bluuebunny/crossref_metadata_2025 huggingface dataset:
CD21−/low B cells: A Snapshot of a Unique B Cell Subset in Health and Disease
Authors: Thorarinsdottir K. , Camponeschi A. , Gjertsson I. , Mårtensson I.‐L.
Published: June 2015

B cells represent one of the cellular components of the immune system that protects the individual from invading pathogens. In response to the invader, these cells differentiate into plasma cells and produce large amounts of antibodies that bind to and eliminate the pathogen. A hallmark of autoimmune diseases is the production of autoantibodies i.e. antibodies that recognize self. Those that are considered pathogenic can damage tissues and organs, either by direct binding or when deposited as immune complexes. For decades, B cells have been considered to play a major role in autoimmune diseases by antibody production. However, as pathogenic autoantibodies appear to derive mainly from T cell dependent responses, T cells have been the focus for many years. The successful treatment of patients with autoimmune diseases with either B cell depletion therapy (rituximab) or inhibition of B cell survival (belimumab), suggested that not only the autoantibodies but also other B cell features are important. This has caused a surge of interest in B cells and their biology resulting in the identification of various subsets e.g. regulatory B cells, several memory B cell subsets etc. Also, in other conditions such as chronic viral infections and primary immunodeficiency, several B cell subsets with unique characteristics have been identified. In this review, we will discuss one of these subsets, a subset that is expanded in conditions characterized by chronic immune stimulation. This B cell subset lacks, or expresses low, surface levels of the complement receptor 2 (CD21) and has therefore been termed CD21−/low B cells.
Effect of long‐term prophylaxis in the development of cytomegalovirus‐specific T‐cell immunity in D+/R− solid organ transplant recipients
Authors: San‐Juan R. , Navarro D. , García‐Reyne A. , Montejo M. , Muñoz P. , Carratala J. , Len O. , Fortun J. , Muñoz‐Cobo B. , Gimenez E. , Eworo A. , Sabe N. , Meije Y. , Martín‐Davila P. , Andres A. , Delgado J. , Jimenez C. , Amat P. , Fernández‐Ruiz M. , López‐Medrano F. , Lumbreras C. , Aguado J.M. ,   REIPI Network
Published: July 2015

Background

This study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)‐specific cell‐mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long‐term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease.

Methods

A prospective multicenter study was conducted in Spain from September 2009 to September 2012. Whole blood specimens were prospectively collected at 30, 90, 120, 200, and 365 days after SOT, and CMI was determined by enumeration of CMV pp65 and IE‐1‐specific CD69+/interferon‐γ‐producing CD8+ and CD4+ T cells by flow cytometry for intracellular cytokine staining. As part of a simultaneous clinical trial, patients received either early prophylaxis (in the first 3 days after transplantation) in the first period of the study or delayed prophylaxis (initiated at day 14) during the second period of the study. The impact of the dynamics of acquisition of CMV‐specific CMI on the incidence of CMV disease was evaluated by Kaplan–Meier survival analysis.

Results

A total of 95 SOT recipients were recruited. CMV infection and disease occurred in 38 (40%) and 26 (27.4%) patients, respectively. The proportion of patients achieving any detectable CMV‐specific CMI response at each of the different monitoring points was higher in liver transplant recipients, as compared to kidney or heart transplant recipients. The presence of any detectable response at day 120 or 200 was protective against the development of CMV disease (positive predictive values 92% and 93%, respectively).

Conclusions

The rate of acquisition of CMV‐specific CMI in SOT recipients undergoing antiviral prophylaxis differed significantly between different SOT populations. Patients developing any detectable CMI response were protected against the occurrence of CMV disease.
Allele frequencies of human platelet antigens in Banjar, Bugis, Champa, Jawa and Kelantan Malays in Peninsular Malaysia
Authors: Wan Syafawati W. U. , Norhalifah H. K. , Zefarina Z. , Zafarina Z. , Panneerchelvam S. , Norazmi M. N. , Chambers G. K. , Edinur H. A.
Published: July 2015

Objectives

The major aims of this study are to characterise and compile allelic data of human platelet antigen (HPA)‐1 to ‐6 and ‐15 systems in five Malay sub‐ethnic groups in Peninsular Malaysia.

Background

HPAs are polymorphic glycoproteins expressed on the surface of platelet membranes and are genetically differentiated across ethnogeographically unrelated populations.

Methods

Blood samples were obtained with informed consent from 192 volunteers: Banjar (n = 30), Bugis (n = 37), Champa (n = 51), Jawa (n = 39) and Kelantan (n = 35). Genotyping was done using polymerase chain reaction‐sequence specific primer method.

Results

In general, frequencies of HPAs in the Malay sub‐ethnic groups are more similar to those in Asian populations compared with other more distinct populations such as Indians, Australian Aborigines and Europeans.

