bluuebunny/crossref_metadata_2025_split huggingface dataset:
BisPin and BFAST-Gap: Mapping Bisulfite-Treated Reads
Authors: Porter Jacob , Zhang Liqing 
Published: March 2018

AbstractBackgroundBisPin is a new multiprocess bisulfite-treated short DNA read mapper written in Python 2.7. It performs alignments using BFAST, leveraging its multithreading functionality and thorough hash-based indexing strategy. BisPin is feature rich and supports directional, nondirectional, PBAT, and hairpin construction strategies. BisPin approaches read mapping by converting the Cs to Ts and the Gs to As in both the reads and the reference genome. BisPin uses fast rescoring to disambiguate ambiguously aligned reads for a superior amount of uniquely mapped reads compared to other mappers. The performance of BisPin was evaluated on both real and simulated data in comparison to other read mappers.BFAST-Gap is a modified version of BFAST meant for Ion Torrent reads. It uses a parameterized logistic function to determine the weights of the gap open and extension penalties based on the homopolymer run length of the DNA read. This is because the Ion Torrent sequencing technology can overcall and undercall homopolymer runs. BisPin works with both BFAST-Gap and BFAST. BFAST-Gap is compatible with indexes built with BFAST. There are few mappers that specifically address Ion Torrent data. BFAST-Gap works with Illumina reads as well.ResultsBisPin with BFAST consistently had a higher amount of uniquely mapped reads compared to other mappers on real data using a variety of construction strategies. Using a hairpin validation strategy, BisPin was superior using the maximum score, and it mapped 73% of reads correctly.BisPin with BFAST-Gap on Ion Torrent reads with a logistic gap open penalty function improved mapping accuracy with real and simulated data. On simulated bisulfite Ion Torrent data, the area under the curve was improved by approximately seven, and on one real data set, the uniquely mapped percent was improved by seven percent. BFAST-Gap performed better than TMAP on simulated regular Ion Torrent reads, and TMAP is designed for Ion Torrent reads. Other read mappers had worse performance.ConclusionsBisPin and BFAST-Gap have consistently good accuracy with a variety of data. BisPin is feature-rich. This makes BisPin and BFAST-Gap useful additions to read mapping software.
Reference-based annotation of single cell transcriptomes identifies a profibrotic macrophage niche after tissue injury
Authors: Aran Dvir , Looney Agnieszka P. , Liu Leqian , Fong Valerie , Hsu Austin , Wolters Paul J. , Abate Adam , Butte Atul J. , Bhattacharya Mallar 
Published: March 2018

AbstractMyeloid cells localize to peripheral tissues in a wide range of pathologic contexts. However, appreciation of distinct myeloid subtypes has been limited by the signal averaging inherent to bulk sequencing approaches. Here we applied single-cell RNA sequencing (scRNA-seq) to map cellular heterogeneity in lung fibrosis induced by bleomycin injury in mice. We first developed a computational framework that enables unbiased, granular cell-type annotation of scRNA-seq. This approach identified a macrophage subpopulation that was specific to injured lung and notable for high expression of Cx3cr1+ and MHCII genes. We found that these macrophages, which bear a gene expression profile consistent with monocytic origin, progressively acquire alveolar macrophage identity and localize to sites of fibroblast accumulation. Probing their functional role, in vitro studies showed a trophic effect of these cells on fibroblast activation, and ablation of Cx3cr1-expressing cells suppressed fibrosis in vivo. We also found by gene set analysis and immunofluorescence that markers of these macrophages were upregulated in samples from patients with lung fibrosis compared with healthy controls. Taken together, our results uncover a specific pathologic subgroup of macrophages with markers that could enable their therapeutic targeting for fibrosis.
Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease
Authors: Kucukkilic Ezgi , Brookes Keeley , Barber Imelda , Guetta-Baranes Tamar , Morgan Kevin , Hollox Edward J 
Published: March 2018

