bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myc instructs and maintains pancreatic adenocarcinoma phenotype
Authors: Sodir Nicole M. , Kortlever Roderik M. , Barthet Valentin J.A. , Pellegrinet Luca , Campos Tania , Kupczak Steven , Swigart Lamorna Brown , Soucek Laura , Arends Mark J. , Littlewood Trevor D. , Evan Gerard I. 
Published: February 2019

SUMMARYPancreatic ductal adenocarcinoma (PDAC) is characterized by its dismal prognosis and its signature fibroinflammatory phenotype. We show that activation of Myc in PanIN epithelial cells is alone sufficient to instruct and maintain immediate transition of indolent PanINs to PDACs phenotypically identical to the spontaneous human disease. Myc does this by inducing a distinct, tissue-specific ensemble of instructive signals that, together, coordinate changes in multiple, stromal and inflammatory cell types to generate the signature PDAC stroma. We also demonstrate that the Myc PDAC switch is completely reversible and that Myc deactivation immediately triggers meticulous disassembly of both PDAC tumor and stroma. Hence, both the formation and deconstruction of the complex PDAC phenotype may be mediated by a single, reversible molecular switch.SIGNIFICANCEPancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and lacks effective therapies. We show that Myc is a single molecular switch that directly and immediately instructs transition from indolent KRasG12D-induced PanIN to the characteristic complex, multi-cell-type fibroinflammatory and immune-cold PDAC phenotype through the release of a distinct, tissuespecific set of instructive signals. The same combination of KRasG12Dand Myc drives a very different phenotype in lung, indicating that the principal phenotypes of adenocarcinomas are dictated by tissue of origin not specific oncogenes. We also show that the Myc switch is immediately and completely reversible: blocking Myc function triggers meticulous disassembly of the entire PDAC tumor-stromal edifice demonstrating that phenotypic complexity is not a barrier to effective treatment of cancers.
Noradrenergic signaling in wakeful states inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex
Authors: Stowell Rianne D. , Sipe Grayson O. , Dawes Ryan P. , Batchelor Hanna N. , Lordy Katheryn A. , Bidlack Jean M. , Brown Edward , Sur Mriganka , Majewska Ania K. 
Published: February 2019

AbstractMicroglia are the innate immune cells of the brain with roles in neuroimmunology and synaptic plasticity. Microglial processes continuously survey the brain parenchyma interacting with synaptic elements and maintaining tissue homeostasis. However, the mechanisms that control surveillance and its role in synaptic plasticity are poorly understood. Microglial dynamicsin vivohave been primarily studied in anesthetized animals, where slow-wave neural activity resembles sleep-like states. We report that microglial surveillance and injury response in awake animals are reduced compared to when animals are anesthetized, suggesting that arousal state profoundly modulates microglial roles in the physiological brain. Stimulating β2-adrenergic receptors recapitulated these observations and also disrupted experience-dependent plasticity only when intact β2-adrenergic receptors were present in microglia specifically. These results indicate that microglial roles in surveillance and synaptic plasticity in the healthy brain are modulated by noradrenergic fluctuations between arousal states and raises new considerations for sleep/wake disruption in neurodevelopment and neuropathology.
3D cell culture stimulates the secretion of in vivo like extracellular vesicles
Authors: Thippabhotla Sirisha , Zhong Cuncong , He Mei 
Published: February 2019

