192 research outputs found

    Inter-Enterprise architecture and Internet of the future

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    The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-37291-9_3This paper proposes the concept of Inter-Enterprise Architecture (IEA), which seeks the application of tools and methodologies developed in the Enterprise Architecture (EA) field for the individual firm, adapting to an environment of collaboration between several companies that make networks or supply chains, in order to facilitate the integration and interoperability of their collaborative processes in line with its IS/IT (Information Systems/ Information Technology) to harmonize the joint processes, reduce risk and duplication, increase service and customer responsiveness, reduce technology costs and align the joint business to IS/IT.Vargas, A.; Boza GarcĂ­a, A.; Cuenca, L.; Sacala, I. (2013). Inter-Enterprise architecture and Internet of the future. En Technological Innovation for the Internet of Things: 4th IFIP WG 5.5/SOCOLNET Doctoral Conference on Computing, Electrical and Industrial Systems, DoCEIS 2013, Costa de Caparica, Portugal, April 15-17, 2013. Proceedings. Springer. 25-32. doi:10.1007/978-3-642-37291-9_3S2532Information Society and Media European Commission: FInES Cluster Position Paper. Future Internet Enterprise Systems (FInES) Cluster (September 2009)Vargas, A., Boza, A., Cuenca, L.: Lograr la alineaciĂłn estratĂ©gica de negocio y las tecnologĂ­as de la informaciĂłn a travĂ©s de Arquitecturas Empresariales: RevisiĂłn de la Literatura. In: Cartagena, XV Congreso de IngenierĂ­a de OrganizaciĂłn, pp. 1061–1070 (2011a)Vargas, A., Boza, A., Cuenca, L.: Towards Interoperability through Inter-enterprise Collaboration Architectures. In: Meersman, R., Dillon, T., Herrero, P. (eds.) OTM 2011 Workshops. LNCS, vol. 7046, pp. 102–111. Springer, Heidelberg (2011)Vargas, A., Boza, A., Cuenca, L., Ortiz, A.: The importance of strategic alignment in enterprise collaboration. In: 6th International Conference on Industrial Engineering and Industrial Management, Vigo (2012)Henderson, J., Venkatraman, N.: Strategic alignment: Leveraging information technology for transforming organizations. IBM Systems Journal 32(1), 472–484 (1993)Luftman, J.: Assessing Business-IT alignment maturity. Communications of the Association for Information Systems 4 (2000)Cuenca, L., Boza, A., Ortiz, A.: An enterprise engineering approach for the alignment of business and information technology strategy. International Journal of Computer Integrated Manufacturing 24(11) (2011)Kilger, C., Reuter, B., Stadtler, H.: Collaborative Planning. In: Stadtler, H., Kilger, C. (eds.) Supply Chain Management and Advanced Planning-—Concepts, Models Software and Case Studies, pp. 263–284. Springer, Heidelberg (2008)Audy, J., Lehoux, N., D’Amours, S.: A framework for an efficient implementation of logistics collaborations. International Transactions in Operational Research, 1–25 (2010)Stadtler, H.: A framework for collaborative planning and state-of-the-art. OR Spectrum 31, 5–30 (2010)CIMOSA Association: CIMOSA Primer on key concepts, purpose and business value, http://cimosa.cnt.pl/Chen, D., Vallespir, B., Doumeingts, G.: GRAI integrated methodology and its mapping onto generic enterprise reference architecture and methodology. Computers in Industry 33, 387–394 (1997)Williams, T., Li, H.: PERA and GERAM enterprise reference architectures in enterprise integration. Information Infrastructure Systems for Manufacturing, 1–27 (1998)Ortiz, A.: Propuesta para el Desarrollo de Programas de IntegraciĂłn Empresarial en Empresas Industriales. AplicaciĂłn a una Empresa del Sector CerĂĄmico. Ph.D Dissertation. Universidad PolitĂ©cnica de Valencia (1998)The Open Group, https://www.opengroup.org/index.htmChalmeta, R., Grangel, R.: ARDIN extension for virtual enterprise integration. The Journal of Systems and Software 67 (2003)Scheer, A., Schneider, K.: ARIS – Architecture of Integrated Information. In: Handbook on Architectures of Information Systems. International Handbooks on Information Systems, s.l., vol. 3, pp. 605–623 (2006)Bernard, S.: An introduction to enterprise architecture. Author House, Bloomington (2005)Cuenca, L., Ortiz, A., Boza, A.: Arquitectura de Empresa. VisiĂłn General. In: IX Congreso de IngenierĂ­a de OrganizaciĂłn, GijĂłn, pp. 1–8 (2005)Burlacu, G., Stanescu, A., Sacala, I., Cojocaru, L.: Development of a Modeling Framework for Future Internet Enterprise Systems. In: IEEE 16th International Conference on System Theory, Control and Computing, Sinaia, October 12-14 (2012

