bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistically consistent divide-and-conquer pipelines for phylogeny estimation using NJMerge
Authors: Molloy Erin K. , Warnow Tandy 
Published: November 2018

AbstractBackgroundDivide-and-conquer methods, which divide the species set into overlapping subsets, construct a tree on each subset, and then combine the subset trees using a supertree method, provide a key algorithmic framework for boosting the scalability of phylogeny estimation methods to large datasets. Yet the use of supertree methods, which typically attempt to solve NP-hard optimization problems, limits the scalability of such approaches.ResultsIn this paper, we introduce a divide-and-conquer approach that does not require supertree estimation: we divide the species set into pairwise disjoint subsets, construct a tree on each subset using a base method, and then combine the subset trees using a distance matrix. For this merger step, we present a new method, called NJMerge, which is a polynomial-time extension of Neighbor Joining (NJ); thus, NJMerge can be viewed either as a method for improving traditional NJ or as a method for scaling the base method to larger datasets. We prove that NJMerge can be used to create divide-and-conquer pipelines that are statistically consistent under some models of evolution. We also report the results of an extensive simulation study evaluating NJMerge on multi-locus datasets with up to 1000 species. We found that NJMerge sometimes improved the accuracy of traditional NJ and substantially reduced the running time of three popular species tree methods (ASTRAL-III, SVDquartets, and “concatenation” using RAxML) without sacrificing accuracy. Finally, although NJMerge can fail to return a tree, in our experiments, NJMerge failed on only 11 out of 2560 test cases.ConclusionsTheoretical and empirical results suggest that NJMerge is a valuable technique for large-scale phylogeny estimation, especially when computational resources are limited. NJMerge is freely available on Github (http://github.com/ekmolloy/njmerge).
A mathematical framework for modelling the metastatic spread of cancer
Authors: Franßen Linnéa C , Lorenzi Tommaso , Burgess Andrew EF , Chaplain Mark AJ 
Published: November 2018

AbstractCancer is a complex disease that starts with mutations of key genes in one cell or a small group of cells at a primary site in the body. If these cancer cells continue to grow successfully and, at some later stage, invade the surrounding tissue and acquire a vascular network (tumour-induced angiogenesis), they can spread to distant secondary sites in the body. This process, known asmetastatic spread, is responsible for around 90% of deaths from cancer and is one of the so-calledhallmarks of cancer.To shed light on the metastatic process, we present a mathematical modelling framework that captures for the first time the interconnected processes of invasion and metastatic spread of individual cancer cells in a spatially explicit manner — a multi-grid, hybrid, individual-based approach. This framework accounts for the spatio-temporal evolution of mesenchymal- and epithelial-like cancer cells, as well as MT1-MMP and MMP-2 dynamics, and interactions with the extracellular matrix.Using computational simulations, we demonstrate that our model captures all the key steps of the invasion-metastasis cascade, i.e. invasion by both heterogeneous cancer cell clusters and by single mesenchymal-like cancer cells; intravasation of these clusters and single cells both via active mechanisms mediated by matrix degrading enzymes (MDEs) and via passive shedding; circulation of cancer cell clusters and single cancer cells in the vasculature with the associated risk of cell death and disaggregation of clusters; extravasation of clusters and single cells; and metastatic growth at distant secondary sites in the body. By faithfully reproducing experimental results, our simulations support the evidence-based hypothesis that the membrane-bound MT1-MMP is the main driver of invasive spread rather than diffusible MDEs like MMP-2.
LINGO3 interacts with Trefoil factor 2 to enforce mucosal barrier integrity and drive tissue repair during colitis
Authors: Zullo Kelly M. , Ji Yingbiao , Wei Yun , Herbine Karl , Maloney Nicole , Cohen Rachel , Pastore Christopher , Samsouk Ma , Srivatsa Sriram , Hung Li Yin , Kohanski Michael H. , Cohen Noam A. , Herbert De’Broski R. 
Published: November 2018

