bluuebunny/crossref_metadata_2025_split huggingface dataset:
ISO 9001 overall performance dimensions: an exploratory study
Authors: Psomas Evangelos , Pantouvakis Angelos 
Published: August 2015

Purpose
– The purpose of this paper is to validate and assess the performance dimensions reflecting ISO 9001 benefits in service companies and to determine their relationships.

Design/methodology/approach
– A research study was carried out in 198 ISO 9001:2008 certified Greek service companies. Data were obtained through a structured questionnaire and have been analyzed with exploratory and confirmatory factor analyses.

Findings
– Four performance dimensions reflecting ISO 9001 benefits are extracted and validated, namely, product/service quality, operational, market and financial performance.

Research limitations/implications
– The research sample is limited to small and medium-sized enterprises operating in a specific European country. Further research may confirm the findings of this study to other countries as well.

Practical implications
– By determining and evaluating the performance dimensions and their inter-relationships, the ISO 9001 certified service companies are assisted to select an appropriate strategy to further improve their performance and competitiveness. The suggested model can be also used as a self-assessment and benchmarking tool for managers and practitioners alike.

Originality/value
– The present study provides a comprehensive model of performance dimensions reflecting ISO 9001 benefits in service companies.
An in-depth review of the internal relationships of the EFQM model
Authors: Gómez Joaquín Gómez , Martínez Costa Micaela , Martínez Lorente Angel R. 
Published: August 2015

Purpose– The European Foundation for Quality Management (EFQM) model is widely used as a management tool in companies. Consequently, it is of great importance to understand the relationships within it, and inform managers about appropriate ways to manage events in order to get the desired results in general, and for specific interest groups (stakeholders). The paper aims to discuss these issues.Design/methodology/approach– This paper analyzes the internal relationships of the EFQM model using empirical data from a sample of 199 Spanish companies. Four managers in each company were interviewed, to eliminate single respondent bias. Structural equation modeling is used for the analysis.Findings– The results obtained from the empirical analysis provide evidence of an underlying logic in the EFQM model that does not match the official model. New significant relationships between the enablers and results not considered in the official model have been found.Research limitations/implications– The study focusses on Spanish industrial companies with 50-500 workers and uses a cross-sectional design.Practical implications– Managers should look at the EFQM model as a tool for finding their own way to excellence, but it is not a precise map, because the model may have some problems of definition. Managers should introduce its elements only after deep reflection on its benefit for their company.Originality/value– Despite the previous research on this issue, there is still no clear consensus. Relationships that are not reflected in the theoretical model have been identified.
Anti‐infective immunoadhesins from plants
Authors: Wycoff Keith , Maclean James , Belle Archana , Yu Lloyd , Tran Y , Roy Chad , Hayden Frederick 
Published: August 2015

SummaryImmunoadhesins are recombinant proteins that combine the ligand‐binding region of a receptor or adhesion molecule with immunoglobulin constant domains. All FDA‐approved immunoadhesins are designed to modulate the interaction of a human receptor with its normal ligand, such as Etanercept (Enbrel®), which interferes with the binding of tumour necrosis factor (TNF) to the TNF‐alpha receptor and is used to treat inflammatory diseases such as rheumatoid arthritis. Like antibodies, immunoadhesins have long circulating half‐lives, are readily purified by affinity‐based methods and have the avidity advantages conferred by bivalency. Immunoadhesins that incorporate normal cellular receptors for viruses or bacterial toxins hold great, but as yet unrealized, potential for treating infectious disease. As decoy receptors, immunoadhesins have potential advantages over pathogen‐targeted monoclonal antibodies. Planet Biotechnology has specialized in developing anti‐infective immunoadhesins using plant expression systems. An immunoadhesin incorporating the cellular receptor for anthrax toxin, CMG2, potently blocks toxin activity in vitro and protects animals against inhalational anthrax. An immunoadhesin based on the receptor for human rhinovirus, ICAM‐1, potently blocks infection of human cells by one of the major causes of the common cold. An immunoadhesin targeting the MERS coronavirus is in an early stage of development. We describe here the unique challenges involved in designing and developing immunoadhesins targeting infectious diseases in the hope of inspiring further research into this promising class of drugs.
Vibrio cholerae CsrA Regulates ToxR Levels in Response to Amino Acids and Is Essential for Virulence
Authors: Mey Alexandra R. , Butz Heidi A. , Payne Shelley M. 
Published: August 2015