    Serum concentrations of cortisol, interleukin 6, leptin and adiponectin predict stress induced insulin resistance in acute inflammatory reactions

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    Introduction Inflammatory stimuli are causative for insulin resistance in obesity as well as in acute inflammatory reactions. Ongoing research has identified a variety of secreted proteins that are released from immune cells and adipocytes as mediators of insulin resistance; however, knowledge about their relevance for acute inflammatory insulin resistance remains limited. In this study we aimed for a clarification of the relevance of different insulin resistance mediating factors in an acute inflammatory situation. Methods Insulin resistance was measured in a cohort of 37 nondiabetic patients undergoing cardiac surgery by assessment of insulin requirement to maintain euglycaemia and repeated measurements of an insulin glycaemic index. The kinetics of cortisol, interleukin 6 (IL6), tumour necrosis factor alpha (TNF alpha), resistin, leptin and adiponectin were assessed by repeated measurements in a period of 48 h. Results Insulin resistance increased during the observation period and peaked 22 h after the beginning of the operation. IL6 and TNF alpha displayed an early increase with peak concentrations at the 4-h time point. Serum levels of cortisol, resistin and leptin increased more slowly and peaked at the 22-h time point, while adiponectin declined, reaching a base at the 22-h time point. Model assessment identified cortisol as the best predictor of insulin resistance, followed by IL6, leptin and adiponectin. No additional information was gained by modelling for TNF alpha, resistin, catecholamine infusion rate, sex, age, body mass index (BMI), operation time or medication. Conclusions Serum cortisol levels are the best predictor for inflammatory insulin resistance followed by IL6, leptin and adiponectin. TNF alpha, and resistin have minor relevance as predictors of stress dependent insulin resistance