AbstractMucosal epithelia are constantly exposed to damaging stimuli from mechanical, chemical, or biologic entities, and depend on rapid repair mechanisms to maintain tissue homeostasis and immunological quiescence. The reparative cytokine Trefoil factor 2 (TFF2) serves to enforce mucosal barrier integrity, but whether TFF2 receptor(s) exist is controversial. Herein, we demonstrate leucine rich repeat and immunoglobulin like domain containing nogo receptor interacting protein 3 (LINGO3) is a necessary transmembrane component for TFF2-mediated ERK signaling, proliferation, and recovery of trans-epithelial resistance of primary epithelia during wound healing. Human respiratory and intestinal epithelia express LINGO3 and mice lacking Lingo3 have impaired intestinal barrier function and fail to recover from DSS-induced colitis. Compared to wild-type controls, LINGO3 deficiency impairs both crypt regeneration and expression of the intestinal stem cell marker Lgr5. Importantly, Lingo3-/- mice display a phenotype similar to that previously reported for Tff2 deficiency, with increased paracellular permeability, and significant accumulation of mucosal CD4+ TH1 cells expressing IFNγ+ TNF+ even under steady-state conditions. Combined, these data reveal a previously unrecognized role for LINGO3 as a putative TFF2 receptor that regulates mucosal barrier integrity and GI inflammation.SignificanceIntestinal epithelial cells (IEC) are necessary for maintenance of homeostasis, resistance to infectious organisms, and overall organismal health. When injured the IEC and the underlying stroma and progenitor cell pool undergo restitutive and regenerative processes driven by the reparative cytokine Trefoil factor 2 (TFF2). This report identifies a novel receptor component for TFF2 signaling expressed on both human and mouse epithelial cells that is necessary for barrier integrity at the steady state and during colitic disease. The discovery of a novel TFF2-LINGO3 axis sheds new light on the processes controlling tissue repair, restitution, and regeneration at the mucosal interface.
TFF3 is a ligand for LINGO2 that de-represses EGFR to control disease outcome during colitis and gastrointestinal nematode infection
Authors: Ji Yingbiao , Wei Yun , Park JoonHyung , Hung Li Yin , Young Tanner , Herbine Karl , Oniskey Taylor , Pastore Christopher , Nieves Wildaliz , Somsouk Ma , Herbert De’Broski R. 
Published: November 2018

SummaryIntestinal epithelial cells (IEC) comprise diverse lineages that serve distinct roles necessary for regulation of nutrient absorption, regeneration, immunity, and homeostasis1,2. Goblet cells secrete Trefoil factor 3 (TFF3) to maintain mucus viscosity and drive mucosal healing by inhibiting cell death and influencing tight junction protein expression3. However, whether TFF3 signaling relies upon conventional ligand-receptor interactions has been unclear for decades. This study demonstrates that the orphan transmembrane protein leucine rich repeat receptor and nogo-interacting protein 2 (LINGO2) immunoprecipitates with TFF3, that LINGO2 and TFF3 co-localize at the IEC cell surface, and that TFF3/LINGO2 interactions block IEC apoptosis. Loss of function studies show that TFF3-driven STAT3 and EGFR activation are both LINGO2 dependent. Importantly, we demonstrate that TFF3 disrupts LINGO2/EGFR interactions that normally restrict EGFR activity, resulting in enhanced EGFR signaling. Excessive EGFR activation in Lingo2 gene deficient mice exacerbates colitic disease and accelerates host resistance to parasitic nematodes, whereas TFF3 deficiency results in host susceptibility. Thus, our data demonstrating that TFF3 functions through a previously unrecognized ligand-receptor interaction with LINGO2 to de-repress LINGO2-dependent inhibition of EGFR activation provides a novel conceptual framework explaining how TFF3-mediates mucosal wound healing through enhanced activation of the EGFR pathway.
Higher order assembly of Sorting Nexin 16 controls tubulation and distribution of neuronal endosomes
Authors: Wang ShiYu , Zhao Zechuan , Rodal Avital A. 
Published: November 2018

