bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-Experiment Nonlinear Mixed Effect Modeling of Single-Cell Translation Kinetics after Transfection
Authors: Fröhlich F. , Reiser A. , Fink L. , Woschée D. , Ligon T. , Theis F. J. , Rädler J. O. , Hasenauer J. 
Published: March 2018

SummarySingle-cell time-lapse studies have advanced the quantitative understanding of cell-to-cell variability. However, as the information content of individual experiments is limited, methods to integrate data collected under different conditions are required.Here we present a multi-experiment nonlinear mixed effect modeling approach for mechanistic pathway models, which allows the integration of multiple single-cell perturbation experiments. We apply this approach to the translation of green fluorescent protein after transfection using a massively parallel read-out of micropatterned single-cell arrays. We demonstrate that the integration of data from perturbation experiments allows the robust reconstruction of cell-to-cell variability, i.e., parameter densities, while each individual experiment provides insufficient information. Indeed, we show that the integration of the datasets on the population level also improves the estimates for individual cells by breaking symmetries, although each of them is only measured in one experiment. Moreover, we confirmed that the suggested approach is robust with respect to batch effects across experimental replicates and can provide mechanistic insights into the nature of batch effects. We anticipate that the proposed multi-experiment nonlinear mixed effect modeling approach will serve as a basis for the analysis of cellular heterogeneity in single-cell dynamics.
Leveraging Existing 16S rRNA Gene Surveys to Identify Reproducible Biomarkers in Individuals with Colorectal Tumors
Authors: Sze Marc A , Schloss Patrick D 
Published: March 2018

AbstractAn increasing body of literature suggests that both individual and collections of bacteria are associated with the progression of colorectal cancer. As the number of studies investigating these associations increases and the number of subjects in each study increases, a meta-analysis to identify the associations that are the most predictive of disease progression is warranted. We analyzed previously published 16S rRNA gene sequencing data collected from feces and colon tissue. We quantified the odds ratios (ORs) for individual bacterial taxa that were associated with an individual having tumors relative to a normal colon. Among the fecal samples, there were no taxa that had significant ORs associated with adenoma and there were 8 taxa with significant ORs associated with carcinoma. Similarly, among the tissue samples, there were no taxa that had a significant OR associated with adenoma and there were 3 taxa with significant ORs associated with carcinoma. Among the significant ORs, the association between individual taxa and tumor diagnosis was equal or below 7.11. Because individual taxa had limited association with tumor diagnosis, we trained Random Forest classification models using only the taxa that had significant ORs, using the entire collection of taxa found in each study, and using operational taxonomic units defined based on a 97% similarity threshold. All training approaches yielded similar classification success as measured using the Area Under the Curve. The ability to correctly classify individuals with adenomas was poor and the ability to classify individuals with carcinomas was considerably better using sequences from fecal or tissue.ImportanceColorectal cancer is a significant and growing health problem in which animal models and epidemiological data suggest that the colonic microbiota have a role in tumorigenesis. These observations indicate that the colonic microbiota is a reservoir of biomarkers that may improve our ability to detect colonic tumors using non-invasive approaches. This meta-analysis identifies and validates a set of 8 bacterial taxa that can be used within a Random Forest modeling framework to differentiate individuals as having normal colons or carcinomas. When models trained using one dataset were tested on other datasets, the models performed well. These results lend support to the use of fecal biomarkers for the detection of tumors. Furthermore, these biomarkers are plausible candidates for further mechanistic studies into the role of the gut microbiota in tumorigenesis.
Error Correcting Optical Mapping Data
Authors: Mukherjee Kingshuk , Washimkar Darshan , Muggli Martin D. , Salmela Leena , Boucher Christina 
Published: March 2018

