bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteocyte specific responses to soluble and mechanical stimuli in a stem cell derived culture model
Authors: Thompson William R. , Uzer Gunes , Brobst Kaitlyn E. , Xie Zhihui , Sen Buer , Yen Sherwin S. , Styner Maya , Rubin Janet 
Published: June 2015

AbstractStudying osteocyte behavior in culture has proven difficult because these embedded cells require spatially coordinated interactions with the matrix and surrounding cells to achieve the osteocyte phenotype. Using an easily attainable source of bone marrow mesenchymal stem cells, we generated cells with the osteocyte phenotype within two weeks. These “stem cell derived-osteocytes” (SCD-O) displayed stellate morphology and lacunocanalicular ultrastructure. Osteocytic genes Sost, Dmp1, E11 and Fgf23 were maximally expressed at 15 days and responded to PTH and 1,25(OH)2D3. Production of sclerostin mRNA and protein, within 15 days of culture makes the SCD-O model ideal for elucidating regulatory mechanisms. We found sclerostin to be regulated by mechanical factors, where low intensity vibration significantly reduced Sost expression. Additionally, this model recapitulates sclerostin production in response to osteoactive hormones, as PTH or LIV repressed secretion of sclerostin, significantly impacting Wnt-mediated Axin2 expression, via β-catenin signaling. In summary, SCD-O cells produce abundant matrix, rapidly attain the osteocyte phenotype and secrete functional factors including sclerostin under non-immortalized conditions. This culture model enables ex vivo observations of osteocyte behavior while preserving an organ-like environment. Furthermore, as marrow-derived mesenchymal stem cells can be obtained from transgenic animals; our model enables study of genetic control of osteocyte behaviors.
Cell proliferation by silk gut incorporating FGF-2 protein microcrystals
Authors: Kotani Eiji , Yamamoto Naoto , Kobayashi Isao , Uchino Keiro , Muto Sayaka , Ijiri Hiroshi , Shimabukuro Junji , Tamura Toshiki , Sezutsu Hideki , Mori Hajime 
Published: June 2015

AbstractSilk gut processed from the silk glands of the silkworm could be an ideal biodegradable carrier for cell growth factors. We previously demonstrated that polyhedra, microcrystals of Cypovirus 1 polyhedrin, can serve as versatile carrier proteins. Here, we report the generation of a transgenic silkworm that expresses polyhedrin together with human basic fibroblast growth factor (FGF-2) in its posterior silk glands to utilize silk gut as a proteinaceous carrier to protect and slowly release active cell growth factors. In the posterior silk glands, polyhedrin formed polyhedral microcrystals and FGF-2 became encapsulated within the polyhedra due to a polyhedron-immobilization signal. Silk gut powder prepared from posterior silk glands containing polyhedron-encapsulated FGF-2 stimulated the phosphorylation of p44/p42 MAP kinase and induced the proliferation of serum-starved NIH3T3 cells by releasing bioactive FGF-2. Even after a one-week incubation at 25 °C, significantly higher biological activity of FGF-2 was observed for silk gut powder incorporating polyhedron-encapsulated FGF-2 relative to silk gut powder with non-encapsulated FGF-2. Our results demonstrate that posterior silk glands incorporating polyhedron-encapsulated FGF-2 are applicable to the preparation of biodegradable silk gut, which can protect and release FGF-2 that is produced in a virus- and serum-free expression system with significant application potential.
Comprehensive prediction of drug-protein interactions and side effects for the human proteome
Authors: Zhou Hongyi , Gao Mu , Skolnick Jeffrey 
Published: June 2015

AbstractIdentifying unexpected drug-protein interactions is crucial for drug repurposing. We develop a comprehensive proteome scale approach that predicts human protein targets and side effects of drugs. For drug-protein interaction prediction, FINDSITEcomb, whose average precision is ~30% and recall ~27%, is employed. For side effect prediction, a new method is developed with a precision of ~57% and a recall of ~24%. Our predictions show that drugs are quite promiscuous, with the average (median) number of human targets per drug of 329 (38), while a given protein interacts with 57 drugs. The result implies that drug side effects are inevitable and existing drugs may be useful for repurposing, with only ~1,000 human proteins likely causing serious side effects. Akilling indexderived from serious side effects has a strong correlation with FDA approved drugs being withdrawn. Therefore, it provides a pre-filter for new drug development. The methodology is free to the academic community on the DR. PRODIS (DRugome, PROteome and DISeasome) webserver athttp://cssb.biology.gatech.edu/dr.prodis/. DR. PRODIS provides protein targets of drugs, drugs for a given protein target, associated diseases and side effects of drugs, as well as an interface for the virtual target screening of new compounds.
Antioxidant treatment enhances human mesenchymal stem cell anti-stress ability and therapeutic efficacy in an acute liver failure model
Authors: Zeng Wen , Xiao Jia , Zheng Gang , Xing Feiyue , Tipoe George L. , Wang Xiaogang , He Chengyi , Chen Zhi-Ying , Liu Yingxia 
Published: June 2015