ABSTRACTFor studying cellular communications ex-vivo, a two-dimensional (2D) cell culture model is currently used as the “gold standard”. 2D culture models are also widely used in the study of RNA expression profiles from tumor cells secreted extracellular vesicles (EVs) for tumor biomarker discovery. Although the 2D culture system is simple and easily accessible, the culture environment is unable to represent in vivo extracellular matrix (ECM) microenvironment. Our study observed that 2D culture-derived EVs showed significantly different profiles in terms of secretion dynamics and essential signaling molecular contents (RNAs and DNAs), when compared to the three-dimensional (3D) culture-derived EVs. By performing small RNA next-generation sequencing (NGS) analysis of cervical cancer cells and their EVs compared with cervical cancer patient plasma EV-derived small RNAs, we observed that 3D culture-derived EV small RNAs differ from their parent cell small RNA profile which may indicate a specific sorting process. Most importantly, the 3D culture derived EV small RNA profile exhibited a much higher similarity (~96%) to in vivo circulating EVs derived from cervical cancer patient plasma. However, 2D culture derived EV small RNA profile correlated better with only their parent cells cultured in 2D. On the other hand, DNA sequencing analysis suggests that culture and growth conditions do not affect the genomic information carried by EV secretion. This work also suggests that tackling EV molecular alterations secreted into interstitial fluids can provide an alternative, non-invasive approach for investigating 3D tissue behaviors at the molecular precision. This work could serve as a foundation for building precise models employed in mimicking in vivo tissue system with EVs as the molecular indicators or transporters. Such models could be used for investigating tumor biomarkers, drug screening, and understanding tumor progression and metastasis.
A cellular taxonomy of the bone marrow stroma in homeostasis and leukemia demonstrates cancer-crosstalk with stroma to impair normal tissue function
Authors: Ninib Baryawno , Dariusz Przybylski , Kowalczyk Monika S. , Youmna Kfoury , Nicolas Severe , Karin Gustafsson , Francois Mercier , Marcin Tabaka , Matan Hofree , Danielle Dionne , Ani Papazian , Dongjun Lee , Orit Rozenblatt-Rosen , Aviv Regev , Scadden David T 
Published: February 2019

ABSTRACTStroma is a poorly defined non-parenchymal component of virtually every organ with key roles in organ development, homeostasis and repair. Studies of the bone marrow stroma have defined individual populations in the stem cell niche regulating hematopoietic regeneration and capable of initiating leukemia. Here, we use single-cell RNA-seq to define a cellular taxonomy of the mouse bone marrow stroma and its perturbation by malignancy. We identified seventeen stromal subsets expressing distinct hematopoietic regulatory genes, spanning new fibroblastic, and osteoblastic subpopulations. Emerging acute myeloid leukemia resulted in impaired osteogenic differentiation and reduced production of hematopoietic regulatory molecules necessary for normal hematopoiesis. Thus, cancer can affect tissue stroma in which they reside to disadvantage normal parenchymal cells. Our taxonomy of the regulatory stromal compartment provides experimental support for a model where malignant clone is not a destroyer of normal tissue but an architect of it, remodeling tissue stroma to enable emergent cancer.
Protective role of the deSUMOylating enzyme SENP3 in myocardial ischaemia-reperfusion injury
Authors: Rawlings Nadiia , Lee Laura , Nakamura Yasuko , Wilkinson Kevin A. , Henley Jeremy M 
Published: February 2019

AbstractInterruption of blood supply to the heart is a leading cause of death and disability. However, the molecular events that occur during heart ischaemia, and how these changes prime consequent cell death upon reperfusion, are poorly understood. Protein SUMOylation is a post-translational modification that has been strongly implicated in the protection of cells against a variety of stressors, including ischaemia-reperfusion. In particular, the SUMO2/3-specific protease SENP3 has emerged as an important determinant of cell survival after ischaemic infarct. Here, we used the Langendorff perfusion model to examine changes in the levels and localisation of SUMOylated target proteins and SENP3 in whole heart. We observed a 50% loss of SENP3 from the cytosolic fraction of hearts after preconditioning, a 90% loss after ischaemia and an 80% loss after ischaemia-reperfusion. To examine these effects further, we performed ischaemia and ischaemia-reperfusion experiments in the cardiomyocyte H9C2 cell line. Similar to whole hearts, ischaemia induced a decrease in cytosolic SENP3. Furthermore, shRNA-mediated knockdown of SENP3 led to an increase in the rate of cell death upon reperfusion. Together, our results indicate that cardiac ischaemia dramatically alter levels of SENP3 and suggest that this may a mechanism to promote cell survival after ischaemia-reperfusion in heart.
On-line orbit planning and guidance for advanced upper stage
Authors: Zhang Liang , Wei Changzhu , Diao Yin , Cui Naigang 
Published: February 2019

Purpose
This paper aims to investigate the problem of on-line orbit planning and guidance for an advanced upper stage.