AbstractOptical mapping is a unique system that is capable of producing high-resolution, high-throughput genomic map data that gives information about the structure of a genome [21]. Recently it has been used for scaffolding contigs and assembly validation for large-scale sequencing projects, including the maize [32], goat [6], and amborella [4] genomes. However, a major impediment in the use of this data is the variety and quantity of errors in the raw optical mapping data, which are called Rmaps. The challenges associated with using Rmap data are analogous to dealing with insertions and deletions in the alignment of long reads. Moreover, they are arguably harder to tackle since the data is numerical and susceptible to inaccuracy. We develop cOMet to error correct Rmap data, which to the best of our knowledge is the only optical mapping error correction method. Our experimental results demonstrate that cOMet has high prevision and corrects 82.49% of insertion errors and 77.38% of deletion errors in Rmap data generated from the E. coli K-12 reference genome. Out of the deletion errors corrected, 98.26% are true errors. Similarly, out of the insertion errors corrected, 82.19% are true errors. It also successfully scales to large genomes, improving the quality of 78% and 99% of the Rmaps in the plum and goat genomes, respectively. Lastly, we show the utility of error correction by demonstrating how it improves the assembly of Rmap data. Error corrected Rmap data results in an assembly that is more contiguous, and covers a larger fraction of the genome.
Association of predicted deleterious single nucleotide polymorphisms with carcass traits in meat-type chickens
Authors: Trevisoli Priscila Anchieta , Monteiro Moreira Gabriel Costa , Boschiero Clarissa , Mello Cesar Aline Silva , Petrini Juliana , Ledur Mônica Corrêa , Mourão Gerson Barreto , Coutinho Luiz Lehmann 
Published: March 2018

ABSTRACTIn previous studies, we used genome wide association (GWAS) to identify quantitative trait loci (QTL) associated with weight and yield of abdominal fat, drumstick, thigh and breast traits in chickens. However, this methodology assumes that the studied variants are in linkage disequilibrium with the causal mutation and consequently do not identify it. In an attempt to identify causal mutations in candidate genes for carcass traits in broilers, we selected 20 predicted deleterious SNPs within QTLs for association analysis. Additive, dominance and allele substitution effects were tested. From the 20 SNPs analyzed, we identified six SNPs with significant association (p-value <0.05) with carcass traits, and three are highlighted here. The SNP rs736010549 was associated with drumstick weight and yield with significant additive and dominance effects. The SNP rs739508259 was associated with thigh weight and yield, and with significant additive and allele substitution effects. The SNP rs313532967 was associated with breast weight and yield. The three SNPs that were associated with carcass traits (rs736010549, rs739508259 and rs313532967) are respectively located in the coding regions of the WDR77, VWA8 and BARL genes. These genes are involved in biological processes such as steroid hormone signaling pathway, estrogen binding, and regulation of cell proliferation. Our strategy allowed the identification of putative casual mutations associated with muscle growth.
Metabolic adaptations underlie epigenetic vulnerabilities in chemoresistant breast cancer
Authors: Deblois Geneviève , Tonekaboni Seyed Ali Madani , Kao Yunchi Ingrid , Tai Felicia , Liu Xiaojing , Ettayebi Ilias , Guilhamon Paul , Fedor Alexandra , Grillo Giacomo , Murison Alexander , Ba alawi Wail , Cescon David , Arrowsmith Cheryl , DeCarvalho Daniel , Park Morag , Haibe-Kains Benjamin , Locasale Jason W. , Lupien Mathieu 
Published: March 2018

SUMMARYCancer cell survival upon cytotoxic drug exposure leads to changes in cell identity, dictated by the epigenome. Several metabolites serve as substrates or co-factors to chromatin-modifying enzymes, suggesting that metabolic changes can underlie change in cell fate. Here, we show that progression of triple-negative breast cancer (TNBC) to taxane-resistance is characterized by altered methionine metabolism and S-adenosylmethionine (SAM) availability, giving rise to DNA hypomethylation in regions enriched for transposable elements (TE). Compensatory redistribution of H3K27me3 forming Large Organized Chromatin domains of lysine (K) modification (LOCK) prevents expression of TE in taxane-resistant cells. Pharmacological inhibition of EZH2, the H3K27me3 methyltransferase, alleviates TE repression, leading to the accumulation of dsRNA and activation of the interferon viral mimicry-response, specifically inhibiting the growth of taxane-resistant TNBC. Together, our work delineates a role for metabolic adaptations in redefining the epigenome of taxane-resistant TNBC cells and underlies an epigenetic vulnerability toward pharmacological inhibition of EZH2.
Influenza A virus superinfection potential is regulated by viral genomic heterogeneity
Authors: Sun Jiayi , Brooke Christopher B. 
Published: March 2018

