Authors: Frioux Clémence , Fremy Enora , Trottier Camille , Siegel Anne 
Published: July 2018

Abstract

Motivation
The selection of species exhibiting metabolic behaviors of interest is a challenging step when switching from the investigation of a large microbiota to the study of functions effectiveness. Approaches based on a compartmentalized framework are not scalable. The output of scalable approaches based on a non-compartmentalized modeling may be so large that it has neither been explored nor handled so far.

Results
We present the Miscoto tool to facilitate the selection of a community optimizing a desired function in a microbiome by reporting several possibilities which can be then sorted according to biological criteria. Communities are exhaustively identified using logical programming and by combining the non-compartmentalized and the compartmentalized frameworks. The benchmarking of 4.9 million metabolic functions associated with the Human Microbiome Project, shows that Miscoto is suited to screen and classify metabolic producibility in terms of feasibility, functional redundancy and cooperation processes involved. As an illustration of a host-microbial system, screening the Recon 2.2 human metabolism highlights the role of different consortia within a family of 773 intestinal bacteria.

Availability and implementation
Miscoto source code, instructions for use and examples are available at: https://github.com/cfrioux/miscoto.
Protein pocket detection via convex hull surface evolution and associated Reeb graph
Authors: Zhao Rundong , Cang Zixuan , Tong Yiying , Wei Guo-Wei 
Published: July 2018

Abstract

Motivation
Protein pocket information is invaluable for drug target identification, agonist design, virtual screening and receptor-ligand binding analysis. A recent study indicates that about half holoproteins can simultaneously bind multiple interacting ligands in a large pocket containing structured sub-pockets. Although this hierarchical pocket and sub-pocket structure has a significant impact to multi-ligand synergistic interactions in the protein binding site, there is no method available for this analysis. This work introduces a computational tool based on differential geometry, algebraic topology and physics-based simulation to address this pressing issue.

Results
We propose to detect protein pockets by evolving the convex hull surface inwards until it touches the protein surface everywhere. The governing partial differential equations (PDEs) include the mean curvature flow combined with the eikonal equation commonly used in the fast marching algorithm in the Eulerian representation. The surface evolution induced Morse function and Reeb graph are utilized to characterize the hierarchical pocket and sub-pocket structure in controllable detail. The proposed method is validated on PDBbind refined sets of 4414 protein-ligand complexes. Extensive numerical tests indicate that the proposed method not only provides a unique description of pocket-sub-pocket relations, but also offers efficient estimations of pocket surface area, pocket volume and pocket depth.

Availability and implementation
Source code available at https://github.com/rdzhao/ProteinPocketDetection. Webserver available at http://weilab.math.msu.edu/PPD/.
Time and space adaptivity of the wave equation discretized in time by a second-order scheme
Authors: Gorynina Olga , Lozinski Alexei , Picasso Marco 
Published: July 2018

AbstractThe aim of this paper is to obtain a posteriori error bounds of optimal order in time and space for the linear second-order wave equation discretized by the Newmark scheme in time and the finite element method in space. An error estimate is derived in the $L^{\infty }$-in-time/energy-in-space norm. Numerical experiments are reported for several test cases and confirm equivalence of the proposed estimator and the true error.
Local BPS Invariants: Enumerative Aspects and Wall-Crossing
Authors: Choi Jinwon , van Garrel Michel , Katz Sheldon , Takahashi Nobuyoshi 
Published: July 2018

AbstractWe study the BPS invariants for local del Pezzo surfaces, which can be obtained as the signed Euler characteristic of the moduli spaces of stable one-dimensional sheaves on the surface $S$. We calculate the Poincaré polynomials of the moduli spaces for the curve classes $\beta $ having arithmetic genus at most 2. We formulate a conjecture that these Poincaré polynomials are divisible by the Poincaré polynomials of $((-K_S).\beta -1)$-dimensional projective space. This conjecture motivates the upcoming work on log BPS numbers [8].
Properties of the epigenetic clock and age acceleration
Authors: Khoury Louis El , Gorrie-Stone Tyler , Smart Melissa , Hughes Amanda , Bao Yanchun , Andrayas Alexandria , Burrage Joe , Hannon Eilis , Kumari Meena , Mill Jonathan , Schalkwyk Leonard C 
Published: July 2018