AbstractThe activities of neuronal signaling receptors depend on the maturation state of the endosomal compartments in which they reside. However, it remains unclear how the distribution of these compartments within the uniquely complex morphology of neurons is regulated, and how this distribution itself affects signaling. Here we identified mechanisms by which Sorting Nexin 16 (SNX16) controls neuronal endosomal maturation and distribution. We found that higher-order assembly of SNX16 via its coiled-coil domain drives membrane tubulation in vitro and endosome association in cells. In Drosophila motor neurons, activation of Rab5 and coiled-coil-dependent self-association of SNX16 lead to its endosomal enrichment, concomitant with depletion of SNX16-positive endosomes from the synapse, and their accumulation as Rab5- and Rab7-positive tubulated compartments at the cell body. This leads to higher levels of synaptic growth-promoting BMP receptors at the cell body, and correlates with increased synaptic growth. Our results indicate that Rab regulation of SNX16 assembly controls the endosomal distribution and signaling activities of neuronal receptors.
From Space to Sequence and Back Again: Iterative DNA Proximity Ligation and its Applications to DNA-Based Imaging
Authors: Boulgakov Alexander A. , Xiong Erhu , Bhadra Sanchita , Ellington Andrew D. , Marcotte Edward M. 
Published: November 2018

AbstractWe extend the concept of DNA proximity ligation from a single readout per oligonucleotide pair to multiple reversible, iterative ligations re-using the same oligonucleotide molecules. Using iterative proximity ligation (IPL), we can in principle capture multiple ligation events between each oligonucleotide and its various neighbors and thus recover a far richer knowledge about their relative positions than single, irreversible ligation events. IPL would thus act to sample and record local molecular neighborhoods. By integrating a unique DNA barcode into each participating oligonucleotide, we can catalog the individual ligation events and thus capture the positional information contained therein in a high throughput manner using next-generation DNA sequencing. We propose that by interpreting IPL sequencing results in the context of graph theory and by applying spring layout algorithms, we can recover geometric patterns of objects labeled by DNA. Using simulations, we demonstrate that we can in principle recover letter patterns photolithographed onto slide surfaces using only IPL sequencing data, illustrating how our technique maps complex spatial configurations into DNA sequences and then – using only this sequence information – recovers them. We complement our theoretical work with an experimental proof-of-concept of iterative proximity ligation on an oligonucleotide population.
How motivations and satisfaction influence wine tourists’ loyalty? An analysis of the Italian case
Authors: Brandano Maria Giovanna , Osti Linda , Pulina Manuela 
Published: November 2018

Purpose
The purpose of this paper is to assess the “motivation-satisfaction-loyalty” framework. Through a structural equation model (SEM), it is possible to disentangle attitudinal and behavioral loyalty as a multifaceted latent variable.

Design/methodology/approach
The empirical analysis is based on data collected in wineries located in two important wine destinations: Trentino and South Tyrol (Italy). Notably, the motivation–satisfaction relationship is confirmed, and the SEM has also assessed the importance of winery services in affecting loyalty, expressed in terms of “visit other cellars,” “repeat a wine vacation” and “recommend wine routes.”

Findings
Destination managers should consider the wine-related “relaxation” as the main push motivation, while the interactions experience are important pull motivations to drive wine tourists’ satisfaction. Nevertheless, the findings reveal that more proactive policies are needed to enhance local wines loyalty.