AbstractSingle nucleotide variants (SNVs) within and surrounding the complement receptor 1 (CR1) gene show some of the strongest genome-wide association signals with late-onset Alzheimer’s disease. Some studies have suggested that this association signal is due to a duplication allele (CR1-B) of a low copy repeat (LCR) within theCR1gene, which increases the number of complement C3b/C4b-binding sites in the mature receptor. In this study, we develop a triplex paralogue ratio test (PRT) assay forCR1LCR copy number allowing large numbers of samples to be typed with a limited amount of DNA. We also develop aCR1-B allele-specific PCR based on the junction generated by an historical non-allelic homologous recombination event betweenCR1LCRs. We use these methods to genotypeCR1and measureCR1-B allele frequency in both late-onset and early-onset cases and unaffected controls from the United Kingdom. Our data support an association of late-onset Alzheimer’s disease with theCR1-B allele, and confirm that this allele occurs most frequently on the risk haplotype defined by SNV alleles. Furthermore, regression models incorporatingCR1-B genotype provide a bitter fit to our data compared to incorporating the SNP-defined risk haplotype, supporting theCR1-B allele as the variant underlying the increased risk of late-onset Alzheimer’s disease.
Establishment of signaling interactions with cellular resolution for every cell cycle of embryogenesis
Authors: Chen Long , Ho Vincy Wing Sze , Wong Ming-Kin , Huang Xiaotai , Chan Lu-yan , Ng Hon Chun Kaoru , Ren Xiaoliang , Yan Hong , Zhao Zhongying 
Published: March 2018

AbstractIntercellular signaling interaction plays a key role in breaking fate symmetry during animal development. Identification of the signaling interaction at cellular resolution is technically challenging, especially in a developing embryo. Here we develop a platform that allows automated inference and validation of signaling interaction for every cell cycle ofC. elegansembryogenesis. This is achieved by generation of a systems-level cell contact map that consists of 1,114 highly confident intercellular contacts by modeling analysis and is validated through cell membrane labeling coupled with cell lineage analysis. We apply the map to identify cell pairs between which a Notch signaling interaction takes place. By generating expression patterns for two ligands and two receptors of Notch signaling pathway with cellular resolution using automated expression profiling technique, we are able to refine existing and identify novel Notch interactions duringC. elegansembryogenesis. Targeted cell ablation followed by cell lineage analysis demonstrates the roles of signaling interactions over cell division in breaking fate symmetry. We finally develop a website that allows online access to the cell-cell contact map for mapping of other signaling interaction in the community. The platform can be adapted to establish cellular interaction from any other signaling pathways.
Semi-soft Clustering of Single Cell Data
Authors: Zhu Lingxue , Lei Jing , Devlin Bernie , Roeder Kathryn 
Published: March 2018

AbstractMotivated by the dynamics of development, in which cells of recognizable types, or pure cell types, transition into other types over time, we propose a method of semi-soft clustering that can classify both pure and intermediate cell types from data on gene expression or protein abundance from individual cells. Called SOUP, for Semi-sOft clUstering with Pure cells, this novel algorithm reveals the clustering structure for both pure cells, which belong to one single cluster, as well as transitional cells with soft memberships. SOUP involves a two-step process: identify the set of pure cells and then estimate a membership matrix. To find pure cells, SOUP uses the special block structure the K cell types form in a similarity matrix, devised by pairwise comparison of the gene expression profiles of individual cells. Once pure cells are identified, they provide the key information from which the membership matrix can be computed. SOUP is applicable to general clustering problems as well, as long as the unrestrictive modeling assumptions hold. The performance of SOUP is documented via extensive simulation studies. Using SOUP to analyze two single cell data sets from brain shows it produce sensible and interpretable results.
Chromatin features constrain structural variation across evolutionary timescales
Authors: Fudenberg Geoff , Pollard Katherine S. 
Published: March 2018

