bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of a pig influenza challenge model for evaluation of monoclonal antibody delivery platforms
Authors: McNee Adam , Smith Trevor , Holzer Barbara , Clark Becky , Bessell Emily , Guibinga Ghiabe , Brown Heather , Schultheis Katherine , Fisher Paul , Ramos Stephanie , Nunez Alejandro , Bernard Matthieu , Martini Veronica , Chrun Tiphany , Xiao Yongli , Kash John C. , Taubenberger Jeffery K. , Elliott Sarah , Patel Ami , Beverley Peter , Rijal Pramila , Weiner David , Townsend Alain , Broderick Kate , Tchilian Elma 
Published: March 2020

AbstractMonoclonal antibodies are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing monoclonal antibodies. We show that a strongly neutralizing monoclonal antibody (2-12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2-12C or a DNA plasmid encoded version of 2-12C, reduced pathology and viral load in the lungs, but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate monoclonal antibodies and emerging delivery platforms prior to human trials.
Targeted mutagenesis of Δ5 and Δ6 fatty acyl desaturases induce multiplex-mutagenesis and lipogenesis in Atlantic salmon (Salmo salar)
Authors: Jin Yang , Datsomor Alex K. , Olsen Rolf E. , Vik Jon Olav , Torgersen Jacob S. , Edvardsen Rolf B. , Wargelius Anna , Winge Per , Grammes Fabian 
Published: March 2020

AbstractWith declining wild fish populations, farmed Atlantic salmon (Salmo salar) has gained popularity as a source for healthy long-chain highly unsaturated fatty acids (LC-HUFA) including 20:5n-3 and 22:6n-3. However, the introduction of plant-based oil in fish diets has reduced the content of these beneficial LC-HUFA. The capability of biosynthesis of LC-HUFAs depends on fatty acids supplied in diets and the genetic potential residing in the fish. Key proteins involved in LC-HUFA synthesis in salmon include fatty acid desaturases 2 (Fads2). In a recent study we used CRISPR/Cas9 to generate two F0 mutant strains of salmon, 1)Δ6abc/5Mtwith mutations inΔ5fads2, Δ6fads2-a, Δ6fads2-b and Δ6fads2-cgenes, and 2)Δ6bcMtwith mutations inΔ6fads2-b and Δ6fads2-cgenes. The CRISPR mutated salmon (crispants) had reduced levels of LC-HUFA and expression of targetedfads2genes. In present study we apply whole transcriptome analysis on thesefads2crispants. Our purpose is to evaluate the genetic mosaicism infads2crispants and the effect these mutations had on other lipid metabolism pathways in fish. BothΔ6abc/5MtandΔ6bcMtcrispants demonstrated high percentage of indels within all intended target genes, though different indel types and percentage were observed between individuals. Skipping of a CRISPR-targeted exon was observed inΔ6fads2-agene ofΔ6abc/5Mtsalmon. TheΔ6abc/5Mtfish also displayed several disruptive indels which resulted in over 100 differentially expressed genes (DEGs) enriched in lipid metabolism pathways in liver. This includes up-regulation ofsrebp1genes as well as genes involved in fatty acidde-novosynthesis, fatty acidβ-oxidation and lipogenesis. Bothelovl5andelovl2genes were not changed, suggesting that the genes were not targeted by Srebp1. The mutation ofΔ6bcMtsurprisingly resulted in over 3000 DEGs which were enriched in factors encoding genes involved in mRNA regulation and stability.
Molecular resolution imaging by post-labeling expansion single-molecule localization microscopy (Ex-SMLM)
Authors: Zwettler Fabian U. , Reinhard Sebastian , Gambarotto Davide , Bell Toby D. M. , Hamel Virginie , Guichard Paul , Sauer Markus 
Published: March 2020