AbstractDefining the specific factors that govern the evolution and transmission of influenza A virus (IAV) populations is of critical importance for designing more effective prediction and control strategies. Superinfection, the sequential infection of a single cell by two or more virions, plays an important role in determining the replicative and evolutionary potential of IAV populations. The prevalence of superinfection during natural infection, and the specific mechanisms that regulate it, remain poorly understood. Here, we used a novel single virion infection approach to directly assess the effects of individual IAV genes on superinfection efficiency. Rather than implicating a specific viral gene, this approach revealed that superinfection susceptibility is determined by the total number of viral genes expressed, independent of their identity. IAV particles that expressed a complete set of viral genes potently inhibit superinfection, while semi-infectious particles (SIPs) that express incomplete subsets of viral genes do not. As a result, virus populations that contain more SIPs undergo more frequent superinfection. These findings identify both a major determinant of IAV superinfection potential and a prominent role for SIPs in promoting viral co-infection.
Frequent Monitoring of C-peptide Levels in Newly Diagnosed Type 1 Subjects Using Dried Blood Spots Collected at Home
Authors: Willemsen Ruben H. , Burling Keith , Barker Peter , Ackland Fran , Dias Renuka P. , Edge Julie , Smith Anne , Todd John , Lopez Boryana , Mander Adrian P. , Guy Catherine , Dunger David B. 
Published: March 2018

AbstractObjectiveTo evaluate a novel approach to measure ß-cell function by frequent testing of C-peptide concentrations in ‘dried blood spots’ (DBS)PatientsThirty-two children, aged 7-17 years, recently diagnosed with type 1 diabetes.DesignMixed-meal-tolerance-test (MMTT) within 6 and again 12 months after diagnosis with paired venous and DBS C-peptide sampling at 0 and 90 minutes. Weekly DBS C-peptide before and after standardized breakfasts collected at home.ResultsDBS and plasma C-peptide levels (n=115) correlated strongly (r=0·91; p<0.001). The Bland-Altman plot indicated good agreement. The median number of home-collected DBS cards per participant was 24 over a median of 6.9 months. Repeated DBS C-peptide levels varied considerably within and between subjects. Adjustment for corresponding home glucose measurements reduced the variance permitting accurate description of changes over time. The correlation of the C-peptide slope over time assessed by repeated home DBS versus area under the curve during the two MMTTs was r=0·73; p<0.001. Mixed models showed that a 1-month increase of diabetes duration was associated with 17 pmol/l decline in fasting DBS C-peptide, whereas increases of 1 mmol/l in glucose, 1 year older age-at-diagnosis and 100 pmol/l higher baseline plasma C-peptide were associated with 18, 17 and 61 pmol/l higher fasting DBS C-peptide levels, respectively. In addition, glucose responsiveness decreased with longer diabetes duration.ConclusionOur approach permitted frequent assessment of C-peptide, making it feasible to monitor ß-cell function at home. Evaluation of changes in the slope of C-peptide using this method may permit short-term evaluation of promising interventions.
Of Rats And Men: Peer Presence And Familiarity Are Key Factors Which Reduce Drug Intake
Authors: Giorla E , Nordmann S , Pelloux Y , Roux P , Rosellini S , Davranche K , Montanari C , Vilotitch A , Huguet P , Carrieri P , Baunez C 
Published: March 2018

