bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of stem cell enrichment in healthy tissues and tumors: implications for non-genetic drug resistance
Authors: Weiss Lora D. , van den Driessche P. , Lowengrub John S. , Wodarz Dominik , Komarova Natalia L. 
Published: June 2019

AbstractDrug resistance is a major challenge for cancer therapy. While resistance mutations are often the focus of investigation, non-genetic resistance mechanisms are also important. One such mechanism is the presence of relatively high fractions of cancer stem cells (CSCs), which have reduced susceptibility to chemotherapy, radiation, and targeted treatments compared to more differentiated cells. The reasons for high CSC fractions (CSC enrichment) are not well understood. Previous experimental and mathematical modeling work identified a particular feedback loop in tumors that can promote CSC enrichment. Here, we use mathematical models of hierarchically structured cell populations to build on this work and to provide a comprehensive analysis of how different feedback regulatory processes that might partially operate in tumors can influence the stem cell fractions during somatic evolution of healthy tissue or during tumor growth. We find that depending on the particular feedback loops that are present, CSC fractions can increase or decrease. We define characteristics of the feedback mechanisms that are required for CSC enrichment to occur, and show how the magnitude of enrichment is determined by parameters. In particular, enrichment requires a reduction in division rates or an increase in death rates with higher population sizes, and the feedback mediators that achieve this can be secreted by either CSCs or by more differentiated cells. The extent of enrichment is determined by the death rate of CSCs, the probability of CSC self-renewal, and by the strength of feedback on cell divisions. Defining these characteristics can guide experimental approaches that aim to screen for and identify feedback mediators that can promote CSC enrichment in specific cancers, which in turn can help understand and overcome the phenomenon of CSC-based therapy resistance.
A stochastic detailed scheduling model for periodic maintenance of military rotorcraft
Authors: Semaan Nabil M. , Yehia Nabhan 
Published: June 2019

Purpose
The purpose of this paper is to develop a stochastic detailed schedule for a preventive/scheduled/periodic maintenance program of a military aircraft, specifically a rotorcraft or helicopter.

Design/methodology/approach
The new model, entitled the military “periodic aviation maintenance stochastic schedule” (PAM-SS), develops a stochastic detailed schedule for a PUMA SA 330SM helicopter for the 50-h periodic inspection, using cyclic operation network (CYCLONE) and Monte Carlo simulation (MCS) techniques. The PAM-SS model identifies the different periodic inspection tasks of the maintenance schedule, allocates the resources required for each task, evaluates a stochastic duration of each inspection task, evaluates the probability of occurrence for each breakdown or repair, develops the CYCLONE model of the stochastic schedule and simulates the model using MCS.

Findings
The 50-h maintenance stochastic duration follows a normal probability distribution and has a mean value of 323 min and a standard deviation of 23.7 min. Also, the stochastic maintenance schedule lies between 299 and 306 min for a 99 per cent confidence level. Furthermore, except the pilot and the electrical team (approximately 90 per cent idle), all other teams are around 40 per cent idle. A sensitivity analysis is also performed and yielded that the PAM-SS model is not sensitive to the number of technicians in each team; however, it is highly sensitive to the probability of occurrence of the breakdowns/repairs.

Practical implications
The PAM-SS model is specifically developed for military rotorcrafts, to manage the different resources involved in the detailed planning and scheduling of the periodic/scheduled maintenance, mainly the 50-h inspection. It evaluates the resources utilization (idleness and queue), the stochastic maintenance duration and identifies backlogs and bottlenecks.

Originality/value
The PAM-SS tackles military aircraft planning and scheduling in a stochastic methodology, considering uncertainties in all inspection task durations and breakdown or repair durations. The PAM-SS, although developed for rotorcrafts can be further developed for any other type of military aircraft or any other scheduled maintenance program interval.
Modern slavery and international business scholarship: the governance nexus
Authors: Burmester Brent , Michailova Snejina , Stringer Christina 
Published: June 2019

Purpose
Modern slavery is a problem that international business (IB) research can no longer ignore. Multinational enterprises (MNEs) are often contributors to the persistence of modern slavery, by virtue of the regulatory challenge they pose to states and their insufficient oversight of supply chains. The purpose of this paper is to show that governance inadequacies with respect to modern slavery will be lessened if IB scholars give more attention to MNEs’ governing role within and beyond global value chains.