Design/methodology/approach
The double impulse optimal transfer orbit is planned by the Lambert algorithm and the improved particle swarm optimization (IPSO) method, which can reduce the total velocity increment of the transfer orbit. More specially, a simplified formula is developed to obtain the working time of the main engine for two phases of flight based on the theorem of impulse. Subsequently, the true anomalies of the start position and the end position for both two phases are planned by the Newton iterative algorithm and the Kepler equation. Finally, the first phase of flight is guided by a novel iterative guidance (NIG) law based on the true anomaly update with respect to the geometrical relationship. Also, a completely analytical powered explicit guidance (APEG) law is presented to realize orbital injection for the second phase of flight.

Findings
Simulations including Monte Carlo and three typical orbit transfer missions are carried out to demonstrate the efficiency of the proposed scheme.

Originality/value
A novel on-line orbit planning algorithm is developed based on the Lambert problem, IPSO optimization method and Newton iterative algorithm. The NIG and APEG are presented to realize the designed transfer orbit for the first and second phases of flight. Both two guidance laws achieve higher orbit injection accuracies than traditional guidance laws.
Implementing gender quotas in academia: a practice lens
Authors: Voorspoels Jolien , Bleijenbergh Inge 
Published: February 2019

Purpose
The purpose of this paper is to explore the practices utilized by university actors when implementing gender quotas, and study how these practices affect gender equality in academic decision-making bodies.

Design/methodology/approach
The study applies a practice theory lens to the case study of a Belgian university implementing a gender quota by performing 26 semi-structured interviews with actors, and collecting and analyzing relevant organizational documents.

Findings
This study shows that university actors implement gender quotas through three practices: gender-specific calls, scouting and “playing around”. Identifying this variation in practices helps to understand both actors’ sense-making of compliance with gender quotas and women’s decision-making power in academic bodies.

Research limitations/implications
This study explores how practices interact with the organization’s broader context and its power dynamics. In future studies, adding ethnographic observations would strengthen the practice approach.

Practical implications
The study indicates that implementing gender quotas can foster women’s representation in decision-making, but that a strictly procedural sense-making of gender quotas could also undermine this. Universities should continue implementing gender quotas, further analyze their implementation practices and comprehensively adapt their organizational policies and practices to comply with gender equality goals substantively.

Originality/value
Through a practice theory approach, this paper offers original insight into how actors comply with gender quotas. Uncovering the implementation process in particular, the paper reveals how gender quotas could foster gender equality in academic decision-making.
Work-readiness integrated competence model
Authors: Prikshat Verma , Kumar Sanjeev , Nankervis Alan 
Published: February 2019

PurposeThe purpose of this paper is to conceptualise graduate work-readiness (GWR) and to develop a scale to measure it.Design/methodology/approachThe methodology entailed the compilation of a literature review and the conduct of qualitative interviews and a focus group to generate items. This study used the “resource-based view” approach to conceptualise a multi-dimensional–“work-readiness integrated competence model (WRICM)”–consisting of four main factors (namely, intellectual, personality, meta-skill and job-specific resources), with a further ten sub-dimensions. Further, a series of tests were performed to assess its reliability and validity.FindingsA final 53-item WRICM scale covering four dimensions and ten sub-dimensions of GWR was developed based on the perceptions of 362 HR professionals and managers from seven Asia-Pacific countries. The ten sub-dimensions covering 53 work-readiness skills reflect the perceptions of stakeholders regarding the work-readiness of graduates. The scale was found to be psychometrically sound for measuring GWR.Research limitations/implicationsThough the WRICM model is based on the inputs of different stakeholders of GWR (employers, educators, policy makers and graduates), the development of the WRICM scale is based on the perspectives of industry/employers only.Practical implicationsThe WRICM model has implications for education, industry, professional associations, policy makers and for graduates. These stakeholders can adapt this scale in assessing the work-readiness of graduates in different streams of education.Originality/valueThe authors believe that the WRICM model is the first multi-dimensional construct that is based on a sound theory and from the inputs from graduate work-readiness stakeholders from seven Asia-Pacific countries.
Decentralization of Indonesia social health insurance
Authors: Bintang Sanusi , Mujibussalim Mujibussalim , Fikri Fikri 
Published: February 2019