AbstractExpansion microscopy (ExM) enables super-resolution fluorescence imaging of physically expanded biological samples with conventional microscopes. By combining expansion microscopy (ExM) with single-molecule localization microscopy (SMLM) it is potentially possible to approach the resolution of electron microscopy. However, current attempts to combine both methods remained challenging because of protein and fluorophore loss during digestion or denaturation, gelation, and the incompatibility of expanded polyelectrolyte hydrogels with photoswitching buffers. Here we show that re-embedding of expanded hydrogels enablesdSTORM imaging of expanded samples and demonstrate that post-labeling ExM resolves the current limitations of super-resolution microscopy. Using microtubules as a reference structure and centrioles, we demonstrate that post-labeling Ex-SMLM preserves ultrastructural details, improves the labeling efficiency and reduces the positional error arising from linking fluorophores into the gel thus paving the way for super-resolution imaging of immunolabeled endogenous proteins with true molecular resolution.
Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size
Authors: Buenzli Pascal R. , Lanaro Matthew , Wong Cynthia S. , McLaughlin Maximilian P. , Allenby Mark C. , Woodruff Maria A. , Simpson Matthew J. 
Published: March 2020

AbstractTissue growth in bioscaffolds is influenced significantly by pore geometry, but how this geometric dependence emerges from dynamic cellular processes such as cell proliferation and cell migration remains poorly understood. Here we investigate the influence of pore size on the time required to bridge pores in thin 3D-printed scaffolds. Experimentally, new tissue infills the pores continually from their perimeter under strong curvature control, which leads the tissue front to round off with time. Despite the varied shapes assumed by the tissue during this evolution, we find that time to bridge a pore simply increases linearly with the overall pore size. To disentangle the biological influence of cell behaviour and the mechanistic influence of geometry in this experimental observation, we propose a simple reaction–diffusion model of tissue growth based on Porous-Fisher invasion of cells into the pores. First, this model provides a good qualitative representation of the evolution of the tissue; new tissue in the model grows at an effective rate that depends on the local curvature of the tissue substrate. Second, the model suggests that a linear dependence of bridging time with pore size arises due to geometric reasons alone, not to differences in cell behaviours across pores of different sizes. Our analysis suggests that tissue growth dynamics in these experimental constructs is dominated by mechanistic crowding effects that influence collective cell proliferation and migration processes, and that can be predicted by simple reaction–diffusion models of cells that have robust, consistent behaviours.
HisTrader: A Tool to Identify Nucleosome Free Regions from ChIP-Seq of Histone Post-Translational Modifications
Authors: Yan Yifei , Gnanapragasam Ansley , Bailey Swneke 
Published: March 2020

ABSTRACTMotivationChromatin immuno-precipitation sequencing (ChIP-Seq) of histone post-translational modifications coupled withde novomotif elucidation and enrichment analyses can identify transcription factors responsible for orchestrating transitions between cell-and disease-states. However, the identified regulatory elements can span several kilobases (kb) in length, which complicates motif-based analyses. Restricting the length of the target DNA sequence(s) can reduce false positives. Therefore, we present HisTrader, a computational tool to identify the regions accessible to transcription factors, nucleosome free regions (NFRs), within histone modification peaks to reduce the DNA sequence length required for motif analyses.ResultsHisTrader accurately identifies NFRs from H3K27Ac ChIP-seq profiles of the lung cancer cell line A549, which are validated by the presence of DNaseI hypersensitivity. In addition, HisTrader reveals that multiple NFRs are common within individual regulatory elements; an easily overlooked feature that should be considered to improve sensitivity of motif analyses using histone modification ChIP-seq data.Availability and implementationThe HisTrader script is open-source and available on GitHub (https://github.com/SvenBaileyLab/Histrader) under a GNU general public license (GPLv3). HisTrader is written in PERL and can be run on any platform with PERL installed.
Autofluorescence imaging of 3D tumor-macrophage microscale cultures resolves spatial and temporal dynamics of macrophage metabolism
Authors: Heaster Tiffany M. , Humayun Mouhita , Yu Jiaquan , Beebe David J. , Skala Melissa C. 
Published: March 2020