Conclusions

This study provides the first HPA datasets for the selected Malay sub‐ethnic groups. Subsequent analyses including previously reported HPA data of Malays, Chinese and Indians revealed details of the genetic relationships and ancestry of various sub‐populations in Peninsular Malaysia. Furthermore, the comprehensive HPA allele frequency information from Peninsular Malaysia provided in this report has potential applications for future study of diseases, estimating risks associated with HPA alloimmunization and for developing an efficient HPA‐typed donor recruitment strategy.
A conserved role for CUP‐SHAPED COTYLEDON genes during ovule development
Authors: Gonçalves Beatriz , Hasson Alice , Belcram Katia , Cortizo Millán , Morin Halima , Nikovics Krisztina , Vialette‐Guiraud Aurélie , Takeda Seiji , Aida Mitsuhiro , Laufs Patrick , Arnaud Nicolas
Published: June 2015

The evolution of plant reproductive strategies has led to a remarkable diversity of structures, especially within the flower, a structure characteristic of the angiosperms. In flowering plants, sexual reproduction depends notably on the development of the gynoecium that produces and protects the ovules. In Arabidopsis thaliana, ovule initiation is promoted by the concerted action of auxin with CUC1 (CUP‐SHAPED COTYLEDON1) and CUC2, two genes that encode transcription factors of the NAC family (NAM/ATAF1,2/CUC). Here we highlight an additional role for CUC2 and CUC3 in Arabidopsis thaliana ovule separation. While CUC1 and CUC2 are broadly expressed in the medial tissue of the gynoecium, CUC2 and CUC3 are expressed in the placental tissue between developing ovules. Consistent with the partial overlap between CUC1, CUC2 and CUC3 expression patterns, we show that CUC proteins can physically interact, both in yeast cells and in planta. We found that the cuc2;cuc3 double mutant specifically harbours defects in ovule separation, producing fused seeds that share the seed coat, and suggesting that CUC2 and CUC3 promote ovule separation in a partially redundant manner. Functional analyses show that CUC transcription factors are also involved in ovule development in Cardamine hirsuta. Additionally we show a conserved expression pattern of CUC orthologues between ovule primordia in other phylogenetically distant species with different gynoecium architectures. Taken together these results suggest an ancient role for CUC transcription factors in ovule separation, and shed light on the conservation of mechanisms involved in the development of innovative structures.
JMJ24 binds to RDR2 and is required for the basal level transcription of silenced loci in Arabidopsis
Authors: Deng Shulin , Xu Jun , Liu Jun , Kim Sang‐Hee , Shi Suhua , Chua Nam‐Hai
Published: June 2015

Transposable elements (TEs) and repetitive sequences are ubiquitously present in eukaryotic genomes which are in general epigenetically silenced by DNA methylation and/or histone 3 lysine 9 methylation (H3K9me). RNA‐directed DNA methylation (RdDM) is the major pathway that initiates de novo DNA methylation in Arabidopsis and sets up a self‐reinforcing silencing loop between DNA methylation and H3K9me. However, a key issue is the requirement of a basal level transcript from the target loci to initiate the RNA‐based silencing. How the heterochromatic silenced loci are transcribed remains largely unknown. Here, we show that JMJ24, a JmjC domain‐containing protein counteracts H3K9me to promote basal level transcription of endogenous silenced loci in Arabidopsis. JMJ24 functionally resembles the fission yeast JmjC protein Epe1. The transcript promoted by JMJ24 is, at least in part, processed to small RNA to initiate the RdDM. Genome‐wide transcriptome profiling indicates that transcript levels of TEs are more likely regulated by JMJ24, compared with protein‐coding genes. Our data suggest that JMJ24 plays a conserved role in promoting basal level transcription of endogenous silenced loci to reinforce the silencing. We also provide evidence of a physical association between JMJ24 and RNA‐dependent RNA polymerase 2 (RDR2), which represents an evolved property of the RNA silencing pathway.
Exploring diterpene metabolism in non‐model species: transcriptome‐enabled discovery and functional characterization of labda‐7,13E‐dienyl diphosphate synthase from Grindelia robusta
Authors: Zerbe Philipp , Rodriguez Selina M. , Mafu Sibongile , Chiang Angela , Sandhu Harpreet K. , O'Neil‐Johnson Mark , Starks Courtney M. , Bohlmann Jörg
Published: June 2015

Grindelia robusta or gumweed, is a medicinal herb of the sunflower family that forms a diverse suite of diterpenoid natural products. Its major constituents, grindelic acid and related grindelane diterpenoids accumulate in a resinous exudate covering the plants’ surfaces, most prominently the unopened composite flower. Recent studies demonstrated potential pharmaceutical applications for grindelic acid and its synthetic derivatives. Mining of the previously published transcriptome of G. robusta flower tissue identified two additional diterpene synthases (diTPSs). We report the in vitro and in vivo functional characterization of an ent‐kaurene synthase of general metabolism (GrTPS4) and a class II diTPS (GrTPS2) of specialized metabolism that converts geranylgeranyl diphosphate (GGPP) into labda‐7,13E‐dienyl diphosphate as verified by nuclear magnetic resonance (NMR) analysis. Tissue‐specific transcript abundance of GrTPS2 in leaves and flowers accompanied by the presence of an endocyclic 7,13 double bond in labda‐7,13E‐dienyl diphosphate suggest that GrTPS2 catalyzes the first committed reaction in the biosynthesis of grindelic acid and related grindelane metabolites. With the formation of labda‐7,13E‐dienyl diphosphate, GrTPS2 adds an additional function to the portfolio of monofunctional class II diTPSs, which catalytically most closely resembles the bifunctional labda‐7,13E‐dien‐15‐ol synthase of the lycopod Selaginella moellendorffii. Together with a recently identified functional diTPS pair of G. robusta producing manoyl oxide, GrTPS2 lays the biosynthetic foundation of the diverse array of labdane‐related diterpenoids in the genus Grindelia. Knowledge of these natural diterpenoid metabolic pathways paves the way for developing biotechnology approaches toward producing grindelic acid and related bioproducts.
Long‐term stability, functional competence, and safety of microencapsulated specific pathogen‐free neonatal porcine Sertoli cells: a potential product for cell transplant therapy
Authors: Luca Giovanni , Mancuso Francesca , Calvitti Mario , Arato Iva , Falabella Giulia , Bufalari Antonello , De Monte Valentina , Tresoldi Enrico , Nastruzzi Claudio , Basta Giuseppe , Fallarino Francesca , Lilli Cinzia , Bellucci Catia , Baroni Tiziano , Aglietti Maria Chiara , Giovagnoli Stefano , Cameron Don F. , Bodo Maria , Calafiore Riccardo
Published: July 2015