AbstractThe potential impact of structural variants includes not only the duplication or deletion of coding sequences, but also the perturbation of non-coding DNA regulatory elements and structural chromatin features, including topological domains (TADs). Structural variants disrupting TAD boundaries have been implicated both in cancer and developmental disease; this likely occurs via ‘enhancer hijacking’, whereby removal of the TAD boundary exposes enhancers to new target transcription start sites (TSSs). With this functional role, we hypothesized that boundaries would display evidence for negative selection. Here we demonstrate that the chromatin landscape constrains structural variation both within healthy humans and across primate evolution. In contrast, in patients with developmental delay, variants occur remarkably uniformly across genomic features, suggesting a potentially broad role for enhancer hijacking in human disease.
Design and implementation of crawling algorithm to collect deep web information for web archiving
Authors: Oh Hyo-Jung , Won Dong-Hyun , Kim Chonghyuck , Park Sung-Hee , Kim Yong 
Published: March 2018

PurposeThe purpose of this paper is to describe the development of an algorithm for realizing web crawlers that automatically collect dynamically generated webpages from the deep web.Design/methodology/approachThis study proposes and develops an algorithm to collect web information as if the web crawler gathers static webpages by managing script commands as links. The proposed web crawler actually experiments with the algorithm by collecting deep webpages.FindingsAmong the findings of this study is that if the actual crawling process provides search results as script pages, the outcome only collects the first page. However, the proposed algorithm can collect deep webpages in this case.Research limitations/implicationsTo use a script as a link, a human must first analyze the web document. This study uses the web browser object provided by Microsoft Visual Studio as a script launcher, so it cannot collect deep webpages if the web browser object cannot launch the script, or if the web document contains script errors.Practical implicationsThe research results show deep webs are estimated to have 450 to 550 times more information than surface webpages, and it is difficult to collect web documents. However, this algorithm helps to enable deep web collection through script runs.Originality/valueThis study presents a new method to be utilized with script links instead of adopting previous keywords. The proposed algorithm is available as an ordinary URL. From the conducted experiment, analysis of scripts on individual websites is needed to employ them as links.
The safe tweet: social media use by Ontario fire services
Authors: Lauricella Sharon , Pankhurst Kristy-Lynn 
Published: March 2018

Purpose
The purpose of this paper is to examine how fire services use social media to educate the public about safety and fire prevention.

Design/methodology/approach
Grounded theoretical methods were employed in a rigorous qualitative analysis of five significant fire services’ Twitter accounts in Ontario, Canada.

Findings
Seven main themes emerged from the data, with an overarching conclusion that tweets made by fire service organisations and professionals do not focus primarily on fire safety.

Research limitations/implications
This paper addresses a gap in the literature in terms of understanding how social media communicates information about all three lines of defence against fire, with a focus on the first two: public fire safety education, fire safety standards and enforcement and emergency response.

Practical implications
The authors suggest that fire services need to employ a more segmented approach to social media posts with an objective to engage and educate the public.

Originality/value
This paper is the first extensive qualitative analysis to consider the particulars of fire services’ social media presence.
The analysis of entry of Ethiopian enterprises into the export-markets and the associated factors
Authors: Lemessa Sisay Diriba , Watabaji Mulugeta Damie , Yismaw Molla Alemayehu 
Published: March 2018

PurposeThough many studies in the past dealt with the survival and growth of enterprises both in the local- and export-markets, less attention was given to the analysis of the duration of enterprises entry into the export-markets. The aim of this paper is, therefore, to analyze the duration of Ethiopian enterprises entry into the export-markets.Design/methodology/approachThis paper used data collected from 848 enterprises through a cross-sectional survey method conducted by the World Bank in 2015. In order to estimate the average duration – the time that enterprises need to wait before entering into the export-markets and the associated factors – the authors used the mixture of non-parametric (Kaplan-Meier) and parametric (Weibull) models.FindingsThe non-parametric results show that enterprises are required to wait for an average of about eight years before entering into the export-markets after their establishment. In addition, foreign-owned enterprises were found to be faster in entering into the export-markets than their domestically owned counterparts. The parametric results revealed that enterprises’ product innovation, enterprises’ size and age, and custom and trade regulations are factors that curtail the durations of enterprises entry into the export-markets. On the other hand, enterprises’ operational costs, the size of enterprises’ locality, and enterprises’ location are factors that slow the durations of enterprises’ entry into the export-markets.Originality/valueThis study is the first to offer pioneering evidences on the duration (time in years) that Ethiopian enterprises need to wait before entering into the export-markets and the factors that affect the length of their waiting time.
Existential leadership coaching in a medical partnership
Authors: Spencer Eric David , Albertyn Ruth 
Published: March 2018