AbstractOne of the major problems influencing the therapeutic efficacy of stem cell therapy is the poor cell survival following transplantation. This is partly attributed to insufficient resistance of transplanted stem cells to oxidative and inflammatory stresses at the injured sites. In the current study, we demonstrated the pivotal role of antioxidant levels in human umbilical cord mesenchymal stem cells (hUCMSCs) dynamic in vitro anti-stress abilities against lipopolysaccharide (LPS)/H2O2 intoxication and in vivo therapeutic efficacy in a murine acute liver failure model induced by D-galactosamine/LPS (Gal/LPS) by either reducing the antioxidant levels with diethyl maleate (DEM) or increasing antioxidant levels with edaravone. Both the anti- and pro-oxidant treatments dramatically influenced the survival, apoptosis and reactive oxygen species (ROS) production of hUCMSCs through the MAPK-PKC-Nrf2 pathway in vitro. When compared with untreated and DEM-treated cells, edaravone-treated hUCMSCs rescued NOD/SCID mice from Gal/LPS-induced death, significantly improved hepatic functions and promoted host liver regeneration. These effects were probably from increased stem cell homing, promoted proliferation, decreased apoptosis and enhanced secretion of hepatocyte growth factor (HGF) under hepatic stress environment. In conclusion, elevating levels of antioxidants in hUCMSCs with edaravone can significantly influence their hepatic tissue repair capacity.
Microwave synthesis and actuation of shape memory polycaprolactone foams with high speed
Authors: Zhang Fenghua , Zhou Tianyang , Liu Yanju , Leng Jinsong 
Published: June 2015

AbstractMicrowave technology is a highly effective approach to fast and uniform heating. This article investigates that the microwave heating as a novel method is used to rapidly foam and actuate biocompatible and biodegradable shape memory crosslinked-polycaprolactone (c-PCL) foams. The optical microscope proves that the resulting c-PCL foams have homogenous pore structure. Mechanical behavior and shape memory performance of c-PCL foams are investigated by static materials testing. Shape recovery ratio is approximately 100% and the whole recovery process takes only 98 s when trigged by microwave. Due to the unique principle of microwave heating, the recovery speed of c-PCL foams in microwave oven is several times faster than that in hot water and electric oven. Hence compared to the traditional heating methods, microwave is expected to bring more advantages to modern industry and scientific research in the field of smart materials and structures.
Experimental quantum annealing: case study involving the graph isomorphism problem
Authors: Zick Kenneth M. , Shehab Omar , French Matthew 
Published: June 2015

AbstractQuantum annealing is a proposed combinatorial optimization technique meant to exploit quantum mechanical effects such as tunneling and entanglement. Real-world quantum annealing-based solvers require a combination of annealing and classical pre- and post-processing; at this early stage, little is known about how to partition and optimize the processing. This article presents an experimental case study of quantum annealing and some of the factors involved in real-world solvers, using a 504-qubit D-Wave Two machine and the graph isomorphism problem. To illustrate the role of classical pre-processing, a compact Hamiltonian is presented that enables a reduced Ising model for each problem instance. On random N-vertex graphs, the median number of variables is reduced from N2 to fewer than N log2N and solvable graph sizes increase from N = 5 to N = 13. Additionally, error correction via classical post-processing majority voting is evaluated. While the solution times are not competitive with classical approaches to graph isomorphism, the enhanced solver ultimately classified correctly every problem that was mapped to the processor and demonstrated clear advantages over the baseline approach. The results shed some light on the nature of real-world quantum annealing and the associated hybrid classical-quantum solvers.
Generation of mutant mice via the CRISPR/Cas9 system using FokI-dCas9
Authors: Hara Satoshi , Tamano Moe , Yamashita Satoshi , Kato Tomoko , Saito Takeshi , Sakuma Tetsushi , Yamamoto Takashi , Inui Masafumi , Takada Shuji 
Published: June 2015