Purpose
The purpose of this study is to explain the need for the implementation of decentralization of Indonesia social health insurance (INA-Medicare), with particular emphasis for Aceh Province. First, it discusses the inconsistency of Act on National Social Security System (ANSSS) to the 1945 Constitution, because certain rules in ANSSS are contrary to the 1945 Constitution. This weakens the practice of broader regional autonomy, lessens the importance of public service quality in health care and ignores specific cultural and religious values of the regional people. Then, it explains provisions on central and regional government authority in the 1945 Constitution, Act on Regional Autonomy and Act on Governing of Aceh. Later, it explores current law and practice of INA-Medicare under the national social security system and the centralized administering body. Finally, it provides reasons for decentralization of INA-Medicare, as the solution.

Design/methodology/approach
This study uses doctrinal legal research. It relies on both primary and secondary legal authorities. In additions, it also uses sociolegal research by relying on non-legal materials, including empirical data from books, journals and newspapers. Analysis of legal authorities is by legal reasoning process, whereas analysis of non-legal materials is by qualitative approach.

Findings
This study argues that the decentralization of INA-Medicare is more suitable for Aceh Province because of several reasons, including implementing broader regional autonomy, improving public service quality in health care and implementing the principle of sharia social health insurance.

Originality/value
The study is original because it focuses on a specific regional area of Aceh Province, Indonesia. It concentrates on specific legal issues and provides unique reasons for argumentation. Therefore, it provides important specific information for journal readers.
Comparative analysis between management team and teachers on the impact of ISO 9001 standards in educational centres
Authors: Rodríguez-Mantilla Jesús Miguel , Fernández-Cruz Francisco José , Fernández-Díaz Mª José 
Published: February 2019

PurposeThe purpose of this paper is to analyse and compare the impact of implementation of ISO 9001:2008 Standards perceived by Management Teams and Teachers in schools in four autonomous communities in Spain.Design/methodology/approachTo assess this impact, the authors used an evaluation instrument made up of 93 items assessing seven major dimensions, whose reliability has been excellent for the full scale (Cronbach’sα= 0.987) and dimensions (α> 0.93). The authors conducted descriptive and differential analyses (ANOVA andt-test for independent samples) of the assessments by professional position (managers and teachers) and other variables (size and type of school, years of implantation, etc.). A factorial analysis of variance was conducted to analyse the interaction effect between these variables in each of the evaluated dimensions.FindingsThe most significant results show a high impact on the dimension management, medium on communication, learning process and external relations and low impact on climate, support and recognition and satisfaction. Likewise, the authors found that members of the Management Teams valued the impact that ISO 9001:2008 Standards have had on all dimensions at a higher level, except for external relations, where no significant differences between Teachers and Management Team members were found.Practical implicationsThe study makes it possible to conclude that in general terms, the members of the Management Team of the schools perceive a higher impact of the implementation of ISO 9001:2008 Standards than teacher do in the different dimensions evaluated.Originality/valueThe specialised literature shows the lack of studies related to the impact that the implementation of quality management systems has on organisations. Specifically, this study provides conclusions to the scientific and professional community with objective evidence of the impact ISO 9001:2008 implementation has had on schools, through an indirect system of perceptions of the education community of the changes, which according to them had taken place as a result of implementation. Thus, this study contributes to the development of a new body of knowledge by evaluating this impact.
Establishing transdisciplinary minor programme as a way to embed sustainable development into higher education system
Authors: Jia Qian , Wang Ying , Fengting Li 
Published: February 2019

Purpose
The purpose of this paper is to provide a case study of the establishment and development of a minor program in Sustainable Development in Tongji University, China, and how it contributes to embedding sustainable development into higher education system as an alternative platform for researchers and students to involve in a transdisciplinary teaching and learning process.

