bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real Time PCR for the Evaluation of Treatment Response in Clinical Trials of Adult Chronic Chagas Disease: Usefulness of Serial Blood Sampling and qPCR Replicates
Authors: Parrado Rudy , Ramirez Juan Carlos , de la Barra Anabelle , Alonso-Vega Cristina , Juiz Natalia , Ortiz Lourdes , Illanes Daniel , Torrico Faustino , Gascon Joaquim , Alves Fabiana , Flevaud Laurence , Garcia Lineth , Schijman Alejandro G. , Ribeiro Isabela 
Published: June 2018

AbstractThis work evaluated a serial blood sampling procedure to enhance the sensitivity of duplex real time PCR (qPCR) for baseline detection and quantification of parasitic loads and post-treatment identification of failure in the context of clinical trials for treatment of chronic Chagas disease, namely DNDi-CH-E1224-001 (NCT01489228) and MSF-DNDi PCR sampling optimization study (NCT01678599). Patients from Cochabamba (N= 294), Tarija (N = 257), and Aiquile (N= 220) were enrolled. Three serial blood samples were collected at each time-point, and qPCR triplicates were tested per sample. The first two samples were collected during the same day and the third one seven days later.A patient was considered PCR positive if at least one qPCR replicate was detectable. Cumulative results of multiple samples and qPCR replicates enhanced the proportion of pre-treatment sample positivity from 54.8 to 76.2%, 59.5 to 77.8%, and 73.5 to 90.2% in Cochabamba, Tarija, and Aiquile cohorts, respectively and increased cumulative detection of treatment failure from 72.9 to 91.7%, 77.8 to 88.9%, and 42.9 to 69.1% for E1224 low, short, and high dosage regimes, respectively; and from 4.6 to 15.9% and 9.5 to 32.1% for the benznidazole (BZN) arm in the DNDi-CH-E1224-001 and MSF-DNDi studies, respectively. The monitoring of patients treated with placebo in the DNDi-CH-E1224-001 trial revealed fluctuations in parasitic loads and occasional non-detectable results. This serial sampling strategy enhanced PCR sensitivity to detecting treatment failure during follow-up and has the potential for improving recruitment capacity in Chagas disease trials which require an initial positive qPCR result for patient admission.
SUMO-based expression and purification of dermcidin-derived DCD-1L, a human antimicrobial peptide, inEscherichia coli
Authors: Mohanraj Ushanandini , Kinnunen Oona , Kaya Meryem Ecem , Aranko Aino Sesilja , Viskari Heli , Linder Markus 
Published: June 2018

AbstractThe dermcidin-derived peptide DCD-1L has a broad spectrum of antimicrobial activity over a wide pH range and in high salt concentrations. Thus, it offers a promising alternative to conventional antibiotics. Furthermore, it plays a role in wound healing, atopic dermatitis and acne vulgaris, indicating applications in cosmetic industries. Recently, dermcidin has been identified as a tumor marker improving cancer prognosis. Hence, large quantities of purified DCD-1L peptide are required to meet the needs of basic research and clinical trials. In the current study, we demonstrate SUMO-based heterologous DCD-1L production inEscherichia coli, followed by affinity chromatography purification. The SUMO tag is cleaved with SUMO-specific protease following purification, leaving free DCD-1L peptide without any additional amino acids. The mass of the peptide was further confirmed by MALDI-TOF-TOF analysis. Furthermore, the cleaved DCD-1L showed antimicrobial activity against theE. coliDH5 alpha test strain. The production and purification of DCD-1L using SUMO tag compare advantageously to other protocols previously described. Thus, the SUMO tag system enables large scale recombinant production of the antimicrobial peptide DCD-1L, which constitutes pharmaceutical and therapeutic potential as an alternative antibiotic.
Fungal adaptation to plant defenses through convergent assembly of metabolic modules
Authors: Gluck-Thaler Emile , Vijayakumar Vinod , Slot Jason C. 
Published: June 2018

