Provision of 4-1BB ligand enhances effector and memory CTL responses generated by immunization with dendritic cells expressing a human tumor-associated antigen

Up-regulation of receptor-ligand pairs during interaction of an MHC-presented epitope on dendritic cells (DCs) with cognate TCR may amplify, sustain, and drive diversity in the ensuing T cell immune response. Members of the TNF ligand superfamily and the TNFR superfamily contribute to this costimulatory molecule signaling. In this study, we used replication deficient adenoviruses to introduce a model tumor-associated Ag (the E7 oncoprotein of human papillomavirus 16) and the T cell costimulatory molecule 4-IBBL into murine DCs, and monitored the ability of these recombinant DO to elicit E7-directed T cell responses following immunization. Splenocytes from mice immunized with DCs expressing E7 alone elicited E7-directed effector and memory CTL responses. Coexpression of 4-1BBL in these E7-expressing DO increased effector and memory CTL responses when they were used for immunization. 4-1BBL expression up-regulated CD80 and CD86 second signaling molecules in DO. We also report an additive effect of 4-IBBL and receptor activator of NF-kappaB/receptor activator of NF-kappaB ligand coexpression in E7-transduced DC inummogens on E7-directed effector and memory CTL responses and on MHC class II and CD80/86 expression in DCs. Additionally, expression of 4-1BBL in E7-transduced DCs reduced nonspecific T cell activation characteristic of adenovirus vector-associated immunization. The results have generic implications for improved or tumor Ag-expressing DC vaccines by incorporation of exogenous 4-1BBL. There are also specific implications for an improved DC-based vaccine for human papillomavirus 16-associated cervical carcinoma.

The case for emotional intelligence in organizational research

Since its popularization by Goleman (1995), the concept of emotional intelligence has been the subject of ongoing controversy, so it is understandable that the model we proposed, which includes emotional intelligence as a moderator variable, would attract its share of criticism.

Reciprocal changes in forebrain contents of glycogen and of glutamate/glutamine during early memory consolidation in the day-old chick

Passive avoidance learning is with advantage studied in day-old chicks trained to distinguish between beads of two different colors, of which one at training was associated with aversive taste. During the first 30-min post-training, two periods of glutamate release occur in the forebrain. One period is immediately after the aversive experience, when glutamate release is confined to the left hemisphere. A second release, 30 min later, may be bilateral, perhaps with preponderance of the right hemisphere. The present study showed increased pool sizes of glutamate and glutamine, specifically in the left hemisphere, at the time when the first glutamate release occurs, indicating de novo synthesis of glutamate/glutamine from glucose or glycogen, which are the only possible substrates. Behavioral evidence that memory is extinguished by intracranial administration at this time of iodoacetate, an inhibitor of glycolysis and glycogenolysis, and that the extinction of memory is counteracted by injection of glutamine, supports this concept. A decrease in forebrain glycogen of similar magnitude and coinciding with the increase in glutamate and glutamine suggests that glycogen rather than glucose is the main source of newly synthesized glutamate/glutamine. The second activation of glutamatergic activity 30 min after training, when memory is consolidated into stable, long-term memory, is associated with a bilateral increase in pool size of glutamate/glutamine. No glycogenolysis was observed at this time, but again there is a temporal correlation with sensitivity to inhibition by iodoacetate and rescue by glutamine, indicating the importance of de novo synthesis of glutamate/glutamine from glucose or glycogen. (C) 2003 Elsevier B.V All rights reserved.

Enhanced effector and memory CTL responses generated by incorporation of receptor activator of NF-kappa B(RANK)/RANK ligand costimulatory molecules into dendritic cell immunogens expressing a human tumor-specific antigen

The outcome of dendritic cell (DC) presentation of Ag to T cells via the TCR/MHC synapse is determined by second signaling through CD80/86 and, importantly, by ligation of costimulatory ligands and receptors located at the DC and T cell surfaces. Downstream signaling triggered by costimulatory molecule ligation results in reciprocal DC and T cell activation and survival, which predisposes to enhanced T cell-mediated immune responses. In this study, we used adenoviral vectors to express a model tumor Ag (the E7 oncoprotein of human papillomavirus 16) with or without coexpression of receptor activator of NF-kappaB (RANK)/RANK ligand (RANKL) or CD40/CD40L costimulatory molecules, and used these transgenic DCs to immunize mice for the generation of E7-directed CD8(+) T cell responses. We show that coexpression of RANK/RANKL, but not CD40/CD40L, in E7-expressing DCs augmented E7-specific IFN-gamma-secreting effector and memory T cells and E7-specific CTLs. These responses were also augmented by coexpression of T cell costimulatory molecules (RANKL and CD40L) or DC costimulatory molecules (RANK and CD40) in the E7-expressing DC immunogens. Augmentation of CTL responses correlated with up-regulation of CD80 and CD86 expression in DCs transduced with costimulatory molecules, suggesting a mechanism for enhanced T cell activation/survival. These results have generic implications for improved tumor Ag-expressing DC vaccines, and specific implications for a DC-based vaccine approach for human papillomavirus 16-associated cervical carcinoma.

