Systemic administration of interleukin 2 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines

We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of nontoxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

Cellular strategies for accommodating replication-hindering adducts in DNA: control by the SOS response in Escherichia coli.

The replication of double-stranded plasmids containing a single adduct was analyzed in vivo by means of a sequence heterology that marks the two DNA strands. The single adduct was located within the sequence heterology, making it possible to distinguish trans-lesion synthesis (TLS) events from damage avoidance events in which replication did not proceed through the lesion. When the SOS system of the host bacteria is not induced, the C8-guanine adduct formed by the carcinogen N-2-acetylaminofluorene (AAF) yields less than 1% of TLS events, showing that replication does not readily proceed through the lesion. In contrast, the deacetylated adduct N-(deoxyguanosin-8-yl)-2-aminofluorene yields approximately 70% of TLS events under both SOS-induced and uninduced conditions. These results for TLS in vivo are in good agreement with the observation that AAF blocks DNA replication in vitro, whereas aminofluorene does so only weakly. Induction of the SOS response causes an increase in TLS events through the AAF adduct (approximately 13%). The increase in TLS is accompanied by a proportional increase in the frequency of AAF-induced frameshift mutations. However, the polymerase frameshift error rate per TLS event was essentially constant throughout the SOS response. In an SOS-induced delta umuD/C strain, both US events and mutagenesis are totally abolished even though there is no decrease in plasmid survival. Error-free replication evidently proceeds efficiently by means of the damage avoidance pathway. We conclude that SOS mutagenesis results from increased TLS rather than from an increased frameshift error rate of the polymerase.

Selbstbestimmung und Parteien in Südtirol: Territoriale und europäische Parteistrategien zwischen Autonomie und Sezession = Self-determination and parties in South Tyrol: Territorial and European party strategies between autonomy and secession. EDAP Paper 03/2016 03/2016

Since the final conflict settlement between Italy and Austria in 1992, ethnic politics in South Tyrol experienced insightful transformations. The consociational political system, which was implemented to tame centrifugal tendencies, has been losing its balance over the last decade, with proautonomy stances ceding ground to secessionist pressure in the Germanspeaking intra-ethnic arena. Adopting a contextual and strategic perspective on self-determination, this article traces the evolution of ethno-regionalist party strategies on the territorial and European dimension of party competition through a quantitative and qualitative content analysis of their electoral manifestos in the period between 1993 and 2013. In line with newest research on party strategies, the article empirically shows the strategic capacity of ethnic minority parties to challenge each other not only by shifting their positions on the different issue dimensions but also by the reframing of issues. While the increasing competition on the center-periphery axis leads to a new territorial frame, the rise of secessionism is accompagned by an end to the pro-European elite consensus.

As lojas sociais como estruturas de apoio aos indivíduos em situação de vulnerabilidade económica

Dissertação de mestrado na área de Educação Social e Intervenção Comunitária

Fighting, anger, frustration and tears: Matthew's story of hegemonic masculinity

This paper draws on Matthew's story to illustrate the conflicting discourses of being a boy and being a student. Matthew is 12 years old and in Grade Six, his final year at Banrock Primary ( a K- 6 Australian State School). School is far from a happy place for Matthew - his tearful accounts of his combative relationships with his peers and his teacher highlight his emotional distress. The paper's analytic focus draws attention to some of the ways Matthew's harmful storylines of hegemonic masculinity are made possible through, in particular, his teacher's gendered philosophies and her strategies of individualism and control. In this regard, Matthew's story provides insight into the potentially counterproductive realities of teacher practice in relation to addressing issues of masculinity within the school environment. Against this backdrop, the paper stresses the importance of teachers drawing on a sound research-based framework of gender knowledges that can illuminate how masculinities are constructed, regulated and, indeed, transformed through the power relations of everyday social practice, including teacher practice.

Recent advances in the molecular biology of Leifsonia xyli subsp xyli, causal organism of ratoon stunting disease

Twelve years ago our understanding of ratoon stunting disease (RSD) was confined almost exclusively to diagnosis of the disease and control via farm hygiene, with little understanding of the biology of the interaction between the causal agent (Leifsonia xyli subsp. xyli) and the host plant sugarcane (Saccharum spp. hybrids). Since then, research has focused on developing the molecular tools to dissect L. xyli subsp. xyli, so that better control strategies can be developed to prevent losses from RSD. Within this review, we give a brief overview of the progression in research on L. xyli subsp. xyli and highlight future challenges. After a brief historical background on RSD, we discuss the development of molecular tools such as transformation and transposon mutagenesis and discuss the apparent lack of genetic diversity within the L. xyli subsp. xyli world population. We go on to discuss the sequencing of the genome of L. xyli subsp. xyli, describe the key findings and suggest some future research based on known deficiencies that will capitalise on this tremendous knowledge base to which we now have access.