AbstractGenome editing, which introduces mutations in genes of interest using artificial DNA nucleases such as the ZFN, TALEN and CRISPR/Cas9 systems in living cells, is a useful tool for generating mutant animals. Although CRISPR/Cas9 provides advantages over the two other systems, such as an easier vector construction and high efficiency of genome editing, it raises concerns of off-target effects when single guide RNA (gRNA) is used. Recently, FokI-dCas9 (fCas9), a fusion protein comprised of the inactivated mutant form of Cas9 and the DNA nuclease domain of FokI, has been developed. It enables genome editing with reduced risks of off-target effects in mammalian cultured cell lines, as fCas9 requires gRNAs to bind opposite strands with an appropriate distance between them. Here, we demonstrated that fCas9 efficiently generates living mutant mice through microinjection of its mRNA and gRNAs into zygotes. A comparison of the relative efficiencies of genome editing using fCas9 and other modified Cas9s showed that these mutagenesis efficiencies are similar when the targets of two gRNAs are separated by an appropriate distance, suggesting that in addition to the ease of vector construction, fCas9 exhibit high efficiency in producing mutant mice and in reducing risks of off-target effects.
Effective knowledge management boosts virtual teams
Authors: Pathak Atul Arun 
Published: June 2015

Purpose
– Describes the role of human-resource management (HRM) in ensuring effective knowledge management in virtual teams.

Design/methodology/approach
– Explains how the various policies and processes designed and implemented by the HRM enable virtual teams to manage knowledge effectively and thereby provide a competitive advantage to an organization.

Findings
– Highlights how developments in information technology have made virtual teams more common.

Practical implications
– Advances the view that appropriate recruitment, induction, training and appraisal processes are needed to ensure effective knowledge management in virtual teams.

Social implications
– Reveals that virtual teams are increasingly common across a wide range of industries and sectors and so their effective management is growing in importance.

Originality/value
– Provides insights into how the challenge of managing knowledge in virtual teams can be overcome by suitably designed and implemented HRM practices.
Engaged leaders develop schools as quality organisations
Authors: Snyder Kristen 
Published: June 2015

Purpose
– This paper explores the question, “what does it mean to be an engaged school leader in an educational context that promotes standards-based accountability as a model of quality development?” Specifically, what drives educational leaders? What do they do to lead schools as quality organisations? and How do they lead schools as quality organisations?

Design/methodology/approach
– An ethnographically grounded theory case study was conducted with 16 principles in Sweden, USA and Finland, who participated in a three-year project to lead schools as global learning centers.

Findings
– Findings showed that school leaders used a variety of leadership styles as they developed worked cultures grounded in a value system, to support student learning and development. Also, work cultures that engaged members of the school and community were critical for leading schools as learning organisations.

Research limitations/implications
– The small sample may not be generalizable to all educational systems.

Practical implications
– This study provides evidence about the complexities for school leadership today that are not currently addressed in most principal preparation programs. The findings can serve to help inform further development of principal preparation.

Originality/value
– The experiences shared in this study provide an alternative perspective about what it is that school leaders do and think about amidst a high-stakes testing context of school development. The grounded theory nature of this study, combined with an ethnographic approach, provides deep insights into the daily working life of engaged school leaders to learn first hand from their dialogue about what it takes to lead schools as quality organisations.
First evidences from “lean
&
safety” projects
Authors: Crema Maria , Verbano Chiara , Chiozza Maria Laura 
Published: June 2015

Purpose
– The purpose of this paper is to investigate the significant features that characterize these projects: organizational aspects, phases and activities, tools, techniques, practices and key factors for successful implementation. No studies in the academic literature have yet focused on the relation between healthcare lean management (HLM) and clinical risk management (CRM) to enhance multiple aspects of performance, although the possibility of implementing “lean
&
safety” projects has been highlighted.

Design/methodology/approach
– Two significant projects have been selected from the same Italian hospital in two different fields of application. Within- and cross-case analyses have been performed to obtain useful findings.

Findings
– The results suggest that HLM can provide support for CRM, and an integrated methodology should be considered. The first indications concerning how this new synergistic methodology may be developed are provided and these should stimulate future research, testing and exploiting the methodology in other contexts.

Originality/value
– From the results of this paper, guidelines for the implementation of a “lean
&
safety” project could be developed to improve the management of clinical processes pursuing multiple objectives. This study could contribute to the development of safer and more sustainable health care systems for the benefit of the entire community.
The paradigm shift to Business Excellence 2.0
Authors: Enquist Bo , Johnson Mikael , Rönnbäck Åsa 
Published: June 2015

Purpose
– This paper aims to contribute to the debate on business excellence by comparing the business excellence models of Malcolm Baldrige, European Foundation for Quality Management and Swedish Institute for Quality. By assessing these in relation to today’s new business landscape, the authors suggest that emphasising issues such as stakeholder co-creation of value, stakeholder dialogue, service innovation, service logic, business ethics and different views on resource integration can alter the view of quality improvement from economic, social and environmental perspectives, in turn, leading to Business Excellence 2.0.

