bluuebunny/crossref_metadata_2025_split huggingface dataset:
A conserved MFS orchestrates a subset of O-glycosylation to facilitate macrophage dissemination and tissue invasion
Authors: Valošková Katarína , Biebl Julia , Roblek Marko , Emtenani Shamsi , Gyoergy Attila , Mišová Michaela , Ratheesh Aparna , Shkarina Kateryna , Larsen Ida S.B. , Vakhrushev Sergey Y. , Clausen Henrik , Siekhaus Daria E. 
Published: September 2018

SUMMARYAberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen inDrosophila melanogastermacrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of theDrosophila melanogasterembryo, and determine that Minerva increases the presence of T-antigen on protein pathways previously linked to cancer, most strongly on the protein sulfhydryl oxidase Qsox1 which we show is required for macrophage invasion. Minerva’s vertebrate ortholog, MFSD1, rescues theminervamutant’s migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis.
Versican Proteolysis Predicts Immune Effector Infiltration and Post-Transplant Survival in Myeloma
Authors: Dhakal Binod , Pagenkopf Adam , Mushtaq Muhammad Umair , Cunningham Ashley M , Flietner Evan , Morrow Zachary , Papadas Athanasios , Hope Chelsea , Leith Catherine , Hematti Peiman , Hari Parameswaran , Callander Natalie S , Asimakopoulos Fotis 
Published: September 2018

ABSTRACTHigh-dose alkylator-based conditioning followed by autologous stem-cell transplantation (ASCT) is a therapeutic mainstay for eligible patients with multiple myeloma. However, post-transplant relapses are common and prognostic biomarkers are scarce. Relapses are characterized by the influx of regulatory myeloid cells and dysfunctional T effectors. We have shown that myeloma-infiltrating myeloid cells produce versican (VCAN), a large matrix proteoglycan with tolerogenic activities. VCAN proteolysis by a-disintegrin-and-metalloproteinase-with-thrombospondin-motifs (ADAMTS) proteases generates versikine, a bioactive fragment (“matrikine”) that regulates Batf3-dendritic cells, known to control CD8+-attracting chemokine networks. Here we demonstrate that intense VCAN proteolysis predicts CD8+ infiltration post-transplant and paradoxically portends significantly inferior survival outcomes. Our data suggest that VCAN proteolysis promotes the influx of CD8+ effectors that are rendered overwhelmingly dysfunctional and/or frankly immunoregulatory (CD8+ Treg) at the tumor site. Thus, complex immunosuppressive circuits orchestrated through VCAN accumulation and turnover generate conditions favorable for myeloma tumor regrowth and point to a readily-assayed biomarker to identify the patients at risk for relapse and early death. The dismal outcomes associated with VCAN proteolysis may be rationally overcome through immunotherapies such as checkpoint inhibition (e.g., anti-TIGIT), tumor vaccines or anti-myeloid (e.g., anti-CSF-1R) approaches.
Synthetic Lethality of Wnt Pathway Activation and Asparaginase in Drug-Resistant Acute Leukemias
Authors: Hinze Laura , Pfirrmann Maren , Karim Salmaan , Degar James , McGuckin Connor , Vinjamur Divya , Sacher Joshua , Stevenson Kristen E. , Neuberg Donna S. , Bauer Daniel E. , Wagner Florence , Stegmaier Kimberly , Gutierrez Alejandro 
Published: September 2018

SUMMARYResistance to asparaginase, an antileukemic enzyme that depletes asparagine, is a common clinical problem. Using a genome-wide CRISPR/Cas9 screen, we found a synthetic lethal interaction between Wnt pathway activation and asparaginase in acute leukemias resistant to this enzyme. Wnt pathway activation induced asparaginase sensitivity in distinct treatment-resistant subtypes of acute leukemia, including T-lymphoblastic, hypodiploid B-lymphoblastic, and acute myeloid leukemias, but not in normal hematopoietic progenitors. Sensitization to asparaginase was mediated by Wnt-dependent stabilization of proteins (Wnt/STOP), which inhibits GSK3-dependent protein ubiquitination and degradation. Inhibiting the alpha isoform of GSK3 phenocopied this effect, and pharmacologic GSK3α inhibition profoundly sensitized drug-resistant leukemias to asparaginase. Our findings provide a molecular rationale for activation of Wnt/STOP signaling to improve the therapeutic index of asparaginase.SIGNIFICANCEThe intensification of asparaginase-based therapy has improved outcomes for several subtypes of acute leukemia, but the development of treatment resistance has a poor prognosis. We hypothesized, from the concept of synthetic lethality, that gain-of-fitness alterations in drug-resistant cells had conferred a survival advantage that could be exploited therapeutically. We found a synthetic lethal interaction between activation of Wnt-dependent stabilization of proteins (Wnt/STOP) and asparaginase in acute leukemias resistant to this enzyme. Inhibition of the alpha isoform of GSK3 was sufficient to phenocopy this effect, and the combination of GSK3α-selective inhibitors and asparaginase had marked therapeutic activity against leukemias resistant to monotherapy with either agent. These data indicate that drug-drug synthetic lethal interactions can improve the therapeutic index of cancer therapy.
Multiple sources of signal amplification within the B cell Ras/MAPK pathway
Authors: Mclaurin Justin D. , Weiner Orion D. 
Published: September 2018