Design/methodology/approach
A set of arguments is presented in support of intensified effort in IB research with respect to studying the role of MNEs in transnational labour governance. The paper draws inspiration from IB theory and the conceptualisation of the MNE in neighbouring disciplines that regard it as a bearer of duties toward labour, consistent with its role in multilevel governance. Insights from the literature on global and multi-level governance are utilised.

Findings
The paper construes modern slavery as a multi-level governance challenge and argues that MNE capabilities and responsibilities with respect to labour governance and the deterrence of slavery exceed those identified on the margins of IB literature. MNEs are underappreciated as governors within the multilevel transnational labour governance system. The IB discipline is in a strong position to develop our understanding of the MNE’s different roles in governance and thereby contribute to the reduced incidence of modern slavery.

Originality/value
This paper represents an attempt to mobilise the IB academy to help eliminate slavery from workplaces that rely on MNE patronage or where labour rights abuses are made possible by MNE diversion of governance resources. It places particular emphasis on the use and abuse of MNEs’ governance capabilities in the sphere of international relations and calls attention to over-simplification of the MNE, IB’s primary unit of analysis.
Critical and mainstream international business research
Authors: Dörrenbächer Christoph , Gammelgaard Jens 
Published: June 2019

Purpose
This paper aims to address the relationship between critical and mainstream international business (IB) research and discuss the ways forward for the former.

Design/methodology/approach
The paper empirically maps critical IB scholarship by analysing more than 250 academic articles published in critical perspectives on international business (cpoib) from 2005 to 2017. The paper also includes a citation analysis that uncovers how critical IB research is recognized and discussed in mainstream IB studies.

Findings
The extant critical IB research can be broken into five main topical clusters: positioning critical IB research, postcolonial IB studies, effects of international business activities, financialization and the global financial crisis and “Black IB” and corporate social responsibility. The citation analysis demonstrates that critical IB research is rarely recognized in mainstream IB academic outlets.

Originality/value
This paper is the first to empirically map critical IB research and to measure its impact on mainstream IB research. Based on these insights, as well as discussions of the more critical voices within mainstream IB studies and the debate over critical performativity in critical management studies, ways of developing critical IB research are examined.
Global health and international business: new frontiers of international business research
Authors: Ahen Frederick 
Published: June 2019

Purpose
The purpose of this study is to revisit the interdisciplinary roots of international business (IB) by challenging the compartmentalized and obscured nature of certain major themes in current IB research. Here, the author broadens IB’s natural scope by introducing the links with global health while preemptively removing the existing limits of critical perspectives.

Design/methodology/approach
The study synthesizes ignored common insights from IB and global health governance. It supplies a select composite of emerging themes mostly at the interface of IB and global health as foundational proposals for reengaging IB for radical social change. This is in response to the urgent calls for inquiries into the “extra dimensions” of IB in answering wicked questions of global sustainability, injustice and inequality and other emergent grand challenges whilst embracing novel conceptual, theoretical and empirical opportunities.

Findings
This study demonstrates that IB research in its current form is reductive, quintessentially compartmentalized and evidently weak in responding to the emergent wicked problems of global scale. This is because several layers of complex, burning interconnected questions with roots in IB hardly receive exposure in research although they are the very existential and emerging issues with massive impacts on populations both in home and host countries.

Practical implications
This study sets new research agendas for critically studying IB and global health topics of vital relevance to reflect the changing frontiers of knowledge production in the fourth industrial revolution.