Background

Porcine Sertoli cells (pSCs) have been employed for cell therapy in pre‐clinical studies for several chronic/immune diseases as they deliver molecules associated with trophic and anti‐inflammatory effects. To be employed for human xenografts, pSCs products need to comply with safety and stability. To fulfill such requirements, we employed a microencapsulation technology to increase pre‐transplant storage stability of specific pathogen‐free pSCs (SPF‐pSCs) and evaluated the in vivo long‐term viability and safety of grafts.

Methods

Specific pathogen free neonatal pigs underwent testis excision under sterility. pSCs were isolated, characterized by immunofluorescence (IF) and cytofluorimetric analysis (CA) and examined in terms of viability and function [namely, production of anti‐müllerian hormone (AMH), inhibin B, and transforming growth factor beta‐1 (TFGβ‐1)]. After microencapsulation in barium alginate microcapsules (Ba‐MC), long‐term SPF‐pSCs (Ba‐MCpSCs) viability and barium concentrations were evaluated at 1, 24 throughout 40 h to establish pre‐transplant storage conditions.

Results

The purity of isolated pSCs was about 95% with negligible contaminating cells. Cultured pSCs monolayers, both prior to and after microencapsulation, maintained high function and full viability up to 24 h of storage. At 40 h post‐encapsulation, pSCs viability decreased to 80%. Barium concentration in Ba‐MCpSCs lagged below the normal maximum daily allowance and was stable for 4 months in mice with no evident side effects.

Conclusions

Such results suggest that this protocol for the isolation and microencapsulation of pSCs is compatible with long‐haul transportation and that Ba‐MCpSCs could be potentially employable for xenotransplantation.
Modelling of biomass fractions and radial increment of the selected Norway spruce forest stands in the region of the Moravian-Silesian Beskids
Authors: Palát Milan
Published: June 2015

Norway spruce (Picea abies /L./ Karst.) appears to be the most important conifer species in our mountain regions. Statistically significant differences were determined in the diameter and height increments for particular types of branching. There were verified regression functions for estimation biomass fractions. Using model calculations, fractions of above-ground and underground biomass were determined for selected permanent sample plots of the Moravian-Silesian Beskids from lower altitudes. Statistically significant differences were determined in the diameter and height increments for particular types of branching. From the branching type 1.5 (fascicle/comb-shaped) across type 2 (fascicle-shaped) and type 2.5 (fascicle/plate-shaped to type 3 (plate-shaped) both d.b.h., total tree height and radial increment decrease. For a man-made Norway spruce ecosystem regression functions determined by fitting the data from 45 sample spruce trees were derived (at Drahanská Upland) and used also for sample plots in Beskids.
Moisture conditions of the soil in spruce ecosystem in Oravská Polhora-Borsučie in growing seasons of 2012 and 2013
Authors: Tužinský Ladislav , Tužinský Marek , Gregor Juraj
Published: June 2015

The paper presents the research results of soil water regime under the spruce stand in the Upper Orava, in Oravská Polhora - Borsučie in the growing seasons of 2012 and 2013. There are characterized different ranges of soil moisture, soil water categories and its accessibility for plants, particularly for the surface layer from 20 cm to 100 cm deep physiological soil profile. Dominant interval of moisture during the growing season is the semiuvidic interval with the soil moisture between hydrolimits MCC and PDA. Amount of water presents mostly capillary less moving water, in the surface layer of soil sufficient, for short time insufficient supply of usable water. The amount of water decreseases for a short time after dry days. Semiaridic interval with the soil moisture between hydrolimits PDA and WP, up to the upper third of the variation range means that the vegetation has available stationary capillary water in the surface layer. In prolonged dry season such humidity condition can be one of the main causes of physiological weakening of spruce.
Aboveground biomass estimation with airborne hyperspectral and LiDAR data in Tesinske Beskydy Mountains
Authors: Brovkina Olga , Zemek František , Fabiánek Tomáš
Published: June 2015

The study presents three models for estimation of forest aboveground biomass (AGB) for plot level using different categories of airborne data. The first and the second models estimate AGB from metrics of airborne LiDAR data. The third model estimates AGB from integration of metrics of airborne hyperspectral and LiDAR data. The results are compared with plot level biomass estimated from field measurements. The results show that the best AGB estimate is obtained from the model utilizing a fusion of hyperspectral and LiDAR metrics. Study results expand existing research on the applicability of airborne hyperspectral and LiDAR datasets for AGB assessment. It evidences the efficiency of using a predicting model based on hyperspectral and LiDAR data for study area.
Influence of different tree densities on CO2 flux from soil in Norway spruce monoculture
Authors: Fabiánek Tomáš , Menšík Ladislav , Kulhavý Jiří
Published: June 2015