Purpose
This paper aims to report on a case study conducted in a private medical partnership of more than 50 specialist physicians where the researcher applied a leadership coaching model grounded in existential philosophy. The paper asserts that existential leadership coaching can be a novel and effective means to address leadership development needs in the unique context of a professional partnership.

Design/methodology/approach
The qualitative phenomenological study used a bounded case study design using four purposively selected specialist physicians who were involved in four individual structured coaching sessions over an eight-week period. Data came in writing from participants in the form of reflective questions before and after the coaching, and note-taking on index cards during the coaching process. Data also came from the coach/researcher as a participant observer in the form of note-taking and a reflective journal.

Findings
Findings indicate that working with perceptions of leadership in existential coaching conversations can provide a mechanism for members of a partnership to find greater purpose, and choose how they can contribute better to leadership development in their collective. Findings indicate that the process of imaging the perceptions of fellow partners can unlock the identification of and choice for developmental actions and contributions to the collective.

Research limitations/implications
For the selected qualitative design, the researcher as the participant observer provided advantages such as insider access and depth of engagement. The study was limited to a small sample in a particular time and context. Findings are thus viewed in the light of this unique case.

Practical implications
Such a qualitative phenomenological case study provides glimpses into the lives of real-life leaders and offers the coaching, academic and medical fraternities an insider understanding of leadership development in the case of professional partnerships.

Originality/value
The paper points to a mechanism which may be a means to unlock potential and facilitate leadership development in the context of professional partnerships.
Does external auditing combat corruption? Evidence from private firms
Authors: Farooq Omar , Shehata Nermeen F. 
Published: March 2018

PurposeThis paper aims to document whether firms with audited financial statements pay lower bribes to get contracts than firms without audited financial statements. In other words, this study assesses whether external auditing helps combat corruption.Design/methodology/approachThe World Bank Enterprise Survey data covering the period between 2006 and 2014 is used. The total sample comprised more than 50,000 firms in 126 countries.FindingsThis paper finds that firms with audited financial statements pay significantly lower bribes compared to firms with unaudited financial statements. The results are robust across various estimation procedures, various proxies for bribery and various sub-samples. It is also found that the relationship between audited financial statements and bribery is more pronounced in environments where firms face higher pressure to engage in corrupt practices.Practical implicationsThe results imply that auditing of financial statements can act as a disciplining device to curb bribery in environments that encourage corruption.Originality/valueThis paper is the first attempt, according to the authors’ knowledge, to examine the relationship between external auditing and corruption using firm-level data that cover 126 countries and is gathered over a 14-year period. Therefore, the results derived from this study are generalizable.
Design, qualification and Shariah governance of stock screening methodologies in selected Gulf Cooperation Council (GCC) countries in comparison with the United States
Authors: Kasi Umayal , Muhammad Junaina 
Published: March 2018

Purpose
This paper aims to compare and analyse the aspects of Shariah screening methodologies within the selected Gulf Cooperation Council (GCC) countries as well as comparing the methodologies with the USA, and to examine how Shariah screening methodologies affect financing and investing activities of a firm.

Design/methodology/approach
Shariah screening methodologies within the selected GCC countries and between the GCC countries and the USA are compared on the basis of the data collected from secondary sources.

Findings
Design, qualification and Shariah governance set the Shariah screening methodologies within the GCC countries apart. Feasibility, duration, economic viability and funds required differentiate these Shariah screening methodologies between the GCC countries and the USA. Shariah screening methodologies implied in the USA is more stringent than in the GCC countries.