AbstractThe ongoing diversification of plant defense compounds exerts dynamic selection pressures on the microorganisms that colonize plant tissues. Evolutionary processes that generate resistance towards these compounds increase microbial fitness by giving access to plant resources and increasing pathogen virulence. These processes entail sequence-based mechanisms that result in adaptive gene functions, and combinatorial mechanisms that result in novel syntheses of existing gene functions. However, the priority and interactions among these processes in adaptive resistance remains poorly understood. Using a combination of molecular genetic and computational approaches, we investigated the contributions of sequence-based and combinatorial processes to the evolution of fungal metabolic gene clusters encoding stilbene cleavage oxygenases (SCOs), which catalyze the degradation of biphenolic plant defense compounds known as stilbenes into monophenolic molecules. We present phylogenetic evidence of convergent assembly among three distinct types of SCO gene clusters containing alternate combinations of phenolic catabolism. Multiple evolutionary transitions between different cluster types suggest recurrent selection for distinct gene assemblages. By comparison, we found that the substrate specificities of heterologously expressed SCO enzymes encoded in different clusters types were all limited to stilbenes and related molecules with a 4’-OH group, and differed modestly in substrate range and activity under the experimental conditions. Together, this work suggests a primary role for genome structural rearrangement, and the importance of enzyme modularity, in promoting fungal metabolic adaptation to plant defense chemistry.
X-ray structures of human ETBreceptor provide mechanistic insight into receptor activation and partial activation
Authors: Shihoya Wataru , Izume Tamaki , Inoue Asuka , Yamashita Keitaro , Marie Ngako Kadji Francois , Hirata Kunio , Aoki Junken , Nishizawa Tomohiro , Nureki Osamu 
Published: June 2018

AbstractEndothelin receptors (ETAand ETB) are class A GPCRs activated by vasoactive peptide endothelins, and are involved in blood pressure regulation. ETB-selective signaling induces vasorelaxation, and thus selective ETBagonists are expected to be utilized for improved anti-tumour drug delivery and neuroprotection. The effectiveness of a highly ETB-selective endothelin analogue, IRL1620, has been investigated in clinical trials. Here, we report the crystal structures of human ETBreceptor in complex with ETB-selective agonists, endohelin-3 and IRL1620. The 2.0 Å-resolution structure of the endothelin-3-bound receptor revealed that the disruption of water-mediated interactions between W6.48 and D2.50, which are highly conserved among class A GPCRs, is critical for receptor activation. These hydrogen-bonding interactions are partially preserved in the IRL1620-bound structure, and a functional analysis revealed the partial agonistic effect of IRL1620. The current findings clarify the detailed molecular mechanism for the coupling between the orthosteric pocket and the G-protein binding, and the partial agonistic effect of IRL1620, thus paving the way for the design of improved agonistic drugs targeting ETB.
Identification of Novel Common Breast Cancer Risk Variants in Latinas at the 6q25 Locus
Authors: Hoffman Joshua , Fejerman Laura , Hu Donglei , Huntsman Scott , Li Min , John Esther , Mejia Gabriela Torres , Kushi Larry , Ding Yuan Chun , Weitzel Jeffrey , Neuhausen Susan L. , Lott Paul ,   COLUMBUS Consortium, Echeverry Magdalena , Carmona Luis Carvajal , Burchard Esteban , Eng Celeste , Zheng Wei , Long Jirong , Olopade Olufunmilayo , Huo Dezheng , Haiman Christopher , Ziv Elad 
Published: June 2018