One of the most important components of the carbon cycle in forest ecosystems is the CO2exchange between soil and atmosphere. Hence, forestry management has the potential to change flux and sink of the carbon dioxide in the soil. The objective of this study is to analyze and to compare soil respiration during the 2010 vegetation season in commercial Norway spruce (Picea abies(L.) Karst.) forest stands. Research plots are located at the Drahanská vrchovina Highlands (on the eastern edge of the Bohemian Massive), where optimal conditions for Norway spruce stands cultivation can be found in the Czech Republic (600–700 m a. s. l.). Measured soil respiration data and other soil characteristics were evaluated in young monoculture stands with different methods of forestry management. The volume of C released from the soil was measured in the range of 8.2–9.4 t.ha-1.year and the velocity of respiration at 10 °C in the range of 2.7–3.0 μmol.m-2.s-1, depending on the tree density. The amount of C leached from the forest floor was found to be near 0.08 t.ha-1per year.
Potential of Douglas­‑fir as a partial substitute for Norway spruce – review of the newest Czech literature
Authors: Podrázský Vilém
Published: June 2015

Presentation summarizes the results concerning the effects of cultivation of Douglas­‑fir (Pseudotsuga menziesii /Mirb./ Franco), especially in the last decades, on the intensity of production as well as non­‑production forest functions in the conditions of the Czech Republic. It analyzes the research outcomes from the point of view of volume and value production in comparison with other native tree species, from the point of view of the soil effects and effects on the ground vegetation diversity, and from point of view of stability and cultivation in the last period. Main aim is represented by the comparison with the Norway spruce, which can be with advantages replaced by this species, with favourable impact on amount and value of the timber production, on the soil and biodiversity status of the ground vegetation. Also the stability of forest stands can be supported considerably. Douglas­‑fir represents favourable alternative to the Norway spruce in lower and middle altitudes and it can contribute highly to the competitiveness of the Czech forestry.
An Appraisal of System Mean Void Fraction and Its Application for the Moving Boundary Simulation of Phase-Change Heat Exchangers
Authors: Datta S. P. , Chandra R. K. , Das P. K.
Published: July 2015

In gas–liquid two-phase flow, void fraction is the most unique parameter which influences all the transport processes. In the most general case, though the void fraction varies nonlinearly with the channel length, many practical simulations make use of the “system mean void fraction.” The present investigation makes a critical assessment of different system mean void fraction models for a wide range of slip velocity and density difference between the phases. To this end, different correlations for slip ratio have been considered and, for all the cases, closed form expression for the system mean void fraction has been presented. The local as well as the system mean void fractions have also been estimated numerically from a heat transfer based model. Predictions from the heat transfer based model and the slip ratio based model have been compared. As an application, the slip ratio based system mean void fraction is used in to build the moving boundary model for phase-change heat exchangers. The prediction of startup transients for both an evaporator and a condenser of an automotive air conditioning system (AACS) agrees well with the experimental results.
The ParB-
parS
Chromosome Segregation System Modulates Competence Development in Streptococcus pneumoniae
Authors: Attaiech Laetitia , Minnen Anita , Kjos Morten , Gruber Stephan , Veening Jan-Willem
Published: July 2015

ParB proteins bind centromere-like DNA sequences called
parS
sites and are involved in plasmid and chromosome segregation in bacteria. We previously showed that the opportunistic human pathogen
Streptococcus pneumoniae
contains four
parS
sequences located close to the origin of replication which are bound by ParB. Using chromatin immunoprecipitation (ChIP), we found here that ParB spreads out from one of these
parS
sites,
parS
(−1.6°), for more than 5 kb and occupies the nearby
comCDE
operon, which drives competence development. Competence allows
S. pneumoniae
to take up DNA from its environment, thereby mediating horizontal gene transfer, and is also employed as a general stress response. Mutating
parS
(−1.6°) or deleting
parB
resulted in transcriptional up-regulation of
comCDE
and
ssbB
(a gene belonging to the competence regulon), demonstrating that ParB acts as a repressor of competence. However, genome-wide transcription analysis showed that ParB is not a global transcriptional regulator. Different factors, such as the composition of the growth medium and antibiotic-induced stress, can trigger the sensitive switch driving competence. This work shows that the ParB-
parS
chromosome segregation machinery also influences this developmental process.

IMPORTANCE
Streptococcus pneumoniae
(pneumococcus) is an important human pathogen responsible for more than a million deaths each year. Like all other organisms,
S. pneumoniae
must be able to segregate its chromosomes properly. Not only is understanding the molecular mechanisms underlying chromosome segregation in
S. pneumoniae
therefore of fundamental importance, but also, this knowledge might offer new leads for ways to target this pathogen. Here, we identified a link between the pneumococcal chromosome segregation system and the competence-developmental system. Competence allows
S. pneumoniae
to take up and integrate exogenous DNA in its chromosome. This process plays a crucial role in successful adaptation to—and escape from—host defenses, antibiotic treatments, and vaccination strategies. We show that the chromosome segregation protein ParB acts as a repressor of competence. To the best of our knowledge, this is the first example of a ParB protein controlling bacterial competence.
Varicella paediatric hospitalisations in Belgium: a 1-year national survey
Authors: Blumental Sophie , Sabbe Martine , Lepage Philippe
Published: July 2015

Background

Varicella universal vaccination (UV) has been implemented in many countries for several years. Nevertheless, varicella UV remains debated in Europe and few data are available on the real burden of infection. We assessed the burden of varicella in Belgium through analysis of hospitalised cases during a 1-year period.