Research limitations/implications
The suggestions in this study include using a longer research timeline, examining many more number of countries’ Shariah screening methodologies and exploring other types of Shariah screening methodologies.

Practical implications
The possibility of generalising the implementation of strict and uniform Shariah screening methodologies across all the country-specific Shariah indices amongst Muslim nations, globally, is likely to benefit all the Muslim countries, by strengthening the understanding, interaction and economic co-operation amongst these countries.

Social implications
People’s needs can be tended to if Maqasid Al-Shariah (objectives of Shariah) is achieved through flexibility, dynamism and creativity within the social policy.

Originality/value
Aspects of Shariah screening methodologies are compared and contrasted within the selected GCC countries as well as between the GCC countries and the United States and the role of Shariah screening methodologies is examined in order to determine the extent of what is Shariah-Compliant and what is Non-Shariah Compliant for a firm.
Cell Swelling Induced by the Antimalarial KAE609 (Cipargamin) and Other PfATP4-Associated Antimalarials
Authors: Dennis Adelaide S. M. , Lehane Adele M. , Ridgway Melanie C. , Holleran John P. , Kirk Kiaran 
Published: March 2018

ABSTRACT

For an increasing number of antimalarial agents identified in high-throughput phenotypic screens, there is evidence that they target PfATP4, a putative Na
+
efflux transporter on the plasma membrane of the human malaria parasite
Plasmodium falciparum
. For several such “PfATP4-associated” compounds, it has been noted that their addition to parasitized erythrocytes results in cell swelling. Here we show that six structurally diverse PfATP4-associated compounds, including the clinical candidate KAE609 (cipargamin), induce swelling of both isolated blood-stage parasites and intact parasitized erythrocytes. The swelling of isolated parasites is dependent on the presence of Na
+
in the external environment and may be attributed to the osmotic consequences of Na
+
uptake. The swelling of the parasitized erythrocyte results in an increase in its osmotic fragility. Countering cell swelling by increasing the osmolarity of the extracellular medium reduces the antiplasmodial efficacy of PfATP4-associated compounds, consistent with cell swelling playing a role in the antimalarial activity of this class of compounds.
Outcome of E1224-Benznidazole Combination Treatment for Infection with a Multidrug-Resistant Trypanosoma cruzi Strain in Mice
Authors: Diniz Lívia de Figueiredo , Mazzeti Ana Lia , Caldas Ivo Santana , Ribeiro Isabela , Bahia Maria Terezinha 
Published: March 2018

ABSTRACT

Combination therapy has been proposed as an alternative therapeutic approach for the treatment of Chagas disease. In this study, we evaluated the effect of treatment with benznidazole combined with E1224 (ravuconazole prodrug) in an experimental murine model of acute infection. The first set of experiments assessed the range of E1224 doses required to induce parasitological cure using
Trypanosoma cruzi
strains with different susceptibilities to benznidazole (Y and Colombian). All E1224 doses were effective in suppressing the parasitemia and preventing death; however, parasitological cure was observed only in mice infected with Y strain. Considering these results, we evaluated the effect of combined treatment against Colombian, a multidrug-resistant
T. cruzi
strain. After exclusion of antagonistic effects using
in vitro
assays, infected mice were treated with E1224 and benznidazole in monotherapy or in combination at day 4 or 10 postinoculation. All treatments were well tolerated and effective in suppressing parasitemia; however, parasitological and PCR assays indicated no cure among mice treated with monotherapies. Intriguingly, the outcome of combination therapy was dependent on treatment onset. Early treatment using optimal doses of E1224-benznidazole induced a 100% cure rate, but this association could not eliminate a well-established infection. The beneficial effect of combination therapy was evidenced by further reductions of the patent parasitemia period in the group receiving combined therapy compared with monotherapies. Our results demonstrated a positive interaction between E1224 and benznidazole against murine
T. cruzi
infection using a multidrug-resistant strain and highlighted the importance of a stringent experimental model in the evaluation of new therapies.