AbstractBackground: Breast cancer is a partially heritable trait and over 180 common genetic variants have been associated with breast cancer in genome wide association studies (GWAS). We have previously performed breast cancer GWAS in Latinas and identified a strongly protective single nucleotide polymorphism (SNP) at 6q25 with the protective minor allele originating from Indigenous American ancestry. Here we report on additional GWAS and replication in Latinas.Methods: We performed GWAS in 2385 cases and 7342 controls who were either U.S. Latinas or Mexican women. We replicated 2412 cases and 1620 controls of U.S Latina, Mexican, and Colombian women. In addition, we replicated the top novel variants in study of African American and African women and in one study of Chinese women. In each dataset we used logistic regression models to test the association between SNPs and breast cancer risk and corrected for genetic ancestry using either principal components or genetic ancestry inferred from ancestry informative markers using a model based approach.Results: We identified 3 SNPs (p=1.9×10-8 - 2.8×10-8) at 6q25 locus not in linkage disequilibrium (LD) with variants previously reported at this locus. These SNPs were in high LD with each other, with the top SNP, rs3778609, associated with breast cancer with an odds ratio (OR) and 95% confidence interval (95% CI) of 0.75 (0.68-0.83). In a replication in women of Latin American origin, we also observed a consistent effect (OR: 0.88; 95% CI: 0.78-0.99; p=0.037). Since the minor allele was common in East Asians and African American but not European ancestry populations, we replicated in a meta-analysis of those populations and also observed a consistent effect (OR 0.94; 95% CI: 0.91 – 0.97; p=0.013).Conclusion: The effect size of this variant is relatively large compared to other common variants associated with breast cancer and adds to evidence about the importance of the 6q25 locus for breast cancer susceptibility. Our finding also highlights the utility of performing additional searches for genetic variants for breast cancer in non-European populations.
Data-driven multiscale modeling reveals the role of metabolic coupling for the spatio-temporal growth dynamics of yeast colonies
Authors: Intosalmi Jukka , Scott Adrian C. , Hays Michelle , Flann Nicholas , Yli-Harja Olli , Lähdesmäki Harri , Dudley Aimée M. , Skupin Alexander 
Published: June 2018

AbstractMotivationMulticellular entities, such as mammalian tissues or microbial biofilms, typically exhibit complex spatial arrangements that are adapted to their specific functions or environments. These structures result from intercellular signaling as well as from the interaction with the environment that allow cells of the same genotype to differentiate into well-organized communities of diversified cells. Despite its importance, our understanding on how cell–cell and metabolic coupling produce functionally optimized structures is still limited.ResultsHere, we present a data-driven spatial framework to computationally investigate the development of one multicellular structure, yeast colonies. Using experimental growth data from homogeneous liquid media conditions, we develop and parameterize a dynamic cell state and growth model. We then use the resulting model in a coarse-grained spatial model, which we calibrate using experimental time-course data of colony growth. Throughout the model development process, we use state-of-the-art statistical techniques to handle the uncertainty of model structure and parameterization. Further, we validate the model predictions against independent experimental data and illustrate how metabolic coupling plays a central role in colony formation.AvailabilityExperimental data and a computational implementation to reproduce the results are available athttp://research.cs.aalto.fi/csb/software/multiscale/code.zip.Contactjukka.intosalmi@aalto.fi,alexander.skupin@uni.lu
SSCC: a novel computational framework for rapid and accurate clustering large single cell RNA-seq data
Authors: Ren Xianwen , Zheng Liangtao , Zhang Zemin 
Published: June 2018

ABSTRACTClustering is a prevalent analytical means to analyze single cell RNA sequencing data but the rapidly expanding data volume can make this process computational challenging. New methods for both accurate and efficient clustering are of pressing needs. Here we proposed a new clustering framework based on random projection and feature construction for large scale single-cell RNA sequencing data, which greatly improves clustering accuracy, robustness and computational efficacy for various state-of-the-art algorithms benchmarked on multiple real datasets. On a dataset with 68,578 human blood cells, our method reached 20% improvements for clustering accuracy and 50-fold acceleration but only consumed 66% memory usage compared to the widely-used software package SC3. Compared to k-means, the accuracy improvement can reach 3-fold depending on the concrete dataset. An R implementation of the framework is available from https://github.com/Japrin/sscClust.
Parent of origin gene expression in a founder population identifies two new imprinted genes at known imprinted regions
Authors: Mozaffari Sahar V. , Stein Michelle M. , Magnaye Kevin M. , Nicolae Dan L. , Ober Carole 
Published: June 2018

