bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knowledge discovery with Bayesian Rule Learning for actionable biomedicine
Authors: Balasubramanian Jeya Balaji , Kip Kevin E. , Reis Steven E. , Gopalakrishnan Vanathi 
Published: September 2019

AbstractBiomarker discovery is critical for both biomedical research and for clinical diagnostic, prognostic, and therapeutic decision-making. They help improve our understanding of the underlying physiological processes within an individual. Discovery of biomarkers from complex biomedical datasets is done using data mining algorithms. Hundreds of thousands of biomarkers have been discovered and reported in literature but only a few dozen have been found to be clinically useful. This discrepancy is because statistical significance is not clinical relevance. Statistical significance only accounts for the correctness of the learned associations. Clinical relevance, in addition to statistical significance, also accounts for clinical utility such as cost-effectiveness, non-invasiveness, efficacy, and safety of the proposed biomarkers. We need models that are statistically significant and clinically relevant, all the while keeping it interpretable. Interpretable classifiers are more actionable in medicine because they offer human-readable explanations for their predictions. Traditional data mining methods cannot account for clinical relevance. We formulate this as a knowledge discovery problem. In computer science, knowledge discovery in databases is “a non-trivial process of the extraction of valid, novel, potentially useful, and ultimately understandable patterns in data”. Bayesian Rule Learning (BRL) finds an optimal Bayesian network to explain the training data and translates that into an interpretable rule model. In this paper, we extend BRL for knowledge discovery (BRL-KD) to enable BRL to incorporate a clinical utility function to learn models that are clinically more relevant. We demonstrate this using a real-world dataset to predict cardiovascular disease outcome. We evaluate predictive performance with the area under the receiver operating characteristic curve (AUROC) and clinical utility with the cost of the model. We show that BRL-KD successfully generates a set of models offering different trade-offs between AUROC and cost. Based on the clinical standard, a model with an acceptable trade-off can then be chosen.
Multiscale mechanical model for cell division orientation in developing biological systems
Authors: Leggio B. , Laussu J. , Faure E. , Lemaire P. , Godin C. 
Published: September 2019

Developing biological structures are highly complex systems, within which shape dynamics at different places is tightly coordinated. One key process at play during development is the regulation of cell division orientation. In this work, through a reformulation of cell division in terms of its energetic cost, we propose that oriented cell division is one mechanism by which cells can read and react to mechanical forces propagating in a tissue even in the absence of interphase cellular elongation in the direction of these forces. This view reproduces standard geometric division long-axis rules as a special case of a more general behaviour, in which systematic deviations from these rules can emerge. We show that states of anisotropic tension in multicellular systems can be the cause of these deviations, as often experimentally found in living tissues. Our results provide a unifying view on the different intracellular mechanisms at play in orienting cell division: they are processes which minimize energy loss, reflecting a trade-off between local and long-range mechanical signals. The consequences of this competition are explored in simulated tissues and confirmed in vivo during both the development of the pupal epithelium of dorsal thorax in D. melanogaster and the epidermal morphogenesis of ascidian embryos.Author summaryIn this work we reformulate the process of cell division orientation in development as a mechanical-energy optimization. We show that classical rules for division orientation naturally emerge when a cell minimizes the work performed against its local environment. Moreover, when multicellular stress profiles are taken into account, observed systematic violations of these rules are explained in correlation with states of anisotropic tension within the tissue. We confirm our findings experimentally on developing systems imaged with cellular resolution. Our results provide a new paradigm to understand cell division in multicellular contexts and contribute to building a physical view of biological phenomena.
A hybrid stochastic-deterministic mechanochemical model of cell polarization
Authors: Copos Calina , Mogilner Alex 
Published: September 2019

AbstractPolarization is a crucial component in cell differentiation, development, and motility and its details are not yet well understood. At the onset of cell locomotion, cells break symmetry to form a well-defined cell front and rear. This polarity establishment varies across cell types: inDictyostelium discoideumcells, it is mediated by biochemical signaling pathways and can function in the absence of a cytoskeleton, while in keratocytes it is tightly connected to cytoskeletal dynamics and mechanics. Theoretical models that have been developed to understand the onset of polarization have explored either signaling or mechanical pathways, yet few have explored mechanochemical mechanisms. However, many motile cells rely on both signaling modules and actin cytoskeleton to break symmetry and achieve a stable polarized state. We propose a general mechanochemical polarization model based on the coupling between a stochastic model for the segregation of signaling molecules and a simplified mechanical model for actin cytoskeleton network competition. We find that local linear coupling between minimally nonlinear signaling and cytoskeletal systems, separately not supporting stable polarization, yields a robustly polarized cell state.
TAK1 Regulates Endothelial Integrity Through Stabilization of Junctions via GSK3β and FoxO1
Authors: Regmi Sushil C. , Soni Dheeraj , Wang Dong-Mei , Vogel Stephen M. , Malik Asrar B. , Tiruppathi Chinnaswamy 
Published: September 2019