ABSTRACT

ToxR is a major virulence gene regulator in
Vibrio cholerae
. Although constitutively expressed under many laboratory conditions, our previous work demonstrated that the level of ToxR increases significantly when cells are grown in the presence of the 4 amino acids asparagine, arginine, glutamate, and serine (NRES). We show here that the increase in ToxR production in response to NRES requires the Var/Csr global regulatory circuit. The VarS/VarA two-component system controls the amount of active CsrA, a small RNA-binding protein involved in the regulation of a wide range of cellular processes. Our data show that a
varA
mutant, which is expected to overproduce active CsrA, had elevated levels of ToxR in the absence of the NRES stimulus. Conversely, specific amino acid substitutions in CsrA were associated with defects in ToxR production in response to NRES. These data indicate that CsrA is a positive regulator of ToxR levels. Unlike previously described effects of CsrA on virulence gene regulation, the effects of CsrA on ToxR were not mediated through quorum sensing and HapR. CsrA is likely essential in
V. cholerae
, since a complete deletion of
csrA
was not possible; however, point mutations in CsrA were tolerated well. The CsrA Arg6His mutant had wild-type growth
in vitro
but was severely attenuated in the infant mouse model of
V. cholerae
infection, showing that CsrA is critical for pathogenesis. This study has broad implications for our understanding of how
V. cholerae
integrates its response to environmental cues with the regulation of important virulence genes.

IMPORTANCE
In order to colonize the human host,
Vibrio cholerae
must sense and respond to environmental signals to ensure appropriate expression of genes required for pathogenesis. Uncovering how
V. cholerae
senses its environment and activates its virulence gene repertoire is critical for our understanding of how
V. cholerae
transitions from its natural aquatic habitat to the human host. Here we demonstrate a previously unknown link between the global regulator CsrA and the major
V. cholerae
virulence gene regulator ToxR. The role of CsrA in the cell is to receive input from the environment and coordinate an appropriate cellular response. By linking environmental sensing to the ToxR regulon, CsrA effectively acts as a switch that controls pathogenesis in response to specific signals. We demonstrate that CsrA is critical for virulence in the infant mouse model of
V. cholerae
infection, consistent with its role as an
in vivo
regulator of virulence gene expression.
A case–control study of occupational contact levels in the childhood leukaemia cluster at Seascale, Cumbria, UK
Authors: Kinlen Leo J 
Published: August 2015

ObjectivesTo investigate adult occupational contact levels and risk of childhood leukaemia and non-Hodgkin's lymphoma (LNHL) in Seascale, an association found in other situations of rural population mixing (PM).DesignMatched case–control study.SettingSeascale, Cumbria, UK.ParticipantsFor each case of LNHL recorded in patients under age 25 years during 1950–2006, up to 20 matched controls were chosen and parental occupational details obtained; an exception was a single working young adult, whose own occupation (and that of controls) was used.Primary outcome measuresContact levels of occupations were categorised as: low/medium (reference group), high or very high contact levels, as in previous studies, with provision for certain unusual occupations. In particular, specialist policemen responsible for security and access at the nearby Sellafield nuclear complex were allocated to the highest contact category, and those Sellafield employees who worked in controlled areas to the middle (high) category. Since of possible bias, unusual contact aspects noted in the main research and development (R&D) building were reserved for a supplementary analysis. ORs were calculated for the occupational contact levels.ResultsCompared to the reference group, the social class adjusted ORs for the high and very high contact categories were 8.18 (95% CI 0.95 to 70.33) and 14.90 (1.20 to 184.90), respectively, with a significant trend across the categories (p value=0.024). In the supplementary analysis with R&D workers moved to the very high contact category, the OR for the latter became 29.68 (2.12 to 415.79), and the p value for trend, 0.011.ConclusionsThe Seascale LNHL excess was most marked among those young people linked with high occupational contact levels; it is therefore not an exception to the pattern of family infection shown by other PM-related excesses. The findings have implications for the choice of controls in certain types of virus study.
Abstract 1007: Elucidating a role for the translation initiation factor, eIF4G1, in resistance to therapy in inflammatory breast cancer (IBC)
Authors: Price Arianna , Edwards Courtney M. , Evans Myron K. , Devi Gayathri 
Published: August 2015