ABSTRACTSocial environment influences drug consumption, its persistence and evolution. Little is known regarding the influence of the presence of a peer during drug consumption and especially how the relationship between peers (familiarity and dominance) can influence drug consumption. We used here a translational and transdisciplinary approach to explore the influence of peer presence and peer familiarity in rats and humans that self-administer stimulants. In rats, cocaine intake was compared when rats were alone with intake when peers with different characteristics (familiar or not, cocaine naive or not, dominant or subordinate) were present. In humans, 77 cocaine and/or methylphenidate users were asked to detail their most recent drug use episodes and their relationship with peers present at consumption. The results show that in both humans and rats, the risk of cocaine/stimulant consumption was significantly reduced by 37% and 32%, respectively, when a peer was present. Moreover, the lowest risk of consumption was consistently observed when the peer was unfamiliar (vs familiar) with a further 38% and 17% risk reduction, respectively. In rats, a decreased risk of consumption was greater when the peer was cocaine naive (vs non-cocaine naive).The presence of a non-familiar and possibly drug-naive peer is the most efficient condition to diminish stimulant intake. Our results indirectly support the use of harm reduction strategies, in particular supervised consumption rooms for stimulant users.
The intersection of mindsets and self-regulated learning
Authors: Lyons Paul , Bandura Randall 
Published: March 2018

Purpose
The purpose of this paper is to address the intersection of two important areas related to employee development: mindsets and self-regulated learning. These concepts suggest opportunities for managerial influence over employee behavior which may ultimately enhance organizational culture and functioning.

Design/methodology/approach
The concepts of mindsets and self-regulated learning are connected in such a way as to yield some managerial approaches to generate positive outcomes for organizations. A brief summary of the relevant literature provides a base for the positive organizational outcomes that may be obtained through a manager’s combined understanding of these two concepts.

Findings
Understanding how the concepts of mindsets and self-regulated learning are related can provide managers with tools to be used in encouraging employees toward a strengthened ability to learn, adapt, and become more valuable to the organization.

Originality/value
Useful approaches to boosting employees’ inclination to learn, adapt, change, and improve performance are developed from existing academic research.
Younger and older trust in a crisis situation
Authors: Moliner-Tena Miguel Angel , Fandos-Roig Juan Carlos , Estrada-Guillén Marta , Monferrer-Tirado Diego 
Published: March 2018

PurposeThe purpose of this paper is to analyze consumer trust during a financial crisis, studying its antecedents and consequences. The perceptions of older and younger consumers are also compared.Design/methodology/approachThe theoretical model of trust formation is tested on a random sample of 634 individuals from the three largest Spanish cities, Madrid, Barcelona and Valencia, in a period of economic crisis. Structural equation models were used to verify the global hypothesized relationships. Additionally, the total sample was divided into two groups (younger and older consumers) in order to test the moderating effect of age in the proposed relationships.FindingsIn a period of financial crisis, older consumers’ trust is protected by an emotional and experiential shield from the effects of negative news in the surrounding environment. In contrast, trust, although important, is not the core variable for the younger segment, whose preferences are the consequence of a broad range of cognitive and emotional variables.Research limitations/implicationsThis research was carried out on financial services. Emotional, relational and experience-linked variables acquire greater importance as the individual gets older, in contrast to more cognitive evaluations. The difference between the younger and the older segments is that the cornerstone of older consumers’ attitudinal loyalty is trust, whereas for younger people, it is positive switching costs or rewards. Further research on the proposed conceptual model across different industries and countries is needed to determine the generalizability and consistency of the findings from this study.Practical implicationsThis paper has significant managerial implications. The authors believe that the best strategy for a bank during a period of crisis is to follow a customer-friendly orientation, as in the case of banks that took a long-term vision to look after their brand image. The study draws banking companies’ attention to the importance of using age as a segmentation criterion.Originality/valueBased on the life-course paradigm, a theoretical model of trust formation is performed. In a period of economic crisis, trust becomes the key variable in determining older consumers’ preferences.
The effects of the elaboration likelihood model on initial trust formation in financial advisory services
Authors: Silic Mario , Ruf Christian 
Published: March 2018