Representing organizational structures in enterprise architecture : an ontology-based approach

Arquitetura Corporativa promove o estabelecimento de uma visão holística da estrutura e forma de trabalho de uma organização. Um dos aspectos abordados em Arquitetura Corporativa está associada a "estrutura ativa" da organização, que diz respeito a “quem" realiza as atividades organizacionais. Várias abordagens têm sido propostas a fim de proporcionar um meio para a representação de Arquitetura Corporativa, entre as quais ARIS, RM-ODP, UPDM e ArchiMate. Apesar da aceitação por parte da comunidade, as abordagens existentes se concentram em propósitos diferentes, têm limitações de escopo e algumas não têm semântica de mundo real bem definida. Além das abordagens de modelagem, muitas abordagens de ontologias têm sido propostas, a fim de descrever o domínio de estrutura ativa, incluindo as ontologias de SUPER Project, TOVE, Enterprise Ontology e W3C Org Ontology. Embora especificadas para fundamentação semântica e negociação de significado, algumas das abordagens propostas têm fins específicos e cobertura limitada. Além disso, algumas das abordagens não são definidas usando linguagens formais e outras são especificadas usando linguagens sem semântica bem definida. Este trabalho apresenta uma ontologia de referência bem fundamentada para o domínio organizacional. A ontologia organizacional de referência apresentada abrange os aspectos básicos discutidos na literatura organizacional, tais como divisão do trabalho, relações sociais e classificação das unidades estruturais. Além disso, também abrange os aspectos organizacionais definidos em abordagens existentes, levando em consideração tanto abordagens de modelagem quanto abordagens ontológicas. A ontologia resultante é especificada em OntoUML e estende os conceitos sociais de UFO-C.

Going Global: an organizational study of Brazilian foreign policy

This study analyzes the impact of globalisation on the organization and strategies outlined by the Brazilian Ministry of Foreign Affairs. The study intends to understand how countries from the periphery deal with new institutional challenges resulting from globalization, using the case of the Brazilian diplomatic service.

Organizational and accounting change within the context of the environmental agenda: evidence from Portugal

Purpose – The purpose of this paper is to explore the process of organizational change undergone by a large Portuguese business group within the context of the environmental agenda and the role of accounting as a mechanism for change. Design/methodology/approach – The paper reports the results of a case study conducted between 2006 and 2009. Information was obtained from semi-structured interviews and secondary sources. Organizational changes were analyzed using Laughlin’s model in order to identify which category reflected most of the changes introduced to address environmental matters. Findings – This paper offers evidence that change is not a homogeneous phenomenon. Additionally, it confirms previous studies’ findings which found that accounting did not play a significant role in the process of organizational change within the context of the environmental agenda. Originality/value – This paper seeks to complement the research in this area by integrating observations from a case study into an existing model of levels of organizational change according to how a Portuguese business group incorporated environmental issues into its processes, policies and corporate culture.

Cognitive intervention protocol for age-related memory impairments

With the number of elderly people increasing tremendously worldwide, comes the need for effective methods to maintain or improve older adults' cognitive performance. Using continuous neurofeedback, through the use of EEG techniques, people can learn how to train and alter their brain electrical activity. A software platform that puts together the proposed rehabilitation methodology has been developed: a digital game protocol that supports neurofeedback training of alpha and theta rhythms, by reading the EEG activity and presenting it back to the subject, interleaved with neurocognitive tasks such as n-Back and Corsi Block-Tapping. This tool will be used as a potential rehabilitative platform for age-related memory impairments.

Relationships between NPM, the use of PM practices and the organizational performance: empirical evidence from government agencies

Purpose – this paper has two main purposes: (1)explore if government agencies more oriented to NPM postulates are more willing to use PM practices and to improve their performance; and (2) investigate whether the fit between the use of PM practices and the organizationa performance is dependent upon from the capacity of agencies to adapt its structures to changes introduced by NPM reforms. Design/methodology/approach - this paper is based on the survey method and provides empirical evidence from Portuguese government agencies.Findings (mandatory) - Our findings suggest that government agencies that made structural arrangements under the NPM reforms are more willing to use PM practices and will perform better than other agencies. In addition, this paper show that therelationship between the use of PM practices and the organizational performance is dependent upon from the agencies capacity to adopt new structural arrangements under the NPM reforms.Practical implications – this paper has three main contributions: (1) contribute to knowledge about the relationship between the introduction of NPM changes in the use of PM practices; (2) contribute to clarify whether agencies more oriented to NPM postulates are improving performance; and (3) help to clarify the way the organizations should adapt their structures for to be more effective in the use of PM practices. Originality/value - The quantitative empirical research, based on the unique survey applied to Portuguese government agencies on this field, allow us to add to prior research mainly based on case studies and oriented to local governments (Budding, 2004).

COGNITIVE LEGITIMACY, RESOURCE ACCESS, AND ORGANIZATIONAL OUTCOMES

Previous research has demonstrated the importance of developing legitimacy initiatives in order to create new business opportunities, satisfy shareholders, and obtain access to resources. Within this framework, cognitive legitimacy plays a key role. Through a case study of six Spanish public universities, the authors measure the relationship between cognitive legitimacy, access to resources, and organizational results. The results support the assertion that organizations with more cognitive legitimacy have greater access to resources and improved their results. This study contributes with muchneeded empirical research on cognitive legitimacy and demonstrates its usefulness as an explanative factor of organizational success.