Methods

Data on children admitted to hospital with varicella were collected through a national network from November 2011 to October 2012. Inclusion criteria were either acute varicella or related complications up to 3 weeks after the rash.

Results

Participation of 101 hospitals was obtained, covering 97.7% of the total paediatric beds in Belgium. 552 children were included with a median age of 2.1 years. Incidence of paediatric varicella hospitalisations reached 29.5/105person-years, with the highest impact among those 0–4 years old (global incidence and odds of hospitalisation: 79/105person-years and 1.6/100 varicella cases, respectively). Only 14% (79/552) of the cohort had an underlying chronic condition. 65% (357/552) of children had ≥1 complication justifying their admission, 49% were bacterial superinfections and 10% neurological disorders. Only a quarter of children (141/552) received acyclovir. Incidence of complicated hospitalised cases was 19/105person-years. Paediatric intensive care unit admission and surgery were required in 4% and 3% of hospitalised cases, respectively. Mortality among Belgian paediatric population was 0.5/106and fatality ratio 0.2% among our cohort.

Conclusions

Varicella demonstrated a substantial burden of disease in Belgian children, especially among the youngest. Our thorough nationwide study, run in a country without varicella UV, offers data to support varicella UV in Belgium.
Association of coronary to left ventricular microfistulae (vessels of Wearn) with atrial septal defect in an adult without cyanotic heart disease
Authors: Hussain Munem , Roberts Elved Bryn
Published: July 2015

Vessels of Wearn are rare findings during coronary angiography in adults. They are known to be associated with forms of cyanotic congenital heart disease in infants but we are not aware of any published cases of association with non-cyanotic left to right shunts in adults. We present the case of a 69-year-old man with angiographically evident vessels of Wearn draining from the left and right coronary arteries into the left ventricle associated with an asymptomatic atrial septal defect. We postulate a developmental phase association between atrial septal maturation and closure of perfusing microchannels from the ventricular cavities to the epicardial coronary arteries on the same spectrum as that which leads to more widespread defects in infants. We also highlight a common medication side effect that might have been mistaken as a manifestation of the congenital anomalies.
Early opioid prescription and risk of long-term opioid use among US workers with back and shoulder injuries: a retrospective cohort study
Authors: Heins Sara E , Feldman Dorianne R , Bodycombe David , Wegener Stephen T , Castillo Renan C
Published: July 2015

The number of prescription opioid overdose deaths has increased dramatically in recent years and many prescribers are unsure how to balance treatment of pain with secondary prevention. Guidelines recommend low-severity injury patients not receive opioids early in the course of their care, but evidence supporting this guideline is limited. Data from 123 096 workers’ compensation claims with back and shoulder injuries were analysed to evaluate this guideline. Back and shoulder injury claimants with early opioid use (≤1 month after injury) had 33% lower (95% CI 24% to 41% lower) odds and 29% higher (95% CI 6% to 58% higher) odds, respectively, of long-term opioid use (>3 months) than claimants with late opioid use, after adjusting for key covariates. Stratified analyses indicate that early opioid use does not appear to increase the risk of long-term use except in cases where no diagnosis or only the diagnosis of unspecified shoulder pain is given prior to prescription.
Gene of the month:KIT
Authors: Roberts Riyaadh , Govender Dhirendra
Published: July 2015

Deranged pathway activation andKITmutations occur in numerous solid and haematological malignancies, with gain-of-function mutations being the most common demonstrable abnormality. Through a complex series of interactions, activation of the KIT receptor tyrosine kinase leads to cell survival, evasion of apoptosis, angiogenesis, dysregulated cell cycle control and promotion of tumourigenesis. The KIT receptor tyrosine kinase is a well-studied therapeutic target in human malignancies. TheKITmutational status of a neoplasm plays an important role in predicting the response to targeted therapies. In this article we outline the structure, function and mutations of theKITgene, its role in various neoplasms, therapeutic impacts and the role that these play in clinical patient outcome.
Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis
Authors: Cardoso Rhanderson N , Benjo Alexandre M , DiNicolantonio James J , Garcia Daniel C , Macedo Francisco Y B , El-Hayek Georges , Nadkarni Girish N , Gili Sebastiano , Iannaccone Mario , Konstantinidis Ioannis , Reilly John P
Published: July 2015

Background

Dual antiplatelet therapy is the standard of care after coronary stent placement but increases the bleeding risk. The effects of proton pump inhibitors (PPIs) on clopidogrel metabolism have been described, but the clinical significance is not yet definitive. We aimed to do an updated meta-analysis comparing outcomes in patients receiving clopidogrel with and without PPIs.

Methods

We systematically searched PubMed, Scopus and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) and controlled observational studies in patients taking clopidogrel stratified by concomitant PPI use. Heterogeneity was examined with the Cochran Q test and I2statistics; p values inferior to 0.10 and I2>25% were considered significant for heterogeneity.