Originality/value
The novelty of this study is to explore loyalty. In this respect, a multifaceted latent variable is expressed as follows: “buy local wines,” “visit other cellars,” “repeat a wine vacation” as behavioral attitudinal stated loyalty and “recommend wine routes” as attitudinal stated loyalty.
Servitization intent as a factor in the servitization process
Authors: Crowley Edward , Burton Jamie , Zolkiewski Judith 
Published: November 2018

PurposeThis paper aims to investigate the role of servitization intent in the servitization process, and specifically the role dissonance (at an organizational level) in servitization intent can play in creating barriers to the servitization effort. Servitization intent is defined as the desire to achieve a future state of increased servitization.Design/methodology/approachThe research uses elite interviews and secondary data to explore servitization intent and its role during the servitization process. It examines the resistance to change resulting from a misalignment of the executive intent to servitize, and the organizational intent to retain the existing manufacturing business model. By encompassing data from companies representing a significant portion of the total industry (as measured by revenue), the study provides an industry level perspective of servitization intent and alignment.FindingsServitization intent and three key managerial challenges related to servitization intent that act as barriers to servitization were identified: lack of servitization intent, overcoming the manufacturing mindset associated with the organizational intent and the constraints resulting from managerial experience. Servitization intent and its associated managerial challenges were present at an industry level with consistent findings being shown across the major firms in the industry studied. A number of managerial strategies for overcoming these barriers were identified.Research limitations/implicationsThe research focuses on a single industry; the findings, potentially, have application across a broad range of industries.Practical implicationsA key management implication from these findings is the need for a clear understanding of the organizational intent in relation to servitization in addition to the need to bring this organizational intent in alignment with the executives’ servitization intent.Originality/valueThis research makes a contribution by identifying the misalignment between servitization intent in different levels of the organization during the servitization process and the mechanisms that can improve alignment and help effect servitization.
Back to the future: returning to silver-backed money in Sri Lanka
Authors: Sinna Lebbe Suhail , Mohamad Azhar , Mohammad Sifat Imtiaz 
Published: November 2018

Purpose
The purpose of this paper is to investigate the drivers of the behaviour intention to use the Silver-Backed Mobile Payment System (SBMPS) among the residents of Kattankudy, Sri Lanka.

Design/methodology/approach
Based on technology adoption model theory, a conceptual framework was devised, which was later tested via structural equation modelling (SEM) using valid responses from a survey questionnaire.

Findings
The results indicated that perceived usefulness and subjective norms have positive relationships and perceived risk a negative relationship with people’s behavioural intention to adopt SBMPS. In addition, the respondents were primarily motivated by faith (Islam) and also by economic advantages to adopt SBMPS.

Research limitations/implications
Religion, culture, gender, income level, age and educational level could be used as moderating factors for better understanding of people’s behaviour intentions. A Multi-cultural demographic may shed further light.

Social implications
This paper not only makes awareness of the importance of real (commodity) money but also provides the understanding of people’s willingness and the underlying motivations to practically implement the system without threatening the legal tender.

Originality/value
Extant research has mainly focused on the validity and the conceptual ideas to return to gold and silver money. This paper has been an extension to practically implement real money without threatening the legal tender by investigating the determinants of people’s willingness to return to silver money and understanding their motivations underlying those decisions
Does online service failure matter to offline customer loyalty in the integrated multi-channel context? The moderating effect of brand strength
Authors: Wang Xuhui , Zhang Qilin 
Published: November 2018