Design/methodology/approach
This case reviews the institutional setting and the different studying models and requirements for postgraduates and undergraduates. Postgraduate students have to take four core courses, select one module with four themed courses (4 + 4 fixed) and complete a transdisciplinary essay, and undergraduates can choose any three courses in all modules apart from the four core courses (4 + 3 open), with a transdisciplinary group project.

Findings
The development of the minor program reveals the popularity and decline of different modules, because of the popularity of the schools and institutes behind them, the university legacy and the media influence. The program design spurs transdisciplinary thinking on sustainable development but brings about challenges including time conflict with students’ major study. In conclusion, this program explores alternative education practices in embedding sustainable development in education system, contributing to and reflect on Education for Sustainable Development and the education reform in China.

Originality/value
The case presents a unique way of implementing Education for Sustainable Development in higher education system, in which minor education stands between formal and informal curriculum to tackle the barriers in undertaking sustainable development initiatives in curricula, through nurturing the culture and providing organizational support.
Antecedents and consequences of flow state in e-commerce
Authors: Lee Yun Jung , Ha Sejin , Johnson Zachary 
Published: February 2019

Purpose
Flow is an optimal cognitive state that enhances consumer satisfaction. This paper aims to examine the effects of website features (product- and service-related cues) on consumers’ flow experiences and how flow affects satisfaction with e-commerce.

Design/methodology/approach
Responses were collected from 556 respondents who had recently made purchases online. Factor analysis identified a measure of flow applicable within e-commerce. Structural equation modeling (SEM) was used to test hypothesized relationships between product- and service-oriented cues on flow and the influence of flow on satisfaction.

Findings
Flow experiences were favorably (unfavorably) influenced by product (service)-related cues. Of the five flow dimensions identified, three (enjoyment, goal clarity and feedback) positively affected, one (telepresence) negatively affected and one did not affect satisfaction.

Research limitations/implications
Prior research recognized the importance of flow, but its role in e-commerce was unclear, as prior e-commerce flow measures were incongruous and traditional retail findings apply inconsistently online. By empirically establishing a counterintuitive link between controllable Web features and flow and demonstrating how the dimension of flow independently affect satisfaction, the understanding of flow is advanced.

Practical implications
Understanding the influence of controllable marketing factors on flow can help e-commerce managers enhance consumers’ flow experiences and satisfaction.

Originality/value
Product-related cues enhanced while service-related cues degraded flow perceptions, with the later effect running contrary to traditional retail findings. The authors assert that this negative relationship is based on consumers’ use of service-related cues online, which are needed when consumers fail to find information – representing flow disruption.
The gig economy in the UK: a regional perspective
Authors: Johnes Geraint 
Published: February 2019

Purpose
A quarterly series of gig economy activity in the regions of the UK is constructed. Patterns of regional linkages are identified and the implications of spatial patterns for policymakers, businesses, workers and institutions are highlighted.

Design/methodology/approach
The Labour Force Survey data on main job self-employment in key gig economy sectors are used to construct the series. These are then analysed using vector autoregression techniques to identify patterns in the data and provide provisional forecasts.

Findings
The incidence of gig economy activity is greatest in the London region, characterised by high population density and a concentration of service sectors in which gig economy work, particularly of a highly skilled nature, takes place. Growth of gig economy activity in other regions has been more modest. In London, the percentage of workers in the gig economy is expected to rise to around 6.5 per cent over the next few years, while in other regions, the percentage is expected to settle at between 3 and 4.5 per cent.

Originality/value
These are the first regional estimates to be provided of the extent of gig economy activity. This is important in the context of discussions about the future of work, not least because regional disparities imply the need for policies addressing insecurity to have a spatial dimension.