ABSTRACTMacrophages within the tumor microenvironment (TME) exhibit a spectrum of pro-tumor and anti-tumor functions, yet it is unclear how the TME regulates this macrophage heterogeneity. Standard methods to measure macrophage heterogeneity require destructive processing, limiting spatiotemporal studies of function within the live, intact 3D TME. Here, we demonstrate two-photon autofluorescence imaging of NAD(P)H and FAD to non-destructively resolve spatiotemporal metabolic heterogeneity of individual macrophages within 3D microscale TME models. Fluorescence lifetimes and intensities of NAD(P)H and FAD were acquired at 24, 48, and 72 hours post-stimulation for mouse macrophages (RAW 264.7) stimulated with IFN-γ or IL-4 plus IL-13 in 2D culture, validating that autofluorescence measurements capture known metabolic phenotypes. To quantify metabolic dynamics of macrophages within the TME, mouse macrophages or human monocytes (RAW264.7 or THP-1) were cultured alone or with breast cancer cells (mouse PyVMT or primary human IDC) in 3D microfluidic platforms. Human monocytes and mouse macrophages in tumor co-cultures exhibited significantly different FAD mean lifetimes and greater migration than mono-cultures at 24, 48, and 72 hours post-seeding. In co-cultures with primary human cancer cells, actively-migrating monocyte-derived macrophages had greater redox ratios (NAD(P)H/FAD intensity) compared to passively-migrating monocytes at 24 and 48 hours post-seeding, reflecting metabolic heterogeneity in this sub-population of monocytes. Genetic analyses further confirmed this metabolic heterogeneity. These results establish label-free autofluorescence imaging to quantify dynamic metabolism, polarization, and migration of macrophages at single-cell resolution within 3D microscale models. This combined culture and imaging system provides unique insights into spatiotemporal tumor-immune crosstalk within the 3D TME.
A faster and more accurate algorithm for calculating population genetics statistics requiring sums of Stirling numbers of the first kind
Authors: Chen Swaine L. , Temme Nico M. 
Published: March 2020

AbstractStirling numbers of the first kind are used in the derivation of several population genetics statistics, which in turn are useful for testing evolutionary hypotheses directly from DNA sequences. Here, we explore the cumulative distribution function of these Stirling numbers, which enables a single direct estimate of the sum, using representations in terms of the incomplete beta function. This estimator enables an improved method for calculating an asymptotic estimate for one useful statistic, Fu’sFs. By reducing the calculation from a sum of terms involving Stirling numbers to a single estimate, we simultaneously improve accuracy and dramatically increase speed.
The Genetic Architecture of Leaf Stable Carbon Isotope Composition inZea maysand the Effect of Transpiration Efficiency on Elemental Accumulation
Authors: Sorgini Crystal A. , Roberts Lucas M. , Cousins Asaph B. , Baxter Ivan , Studer Anthony J. 
Published: March 2020

ABSTRACTWith increased demand on freshwater resources for agriculture, it is imperative that more water-use efficient crops are developed. Leaf stable carbon isotope composition, δ13C, is a proxy for transpiration efficiency and a possible tool for breeders, but the underlying mechanisms effecting δ13C in C4plants are not known. It has been suggested that differences in specific leaf area, which potentially reflects variation in internal CO2diffusion, can impact leaf δ13C. However, at this point the relationship has not been tested in maize. Furthermore, although it is known that water movement is important for elemental uptake, it is not clear how manipulation of transpiration for increased water-use efficiency may impact nutrient accumulation. Here we characterize the underlying genetic architecture of leaf δ13C and test its relationship to specific leaf area and the ionome in four biparental populations of maize. Five significant QTL for leaf δ13C were identified, including both novel QTL as well as some that were identified previously in maize kernels. One of the QTL regions contains an Erecta-like gene, the ortholog of which has been shown to regulate transpiration efficiency and leaf δ13C inArabidopsis. Our data does not support a relationship between δ13C and specific leaf area, and of the 19 elements analyzed, only a weak correlation between molybdenum and δ13C was detected. Together these data begin to build a genetic understanding of leaf δ13C in maize and suggest the potential to improve plant water use without significantly influencing elemental homeostasis.Article SummaryQuantitative genetics approaches were used to investigate the genetic architecture of leaf stable carbon isotope discrimination (δ13C) in maize. Developing a better understanding of leaf δ13C could facilitate its use in breeding for reduced transpirational water loss. Several genomic regions were identified that contribute to the variation observed in leaf δ13C. Furthermore, contrary to what has been observed in other species, leaf δ13C was not correlated with specific leaf area. Finally, a leaf ionomic analysis indicates that a reduction in transpiration, and thus mass flow, would not result in a decrease in nutrient accumulation.
Preprocessing choices affect RNA velocity results for droplet scRNA-seq data
Authors: Soneson Charlotte , Srivastava Avi , Patro Rob , Stadler Michael B 
Published: March 2020