AbstractTLR4 signaling in endothelial cells (ECs) induces vascular injury by disrupting the endothelial junctional barrier. However, it is not known whether TLR4 signaling can also promote endothelial barrier repair after vascular injury. Here we addressed the role of TAK1 activation downstream of TLR4 in the mechanism of vascular integrity. In inducible EC-restricted TAK1 knockout (TAK1iΔEC) mice, the endothelial barrier was compromised. Blocking TAK1 activity caused spontaneous loss of the endothelial barrier. Importantly, TAK1 inactivated GSK3β via AKT to prevent β-catenin downregulation. We observed in ECs of GSK3βiΔEC mice an increase in β-catenin transfer to the nucleus to form a complex with transcription factor FoxO1, thus repressing the expression of the tight junction protein claudin-5 and causing vascular leak. Strikingly, in TAK1iΔEC mice, FoxO1 expression was dramatically increased while expression of AKT was suppressed, and in vivo inhibition of FoxO1 prevented sepsis-induced lung vascular leak in GSK3βiΔEC and TAK1iΔEC mice. Further, EC-restricted deletion of FoxO1 in mice suppressed sepsis-induced lung vascular leak and mortality. Our findings point to the potential of targeting the TAK1-AKT-GSK3β-FoxO1 axis as a therapeutic approach to treat uncontrolled lung vascular leak in sepsis.
Myt1 kinase promotes mitotic cell cycle exit inDrosophilaintestinal progenitor cells
Authors: Willms Reegan J. , Zeng Jie , Campbell Shelagh D. 
Published: September 2019

SUMMARYInhibitory phosphorylation of Cdk1 is a well-established mechanism for gating mitotic entry during development. However, failure to inhibit Cdk1 in adult organs causes ectopic cell division and tissue dysplasia, indicating that Cdk1 inhibition is also required for cell cycle exit. Two types of progenitor cells populate the adultDrosophilamidgut: intestinal stem cells (ISCs) and post-mitotic enteroblasts (EBs). ISCs are the only mitotic cells under homeostatic conditions, dividing asymmetrically to produce quiescent EB daughter cells. We show here that Myt1, the membrane associated Cdk1 inhibitory kinase, is required for EB quiescence and subsequent differentiation. Loss of Myt1 disrupts EB cell cycle dynamics, promoting Cyclin A-dependent mitosis and accumulation of smaller progenitor-like cells that fail to differentiate. Thus, Myt1 inhibition of Cyclin A/Cdk1 functions as a mechanism for coupling cell cycle arrest with terminal cell differentiation in this developmental context.
Stochastic delays suppress noise in a genetic circuit with negative feedback
Authors: Smith Madeline , Singh Abhyudai 
Published: October 2019

AbstractWe consider a mechanistic stochastic model of an autoregulatory genetic circuit with time delays. More specifically, a protein is expressed in random bursts from its corresponding gene. The synthesized protein is initially inactive and becomes active after a time delay. Rather than considering a deterministic delay, a key aspect of this work is to incorporate stochastic time delays, where delay is an independent and identically distributed random variable. The active protein inhibits its own production creating a negative feedback loop. Our analysis reveals that for an exponentially-distributed time delay, the noise in the protein levels decreases to the Poisson limit with increasing mean time delay. Interesting, for a gamma-distributed time delay contrasting noise behaviors emerge based on the negative feedback strength. At low feedback strengths the protein noise levels monotonically decreases to the Poisson limit with increasing average delay. At intermediate feedback strengths, the noise levels first increase to reach a maximum, and then decease back to the Poisson limit with increasing average delay. Finally, for strong feedbacks the protein noise levels monotonically increase with the average delay. For each of these scenarios we provide approximate analytical formulas for the protein mean and noises levels, and validate these results by performing exact Monte Carlo simulations. In conclusion, our results uncover a counter intuitive feature where inclusion of stochastic delays in a negative feedback circuit can play a beneficial role in buffering deleterious fluctuations in the level of a protein.
Oxidation shuts down an auto-inhibitory mechanism of von Willebrand factor
Authors: Tsai Rachel , Interlandi Gianluca 
Published: October 2019