AbstractGenomic imprinting is the phenomena that leads to silencing of one copy of a gene inherited from a specific parent. Mutations in imprinted regions have been involved in diseases showing parent of origin effects. Identifying genes with evidence of parent of origin expression patterns in family studies allows the detection of more subtle imprinting. Here, we use allele specific expression in lymphoblastoid cell lines from 306 Hutterites related in a single pedigree to provide formal evidence for parent of origin effects. We take advantage of phased genotype data to assign parent of origin to RNA-seq reads in individuals with gene expression data. Our approach identified known imprinted genes, two putative novel imprinted genes, and 14 genes with asymmetrical parent of origin gene expression. We used gene expression in peripheral blood leukocytes (PBL) to validate our findings, and then confirmed imprinting control regions (ICRs) using DNA methylation levels in the PBLs.Author SummaryLarge scale gene expression studies have identified known and novel imprinted genes through allele specific expression without knowing the parental origins of each allele. Here, we take advantage of phased genotype data to assign parent of origin to RNA-seq reads in 306 individuals with gene expression data. We identified known imprinted genes as well as two novel imprinted genes in lymphoblastoid cell line gene expression. We used gene expression in PBLs to validate our findings, and DNA methylation levels in PBLs to confirm previously characterized imprinting control regions that could regulate these imprinted genes.
Corrosion resistance of mild steel in sulphuric acid solution byCoreopsis tinctoriaextract: electrochemical and surface studies
Authors: Kalaiselvi Kathirvel , Chung Ill-Min , Kim Seung-Hyun , Prabakaran Mayakrishnan 
Published: June 2018

PurposeThe purpose of this paper is to investigate the inhibitive performance ofCoreopsis tinctoria(C. tinctoria) plant extract for the corrosion of mild steel in 0.5 M H2SO4.Design/methodology/approachThe inhibition efficiency was studied by weight loss, electrochemical measurements and the surface analysis was done by Raman, scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM-EDS) and atomic absorption spectroscopy (AAS) analysis.FindingsMaximum inhibition efficiency ofC. tinctoriain 0.5 M H2SO4on mild steel is 80.62 per cent (500 ppm) at 303 ± 1K. The adsorption of theC. tinctoriaon the mild steel surface in 0.5 M H2SO4was found to obey Langmuir adsorption isotherm. Temperature studies were carried out and the significant parameters, such as change in enthalpy (ΔH°), change in entropy (ΔS°) and change in free energy (ΔG°ads) and heat of adsorption (Qads), were calculated. The productive layer formed on the mild steel surface in 0.5 M H2SO4were confirmed by the Raman spectral analysis.Originality/valueThis paper provides information on the inhibitive properties ofC. tinctoriaplant extract which is found to be a good corrosion inhibitor for mild steel in 0.5 M H2SO4.
Food safety knowledge, self-reported practices and attitude of poultry meat handling among Slovenian consumers
Authors: Sterniša Meta , Smole Možina Sonja , Levstek Sonja , Kukec Andreja , Raspor Peter , Jevšnik Mojca 
Published: June 2018

Purpose
The purpose of this paper is to investigate Slovenian consumers’ knowledge and self-reported practices in poultry meat handling during purchase, transport, and preparation in home kitchens and to assess the awareness of the microbiological risk associated with poultry meat, with an emphasis on Campylobacter.

Design/methodology/approach
A cross-sectional study of consumers’ food safety knowledge, self-reported practices, and awareness of the microbiological risk was conducted from March to April 2015 at supermarkets in different parts of Slovenia. A convenience sample of 560 consumers was obtained. Gender and age distribution were controlled by 28 interviewers, each of whom distributed 20 questionnaires. The questionnaire included 33 questions divided into four parts.

Findings
The results revealed consumers awareness of food safety issues. Respondents have some basic knowledge about proper food handling. However, a substantial number of consumers still lacks knowledge of the microbiological risk and has bad habits in domestic poultry meat preparation.

Research limitations/implications
The research did not reflect a representative sample of Slovenian consumers.

Practical implications
The results indicate some gaps in consumers’ food safety knowledge and self-reported practices. Current Campylobacter preventive strategies regarding retail poultry meat contamination are not yet sufficiently successful.

Originality/value
The study provides valuable insight into consumers’ food safety knowledge and self-reported practices in poultry meat handling from shopping to eating. Opportunities for improvement in consumers’ formal and informal education and training should be offered.
Is innovation needed in the Old World wine market? The perception of Italian stakeholders
Authors: Wongprawmas Rungsaran , Spadoni Roberta 
Published: June 2018

Purpose
The wine market in Italy has been through several changes in the last decade. Actors in the supply chain need to find new strategies or tools in order to remain competitive in what has become a fiercely competitive sector. Innovation is one of the tools which have been successfully used in the New World wine market, hence innovation might also be a useful resource for actors in the Old World wine market, such as in Italy. The purpose of this paper is to explore stakeholders’ perception of such innovation, including how its usefulness in the Italian wine production and distribution chain is perceived.