AbstractThe Ras-Map kinase (MAPK) cascade underlies functional decisions in a wide range of cell types and organisms. In B cells, positive feedback-driven Ras activation is the proposed source of the digital (all-or-none) MAPK responses following antigen stimulation. However, an inability to measure endogenous Ras activity in living cells has hampered our ability to test this model directly. Here we leverage biosensors of endogenous Ras and ERK activity to revisit this question. We find that BCR ligation drives switch-like Ras activation and that lower BCR signaling output is required for the maintenance versus the initiation of Ras activation. Surprisingly, digital ERK responses persist in the absence of positive feedback-mediated Ras activation, and digital ERK is observed at a threshold level of Ras activation. These data suggest an independent analog-to-digital switch downstream of Ras activation, and reveals that multiple sources of signal amplification exist within the Ras-ERK module of the BCR pathway.
Nanostructured copper-carbon nanotubes composites for aircraft applications
Authors: Graça Isabel , Seixas Tomás , Ferro Alberto C. , Guedes Mafalda 
Published: September 2018

Purpose
The reliable performance of critical components working under extreme conditions is paramount to the safe operation of aircraft, and material selection is critical. Copper alloys are an obvious choice for such applications whenever a combination of transport, mechanical and tribological properties is required. However, low strength and hardness issues require development of new copper alloys and composites to improve service life and reliability. This study aims to investigate the effect of carbon nanotubes as reinforcement phase in copper-matrix composites.

Design/methodology/approach
The development of novel copper-based composites refined to the nanoscale was envisaged through mechanical milling of mixtures containing copper and carbon nanotubes (2 Wt.%). Milling took place in a planetary ball mill for times varying between 1 h and 16 h at 400 rpm. A ball-to-powder ratio of 20:1 and alumina vial and copper spheres were used under dry conditions or with addition of isopropyl alcohol. Scanning electron microscopy/energy dispersive spectroscopy, size distribution, Raman spectroscopy and X-ray diffraction were used to study the produced powders.

Findings
Attained results show that mechanical milling of the studied system produces nanostructured powders containing second-phase carbon nanotubes homogeneously distributed in the metallic matrix, together with severe copper grain refinement. This should correspond to increased residual microstresses, envisaging significant improvement of mechanical properties of the produced copper composites.

Originality/value
The novelty of the work resides in the use of carbon nanotubes for the reinforcement of copper, and on the systematic microstructural characterisation of the produced composites.
Enhancing the value of facilities information management (FIM) through BIM integration
Authors: Wijekoon Christaline , Manewa Anupa , Ross Andrew David 
Published: September 2018

PurposeBuilding information modelling (BIM) provides a robust platform for information management in built environment facilities. However, one of the consequences of the limited application of BIM in facilities information management (FIM) is that the potential value gain through the integration of as-built information during the operations management process has had limited exploration in current practice. The purpose of this paper is to explore the potential impact of BIM to enhance the value of FIM.Design/methodology/approachA detailed literature review was undertaken to identify BIM application in a construction context, and to develop a framework to investigate the value of information. An interpretative approach was adopted for data collection and analysis. A total of 14 semi-structured interviews were conducted with construction industry professionals to identify how value of FIM can be enhanced through BIM integration. The interview data were analysed using open and selective coding.FindingsThe findings confirm that information exchange between the construction and facilities management (FM) phases of a project are important in terms of efficient and effective maintenance of a facility as well as optimising the design task. With these promising benefits, BIM is an efficient mechanism to facilitate construction information exchange. However, there is an uncertainty over the optimum level of information that ought to be on a BIM model for FM purposes. The relationship between different aspects of value is a starting point to filter the required information for each individual project. In contrast, limited awareness of value of information exchange and the potential of BIM enabled FIM during construction is noted.Research limitations/implicationsThe information exchange considered within this investigation was limited to two key phases of the facility life cycle, namely, construction and FM (in-use).Practical implicationsThe findings bring insight into an unseen aspect of FM information needs that should be given priority in upcoming BIM developments. Also, it draws attention to how value is concerned in a daily basis beyond monetary terms.Originality/valueThe investigation of value enhancement through BIM integration in particular to FIM and ongoing research with new value dimensions.
Accountants’ satisfaction following unification of Canadian accounting bodies
Authors: Looknauth Tamaishwar , Bélanger Charles H. 
Published: September 2018