Design/methodology/approach
– This study examines three business excellence models and compares their adoption of the concepts of today’s new business landscape. The study focuses on whether the models’ fundamental principles and concepts are aligned with the views on sustainability, stakeholder co-creation and service innovation.

Findings
– The examined business excellence models do not fully respond to the requirements of today’s business landscape. To gain relevance in the private sector, the fundamental ideas of the models in terms of concepts, criteria and evaluation processes must be rethought. Such an opportunity enables the quality movement and service logic research to come together to develop new business excellence models that incorporate the challenges of today’s business landscape.

Research limitations/implications
– This paper illustrates the need to develop business excellence models to address the perspectives of today’s new business landscape.

Practical implications
– By incorporating strategies in sustainability, stakeholder co-creation and service innovation in business excellence models, organisations can deliver sustainable business growth.

Originality/value
– The paper sheds new light on how business excellence models can incorporate aspects of the new business landscape. It also shows how the quality movement and the ongoing service logic research can come together to develop a new business excellence model that addresses the challenges in the new business landscape.
Integration of CSR principles in quality management
Authors: Frolova Irina , Lapina Inga 
Published: June 2015

Purpose– This paper aims to analyse the case of a non-governmental organization (NGO) and the possibilities of implementing corporate social responsibility (CSR) strategy and principles in an organizational quality management system (QMS) to reduce the rate of staff turnover and improve the overall excellence of the organization. QMS provides a framework for implementing CSR policy, strategy, activities and culture at all management levels of organization, creating a basis for establishing a sustainable development policy and providing overall employee and management commitment and continuous improvement of the system.Design/methodology/approach– Several research methods, such as literature review, logical and comparative analysis, in-depth interviews, Ishikawa diagram method and organization performance assessment via M. Baldrige excellence criteria, were applied in this research.Findings– The authors came to the conclusion that implementing employee-related CSR activities in an organizational QMS in a long-term period can reduce employee turnover, increase loyalty and commitment and improve the overall process performance in an NGO. The QMS framework allows maintaining, monitoring and evaluating continuous effect and execution of CSR principles, and including CSR strategies in organizational policy.Research limitations/implications– The research is restricted due to the fact that the authors cannot disclose the name of the analysed NGO because of ethical and confidentiality considerations.Originality/value– The paper presents an encompassing approach of integration of CSR principles in quality management principles for reducing staff turnover, completing a case study of an NGO.
Comprehensive quality assessment of Czech higher education institutions
Authors: Nenadál Jaroslav 
Published: June 2015

Purpose– The paper aims to sum up the principal and original set of information related to the special project covered by Czech Ministry of Education, Youth and Sports, which was oriented to quality assurance and assessment at Czech higher education institutions. It brings main results and lessons learned from comprehensive quality assessment methodology pilot testing.Design/methodology/approach– Brainstorming conferences, seminars, comparative analysis, interviews, design review and validation were used by the expert team to develop and to test the comprehensive quality assessment methodology.Findings– The EFQM Excellence Model is the most comprehensive tool for quality assurance and quality assessment. It is pragmatic and practical, but it is necessary to adapt this model for effective use at Czech higher education institutions as a set of assessment criteria. The comprehensive quality assessment approach does not only examine what universities and other higher schools have achieved in the past (through lagging indicators), but it also includes assessment of their potential for the future through the so-called leading indicators.Research limitations/implications– The pilot testing of designed methodology of comprehensive quality assessment was performed within 12 Czech higher education institutions, but the lessons learned have common validity for any Czech higher education institution.Originality/value– The proposed methodology of comprehensive quality assessment is a quite new approach from the point of Czech higher education institutions view. It offers new and efficient tool for next higher schools and universities development.
Conceptual generalisation
Authors: Adriaenssen Daniel J. , Johannessen Jon-Arild 
Published: June 2015

Purpose– The purpose of this paper is to make a small contribution to reflections on general methodology, not specific methods, in social science.Design/methodology/approach– Systemic methodology.Findings– First, schematic typology of six conceptual models. Second, typology for determining levels of abstraction for different models and degrees of generalisation. Third, typology for generalisation on the basis of a case study. Fourth, strategy for developing conceptual models.Research limitations/implications– Research falls into two main categories: conceptual generalisation and empirical generalisation. Conceptual generalisation is an investigation whereby the researcher uses other researchers’ empirical findings in conjunction with his or her own process of conceptualisation in order to generalise and identify a pattern. This contrasts with empirical generalisation, where the researcher investigates a phenomenon or problem that is apparent in the empirical data, and only thereafter generalises in the light of his or her own findings.Practical implications– A low level of understanding of conceptual generalisation among masters and PhD students. With this paper the authors try to change this perception among students.Originality/value– Developing a systemic methodology in order for students and university teachers to understand conceptual generalisations.