Design/methodology/approach
Semi-structured interviews were carried out in Emilia-Romagna with a wide range of actors in the Italian wine chain and consumer focus groups and the resulting data were analyzed using the content-summarizing approach.

Findings
These stakeholders agreed that innovation is needed for production and processing as well as in quality control, but only on condition that it should maintain the quality and value of traditional wines. Innovative wine products tend to be unacceptable to consumers. Most stakeholders associate innovation with communication as producers and distributors seek innovative ways to convey information regarding the value of wines to final consumers.

Research limitations/implications
The findings are qualitative and based on a small group of Italian wine industry players and consumers who operate mainly in a domestic context.

Practical implications
The paper provides industrialists with information useful in the search to find the right strategies to make them more competitive in the Italian wine market. It is crucial to find and adopt innovative approaches toward communication throughout the chain. Information appealing to tradition and sentiment could be highly effective ways to reach the consumer.

Originality/value
This is the first in-depth study of the perceptions of all stakeholders (from producers to consumers) regarding innovation in the Italian wine chain; of particular importance as the industry is currently in transition toward globalization.
Corporate entrepreneurship strategy: an analysis of top management teams in SMEs
Authors: Afshar Jahanshahi Asghar , Nawaser Khaled , Brem Alexander 
Published: June 2018

PurposeIn order to learn more about the antecedents of strategy at the top management team’s (TMT) level, the purpose of this paper is to investigate the effects of TMT cultural intelligence on corporate entrepreneurship strategy. Then, the authors examine how TMT’s ambiguity tolerance mediates this relationship.Design/methodology/approachThe authors tested the hypothesis by collecting survey data from 41 TMTs of small- and medium-sized enterprises in the south-east of Iran.FindingsThe survey results confirm that a high level of cultural intelligence in TMTs is conducive to corporate entrepreneurship. Furthermore, the result shows that higher levels of cultural intelligence in TMTs relate to a higher level of ambiguity tolerance, which, in turn, enhances the possibility of pursuing corporate entrepreneurship strategy by SMEs.Research limitations/implicationsThe data for this study were obtained from 41 TMTs in the south-east of Iran, which increases the probability that the results may not be directly transferable to certain companies in Western countries. Future research might attempt to test the ideas developed in this paper across different settings and samples.Originality/valueSeveral theoretical and empirical studies have explored possible antecedents of corporate entrepreneurship. But a few papers investigated the role of TMT dispositions on corporate entrepreneurship strategy. By addressing the prominent role of TMT psychological dispositions on corporate entrepreneurship strategy, this paper attempts to fill this gap.
Supporting business processes through human and IT factors: a maturity model
Authors: Mamoghli Sarra , Cassivi Luc , Trudel Sylvie 
Published: June 2018

Purpose
The purpose of this paper is to assist organizations in the assessment of both information technology (IT) and human factors required to support their business processes (BPs) by taking into account the interdependence and alignment of these factors, rather than considering them independently.

Design/methodology/approach
A design science research methodology was followed to build a maturity model (MM) enabling this assessment. The proposed design process is composed of four steps: problem identification, comparison of 19 existing MMs in business process management (BPM), iterative model development, and model evaluation. The last two steps were specifically based on three research methods: literature analysis, case studies, and expert panels.

Findings
This paper presents a MM that assigns a maturity level to an organization’s BPs in two assessment steps. The first step evaluates the level of sophistication and integration of the IT systems supporting each BP, while the second step assesses the alignment of human factors with the technological efforts.

Research limitations/implications
The research was conducted with SMEs, leading to results that may be specific to this type of organization.

Practical implications
Practitioners can use the proposed model throughout their journey toward process excellence. The application of this model leads to two main process improvement scenarios: upgrading the sophistication and integration of the software technologies in support of the processes, and improving the cohesion of the resources the organization already owns (human and IT resources).

Originality/value
The proposed MM constitutes a first step in the assessment of the interdependence between the factors influencing BPM.