Purpose
This paper aims to assess the levels of satisfaction of legacy designation accountants, namely, Chartered Accountants (CAs), Certified General Accountants (CGAs) and Certified Management Accountants, under the new Chartered Professional Accountants (CPA) banner; to measure differences in satisfaction among the three designations; and to identify the factors associated with the levels of satisfaction.

Design/methodology/approach
A 30-item questionnaire was designed, pilot tested for face validity and further tested for reliability using a Cronbach’s alpha. The questionnaire consisted of three parts: sociodemographic questions, bipolar questions to fit the SERVQUAL model of satisfaction and questions about professional identity and general perceptions of the new CPA organization.

Findings
Legacy accountants in Ontario had a lower level of satisfaction than they expected before unification. A pre- and post-unification comparison found statistically significant differences on all five dimensions of the SERVQUAL model and on overall service. Responses to questions about professional identity and general perceptions of the new organization were mixed. An analysis of variance test revealed a statistically significant difference in satisfaction between CAs and the two other designations – CAs were the least satisfied. A varimax rotated factor analysis indicated that the SERVQUAL’s five dimensions appear to be good predictors of service quality.

Research limitations/implications
Merging professional cultures can be as challenging as merging companies. Increased membership volume needs to translate into additional benefits and services. As indicated by the respondents, the new CPA entity has much work to do, particularly with the former CAs.

Originality/value
This is the first study to examine satisfaction, specifically following the merger of the three accounting designations.
Creating a service platform – how to co-create value in a remote service context
Authors: Löfberg Nina , Åkesson Maria 
Published: September 2018

Purpose
The purpose of this paper is to further develop the construct of service platform and to clarify the definition of service platform in an industrial context. To do so, an understanding of the foundations for service platforms, based on a service perspective, is created.

Design/methodology/approach
The study has adopted a qualitative case study approach and builds on in-depth interviews with remote service teams in two multinational firms: one in the food processing and packaging industry and the other in the pulp and paper industry.

Findings
The foundations for successful service platforms consist of modularising resources, integrations and service processes to create value propositions. The value propositions could result in variations of a service or in variations of different services. When defining the concept service platform, the perspective of service needs to be made evident; therefore, the authors define service platform as: value proposition(s) consisting of a modular structure that invites to and facilitates value co-creation between resources, through integration opportunities in a continuous service process.

Research limitations/implications
The results are based on the perspective of two suppliers in similar industries; only remote services were studied. Firms from different types of industries and other types of services could add to the research on service modularity according to a service perspective. Moreover, information about customers and other actors’ involvement on the platform was gathered from the firms studied, no customers or other actors were interviewed.

Practical implications
This study shows the importance of a firm involving itself in the value creation of the customer, that is, focusing on value co-creation. This implies a close cooperation between the manufacturer and its customer – not only at a given point in time but also over a longer period of cooperation. Through the different types of modules building up the service platform, value co-creation can take place in various ways.

Originality/value
This study offers original empirical contributions on platforms from a service perspective. The study contributes to servitisation, service modularity and service (dominant) logic research by developing an understanding of the foundations for service platforms based on a service perspective. It also contributes to platform research more specifically by developing a definition of service platform in an industrial context.
Role of religiosity in purchase of green products by Muslim students
Authors: Khan Mohammed Naved , Kirmani Mohd Danish 
Published: September 2018

PurposeThis paper aims to investigate the role of religiosity in Indian Muslim students with the objective of mapping their attitude towards green products.Design/methodology/approachData were generated from 306 Muslim students enrolled in educational institutes located in the national capital of India (i.e. New Delhi). The study sample was identified through purposive sampling, and then the questionnaire was personally administered. The data were analysed using SPSS and AMOS, and research hypotheses were validated using structural equation modelling.FindingsThe findings of the present study suggest that environmental concern is a precursor of consumer attitude towards green products, and antecedents of environmental concern are collectivism and eco-literacy. Further, the findings also suggest that religiosity significantly and positively affects collectivism values of consumers. However, religiosity was not found to be significantly associated with the level of eco-literacy of consumers.Practical implicationsReligiosity emerged as one of the main factors that needs to be considered while promoting green products in India. In their promotion messages, green marketers attempting to target Muslim students ought to emphasize that Islamic tenets enjoin upon them to collectively take the responsibility of preserving the environment. The natural resources and the environment may be presented as a gift of Almighty Allah, and steps towards environmental conservation may be projected as a mode of pleasing Allah.Originality/valueThis study is pioneering in the sense that it proposes a comprehensive and practical model for mapping attitude towards green products for young Indian Muslim consumers. In fact, the study takes a lead in examining the role of religiosity as antecedent in mapping of attitude towards green products and the role of collectivism and eco-literacy in influencing environmental concern.
Examining how context change foster service innovation
Authors: Edvardsson Bo , Frow Pennie , Jaakkola Elina , Keiningham Timothy Lee , Koskela-Huotari Kaisa , Mele Cristina , Tombs Alastair 
Published: September 2018