    Towards interoperability through inter-enterprise collaboration architectures

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    Most enterprise architectures published so far are capable of generating reasonably good descriptive models for individual enterprises to enable integration, organization and synchronization of enterprise elements: organizational structure, business processes, information systems and technology infrastructure, among others. However, research in this field applied to the extended enterprise or inter-enterprise architectures that takes into account the growing trend towards complex collaborative environments is very scarce. In this sense, this article seeks to analyze, link and synthesize the researches that has addressed the disciplines of enterprise architecture and business collaboration, in order to identify possible future research needs from the conceptualization made.Vargas, A.; Boza Garcia, A.; Cuenca, L. (2011). Towards interoperability through inter-enterprise collaboration architectures. En On the Move to Meaningful Internet Systems: OTM 2011 Workshops. Springer Verlag (Germany). 7046:102-111. doi:10.1007/978-3-642-25126-9_18S1021117046Adam, O., Hofer, A., Zang, S., Hammer, C., Jerrentrup, M., Leinenbach, S.: A Collaboration Framework for Cross-enterprise Business Process Management. In: First International Conference on Interoperability of Enterprise Software and Application, Geneva (2005)Chalmeta, R., Grangel, R.: ARDIN extension for virtual enterprise integration. The Journal of Systems and Software 67, 141–152 (2003)Choi, Y., Kang, D., Chae, H., Kim, K.: An enterprise architecture framework for collaboration of virtual enterprise chains. The International Journal of Advanced Manufacturing Technology 35, 1065–1078 (2008)Schekkerman, J.: Extended Enterprise Architecture Framework Essentials Guide. Institute For Enterprise Architecture Developments, IFEAD (2006), http://www.enterprise-architecture.info/index.htmISO 15704. Industrial automation systems - Requirements for enterprise-reference architectures and methodologies.: International Organization for Standardization (2000)Kosanke, K., Vernadat, F., Zelm, M.: CIMOSA: Enterprise engineering and integration. Computers in Industry 40, 83–97 (1999)Cuenca, L.: Marco arquitectĂłnico para la propuesta IE-GIP. ExtensiĂłn de la arquitectura CIMOSA. AplicaciĂłn a una empresa del sector cerĂĄmico. PhD thesis. Universidad PolitĂ©cnica de ValenciaMolina, A., Panetto, H., Chen, D., Whitman, L.: Enterprise Integration and Networking: challenges and trends. Studies in Informatics and Control 16(4), 353–368 (2007)Ortiz, A., Lario, F., Ros, L.: Enterprise Integration—Business Processes Integrated Management: a proposal for a methodology to develop Enterprise Integration Programs. Computers in Industry 40, 155–171 (1999)Chalmeta, R., Campos, C., Grangel, R.: References architectures for enterprise integration. The Journal of Systems and Software 57, 175–191 (2001)Vernadat, F.: Enterprise modeling and integration (EMI): Current status and research perspectives. Annual Reviews in Control 26, 15–25 (2002)Williams, T., Li, H.: PERA and GERAM enterprise reference architectures in enterprise integration. Information Infrastructure Systems for Manufacturing, 1–27 (1998)Lankhorst, M.: Enterprise Architecture at Work: Modelling, Communication and Analysis. Springer, Heidelberg (2009)Arango, M., Londoño, J., Zapata, J.: Arquitectura empresarial- Una visiĂłn general. Revista IngenierĂ­as Universidad de MedellĂ­n 9(16), 101–111 (2010)Bernard, S.: An introduction to enterprise architecture. AuthorHouse, Bloomington (2005)Cuenca, L., Ortiz, A., Boza, A.: Arquitectura de Empresa. VisiĂłn General. In: IX Congreso de IngenierĂ­a de OrganizaciĂłn, GijĂłn (2005)Maya, E.: Arquitectura empresarial: un nuevo reto para las empresas de hoy. Centro de InvestigaciĂłn de las Telecomunicaciones. INTERACTIC: InteracciĂłn con la informaciĂłn (2010), http://www.interactic.org.co/THE OPEN GROUP.: ARCHIMATE, The Power of Enterprise Architecture (2009), http://www.archimate.org/en/home/Stelzer, D.: Enterprise Architecture Principles: Literature Review and Research Directions. In: Dan, A., Gittler, F., Toumani, F. (eds.) ICSOC/ServiceWave 2009. LNCS, vol. 6275, pp. 12–21. Springer, Heidelberg (2010)Schekkerman, J.: Enterprise architecture validation. Achieving business-aligned and validated enterprise architectures. Institute For Enterprise Architecture Developments, IFEAD (2004), http://www.enterprise-architecture.info/index.htmKosanke, K.: CIMOSA Primer on key concepts, purpose and business value (1996), http://cimosa.cnt.pl/Chen, D., Vallespir, B., Doumeingts, G.: GRAI integrated methodology and its mapping onto generic enterprise reference architecture and methodology. Computers in Industry 33, 387–394 (1997)Rathwell, G.: PERA Enterprise Integration Web Site (2005), http://www.pera.net/Williams, T., Rathwell, G., Li, H.: A handbook on master planning and implementation for enterprise integration programs. PERA Enterprise Integration Web Site (2001), http://www.pera.net/IFIP.: GERAM: Generalised Enterprise Reference Architecture and Methodology. International Federation for Information Processing (1999), http://dl.ifip.org/index.php/index/indexOrtiz, A.: Propuesta para el Desarrollo de Programas de IntegraciĂłn Empresarial en Empresas Industriales. AplicaciĂłn a una Empresa del Sector CerĂĄmico. Universidad PolitĂ©cnica de Valencia (1998)Cuenca, L., Boza, A., Ortiz, A.: Architecting business and IS/IT strategic alignment for extend enterprises. Studies in Informatics and Control 20(1), 7–18 (2011)The Open Group (2011), https://www.opengroup.org/index.htmGrangel, R.: Propuesta para el Modelado del Conocimiento Empresarial. PhD thesis Universidad Jaume I de Castello (2007)Scheer, A., Schneider, K.: ARIS – Architecture of Integrated Information. Handbook on Architectures of Information Systems. International Handbooks on Information Systems 3, 605–623 (2006)ISO/CEN 19439. Enterprise integration - Framework for enterprise modelling.: International Organization for Standardization (2006)Stadtler, H., Kilger, C.: Supply Chain Management and advance planning. Concepts, Models, Sofware and Cases Studies. Springer, Heidelberg (2002)AlarcĂłn, F., Ortiz, A., Alemany, M., Lario, F.: PlanificaciĂłn Colaborativa en un contexto de varias Cadenas de Suministro: ventajas y desventajas. In: VIII Congreso de IngenierĂ­a de OrganizaciĂłn, LeganĂ©s, pp. 857–866 (2004)AlarcĂłn, F.: Desarrollo de una Arquitectura para la definiciĂłn del proceso de Comprometer Pedidos en contextos de Redes de Suministro Colaborativas. AplicaciĂłn a una Red compuesta por Cadenas de Suministro en los Sectores CerĂĄmico y del Mueble. PhD thesis Universidad PolitĂ©cnica de Valencia (2005)Petersen, K., Ragatz, G., Monczka, R.: An Examination of Collaborative Planning Effectiveness and Supply Chain Performance. The Journal of Supply Chain Management 41(2), 14–25 (2005)Ribas, I., Companys, R.: Estado del arte de la planificaciĂłn colaborativa en la cadena de suministro: Contexto determinista e incierto. Intangible Capital, 91–121 (2007)Ribas, I., Lario, F., Companys, R.: Modelos para la planificaciĂłn colaborativa en la cadena de suministro: contexto determinista e incierto. In: Congreso de ingenierĂ­a de organizaciĂłn, Valencia, pp. 1–10 (2006)Dudek, G.: Collaborative Planning in Supply Chains. Supply Chain Management and Collaborative Planning. Springer, Heidelberg (2009)Stadtler, H.: A framework for collaborative planning and state-of-the-art. OR Spectrum 31, 5–30 (2009)Kilger, C., Reuter, B., Stadtler, H.: Collaborative Planning. In: Stadtler, H., Kilger, C. (eds.) Supply Chain Management and Advanced Planning-—Concepts, Models Software and Case Studies, pp. 263–284. Springer, Heidelberg (2008)Audy, J., Lehoux, N., D’Amours, S.: A framework for an efficient implementation of logistics collaborations. International Transactions in Operational Research, 1–25 (2010)Zachman, J.: A Framework for Information Systems Architecture. IBM Systems Journal 26(3), 454–470 (1987