Abstract
Inflammatory breast cancer (IBC) is a highly invasive and aggressive breast cancer with relatively low survival rates compared with other locally advanced breast cancers. IBC is characterized by its rapid development of resistance to radio- and chemotherapies, which may in part be due to altered translational control driven by overexpression of the translation initiation factor, eIF4G1. This protein has been shown to enhance translation of eukaryotic mRNAs with internal ribosome entry sites (IRES) and enhanced translation in IBC may play a role in the survival of tumor cells during cellular stress, when translation would normally be suppressed. Some inhibitors of apoptosis proteins have 5′-untranslated regions (UTRs) that allow for IRES-mediated translation, and inhibition of apoptosis is one mechanism by which IBC cells have previously been shown to become resistant to therapy. Translational up-regulation of an inhibitor of apoptosis protein in therapy-resistant clones of IBC cell lines has been observed, which is of importance as the 5′UTR of such proteins contain highly active IRES elements. Regulation of such protein expression by eIF4G1-mediated IRES translation may be one reason for this observed therapeutic resistance. We knocked down eIF4G1 in a resistant IBC cell line (rSUM149) and assessed cellular viability after treatment with a powerful apoptosis inducer, TRAIL to evaluate the effect of targeted eIF4G1 knockdown on drug resistance in IBC. We observed that targeted knockdown of eIF4G1 sensitizes rSUM149 cells to TRAIL, significantly decreasing cellular viability. Additionally, using a novel culture system we show that inhibition of eIF4G1 expression decreases both the number of size of tumor emboli, a characteristic feature of IBC progression. These findings demonstrate a vital role for eIF4G1 for the development of therapeutic resistance and ultimately the aggressive pathobiology of IBC.
Citation Format: Arianna Price, Courtney M. Edwards, Myron K. Evans, Gayathri Devi. Elucidating a role for the translation initiation factor, eIF4G1, in resistance to therapy in inflammatory breast cancer (IBC). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1007. doi:10.1158/1538-7445.AM2015-1007
Abstract 1009: Cytotoxic effect of ginsenosides C-K and PPD on glioblastoma cells through cell cycle arrest and down-regulation of cell adhesion proteins
Authors: Kim Eunsoo , Wanderi Cheryl , Choi Chulhee , Choi Kyungsun 
Published: August 2015

Abstract
Ginsenosides, pharmacologically active components of ginseng have been shown to have strong anticancer effects; however, their effect on glioblastoma has not been extensively evaluated. Here, we investigated the anticancer effect and the molecular mechanisms of ginsenosides on glioblastoma. Among 12 ginsenosides tested, compound-K (C-K) and protopanaxadiol (PPD), significantly reduced U251MG cell viability in dose- and time-dependent manner. This cytotoxic effect was accompanied by decreased expression of cell adhesion proteins including N-Cadherin and Integrin β1, which led to reduced phosphorylation of focal adhesion kinase. Furthermore, we observed the reduction of Cyclin D1 and subsequent G1-phase cell cycle arrest. We further demonstrated that C-K and PPD inhibited the phosphorylation of Akt and extracellular signal regulated kinase. Conversely, C-K and PPD stimulated phosphorylation of JNK and cleavage of PARP.
These results collectively indicate that ginsenosides C-K and PPD may provide a new strategy to treat malignant glioblastoma that are quite resistant to conventional anti-cancer treatment. (This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea;grant number : HI14C0042)
Citation Format: Eunsoo Kim, Cheryl Wanderi, Chulhee Choi, Kyungsun Choi. Cytotoxic effect of ginsenosides C-K and PPD on glioblastoma cells through cell cycle arrest and down-regulation of cell adhesion proteins. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1009. doi:10.1158/1538-7445.AM2015-1009
Abstract 1016: Caveolin-1-dependent and -independent uPAR signaling pathways contribute to ganglioside GT1b-induced early apoptosis in A549 lung cancer cells
Authors: Jang Hyun-Jin , Chung Young-Ho , Park Junsoo , Jang Ik-Soon 
Published: August 2015