Originality/value
This study calls for deeper and broader discussions about the limitless opportunities of cross-fertilization of IB and other disciplines whilst highlighting the heretofore-overlooked connections between IB and environmental and medico-techno-scientific disciplines.
Housing attributes and relative house prices in Ghana
Authors: Owusu-Manu De-Graft , Edwards David John , Donkor-Hyiaman Ken A. , Asiedu Richard Ohene , Hosseini M. Reza , Obiri-Yeboah E. 
Published: June 2019

PurposeThe study of house prices has become more relevant in recent times after the global financial crisis. Using a housing data set from three regions of Ghana (collated from real estate agents), the purpose of this paper is to estimate the relative importance of housing attributes to house prices.Design/methodology/approachThe hedonic regression analysis conducted indicates that location is the most powerful determinant of house prices. Other relevant factors are the number of bedrooms, the number of floors, the total floor area, land size, age of the house and luxury finishing.FindingsThe implications of these results are many. Policy wise, the study provides an evidence-based empirical study that supports the need for better urban planning to improve communities, which in turn is associated with house price appreciations. Homeowners, investors and creditors, particularly mortgage lenders could be the immediate beneficiaries. Drawing on this, improved urban planning could mitigate strategic defaults that results from house prices falling below mortgage loan balances. This is important for financial market stability.Originality/valueThe paper provides a comprehensive and unique understanding of the hedonic determinants of house prices in Ghana. Future studies could examine the effect of location upon mortgage lending in Ghana.
Operational competencies and relational resources: a multiple case study
Authors: Zatta Fernando Nascimento , Filho Elmo Tambosi , de Campos Fernando Celso , Freitas Rodrigo Randow 
Published: June 2019

Purpose
The purpose of this study was to use relational vision as a theoretical support for an investigation of how operational competencies are developed from the interaction of shared relational resources in the supply chain and to verify how these competencies allow the resources to be able to function, unity, integration and direction.

Design/methodology/approach
This multihull study was based on semi-structured interviews with 13 representatives of four dyads from companies in the steel, automotive and industrial applications, pulp processing and manufacturing and application of flexible tubes.

Findings
The results indicate that information, knowledge and learning are significant constructs to influence the development of operational skills in the supply chain because they represent the ability of the company to promote skills to efficiently use resources and create a barrier to imitation.

Research limitations/implications
There are limitations in the use of four companies from different industrial segments because it is possible to generalize the results. However, given the cross-sectional nature of the research, new studies may adopt a longitudinal approach to verify the evolution in the area of operations. Future studies may also expand the unit of analysis to understand the role of the relationship between the focus business and its strategic suppliers from the viewpoint of the suppliers. Thus, new research can be expanded to dyads, triads and business networks by investigating the various stages in the supply chain.

Practical implications
This study contributes to the literature and adds the dimension of relational operational skills, which is hitherto little explored in previous studies.

Social implications
This study contributes to the literature in the area of operations management, in collaborative relationships between buyers and sellers, focusing on the relational view of competitiveness.

Originality/value
The growing importance of organizations and the role of collaboration, based on mutual benefits and grouping of skills, tend to increase the competitive benefits of companies operating in this context. The management of this type of arrangement becomes a challenge for researchers, reinforcing the originality of this study.
Source‐independent waveform inversion for attenuation estimation in anisotropic media
Authors: Bai Tong , Tsvankin Ilya 
Published: June 2019

ABSTRACTIn previous publications, we presented a waveform‐inversion algorithm for attenuation analysis in heterogeneous anisotropic media. However, waveform inversion requires an accurate estimate of the source wavelet, which is often difficult to obtain from field data. To address this problem, here we adopt a source‐independent waveform‐inversion algorithm that obviates the need for joint estimation of the source signal and attenuation coefficients. The key operations in that algorithm are the convolutions (1) of the observed wavefield with a reference trace from the modelled data and (2) of the modelled wavefield with a reference trace from the observed data. The influence of the source signature on attenuation estimation is mitigated by defining the objective function as the ℓ2‐norm of the difference between the two convolved data sets. The inversion gradients for the medium parameters are similar to those for conventional waveform‐inversion techniques, with the exception of the adjoint sources computed by convolution and cross‐correlation operations. To make the source‐independent inversion methodology more stable in the presence of velocity errors, we combine it with the local‐similarity technique. The proposed algorithm is validated using transmission tests for a homogeneous transversely isotropic model with a vertical symmetry axis that contains a Gaussian anomaly in the shear‐wave vertical attenuation coefficient. Then the method is applied to the inversion of reflection data for a modified transversely isotropic model from Hess. It should be noted that due to the increased nonlinearity of the inverse problem, the source‐independent algorithm requires a more accurate initial model to obtain inversion results comparable to those produced by conventional waveform inversion with the actual wavelet.
A novel plasmid‐transcribed regulatory sRNA, QfsR, controls chromosomal polycistronic gene expression in Agrobacterium fabrum
Authors: Diel Benjamin , Dequivre Magali , Wisniewski‐Dyé Florence , Vial Ludovic , Hommais Florence 
Published: June 2019