ERVING GOFFMAN, AS INTERAÇÕES NO COTIDIANO ESCOLAR, DESVENDANDO O ESTIGMA DENTRO DA INCLUSÃO ESCOLAR

As pessoas com deficiências são excluídas da sociedade devido à marca negativa de descrédito recebida pelo meio social - por sua aparência ou seu modo de ser diferentes - que os coloca fora da norma classificando-os como seres desviantes. No cotidiano escolar essas marcas se afirmam e se reproduzem, não promovendo às pessoas com deficiências uma superação desse estigma. A pesquisa visa analisar como o estigma incorporado pelos alunos com deficiências influencia no processo de interação e inclusão escolar, de forma a estudar indícios de como se desenvolve o processo de estigmatização no cotidiano escolar sob a luz dos pensamentos de Erving Goffman. O presente estudo utiliza-se uma revisão de literatura especifica do tema, fundamentada nos estudos de Erving Goffman, conjuntamente à pesquisa empírica baseada na etnografia vivenciada pelo autor em seus estudos de comunidade, foram utilizadas como estratégias de pesquisa, entrevistas com três professores e observações registradas por meio de de observação de cenas do cotidiano escolar de ´duas escolas públicas do estado de SPSão Paulo . No capítulo 1 buscamos entender os constructos de Goffman principalmente por meio de sua trajetória acadêmica, no capítulo 2 o trabalho centrou-se na compreensão da interação social e principalmente na questão definida pelo autor como ordem da interação, em queentende-se que as pessoas são autores dentro de um palco social, no capítulo 3. a pesquisa aborda o termo estigma e explica sua influência na interação e no avanço das pessoas com deficiência. Por fim, o trabalho se encerra no capítulo .4 apresentando a análise das entrevistas e dos registros das cenas do cotidiano escolar. As cenas selecionadas apresentam os atores envolvidos, o cenário, e o enredo das interações, identificando as estratégias do estigma incorporado pelos alunos com deficiência e buscando ligações com as políticas inclusivas e as escolas brasileira. A pesquisa identificou que a escola, como meio de socialização e criação de saberes, possui um papel importante neste processo de mudança, apesar de muitas vezes reproduzir o estigma social. Observamos então que a escola pode auxiliar na mudança do olhar que exclui, à maneira que mostra algumas máscaras do social e da própria inclusão; no entanto é importante salientar que sua renovação e de seus agentes sociais deve valorizar as diferenças para construção de novos conhecimentos.(AU)

ESTRATÉGIAS DE EXPANSÃO DE INSTITUIÇÕES DE ENSINO SUPERIOR PRIVADAS NO BRASIL: ESTUDO DE CASO DO CURSO DE BACHARELADO EM ADMINISTRAÇÃO

A dissertação teve como objetivo principal estudar como uma Instituição de Ensino Superior Privada (IES) atuante no Brasil tem crescido pós Lei de Diretrizes e Bases (LDB) de 1996 até 2015, por meio da análise do curso de bacharelado em Administração de Empresas, nas modalidades: presencial, EAD e Flex (semipresencial). Para este fim, foi realizada uma pesquisa exploratória, de caráter qualitativo baseada no método do estudo de caso. Para coleta de evidências foram analisados relatórios corporativos (Annual Report, Relatórios Internos e outros documentos), entrevistas baseadas em roteiro semiestruturado com gestores da IES privada e observações. Dentre os principais achados, verificou-se que as principais estratégicas de crescimento da IES privada estudada se basearam em fusões e aquisições de outras IES, abertura de novos polos de EAD, na abertura de novas unidades próprias, bem como em inovações em várias dimensões da organização. Os programas governamentais de financiamento aos alunos também são fortes contribuintes para este crescimento, como o Fundo de Financiamento ao Estudante do Ensino Superior (FIES) e o Programa Universidade para Todos (Prouni). Com essa nova realidade, o ensino superior privado recebeu incentivo e facilitação para o seu crescimento, a um ritmo acelerado. Consequentemente pode-se concluir que a IES privada estudada adotou as seguintes estratégias de crescimento: Expansão orgânica com fusões/ aquisições de Instituições menores, com desenvolvimento de planos para todos os campi Brasil; Greenfield (por meio de solicitação de autorização de novas unidades e/ou cursos) em cidades sem possibilidades de aquisições/fusões, e aumentando o número de vagas/ matriculas nas unidades já existentes, aderiu aos programas do governo e também cuidou da evasão por meio de: Seguro educacional; gestão preparada para atender necessidades do discente; Sistema de Ensino com currículos integrados nacionalmente; Intercâmbio de alunos e professores entre as diversas unidades em todas as regiões do país e padronização dos processos.

The state of the field in UK management research: reflections of the Research Assessment Exercise (RAE) panel

This paper reviews the state of the field of the sub-disciplines within UK management research, based upon the submissions of 94 UK higher education institutions to the Business and Management Studies Panel in the UK's 2001 Research Assessment Exercise (RAE). It offers observations on the UK model of the assessment of quality in, and funding of, research conducted in publicly funded higher education institutions.