Abstract
Urokinase receptor interacts with α5β1-integrin and enhances cancer cell proliferation and metastasis. Activation of α5β1-integrin requires caveolin-1 and is regulated by uPAR, which upregulates persistently the activated ERK necessary for tumor growth. In this study, we show that the ganglioside GT1b induces proapoptotic signaling through two uPAR-ERK signaling pathways in A549 lung cancer cells. GT1b downregulated the expression of α5β1 integrin, caveolin-1, fibronectin, FAK, and ERK, whereas GT1b upregulated the expression of p53 and uPAR, suggesting GT1b mediated depletion of caveolin-1 in uPAR-expressing A549 cells also disrupts uPAR/integrin complexes, resulting in downregulation of fibronectin-α5β1-integrin-ERK signaling. Following p53 siRNA treatment, FAK and ERK expression was recovered, meaning the presence of reentry uPAR-FAK-ERK signaling pathway. These findings reveal that GT1b is involved in both caveolin-1-dependent uPAR-α5β1-integrin-ERK signaling and caveolin-1-independent uPAR-FAK-ERK signaling. These results suggest a novel function of GT1b as a dual regulator of ERK by modulating caveolin-1 and p53
Citation Format: Hyun-Jin Jang, Young-Ho Chung, Junsoo Park, Ik-Soon Jang. Caveolin-1-dependent and -independent uPAR signaling pathways contribute to ganglioside GT1b-induced early apoptosis in A549 lung cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1016. doi:10.1158/1538-7445.AM2015-1016
Abstract 1019: hnRNPA2/B1 upregulates COX-2 expression and tumor growth and predicts poor prognosis in human lung cancers
Authors: Wang Jingshu , Xuan Yang , Guo Wei , Du Guangwei , Deng Wuguo 
Published: August 2015

Abstract
Constitutive high expression of COX-2 can promote tumor development and has been regarded as a hallmarker for cancers. However, the excise regulation mechanism of COX-2 and its role in lung tumoirgenesis remains unknown. In this study, we discovered and identified hnRNPA2/B1 as a novel regulator of COX-2 promoter in non-small cell lung cancer (NSCLC) cells by a DNA probe-biotin-streptavidin-agarose pulldown and proteomic technique. We showed that hnRNPA2/B1 specifically bound to COX-2 core promoter region, activated COX-2 promoter activity and up-regulated COX-2 expression. Knockdown of hnRNPA2/B1 expression by siRNA significantly suppressed tumor cell growth in NSCLC cell lines in vitro and in a animal model in vivo by inhibiting COX-2 expression. In contrast, overexpression of hnRNPA2/B1 promoted COX-2 expression and tumor cell growth in NSCLC cells. Micro-tissue array and immunohistochemical assay showed that hnRNPA2/B1 expression correlated with COX-2 expression and high expression of hnRNPA2/B1 and COX-2 was associated with worse prognosis in patients with NSCLCs. Mechanistically, hnRNPA2/B1 functions as a regulator of COX-2 to control tumor growth through its interaction with p300, a transcriptional co-activator, in NSCLC cells. Immunoprecipitation and confocal immunofluorescence microscope analysis confirmed the direct interaction of hnRNPA2/B1 with p300 proteins. Overexpression of p300, but not its histon acetyltransferase domain deletion mutation, enhanced the acetylation of hnRNPA2/B1, facilitated the binding of hnRNPA2/B1 to COX-2 promoter, thereby promoted COX-2 expression and tumor cell growth. Therefore, these results indicate that hnRNPA2/B1 acts as an activator to regulate COX-2 expression and tumor growth through the interaction with p300 in NSCLC cells and suggest that the hnRNPA2/B1/COX-2 signaling is a potential therapeutic target for lung cancers.
Note: This abstract was not presented at the meeting.
Citation Format: Jingshu Wang, Yang Xuan, Wei Guo, Guangwei Du, Wuguo Deng. hnRNPA2/B1 upregulates COX-2 expression and tumor growth and predicts poor prognosis in human lung cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1019. doi:10.1158/1538-7445.AM2015-1019
Abstract 1020: Latent membrane protein 1 N-C interaction of EBV facilitates (nuclear factor kappa-light-chain-enhancer of activated B cells transcriptional activity
Authors: Hsu Cheng-Lung , Li Hsin-Pai , Kuo Yung-Chia , Tsang Ngan-Ming , Chang Yu-Sun 
Published: August 2015