SummaryPlasmids are mobile DNAs that can adjust host cell functions for their own amplification and dissemination. We identified Quorum sensing flagella small RNA regulator (QfsR), a small RNA, transcribed from the virulence tumour‐inducing (Ti) plasmid in the phytopathogen Agrobacterium fabrum. QfsR is widely conserved throughout RepABC plasmids carried by Rhizobiaceae. Target prediction, expression analysis and site‐direct mutagenesis experiments showed that QfsR directly pairs within polycistronic mRNAs transcribed from chromosome (genes involved in flagella apparatus) and Ti plasmid (genes involved in conjugative transfer). QfsR leads to a coordinated expression of whole polycistronic mRNA molecules. Whereas a lack of QfsR represses motility, its overproduction increases the quorum sensing signal accumulation and the Ti plasmid conjugative transfer. Based on these observations, we propose QfsR as a hub connecting regulatory networks of motility and plasmid conjugative transfer. To our knowledge, QfsR is the first example of a plasmid‐encoded sRNA that controls chromosomal polycistronic gene expression.
Longevity‐related molecular pathways are subject to midlife “switch” in humans
Authors: Timmons James A. , Volmar Claude‐Henry , Crossland Hannah , Phillips Bethan E. , Sood Sanjana , Janczura Karolina J. , Törmäkangas Timo , Kujala Urho M. , Kraus William E. , Atherton Philip J. , Wahlestedt Claes 
Published: June 2019

AbstractEmerging evidence indicates that molecular aging may follow nonlinear or discontinuous trajectories. Whether this occurs in human neuromuscular tissue, particularly for the noncoding transcriptome, and independent of metabolic and aerobic capacities, is unknown. Applying our novel RNA method to quantify tissue coding and long noncoding RNA (lncRNA), we identified ~800 transcripts tracking with age up to ~60 years in human muscle and brain. In silico analysis demonstrated that this temporary linear “signature” was regulated by drugs, which reduce mortality or extend life span in model organisms, including 24 inhibitors of the IGF‐1/PI3K/mTOR pathway that mimicked, and 5 activators that opposed, the signature. We profiled Rapamycin in nondividing primary human myotubes (n = 32 HTA 2.0 arrays) and determined the transcript signature for reactive oxygen species in neurons, confirming that our age signature was largely regulated in the “pro‐longevity” direction. Quantitative network modeling demonstrated that age‐regulated ncRNA equaled the contribution of protein‐coding RNA within structures, but tended to have a lower heritability, implying lncRNA may better reflect environmental influences. Genes ECSIT, UNC13, and SKAP2 contributed to a network that did not respond to Rapamycin, and was associated with “neuron apoptotic processes” in protein–protein interaction analysis (FDR = 2.4%). ECSIT links inflammation with the continued age‐related downwards trajectory of mitochondrial complex I gene expression (FDR < 0.01%), implying that sustained inhibition of ECSIT may be maladaptive. The present observations link, for the first time, model organism longevity programs with the endogenous but temporary genome‐wide responses to aging in humans, revealing a pattern that may ultimately underpin personalized rates of health span.
Carbon disclosure, emission intensity and cost of equity capital: multi‐country evidence
Authors: Bui Binh , Moses Olayinka , Houqe Muhammad N. 
Published: June 2019