A strategy-as-practice approach to strategy research and education

This conclusion to the Dialog proposes a strategy-as-practice based approach to bringing strategy research and education closer to practice. Strategy-as-practice rejects the choice, proposed in the previous articles, between theory and practice. The authors argue for strategy research based rigorously on sociological theories of practice. Such research complements the parsimony and generalizability of economics-driven theory, extending strategy research to incorporate the messy realities of doing strategy in practice, with a view to developing theory that is high in accuracy. The authors suggest that practice-based research can also inform strategy teaching by providing students with rich case studies of strategy work as actually practiced, analyzed through such sociological lenses as ethnomethodology, dramaturgy, and institutional theory. Strategy-as-practice research does not aim to give students parsimonious models for analysis or expose them to cases of best practice but rather to help them develop practical wisdom through a better understanding of strategy in practice.

Multiple paradigms and organisational research: an analysis of work behaviour in the fire service

The thesis examines Kuhn's (1962, 1970) concept of paradigm, assesses how it is employed for mapping intellectual terrain in the social sciences, and evaluates it's use in research based on multiple theory positions. In so doing it rejects both the theses of total paradigm 'incommensurability' (Kuhn, 1962), and also of liberal 'translation' (Popper, 1970), in favour of a middle ground through the 'language-game of everyday life' (Wittgenstein, 1953). The thesis ultimately argues for the possibility of being 'trained-into' new paradigms, given the premise that 'unorganised experience cannot order perception' (Phillips, 1977). In conducting multiple paradigm research the analysis uses the Burrell and Morgan (1979) model for examining the work organisation of a large provincial fire Service. This analysis accounts for firstly, a 'functionalist' assessment of work design, demonstrating inter alia the decrease in reported motivation with length of service; secondly, an 'interpretive' portrayal of the daily accomplishment of task routines, highlighting the discretionary and negotiated nature of the day's events; thirdly, a 'radical humanist' analysis of workplace ideology, demonstrating the hegemonic role of officer training practices; and finally, a 'radical structuralist' description of the labour process, focusing on the establishment of a 'normal working day'. Although the argument is made for the possibility of conducting multiple paradigm research, the conclusion stresses the many institutional pressures serving to offset development.

Technology adoption in small and medium-sized logistics providers

Purpose - The main aim of the research is to shed light on the role of information and communication technology (ICT) in the logistics innovation process of small and medium-sized third party logistics providers (3PLs). Design/methodology/approach - A triangulated research strategy was designed using a combination of quantitative and qualitative methods. The former involved the use of a questionnaire survey of small and medium-sized Italian 3PLs with 153 usable responses received. The latter comprised a series of focus groups and the use of seven case studies. Findings - There is a relatively low level of ICT expenditure with few companies adopting formal technology investment strategies. The findings highlight the strategic importance of supply chain integration for 3PLs with companies that have embarked on an expansion of their service portfolios showing a higher level of both ICT usage and information integration. Lack of technology skills in the workforce is a major constraint on ICT adoption. Given the proliferation of logistics-related ICT tools and applications in recent years it has been difficult for small and medium-sized 3PLs to select appropriate applications. Research limitations/implications - The paper provides practical guidelines to researchers in the effective use of mixed-methods research based on the concept of methodological triangulation. In particular, it shows how questionnaire surveys, focus groups and case study analysis can be used in combination to provide insights into multi-faceted supply chain phenomena. It also identifies several potentially fruitful avenues for future research in this specific field. Practical implications - The paper's findings provide useful guidance for practitioners on the effective adoption of ICT as part of the logistics innovation process. The findings also provide support for ICT vendors in the design of ICT solutions that are aligned to the needs of small 3PLs. Originality/value - There is currently a paucity of research into the drivers and inhibitors of ICT in the innovation processes of small and medium-sized 3PLs. This paper fills this gap by exploring the issue using a range of complementary research approaches. Copyright © 2013 Emerald Group Publishing Limited. All rights reserved.

Purchasing consortia and electronic markets:a procurement direction in integrated supply chain management

In supply chain management literature, there has been little empirical research investigation on purchasing consortium issues focusing on a detailed analysis of information and communication (ICT) based procurement strategies. Based on the exploration of academic literature and two surveys among purchasing organisations as well as e-Marketplaces / procurement service providers (PSPs) in the automotive and electronics industry sectors, the research methodology follows a positivistic approach in order to assess the overall statement: ‘Effective participation in electronic purchasing consortia (EPC) can have the potential to enhance competitive advantage. Implementation therefore requires a clear and detailed understanding of the major process structures and drivers, based upon thetechnology-organisation-environment framework.’ Key factors and structures that affect the adoption and diffusion of EPC and the performance impact of adoption are investigated. The empirically derived model for EPC can be a valuable starting point to EPC research.

Electronic purchasing consortia:a procurement direction for the future?

In literature, there has been little empirical research investigation on purchasing consortium issues focusing on a detailed analysis of ICT-based procurement strategies. Based on the exploration of academic literature and a survey on e-Marketplaces / procurement service providers (PSPs) in the automotive and electronics industry sectors, an overall statement is proposed: Effective participation in electronic purchasing consortia can have the potential to enhance competitive advantage. Implementation therefore requires a clear and detailed understanding of the major process structures and drivers at the e-Marketplace / PSP level of analysis.