AbstractExperimental single-cell approaches are becoming widely used for many purposes, including investigation of the dynamic behaviour of developing biological systems. Consequently, a large number of computational methods for extracting dynamic information from such data have been developed. One example is RNA velocity analysis, in which spliced and unspliced RNA abundances are jointly modeled in order to infer a ‘direction of change’ and thereby a future state for each cell in the gene expression space.Naturally, the accuracy and interpretability of the inferred RNA velocities depend crucially on the correctness of the estimated abundances. Here, we systematically compare four widely used quantification tools, in total yielding twelve different quantification approaches, in terms of their estimates of spliced and unspliced RNA abundances in four experimental droplet scRNA-seq data sets. We show that there are substantial differences between the quantifications obtained from different tools, and identify typical genes for which such discrepancies are observed. We further show that these abundance differences propagate to the downstream analysis, and can have a large effect on estimated velocities as well as the biological interpretation.Our results highlight that abundance quantification is a crucial aspect of the RNA velocity analysis workflow, and that both the definition of the genomic features of interest and the quantification algorithm itself require careful consideration.
Consumer ethics: insights from business professionals
Authors: Lo Lawrence W.T. , Chan Haksin , Tang Felix , Yeung Kwan-Yu 
Published: March 2020

PurposeThis research aims to generate new insights into consumer ethics by tapping into business executives' first-hand experience. The overarching goal of this novel, discovery-oriented approach is to illuminate the interactive relationships between business and consumer ethics, and to offer contextualized insights into consumers' (un)ethical behaviors.Design/methodology/approachThree focus group interviews were conducted with senior business executives representing nine different industry sectors. Thematic analysis was performed to identify key themes for an integrative model.FindingsFour key themes emerged, highlighting: (1) the mutual influence between business and consumer ethics, (2) the nature and intensity of consumer ethics, (3) the dual influence of digital communication, and (4) the partial influence of consumer education. The themes gave rise to an integrative conceptual model.Research limitations/implicationsThis research was limited somewhat by the small and judgmental sample.Practical implicationsConsumers' growing demands for business ethics underscore the need for companies to elevate ethical considerations. The amplified consumer voice on social media is dreaded by business practitioners and is regarded as unethical consumer behavior to be actively managed.Social implicationsBusiness and consumer ethics can mutually influence each other in a benign or vicious circle. Consumer education is effective in some but not all domains.Originality/valueBusiness practitioners' insights reveal (1) the interactivity of business and consumer ethics and (2) the diversity of (un)ethical consumer behaviors. They point to the need for an enriched definition of consumer ethics and an expansion on the categorical structure of consumers' (un)ethical practices.
Price stabilization or income support? Preferences and cost of programmes
Authors: Mahanta Amarjyoti , Sengupta Bodhisattva 
Published: March 2020

Purpose
Over the past 25 years, direct cash transfers (often abbreviated as direct benefit transfer, DBT) to the poorer section of the society are gaining popularity over explicit subsidization of prices of essential commodities. One of the main arguments in favor of DBT is that it will cost the government less money and yet, the consumer benefit will be high. This paper aims to examine the proposition critically. Removal of price support exposes the consumers to market risk, and any income support programme must compensate the consumers accordingly.