Abstract
Background: Epstein-Barr virus latent membrane protein 1 (LMP1) is known to be involved in the carcinogenesis of numerous cancers, including nasopharyngeal carcinoma and lymphoma. The C-terminus of LMP1 can recruit a spectrum of host cell cytosolic signaling molecules to exert its effects on downstream pathways. However, the function of the cytosolic N-terminus of LMP1 is not clear.
Methods: Partial deletion or point mutation of the N-terminus of LMP1 were made.
Results: Sequence analysis showed that not only were the lengths of LMP1 N- and C-termini different, so too were their distributions of charged amino acid side chains, with negatively charged amino acids being abundant in the C-terminus and positively charged amino acids dominating in the N-terminus. We found that deletion or mutation of N-terminal positively charged amino acids weakened the effects of LMP1 on nuclear factor NF-κB transcriptional activity. Furthermore, co-expressing a short N-terminal peptide of LMP1 enhanced the effect of full-length LMP1 on NF-κB transcriptional activity. We further demonstrated that the LMP1 N- and C-termini interact, which facilitated downstream signal transduction. Mutation of N-termial positively charged side chain amino acid could weaken LMP1 effect on cell motility.
Conclusion: LMP1 N- and C-termini could interact and facilitate NF-κB transcriptional activity and cell motility.
Citation Format: Cheng-Lung Hsu, Hsin-Pai Li, Yung-Chia Kuo, Ngan-Ming Tsang, Yu-Sun Chang. Latent membrane protein 1 N-C interaction of EBV facilitates (nuclear factor kappa-light-chain-enhancer of activated B cells transcriptional activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1020. doi:10.1158/1538-7445.AM2015-1020
Abstract 1026: Role of Group I Paks in MPNST cell proliferation, migration and invasion
Authors: Semenova Galina , Chernoff Jonathan 
Published: August 2015

Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft tissue sarcomas that arise in patients with neurofibromatosis (NF1) or sporadically. MPNSTs are typically chemoresistant, while surgical removal is limited due to invasiveness of the tumors. Recent studies that attempted to discover rational MPNST therapies identified MEK/ERK, PI3K/mTORC1 and Wnt/β-catenin pathways among the most critical for MPNST development and progression. As Group I p21-activated kinases (Paks) are known to regulate all three of these signaling pathways in many cell types, we proposed assess the potential of these kinases as potential therapeutic target for MPNST.
Using genetic and biochemical approaches we showed that loss of PAK1-3 activity significantly suppressed MPNST cell proliferation, as well as migration and invasion capacity. Treatment with specific small molecule PAK1-3 inhibitors Frax1036 and IPA-3 caused reduction of mTORC1 and β-catenin signaling in MPNST cells. MEK/ERK signaling, however, appeared to be intact or upregulated upon chemical Pak inhibition in most of the MPNST cell lines analyzed. Dual inhibition of PAK and MEK (PD0325901) resulted in synergistic cytotoxic effect on MPNST cells. Collectively, these findings suggest that Pak inhibitors might be useful for MPNST therapy, as single agents or in combinatorial treatment strategies.
Citation Format: Galina Semenova, Jonathan Chernoff. Role of Group I Paks in MPNST cell proliferation, migration and invasion. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1026. doi:10.1158/1538-7445.AM2015-1026