    The Effect of Epstein-Barr Virus Latent Membrane Protein 2 Expression on the Kinetics of Early B Cell Infection

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    Infection of human B cells with wild-type Epstein-Barr virus (EBV) in vitro leads to activation and proliferation that result in efficient production of lymphoblastoid cell lines (LCLs). Latent Membrane Protein 2 (LMP2) is expressed early after infection and previous research has suggested a possible role in this process. Therefore, we generated recombinant EBV with knockouts of either or both protein isoforms, LMP2A and LMP2B (Δ2A, Δ2B, Δ2A/Δ2B) to study the effect of LMP2 in early B cell infection. Infection of B cells with Δ2A and Δ2A/Δ2B viruses led to a marked decrease in activation and proliferation relative to wild-type (wt) viruses, and resulted in higher percentages of apoptotic B cells. Δ2B virus infection showed activation levels comparable to wt, but fewer numbers of proliferating B cells. Early B cell infection with wt, Δ2A and Δ2B viruses did not result in changes in latent gene expression, with the exception of elevated LMP2B transcript in Δ2A virus infection. Infection with Δ2A and Δ2B viruses did not affect viral latency, determined by changes in LMP1/Zebra expression following BCR stimulation. However, BCR stimulation of Δ2A/Δ2B cells resulted in decreased LMP1 expression, which suggests loss of stability in viral latency. Long-term outgrowth assays revealed that LMP2A, but not LMP2B, is critical for efficient long-term growth of B cells in vitro. The lowest levels of activation, proliferation, and LCL formation were observed when both isoforms were deleted. These results suggest that LMP2A appears to be critical for efficient activation, proliferation and survival of EBV-infected B cells at early times after infection, which impacts the efficient long-term growth of B cells in culture. In contrast, LMP2B did not appear to play a significant role in these processes, and long-term growth of infected B cells was not affected by the absence of this protein. © 2013 Wasil et al

    Design and Organization of the Dexamethasone, Light Anesthesia and Tight Glucose Control (DeLiT) Trial: a factorial trial evaluating the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery

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    <p>Abstract</p> <p>Background</p> <p>The perioperative period is characterized by an intense inflammatory response. Perioperative inflammation promotes postoperative morbidity and increases mortality. Blunting the inflammatory response to surgical trauma might thus improve perioperative outcomes. We are studying three interventions that potentially modulate perioperative inflammation: corticosteroids, tight glucose control, and light anesthesia.</p> <p>Methods/Design</p> <p>The DeLiT Trial is a factorial randomized single-center trial of dexamethasone vs placebo, intraoperative tight vs. conventional glucose control, and light vs deep anesthesia in patients undergoing major non-cardiac surgery. Anesthetic depth will be estimated with Bispectral Index (BIS) monitoring (Aspect medical, Newton, MA). The primary outcome is a composite of major postoperative morbidity including myocardial infarction, stroke, sepsis, and 30-day mortality. C-reactive protein, a measure of the inflammatory response, will be evaluated as a secondary outcome. One-year all-cause mortality as well as post-operative delirium will be additional secondary outcomes. We will enroll up to 970 patients which will provide 90% power to detect a 40% reduction in the primary outcome, including interim analyses for efficacy and futility at 25%, 50% and 75% enrollment.</p> <p>Discussion</p> <p>The DeLiT trial started in February 2007. We expect to reach our second interim analysis point in 2010. This large randomized controlled trial will provide a reliable assessment of the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery. The factorial design will enable us to simultaneously study the effects of the three interventions in the same population, both individually and in different combinations. Such a design is an economically efficient way to study the three interventions in one clinical trial vs three.</p> <p>Trial registration</p> <p><b>This trial is registered at </b>Clinicaltrials.gov <b>#</b>: NTC00433251</p

    Genetic Analysis of Human Traits In Vitro: Drug Response and Gene Expression in Lymphoblastoid Cell Lines

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    Lymphoblastoid cell lines (LCLs), originally collected as renewable sources of DNA, are now being used as a model system to study genotype–phenotype relationships in human cells, including searches for QTLs influencing levels of individual mRNAs and responses to drugs and radiation. In the course of attempting to map genes for drug response using 269 LCLs from the International HapMap Project, we evaluated the extent to which biological noise and non-genetic confounders contribute to trait variability in LCLs. While drug responses could be technically well measured on a given day, we observed significant day-to-day variability and substantial correlation to non-genetic confounders, such as baseline growth rates and metabolic state in culture. After correcting for these confounders, we were unable to detect any QTLs with genome-wide significance for drug response. A much higher proportion of variance in mRNA levels may be attributed to non-genetic factors (intra-individual variance—i.e., biological noise, levels of the EBV virus used to transform the cells, ATP levels) than to detectable eQTLs. Finally, in an attempt to improve power, we focused analysis on those genes that had both detectable eQTLs and correlation to drug response; we were unable to detect evidence that eQTL SNPs are convincingly associated with drug response in the model. While LCLs are a promising model for pharmacogenetic experiments, biological noise and in vitro artifacts may reduce power and have the potential to create spurious association due to confounding