PurposeThe purpose of this paper is to explore the role of context in service innovation by developing a conceptual framework that illuminates the key elements and trends in context change.Design/methodology/approachThe paper adopts a service ecosystem lens for understanding how elements and trends in context foster service innovation. A conceptual framework identifying the role of context change in fostering service innovation is developed and justified through illustrations across industry settings of health, retailing, banking and education.FindingsContext change is conceptualized by three trends – speed, granularity and liquification – that provide an analytical foundation for understanding how changes in the elements of context – space, resources and institutional arrangements – can foster service innovation. The analysis indicates emerging patterns across industries that allow exploring scenarios, grounded in emerging trends and developments in service innovation toward 2050.Practical implicationsManagers are offered a framework to guide service innovation and help them prepare for the future. The paper also suggests areas for further research.Originality/valueThe paper contributes with a new conceptualization of context change to identify and explain service innovation opportunities. Managers are offered a framework to guide service innovation and help them prepare for 2050. The paper also suggests areas for further service innovation research, zooming in on contextual changes to prepare for 2050.
Consumption or prosumption? A question of resources
Authors: Nagel Duane M. , Cronin Jr J. Joseph , Utecht Richard L. 
Published: September 2018

Purpose
Despite the recent growth of the do-it-yourself market, very little is known as to how or why individuals actually choose to engage in prosumption behavior. The purpose of this study is to specifically examine the decision process of actors when determining the level of resource commitment and integration necessary to prosume or consume a service, thus offering insights to both managers and academics alike.

Design/methodology/approach
A multi-method study using both qualitative and quantitative research examines the decision of actors to consume or prosume a service. A conceptual model is presented and tested.

Findings
The results identify the primary drivers individuals considered when evaluating the resource commitment necessary for a make or buy decision. This research offers empirical support for the application of transaction cost analysis as an appropriate theoretical explanation of how actors decide to prosume or consume a service. The authors further suggest, based on these findings, that transaction cost analysis is a viable middle-range theory to explain the commitment and sharing of resources between actors engaged in co-production within the perspective of a service-dominant logic.

Research limitations/implications
Future research is needed to identify opportunities for hybrid models that consider the appropriateness of these findings within larger service networks, as well as potential moderating or mediating influences of the direct effects identified and investigated.

Originality/value
This study offers an initial attempt to provide a theoretical explanation for the resource integration decisions (e.g. make or buy) faced by individuals in a growing segment of the economy. The findings enable better informed strategies to be identified by both service providers and retailers.
Can threat assessment help police prevent mass public shootings? Testing an intelligence-led policing tool
Authors: Capellan Joel A. , Lewandowski Carla 
Published: September 2018

PurposeThe purpose of this paper is to examine whether threat assessment, an intelligence-led policing (ILP) tool, can prevent mass public shootings.Design/methodology/approachIn order to gauge the potential effectiveness of this ILP tool, the authors conduct a retrospective analysis of 278 mass public shootings that occurred in the USA between 1966 and 2016. This retrospective analysis allows us to determine how successful threat assessment protocols could be in preventing mass public shootings by examining how successful this tool would have been in identifying the offenders in our data.FindingsThe results show that threat assessment has the potential to be an effective tool in the ILP arsenal to identify and prevent impending mass public shootings. However, our results also point to several obstacles for the effective implementation of this ILP tool. The underreporting of threats and using the content of threats and characteristics of threateners are problematic in correctly assigning risk. The authors make suggestions for how to overcome these obstacles.Originality/valueThis study makes several contributions to the intelligence-led policing and mass murder field. This is the first study to test the potential effectiveness of an intelligence-led policing tool to prevent mass public shootings. Additionally, this is one of the first studies to examine the leaks, types, context and follow-though of threats made by mass public shooters in the United States. Consequently, it provides unique information on the foreshowing behaviors of mass public shooters.