AbstractThis study examines the joint effect of carbon disclosure and greenhouse gas (GHG) emissions on firms’ implied cost of equity capital (COC). Based on 4655 firm‐year observations across 34 countries, we find firms’ GHG emission intensity to be positively associated with COC. However, we find also that the penalty linked with higher COC is moderated by extensive carbon disclosure. We provide evidence that the extent of carbon disclosure helps reduce the premium required by investors to compensate for poor carbon performance. Our study provides insights to policymakers, investors and managers on the combined effect of carbon disclosure, and emission intensity.
Synthesis and biological evaluation of morpholines linked coumarin–triazole hybrids as anticancer agents
Authors: Goud Nerella Sridhar , Pooladanda Venkatesh , Mahammad Ghouse S. , Jakkula Pranay , Gatreddi Santhosh , Qureshi Insaf A. , Alvala Ravi , Godugu Chandraiah , Alvala Mallika 
Published: June 2019

AbstractA series of novel morpholines linked coumarin–triazole hybrids (6a–6v) has been synthesized and evaluated for their anti‐proliferative potential on a panel of five human cancer cell lines, namely bone (MG‐63), lung (A549), breast (MDA‐MB‐231), colon (HCT‐15) and liver (HepG2), using MTT assay. Among all, the compound 6n {7‐((1‐(2,4‐dichlorobenzyl)‐1H‐1,2,3‐triazol‐4‐yl) methoxy)‐4‐((2,6‐dimethylmorpholino) methyl)‐2H‐chromen‐2‐one} showed significant growth inhibition against MG‐63 cells with an IC50 value of 0.80 ± 0.22 μM. Further, induction of apoptosis by 6n of MG‐63 cells confirmed as a result of morphological changes, the sub‐G1 phase arrest, increased percentage of apoptotic cells, and decrease in mitochondrial membrane potential and increase in reactive oxygen species levels. The in vitro Gal‐1 expression in cell culture supernatant of MG‐63 cells treated with compound 6n showed dose‐dependent reduction. The binding constant (Ka) of 6n with Gal‐1 was calculated from the intercept value which was observed as 3.0 × 105 M−1 by fluorescence spectroscopy. Surface plasmon resonance showed that 6n binds to Gal‐1 with binding constant (Ka) of 1.29E+04 1/Ms and equilibrium constant KD value of 7.54E−07 M, respectively. Molecular docking studies revealed the binding interactions of 6n with Gal‐1.
Incorporating and interpreting regulatory guidance on estimands in diabetes clinical trials: The PIONEER 1 randomized clinical trial as an example
Authors: Aroda Vanita R. , Saugstrup Trine , Buse John B. , Donsmark Morten , Zacho Jeppe , Davies Melanie J. 
Published: June 2019

AbstractRegulatory guidelines describe the use of estimands in designing and conducting clinical trials. Estimands ensure alignment of the objectives with the design, conduct and analysis of a trial. An estimand is defined by four inter‐related attributes: the population of interest, the variable (endpoint) of interest, the way intercurrent events are handled and the population level summary. A trial may employ multiple estimands to evaluate treatment effects from different perspectives in order to address different scientific questions. As estimands may be an unfamiliar concept for many clinicians treating diabetes, this paper reviews the estimand concept and uses the PIONEER 1 phase 3a clinical trial, which investigated the efficacy and safety of oral semaglutide vs placebo, as an example of the way in which estimands can be implemented and interpreted. In the PIONEER 1 trial, two estimands were employed for each efficacy endpoint and were labelled as: (a) the treatment policy estimand, used to assess the treatment effect regardless of use of rescue medication or discontinuation of trial product, and provides a broad perspective of the treatment effect in the population of patients with type 2 diabetes in clinical practice; and (b) the trial product estimand, used to assess the treatment effect if all patients had continued to use trial product for the planned duration of the trial without rescue medication, thereby providing information on the anticipated treatment effect of the medication. Both approaches are complementary to understanding the effect of the studied treatments.