Results

We included 39 studies with a total of 214 851 patients, of whom 73 731 (34.3%) received the combination of clopidogrel and a PPI. In pooled analysis, all-cause mortality, myocardial infarction, stent thrombosis and cerebrovascular accidents were more common in patients receiving both drugs. However, among 23 552 patients from eight RCTs and propensity-matched studies, there were no significant differences in mortality or ischaemic events between groups. The use of PPIs in patients taking clopidogrel was associated with a significant reduction in the risk of gastrointestinal bleeding.

Conclusions

The results of our meta-analysis suggest that PPIs are a marker of increased cardiovascular risk in patients taking clopidogrel, rather than a direct cause of worse outcomes. The pharmacodynamic interaction between PPIs and clopidogrel most likely has no clinical significance. Furthermore, PPIs have the potential to decrease gastrointestinal bleeding in clopidogrel users.
The British Thoracic Society guidelines on the investigation and management of pulmonary nodules
Authors: Baldwin David R , Callister Matthew EJ
Published: July 2015

The British Thoracic Society guideline for the investigation and management of pulmonary nodules is published as a supplement to this edition of the journal. It provides recommendations for the management of an individual with single or multiple pulmonary nodules and is a comprehensive reference text.
Equiaffine characterization of Lagrangian surfaces in ℝ4
Authors: Craizer Marcos
Published: June 2015

For non-degenerate surfaces in ℝ4, a distinguished transversal bundle called affine normal plane bundle was proposed in [K. Nomizu and L. Vrancken, A new equiaffine theory for surfaces in ℝ4, Internat. J. Math. 4(1) (1993) 127–165]. Lagrangian surfaces have remarkable properties with respect to this normal bundle, like for example, the normal bundle being Lagrangian. In this paper, we characterize those surfaces which are Lagrangian with respect to some parallel symplectic form in ℝ4.
Lane-changing behavior and its effect on energy dissipation using full velocity difference model
Authors: Wang Jian , Ding Jian-Xun , Shi Qin , Kühne Reinhart D.
Published: July 2015

In real urban traffic, roadways are usually multilane with lane-specific velocity limits. Most previous researches are derived from single-lane car-following theory which in the past years has been extensively investigated and applied. In this paper, we extend the continuous single-lane car-following model (full velocity difference model) to simulate the three-lane-changing behavior on an urban roadway which consists of three lanes. To meet incentive and security requirements, a comprehensive lane-changing rule set is constructed, taking safety distance and velocity difference into consideration and setting lane-specific speed restriction for each lane. We also investigate the effect of lane-changing behavior on distribution of cars, velocity, headway, fundamental diagram of traffic and energy dissipation. Simulation results have demonstrated asymmetric lane-changing “attraction” on changeable lane-specific speed-limited roadway, which leads to dramatically increasing energy dissipation.
Parallel Associative Classification Data Mining Frameworks Based MapReduce
Authors: Thabtah Fadi , Hammoud Suhel , Abdel-Jaber Hussein
Published: June 2015

Associative classification (AC) is a research topic that integrates association rules with classification in data mining to build classifiers. After dissemination of the Classification-based Association Rule algorithm (CBA), the majority of its successors have been developed to improve either CBA's prediction accuracy or the search for frequent ruleitems in the rule discovery step. Both of these steps require high demands in processing time and memory especially in cases of large training data sets or a low minimum support threshold value. In this paper, we overcome the problem of mining large training data sets by proposing a new learning method that repeatedly transforms data between line and item spaces to quickly discover frequent ruleitems, generate rules, subsequently rank and prune rules. This new learning method has been implemented in a parallel Map-Reduce (MR) algorithm called MRMCAR which can be considered the first parallel AC algorithm in the literature. The new learning method can be utilised in the different steps within any AC or association rule mining algorithms which scales well if contrasted with current horizontal or vertical methods. Two versions of the learning method (Weka, Hadoop) have been implemented and a number of experiments against different data sets have been conducted. The ground bases of the comparisons are classification accuracy and time required by the algorithm for data initialization, frequent ruleitems discovery, rule generation and rule pruning. The results reveal that MRMCAR is superior to both current AC mining algorithms and rule based classification algorithms in improving the classification performance with respect to accuracy.
Antiproliferative and Pro-Apoptotic Activity of Diarylheptanoids Isolated from the Bark of Alnus japonica in Human Leukemia Cell Lines
Authors: Uto Takuhiro , Tung Nguyen Huu , Appiah-Opong Regina , Aning Abigail , Morinaga Osamu , Edoh Dominic , Nyarko Alexander K. , Shoyama Yukihiro
Published: June 2015