AbstractBackgroundThe methylation status of numerous CpG sites in the human genome varies with age. The Horvath epigenetic clock used a wide variety of published DNA methylation data to produce an age prediction that has been widely used to, predict age in unknown samples, and draw conclusions about speed of ageing in various tissues, environments, and diseases. Despite its utility, there are a number of assumptions in the model that require examination. We explore the characteristics of the model in whole blood and multiple brain regions from older people, who are not well represented in the original training data, and in blood from a cross-sectional population study.ResultsWe find that the model systematically underestimates age in tissues from older people. A decrease in slope of the predicted ages were observed at approximately 60 years, indicating that some loci in the model may change differently with age, and that age acceleration measures will themselves be age-dependent. This is seen most strongly in the cerebellum but is also present in other examined tissues, and is consistently observed in multiple datasets. An apparent association of Alzheimer’s disease with age acceleration disappears when age is used as a covariate. Association tests in the literature use a variety of methods for calculating age acceleration and often do not use age as a covariate. This is a potential cause of misleading findings.ConclusionsAssociations of phenotypes with age acceleration should be evaluated cautiously, and chronological age should be included as a covariate in all analyses.
Sirt7 regulates circadian phase coherence of hepatic circadian clock via a body temperature/Hsp70-Sirt7-Cry1 axis
Authors: Liu Zuojun , Qian Minxian , Tang Xiaolong , Hu Wenjing , Zhang Shuju , Meng Fanbiao , Sun Shimin , Cao Xinyue , Pang Qiuxiang , Zhao Bosheng , Liu Baohua 
Published: July 2018

AbstractThe biological clock is generated in the hypothalamic suprachiasmatic nucleus (SCN), which synchronizes peripheral oscillators to coordinate physiological and behavioral activities throughout the body. Disturbance of circadian phase coherence between the central and peripheral could disrupt rhythms and thus cause diseases and aging. Here, we identified hepatic Sirt7 as an early element responsive to light, which ensures the phase coherence in mouse liver. Loss of Sirt7 leads to advanced liver circadian phase; restricted feeding in daytime entrains hepatic clock more rapidly in Sirt7-/- mice compared to wild-types. Molecularly, a light-driven body temperature (BT) oscillation induces rhythmic expression of Hsp70, which binds to and promotes the ubiquitination and proteasomal degradation of Sirt7. Sirt7 rhythmically deacetylates Cry1 on K565/579 and promotes Fbxl3-mediated degradation, thus coupling hepatic clock to the central pacemaker. Together, our data identify a novel BT/Hsp70-Sirt7-Cry1 axis, which transmits biological timing cues from the central to the peripheral and ensures circadian phase coherence in livers.
Relationship between ACTN3 and ACE polymorphisms and FIFA World averaged rating
Authors: Ilinsky Valery , Zakharova Natalia 
Published: July 2018

AbstractPolymorphisms in ACTN3 and ACE genes were previously reported to be associated with power and endurance performance. We estimated the relationship between their population frequencies in several countries and FIFA World averaged rating (FWAR). The entropy was used as the measure of uncertainty. The FWAR distribution entropy (in nats) was 1.38. The FWAR conditional distribution entropy given ACTN3 RR and ACE II frequencies was 1.27 and 1.24, respectively. Almost same FWAR conditional entropy (1.25) was after adjustment on GDP. Population frequencies of polymorphisms in power and endurance performance genes might be a cause of high or low FWAR (low frequency -- less football players) or an effect of ethnic origin and geographical location of countries, related to GDP.
Characterization of fluorescent proteins, promoters, and selectable markers for applications in the Lyme disease spirocheteBorrelia burgdorferi
Authors: Takacs Constantin N. , Kloos Zachary A. , Scott Molly , Rosa Patricia A. , Jacobs-Wagner Christine 
Published: July 2018

ABSTRACTLyme disease is the most widely reported vector-borne disease in the United States. Its incidence is rapidly increasing and disease symptoms can be debilitating. The need to understand the biology of the disease agent, the spirocheteBorrelia burgdorferi, is thus evermore pressing. Despite important advances inB. burgdorferigenetics, the array of molecular tools available for use in this organism remains limited, especially for cell biological studies. Here, we adapt a palette of bright and mostly monomeric fluorescent proteins for versatile use and multi-color imaging inB. burgdorferi. We also characterize two novel antibiotic selection markers and establish the feasibility of their use in conjunction with extant markers. Lastly, we describe a set of constitutively active promoters of low and intermediate strengths that allow fine-tuning of gene expression levels. These molecular tools complement and expand current experimental capabilities inB. burgdorferi, which will facilitate future investigation of this important human pathogen. To showcase the usefulness of these reagents, we used them to investigate the subcellular localization of BB0323, aB. burgdorferilipoprotein essential for survival in the host and vector environments. We show that BB0323 accumulates at the cell poles and future division sites ofB. burgdorfericells, highlighting the complex subcellular organization of this spirochete.IMPORTANCEGenetic manipulation of the Lyme disease spirocheteB. burgdorferiremains cumbersome, despite significant progress in the field. The scarcity of molecular reagents available for use in this pathogen has slowed research efforts to study its unusual biology. Of interest,B. burgdorferidisplays complex cellular organization features that have yet to be understood. These include an unusual morphology and a highly fragmented genome, both of which are likely to play important roles in the bacterium’s transmission, infectivity, and persistence. Here, we complement and expand the array of molecular tools available for use inB. burgdorferiby generating and characterizing multiple fluorescent proteins, antibiotic selection markers, and constitutively active promoters of different strengths. These tools will facilitate investigations in this important human pathogen, as exemplified by the polar and midcell localization of the cell envelope regulator BB0323, which we uncovered using these reagents.