AbstractThe blood protein von Willebrand factor (VWF) is a key link between inflammation and pathological thrombus formation. In particular, oxidation of methionine residues in specific domains of VWF due to the release of oxidants in inflammatory conditions has been linked to an increased platelet-binding activity. However, the atomistic details how methionine oxidation activates VWF have not been elucidated to date. Yet understanding the activation mechanism of VWF under oxidizing conditions can lead to the development of novel therapeutics that target VWF selectively under inflammatory conditions in order to reduce its thrombotic activity while maintaining its haemostatic function. In this manuscript, we used a combination of a dynamic flow assay and molecular dynamics (MD) simulations to investigate how methionine oxidation removes an auto-inhibitory mechanism of VWF. Results from the dynamic flow assay revealed that oxidation does not directly activate the A1 domain, which is the domain in VWF that contains the binding site to the platelet surface receptor glycoprotein Ibα(GpIbα), but rather removes the inhibitory function of the neighboring A2 and A3 domains. Furthermore, the MD simulations combined with free energy perturbation calculations suggested that methionine oxidation may destabilize the binding interface between the A1 and A2 domains leading to unmasking of the GpIbα-binding site in the A1 domain.
eIF5a reduction via decreased Klf5 leads to cell senescence by mitochondrial fission in VSMCs
Authors: Ma Dong , Zheng Bin , Liu He-liang , Zhao Yong-bo , Liu Xiao , Zhang Xin-hua , Li Qiang , Shi Wei-bo , Suzuki Toru , Wen Jin-kun 
Published: October 2019

AbstractThough dysregulation of mitochondrial dynamics has been linked to cellular senescence, which contributes to advanced age-related disorders, it is unclear how Klf5, an essential transcriptional factor of cardiovascular remodeling, mediates the link between mitochondrial dynamics and vascular smooth muscle cell (VSMC) senescence. Here we show that Klf5 downregulation in VSMCs is correlated with rupture of abdominal aortic aneurysm (AAA), an age-related vascular disease. Mice lacking Klf5 in VSMCs exacerbate vascular senescence and progression of Ang II-induced AAA by facilitating ROS formation. Klf5 knockdown enhances, while Klf5 overexpression suppresses mitochondrial fission. Mechanistically, Klf5 activates eIF5a transcription through binding to the promoter of eIF5a, which in turn preserves mitochondrial integrity by interacting with Mfn1. Accordingly, decreased expression of eIF5a elicited by Klf5 downregulation leads to mitochondrial fission and excessive ROS production. Inhibition of mitochondrial fission decreases ROS production and VSMC senescence. Our studies provide a potential therapeutic target for age-related vascular disorders.
Study on the particle stratification and penetration of a swing vibrating screen by using DEM
Authors: Ning Shuigen , Xiao Jianzhang , Wang Guifeng , Huang Pengcheng 
Published: October 2019

PurposeAs for vibrating screen, the separation of granular materials is a very complicated process, particularly the screening with a swing trace. To study the characteristics of stratification and penetration in the swing vibrating screen, a three-dimensional numerical model was developed to simulate the screening process.Design/methodology/approachThe discrete element method (DEM) was used to perform the numerical simulation, and the kinetic model of the swing screening was established. The regions of stratification and penetration were defined, and the mathematical functions relating fine particle ratio of stratification and penetration to time were presented using the least squares method.FindingsThe results show that the low value of frequency (5 and 10 Hz) has a limited effect on the stratification, while the obvious effect can be found at high frequency. A low frequencies or small swing angles may enhance the particle penetration. By studying the vibration parameters affecting the stratification and penetration rate, it is found that the frequency has more influence than the swing angle.Originality/valueThe higher screening efficiency and processing capacity can be further obtained for the swing vibrating screen by comparing with the linear vibrating screen. These results reveal the fundamental characteristics of particle motion in the swing screening, which will provide reliable guidance for studying the design optimization of vibrating screen.
Habiba Community: brand management for a family business
Authors: Hamed Sara 
Published: October 2019

Learning outcomes
Marketing and brand management examples used in classes usually revolve around publicly traded corporations. Students are expected to learn how to deal with branding problems that can arise in new types of organizations as family businesses.

Case overview/synopsis
The case study discusses a brand identity and brand management problem facing the Founder of Habiba Community, Maged El Said. Habiba Community is an initiative focusing on sustainability and giving back to community. Many foundations were established under Habiba Community, such as its beach lodge, organic farm and learning center. The beach lodge and organic farm were more familiar to tourists and visitors than the other established foundations. The organic farm produced many organic products sold nationally and internationally. The founder was now faced with the challenge of whether to create one brand identity for Habiba Community as a whole or to go for separate brand identities for each of its foundations.