    Early Events Associated with Infection of Epstein-Barr Virus Infection of Primary B-Cells

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    Epstein Barr virus (EBV) is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology) was used to introduce an expression cassette of green fluorescent protein (GFP) by homologous recombination, and the resultant BAC clone, BAC-GFP-EBV was transfected into the HEK 293T epithelial cell line. The resulting recombinant GFP EBV was induced to produce progeny virus by chemical inducer from the stable HEK 293T BAC GFP EBV cell line and the virus was used to immortalize human primary B-cell as monitored by green fluorescence and outgrowth of the primary B cells. The infection, B-cell activation and cell proliferation due to GFP EBV was monitored by the expression of the B-cell surface antigens CD5, CD10, CD19, CD23, CD39, CD40 , CD44 and the intercellular proliferation marker Ki-67 using Flow cytometry. The results show a dramatic increase in Ki-67 which continues to increase by 6–7 days post-infection. Likewise, CD40 signals showed a gradual increase, whereas CD23 signals were increased by 6–12 hours, maximally by 3 days and then decreased. Monitoring the viral gene expression pattern showed an early burst of lytic gene expression. This up-regulation of lytic gene expression prior to latent genes during early infection strongly suggests that EBV infects primary B-cell with an initial burst of lytic gene expression and the resulting progeny virus is competent for infecting new primary B-cells. This process may be critical for establishment of latency prior to cellular transformation. The newly infected primary B-cells can be further analyzed for investigating B cell activation due to EBV infection

    E2F1 Mediated Apoptosis Induced by the DNA Damage Response Is Blocked by EBV Nuclear Antigen 3C in Lymphoblastoid Cells

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    EBV latent antigen EBNA3C is indispensible for in vitro B-cell immortalization resulting in continuously proliferating lymphoblastoid cell lines (LCLs). EBNA3C was previously shown to target pRb for ubiquitin-proteasome mediated degradation, which facilitates G1 to S transition controlled by the major transcriptional activator E2F1. E2F1 also plays a pivotal role in regulating DNA damage induced apoptosis through both p53-dependent and -independent pathways. In this study, we demonstrate that in response to DNA damage LCLs knocked down for EBNA3C undergo a drastic induction of apoptosis, as a possible consequence of both p53- and E2F1-mediated activities. Importantly, EBNA3C was previously shown to suppress p53-induced apoptosis. Now, we also show that EBNA3C efficiently blocks E2F1-mediated apoptosis, as well as its anti-proliferative effects in a p53-independent manner, in response to DNA damage. The N- and C-terminal domains of EBNA3C form a stable pRb independent complex with the N-terminal DNA-binding region of E2F1 responsible for inducing apoptosis. Mechanistically, we show that EBNA3C represses E2F1 transcriptional activity via blocking its DNA-binding activity at the responsive promoters of p73 and Apaf-1 apoptosis induced genes, and also facilitates E2F1 degradation in an ubiquitin-proteasome dependent fashion. Moreover, in response to DNA damage, E2F1 knockdown LCLs exhibited a significant reduction in apoptosis with higher cell-viability. In the presence of normal mitogenic stimuli the growth rate of LCLs knockdown for E2F1 was markedly impaired; indicating that E2F1 plays a dual role in EBV positive cells and that active engagement of the EBNA3C-E2F1 complex is crucial for inhibition of DNA damage induced E2F1-mediated apoptosis. This study offers novel insights into our current understanding of EBV biology and enhances the potential for development of effective therapies against EBV associated B-cell lymphomas

    Genetic Diversity of EBV-Encoded LMP1 in the Swiss HIV Cohort Study and Implication for NF-Κb Activation

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    Epstein-Barr virus (EBV) is associated with several types of cancers including Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-ÎșB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-ÎșB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-ÎșB activation potential. We found that a number of variants mediate higher NF-ÎșB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-ÎșB activation in vitro, were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-ÎșB activation levels compared to B95-8 LMP1
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