Alnus japonica Steud is a tree that grows in damp areas of mountain valleys and has been used as a traditional medicine in Asia. We investigated the antiproliferative activity of hirsutanone (Hir) and oregonin (Ore) in human cancer cell lines and elucidated their mechanisms of action. A cytotoxicity study using a panel of 12 human cancer and 4 normal cell lines indicated that Hir exhibited potent antiproliferative activity against 4 leukemia (Jurkat, U937, THP-1, and HL-60) and 2 colon cancer cell lines (HCT-15 and Colo205). Although Ore suppressed the cell growth of Jurkat and THP-1, its inhibitory potency was weaker than that of Hir. The IC50 values of Hir and Ore in Jurkat were 11.37 μM and 22.16 μM, respectively. Further analysis on Jurkat cells demonstrated that Hir caused a sequence of events involved in apoptosis, including nuclear morphological changes and accumulation of cells with sub-G1 DNA content. Hir led to the cleavage of poly(ADP-ribose) polymerase (PARP) and activation of caspase-3, -8, and -9. In addition, Hir-induced PARP cleavage was completely abolished by specific inhibitors to these caspases. Our data suggested that Hir is a potent antiproliferative compound against the 4 leukemia cell lines and the 2 colon cancer cell lines tested. Furthermore, Hir exerts antiproliferative actions via caspase-dependent apoptotic cell death.
Determination of the magnetic dipole moment of the rho meson using four-pion electroproduction data
Authors: Gudiño D. García , Sánchez G. Toledo
Published: July 2015

We determine the magnetic dipole moment of the rho meson using preliminary data from the BaBar Collaboration for the [Formula: see text] process, in the center of mass energy range from 0.9 to 2.2 GeV. We describe the [Formula: see text] vertex using a vector meson dominance model, including the intermediate resonance contributions relevant at these energies. We find that [Formula: see text] in [Formula: see text] units.
Adaptive Box-Constrained Total Variation Image Restoration Using Iterative Regularization Parameter Adjustment Method
Authors: Zhu Zhining , Cai Guangcheng , Wen You-Wei
Published: June 2015

In this paper, we consider the problem of image restoration with box-constraints. Image restoration problem is ill-conditioned and the regularization approach has widely been used to stabilize the solution. The restored image highly depends on the choice of the regularization parameter. The regularization parameter is generally determined by trial-and-error method when no true original image is available. Obviously, it is time consuming. The main aim in this paper is to develop an algorithm to choose the regularization parameter automatically when the box-constraints are imposed. In the proposed algorithm, the regularization parameter is adaptively determined by the previous iterative solution. Numerical simulations are used to demonstrate the performance of the proposed method.
Robust Localization of Texts in Real-World Images
Authors: Ghanei Shaho , Faez Karim
Published: June 2015

Localization of texts in natural images could be an important stage in many applications such as content-based image retrieval, visual impairment assistance systems, automatic robot navigation in urban environments and tourist assistance systems. However due to the variations of font, script, scale, orientations, color, shadow and lighting conditions, robust scene text localization is still a challenging task. In this paper, we propose a novel method to localize not only Farsi/Arabic and Latin texts with different sizes, fonts and orientations but also low luminance contrast and poor quality ones in the natural images taken with uneven illumination conditions. Firstly, fast weighted median filtering as a nonlinear edge-preserving smoothing filter and then color contrast preserving decolorization are exploited to make the text localization system more robust for low luminance contrast and poor quality texts. In order to extract the Farsi/Arabic and Latin scene texts and also filter the nontext ones, a unified framework is proposed incorporating the maximally stable extremal regions and a novel proposed region detector called Stable Width Stroke Regions which is based on closed boundary regions. Phase congruency and Laplacian operators are exploited to extract the closed boundary regions. Finally, to extract the single text lines, the Meanshift clustering and radon transform were used. Experimental results show that the proposed method localize low luminance contrast and low quality scene texts for both Farsi/Arabic and Latin scripts encouragingly.
Reductions in Anisotropic Errors from Implementation of Phase-Field Wetting Boundary Condition for Off-Grid Objects
Authors: Inoue Yasuhiro , Ishida Kazuki , Takada Naoki , Hojo Masaki
Published: July 2015

In simulations of multiphase fluid flow using the phase-field method (PFM), the wetting boundary condition is required for off-grid objects. In this study, we propose an improved implementation of the wetting boundary condition for off-grid objects to reduce anisotropic errors arising from use of a rectangular grid. Our implementation of the phase-field wetting boundary condition conforms to the immersed-boundary formulation of solid–fluid interfaces; therefore, we call the immersed-boundary phase-field implementation (IB-PFI). We performed simulations with and without IB-PFI for (a) droplets adhering to circular objects and (b) capillary flow in a parallel-plate channel. In simulations without IB-PFI, anisotropic errors were induced by off-grid objects, and the results deviated from theoretical predictions. In contrast, simulations with IB-PFI suppressed the anisotropic errors and agreed with the theoretical predictions. Thus, IB-PFI extends the applicability of the PFM to simulations of multiphase fluid flows under numerous geometric conditions.
Zeta Mahler measures, multiple zeta values and L-values
Authors: Sasaki Yoshitaka
Published: June 2015

The zeta Mahler measure is the generating function of higher Mahler measures. In this article, explicit formulas of higher Mahler measures, and relations between higher Mahler measures and multiple zeta (star) values are showed by observing connections between zeta Mahler measures and the generating functions of multiple zeta (star) values. Additionally, connections between higher Mahler measures and Dirichlet L-values associated with primitive quadratic characters are discussed.
Vertically Aligned ZnO/InxSy Core–Shell Nanorods for High Efficient Dye-Sensitized Solar Cells
Authors: Gonzalez-Valls Irene , Ballesteros Belén , Lira-Cantu Mónica
Published: June 2015