PurposeIn order for financial institutions to cope with increased competitive pressure from the financial technology companies, offering digital services such as a mobile service system (MSS) targeted for high net worth individuals (HNWIs) becomes critical. Despite long-term trustworthy relationships between HNWIs and financial advisors, studies suggest that the formation of initial trust poses a significant challenge. The purpose of this paper is to identify various features related to initial trust antecedents.Design/methodology/approachThe study was conducted using the survey data, and employs variance-based structural equation modeling (SEM) techniques to test hypotheses.FindingsThe findings from a closed experiment with 107 participants suggest that compared to more traditional service systems, customers are more prone to the construct of service quality, and specifically professional, prompt, dependable and timely financial advice.Originality/valueThe study validated key constructs that positively influence the initial trust formation process and ultimately the intention to use in an MSS for the financial advisory. The authorts particularly emphasized the rebalancing and monitoring steps in the financial planning process between HNWIs and client advisors.
Crowdsourcing
Authors: Wilson Kathleen Bridget , Bhakoo Vikram , Samson Danny 
Published: March 2018

PurposeThe purpose of this paper is to link crowdsourcing, operations management (OM) and project management (PM). The study demonstrates how crowdsourcing as an open innovation mechanism is operationalised within a complex PM context. Specifically, the study seeks to understand how crowdsourcing as a novel form of OM improves key outcomes.Design/methodology/approachThe authors conducted exploratory research involving five pure-play crowdsourcing firms based in the USA and Australia.FindingsThe findings indicate that the firms practise a form of crowdsourcing that allows flexible, efficient and low risk operations and links to contemporary notions of PM such as projectification and project society. The crowd can be used in a new manner to boost success factors tied to PM through open innovation and operational novelty. In terms of OM, crowdsourcing offers flexibility, speed, dynamism and scalability to project processes.Research limitations/implicationsThis research is based on five case studies. Further fine-grained, longitudinal research is required to fully understand this phenomenon in a wider range of contexts.Practical implicationsThe paper contributes to practices tied to open innovation and provides guidance on how organisations might use large crowds to enhance PM success.Originality/valueThe study represents early scholarship on crowdsourcing and project operations. It makes three contributions. First, the authors introduce a new theoretical framework linking PM and novel aspects of crowdsourcing to extend understandings of projectification, as well as open innovation frameworks. Second, the authors showcase the flexibility and fluidity of the crowdsourcing project process. Third, the authors examine crowdsourcing operations in terms of size, efficiency and scalability which results in timely and efficient output due to innovative technology, along with the element of trust among stakeholders.
Comparative financing of megacities in multi-level BRICS states
Authors: Salm Marco 
Published: March 2018

PurposeThe BRICS states are based on multi-level government’s architecture whose megacities have an outstanding role in their respective states – not only in terms of population and in terms of economic power, but also in terms of local own-tax revenue collection, which, in turn, implies a very strong administration. At the same time, megacities are facing increasing public expenditures because of infrastructure needs, housing shortage, growth of social inequality, and environmental degradation. In order to outweigh the urban advantages associated with urbanization, reconsidering the fiscal framework is of urgent need. The paper aims to discuss these issues.Design/methodology/approachMost similar case design is applied.FindingsMegacities are at the forefront of national economic growth, that they have an above average tax base, an excellent administration, and therefore, face above average yields of property tax revenues. Rethinking the fiscal framework could considerably improve local finances.Research limitations/implicationsDue to limitations on public finance statistics, the sample draws on four megacities in BRICS, in reference to all megacities, only.Practical implicationsIn context of Habitat III, New Urban Agenda, the practical implications are manyfold: the paper focuses on megacities, its finances (financing for development), and social implications involved.Social implicationsLocal public finance, especially property taxation, has many implications on social level.Originality/valueThe paper is one in a kind.