Complexity academic level
This case study is developed for students of the bachelor level in marketing and design studies. The case difficulty is regarded as intermediate as it includes new trends and ideas from the field of marketing and branding (as eco-branding and family business branding) and new trends in the tourism service industry (as voluntourism). Courses in which this case study can be used are integrated marketing communication, corporate identity, services marketing and brand management under marketing and graphic design studies. The case study is not designed for earlier courses in marketing and design, as students need to have basic knowledge in marketing and branding beforehand.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 8: Marketing
The effect of task conflict on outsourcers’ long-term orientation toward suppliers: the moderating role of formal control and Chinese guanxi
Authors: Li Shuting , Haney Mark H. , Lee Gukseong , Kang Mingu , Ko Changsuk 
Published: October 2019

Purpose
This paper aims to investigate the antecedents of manufacturing firms’ long-term orientation towards their suppliers in the context of outsourcing relationships in China.

Design/methodology/approach
Based on survey data collected from 224 manufacturing firms in China, this study examines the hypothesized relationships.

Findings
The results show that task conflict has a negative effect on long-term orientation, both Chinese guanxi and formal control are useful governance mechanisms to enhance long-term orientation, and the negative effect of task conflict on the long-term orientation weakens as Chinese guanxi between a manufacturer and its supplier increases.

Originality/value
This study contributes to a better understanding of conflict management in outsourcing relationships in China.
A dimensional analysis of psychological empowerment on engagement
Authors: Joo Baek-Kyoo (Brian) , Bozer Gil , Ready Kathryn J. 
Published: October 2019

PurposeThe purpose of this paper is to examine the effects of learning organization culture (LOC), learning goal orientation (LGO) and psychological empowerment (PsyEmp) on employee engagement, focusing on the mediating role of each dimension of PsyEmp (meaning, competence, self-determination and impact).Design/methodology/approachIndividual perceptions of 329 employees in 9 South Korean for-profit companies were obtained by a cross-sectional survey. Construct validity of each measurement model was examined using confirmatory factor analysis, and the hypothesized structural model was tested by structural equation modeling. Bootstrap analyses were used for testing mediation effects of PsyEmp.FindingsThe authors found that PsyEmp had a significant effect on job engagement, and that LOC and LGO significantly predicted the level of PsyEmp and engagement. The four dimensions of PsyEmp partially mediated the relationship between the two predictors (i.e. LOC and LGO) and job engagement. LGO had a stronger effect than LOC on both PsyEmp and job engagement.Practical implicationsEmployees who are high in LGO and perceive that an organization provides opportunities for continuous learning with supportive leadership are more likely to experience improved meaning in their work, competence in their knowledge and skills, and foster self-determination with respect to their personal impact on their work and organization. These important facets of PsyEmp that promote employee engagement should be considered by human resource and OD professionals when recommending workplace changes to improve organizational effectiveness and sustainability.Originality/valueThis study complements the trend to use employee engagement as a proxy for understanding both individual and organizational performance by investigating the relationships among LOC, goal orientation, empowerment and engagement.
A tale of scale: Plot but not neighbourhood tree diversity increases leaf litter ant diversity
Authors: Skarbek Carl J. , Noack Merle , Bruelheide Helge , Härdtle Werner , von Oheimb Goddert , Scholten Thomas , Seitz Steffen , Staab Michael 
Published: September 2019

Abstract

Diversity of producers (e.g. plants) usually increases the diversity of associated organisms, but the scale (i.e. the spatial area of plant diversity considered) at which plant diversity acts on other taxa has rarely been studied. Most evidence for cross‐taxon diversity relations come from above‐ground consumers that directly interact with plants.

Experimental tests of plant diversity effects on elusive organisms inhabiting the leaf litter layer, which are important for nutrient cycling and decomposition, are rare.

Using a large tree diversity experiment, we tested whether tree diversity at the larger plot (i.e. community) or the smaller neighbourhood scale relates to the abundance, species richness, functional and phylogenetic diversity of leaf litter ants, which are dominant organisms in brown food webs.

Contrary to our expectations of scale‐independent positive tree diversity effects, ant diversity increased only with plot but not neighbourhood tree diversity. While the exact causal mechanisms are unclear, nest relocation or small‐scale competition among ants may explain the stronger tree diversity effects at the plot scale.

Our results indicate that even for small and less mobile organisms in the leaf litter, effects of tree diversity are stronger at relatively larger scales. The finding emphasizes the importance of diverse forest stands, in which mixing of tree species is not restricted to small patches, for supporting arthropod diversity in the leaf litter.