Innovative vertically aligned ZnO / In x S y nanorod (NR) electrodes were prepared by successive ion layer adsorption and reaction (SILAR) technique. The In x S y shell layer was deposited on top of ZnO NR electrodes of two different lengths, ~1.6 μm and ~3.2 μm. Two sulfur contents on the In x S y shell layer with different layer thicknesses were analyzed. These electrodes were fully characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction spectroscopy (XRD), Energy-dispersive x-ray spectroscopy (EDS), Infrared spectroscopy (FT-IR), x-ray photoelectron spectroscopy (XPS) and ultraviolet photoemission spectroscopy (UPS) and then applied in dye-sensitized solar cells (DSC). Power conversion efficiency of 2.32% was observed when a low-sulfur content In x S y shell layer was applied in comparison to the stoichiometric In 2 S 3 shell layer (0.21%) or the bare ZnO NRs (0.87%). In the case of low sulfur content, a shell layer of In ( OH )x S y or/and In ( OH )3 is formed as observed by the presence of – OH observed by FTIR analyses. The presence of higher amounts of hydroxide groups modifies the bandgap and work function of the In x S y shell and facilitates dye adsorption, increasing the final solar cell performance.
An ecological model with the p-Laplacian and diffusion
Authors: Rasouli S. H.
Published: June 2015

We study the existence of positive solutions of a population model with diffusion of the form [Formula: see text] where Δp denotes the p-Laplacian operator defined by Δpz = div (∣∇z∣p-2∇z), p > 1, Ω is a bounded domain of RN with smooth boundary, α ∈ (0, 1), a and c are positive constants. Here f : [0, ∞) → R is a continuous function. This model arises in the studies of population biology of one species with u representing the concentration of the species. We discuss the existence of positive solution when f satisfies certain additional conditions. We use the method of sub- and super-solutions to establish our results.
Au-nanocluster-loaded human serum albumin nanoparticles with enhanced cellular uptake for fluorescent imaging
Authors: Khlebtsov Boris , Prilepskii Artur , Lomova Maria , Khlebtsov Nikolai
Published: June 2015

Protein-directed fluorescent Au nanoclusters have been widely studied owing to their potential applications in sensing, imaging, and drug and gene delivery. However, the use of nanoclusters in drug delivery is limited by low cellular uptake. In this study, human serum albumin-directed Au nanoclusters served as building blocks to obtain protein nanoparticles by desolvation. The nanoparticles had a decent quantum yield (QY), high colloidal stability and low cytotoxicity, and they could be readily conjugated with biological molecules. The cellular uptake of the Au nanoclusters and nanocluster-loaded protein nanoparticles were studied by confocal fluorescence microscopy. Agglomeration of the protein-directed Au nanoclusters into 50–150-nm nanoparticles dramatically increased the cellular uptake.
An infeasible interior-point method with improved centering steps for monotone linear complementarity problems
Authors: Asadi Soodabeh , Mansouri Hossein , Darvay Zsolt
Published: June 2015

In this paper, we improve the infeasible full-Newton interior-point algorithm presented by Mansouri et al. [A full-Newton step [Formula: see text] infeasible interior-point algorithm for linear complementarity problems, Nonlinear Anal. Real World Appl. 12 (2011) 545–561] for monotone linear complementarity problems (MLCPs). In each iteration of Mansouri’s algorithm two types of full-Newton steps are used, one feasibility step and some ordinary (centering) steps. In this paper, we use a new search direction, and reduce the number of the centering steps, so that only one centering step is needed. We prove that the complexity of the algorithm is as good as the best-known complexity for infeasible interior-point methods for MLCPs.
Frontal operators in distributive lattices with a generalized implication
Authors: Celani Sergio A. , San Martín Hernán J.
Published: June 2015

We introduce a family of extensions of bounded distributive lattices. These extensions are obtained by adding two operations: an internal unary operation, and a function (called generalized implication) that maps pair of elements to ideals of the lattice. A bounded distributive lattice with a generalized implication is called gi-lattice in [J. E. Castro and S. A. Celani, Quasi-modal lattices, Order 21 (2004) 107–129]. The main goal of this paper is to introduce and study the category of frontal gi-lattices (and some subcategories of it). This category can be seen as a generalization of the category of frontal weak Heyting algebras (see [S. A. Celani and H. J. San Martín, Frontal operators in weak Heyting algebras, Studia Logica 100(1–2) (2012) 91–114]). In particular, we study the case of frontal gi-lattices where the generalized implication is defined as the annihilator (see [B. A. Davey, Some annihilator conditions on distributive lattices, Algebra Universalis 4(1) (1974) 316–322; M. Mandelker, Relative annihilators in lattices, Duke Math. J. 37 (1970) 377–386]). We give a Priestley’s style duality for each one of the new classes of structures considered.
Matrix representations of right ample semigroups
Authors: Guo Junying , Guo Xiaojiang , Shum K. P.
Published: June 2015

The properties of right ample semigroups have been extensively considered and studied by many authors. In this paper, we concentrate on the matrix representations of right ample semigroups. The (left; right) uniform matrix representation is initially defined. After some properties of left uniform matrix representations of a right ample semigroup are given, we prove that any irreducible left uniform representations of a right ample semigroup can be obtained by using an irreducible left uniform representation of some primitive right ample semigroup. In particular, a construction theorem of prime left uniform representation of right ample semigroups is established.