Design/methodology/approach
The authors use a theoretical study where the model of a representative consumer under different specification of preferences is used to compare programme costs under price stabilization and income support programmes.

Findings
What the authors show in the paper that the comparative cost of the programmes crucially depends on the nature of preferences, as well as the good under question. For certain specifications of the indirect utility function and the marginal utility of money, one programme may cost less than the other. Any policymaker must take account of such nuances before making a blanket prescription.

Research limitations/implications
The main limitation is that only a representative consumer is taken.

Practical implications
The specification of indirect utility function plays a decisive role in deciding, which one these two policies, DBT or stabilizing price at a fixed level.

Originality/value
The main novelty of the paper is in the different specifications of the indirect utility function considered in the paper.
Festivals’ social impacts and emotional solidarity
Authors: Yozukmaz Nisan , Bertan Serkan , Alkaya Serap 
Published: March 2020

PurposeInteractions between local people and guests/visitors are the main elements of tourism experience. And local festivals, considered as a significant part of festival tourism, are quite important in this context. Though many studies have been conducted about interaction between local residents and guests tourists, emotional solidarity remains as a concept which has not yet been studied much in tourism literature on local festivals. The aim of this study is to examine emotional solidarity in tourism festival literature and to determine the relationships between perceptions of local people related to social impacts of festivals and emotional solidarity they feel for guests/visitors.Design/methodology/approachIn line with this purpose, a quantitative approach was adopted, and 19th weaving, culture and handicrafts festival held in Buldan was chosen to be studied as it is an important festival for local people dwelling in Buldan, Denizli province located in Aegean Region in Turkey. The study data were obtained through questionnaire method conducted with Buldan residents during the 19th festival (June, 28th–30th, 2019). The sample was determined with random sampling method.FindingsThe data were analyzed via factor and regression analyses. As a result of factor analysis, social impacts of the festivals were grouped under 6 factors (under 3 subfactors of social benefits: communal benefits, cultural–educational benefits, social unity benefits; under 3 subfactors of social costs: concerns related to social resources, concerns related to life quality and concerns related to social order).Practical implicationsLocal people's perceptions of social impacts of festivals must be determined in order to find their impacts on emotional solidarity, and deficiencies must be remedied. Local governments who organize festivals to invigorate local economies usually try to attract more visitors with the purpose of maximizing economic impacts of festivals, and this is done without placing much importance on the social problems and social change that may arise in the future (Crandall, 1994).Originality/valueRelationships were determined between emotional solidarity and residents' perceptions towards social and cultural–educational benefits as well as their concerns related to social resources and life quality.
Value of project management in university–industry R&D collaborations
Authors: Fernandes Gabriela , O' Sullivan David , Pinto Eduardo B. , Araújo Madalena , Machado Ricardo J. 
Published: March 2020

PurposeUniversity–industry projects provide special challenges in understanding and expressing the values required of project management (PM) in delivering stakeholder benefits. This paper presents a framework for understanding, identifying and managing the values of PM in major university–industry R&D projects.Design/methodology/approachThe value framework identifies for each of the key stakeholders, the key PM values that may require to be managed and are largely derived from research literature. Empirical research then explores, prioritises and selects key PM values that need to be managed for a specific project. A large case study is used involving one university and one industry collaborating on a multi-million Euro initiative over six years. Empirical research was conducted by researchers who observed at close quarters, the challenges and successes of managing the competing values of key stakeholders.FindingsThe value framework takes a stakeholders' perspective by identifying the respective PM values for each of six stakeholders: university–industry consortium, university, industry, R&D external entities, funding entity and society.Research limitations/implicationsThe research was performed using only one case study which limits the generalisability of its findings; however, the findings are presented as a decision support aid for project consortia in developing values for their own collaboration.Practical implicationsGuidance and decision support are provided to multi-stakeholder research consortia when selecting values that need to be managed for achieving tangible and intangible project benefits.Originality/valueThe paper demonstrates a proposed framework for designing and managing the value of PM in large multi-stakeholder university–industry R&D projects.