PurposeThe purpose of this paper is to investigate the effect of online service failure on online customer satisfaction and offline customer loyalty, and the moderating role of brand strength is also examined. While extant research on brick and click service mode recognizes the positive spillover effect from offline stores to online stores, this study analyzes the negative spillover effect from online stores to offline stores.Design/methodology/approachThis paper tests the hypotheses by two studies. Study 1 is based on a 2 (failure severity: mild vs severe) × 2 (brand strength: strong vs weak) between-subjects experimental design using scenarios in a brick and click retailer context, while study 2 is based on data collected from a scenario-based questionnaire survey and analyzed through the structural equation modeling.FindingsThe results indicate that participants exposed to severe online service failure show lower online satisfaction as compared to their counterparts exposed to mild online service failure, but they show the similar level of offline loyalty in both degrees of online service failure. Nevertheless, these results are not moderated by brand strength significantly.Research limitations/implicationsAn experimental design and a scenario-based questionnaire survey are used to test the framework. However, the generalizability of the research findings is still limited to a specific study setting. Future research in a different setting is needed to further validate the presented findings.Practical implicationsThe findings suggest that physical service providers should adopt aggressive online expansion strategy to seize the market and pay more attention to online service quality rather than online marketing only.Originality/valueThis is one of few studies to explore the risk of brick and click service mode, and provide a clear understanding of the likely occurrence of online service failure and its impact on online customer satisfaction and offline customer loyalty. It extends prior research by exploring non-existence of negative perceptual effect from online service failure to offline customer loyalty in the short run and weakening brand effect, which contributes to cross-channel spillover effect in the integrated multi-channel context and brand building in the internet era.
Strategic partnerships enhance resources for care of rural-dwelling older adults
Authors: Holley Lyn M. , Kelly Christopher M. , Deichert Jerome , Juanes Silvester , Wolf Loretta 
Published: November 2018

Purpose
The purpose of this paper is to disseminate a new model that addresses the urgent social challenge of providing adequate long-term care in rural circumstances through innovative use of existing resources, and to suggest future research.

Design/methodology/approach
This paper is exploratory in and is based upon the analysis of qualitative observations (interviews and site visits) framed in the financial and operational records of the facility studied, macro- and micro-level demographics, and the scholarly and practice literatures.

Findings
Significant cost savings upon implementation, improvements in quality of care and both worker and client satisfaction were observed.

Research limitations/implications
The model has been in operation only one year; the trend has been positive, however, more research is needed to identify its stability and develop a more refined description of its components: while essential features of this innovative model can be applied in any residential long-term care situation, replicating its success is obviously linked with the skill and authority of the director. Evaluation research is currently in progress.

Practical implications
The paper suggests budget-neutral solutions to persistent challenges of caring for older adults in rural circumstances.

Social implications
Quality and financing of long-term residential care for elders is insufficient and worsening. This model addresses problems central to financing and quality of care by connecting existing resources in new ways. It does not require additional funding or changes in qualifications required for jobs.

Originality/value
The model is the original creation of a residential long-term care facility director working with a network of partnerships that he discovered and developed: partnerships include a broad range of organizations in the public and non-profit sectors, and the state university.
Forensic Performance Analysis of Load‐Limiting Devices in Automotive Seat Belt Retractors
Authors: D'Aulerio Louis , Whitman Gary , Sicher Larry , Cantor Alan , Markushewski Mike 
Published: November 2018

AbstractThe introduction of frontal airbags and seatbelt pretensioners for front seat occupants provided an opportunity to address injuries caused by seatbelt loading by introducing load‐limiters, which were intended to reduce belt loading while maintaining proper restraint. Investigation and forensic analysis of real‐world crashes identified that the implementation of these devices, in some circumstances, increased the potential of injury. This paper focuses on the trade‐offs of load‐limiters, that is, the reduction loading to the occupant versus the corresponding increase in seatbelt webbing and occupant movement. If the additional webbing introduced is not controlled, the risk of injury to the occupant is increased and could result in more frequent and severe injuries rather than a reduction. This paper quantifies the webbing introduced by load‐limiter activation through forensic analysis of the seatbelt involved in real‐world crashes and testing and assesses its effect on the injuries sustained by the occupant.
ACEM involvement in a successful African emergency medicine programme
Authors: Cox Megan 
Published: November 2018

AbstractIn the past 5 years Botswana graduated its first home‐grown doctors and emergency medicine specialists for the country. The postgraduate emergency medicine specialist training arrangement between Botswana and South Africa was challenging in development, implementation and maintenance. Numerous varied supports from ACEM and its International Emergency Medicine Network were integral to these successes. This article encourages further investment of ACEM grants and scholarships in Africa by describing how ACEM supported significant advances in Botswana emergency medicine.