280 resultados para ignorance


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Classical swine fever virus infection of pigs causes disease courses from life-threatening to asymptomatic, depending on the virulence of the virus strain and the immunocompetence of the host. The virus targets immune cells, which are central in orchestrating innate and adaptive immune responses such as macrophages and conventional and plasmacytoid dendritic cells. Here, we review current knowledge and concepts aiming to explain the immunopathogenesis of the disease at both the host and the cellular level. We propose that the interferon type I system and in particular the interaction of the virus with plasmacytoid dendritic cells and macrophages is crucial to understand elements governing the induction of protective rather than pathogenic immune responses. The review also concludes that despite the knowledge available many aspects of classical swine fever immunopathogenesis are still puzzling.

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There are two major mechanisms reported to prevent the autoreactivity of islet-specific CD8+ T cells: ignorance and tolerance. When ignorance is operative, naïve autoreactive CD8+ T cells ignore islet antigens and recirculate without causing damage, unless activated by an external stimulus. In the case of tolerance, CD8+ T cells are deleted. Which factor(s) contributes to each particular outcome was previously unknown. Here, we demonstrate that the concentration of self antigen determines which mechanism operates. When ovalbumin (OVA) was expressed at a relatively low concentration in the pancreatic islets of transgenic mice, there was no detectable cross-presentation, and the CD8+ T cell compartment remained ignorant of OVA. In mice expressing higher doses of OVA, cross-presentation was detectable and led to peripheral deletion of OVA-specific CD8+ T cells. When cross-presentation was prevented by reconstituting the bone marrow compartment with cells incapable of presenting OVA, deletional tolerance was converted to ignorance. Thus, the immune system uses two strategies to avoid CD8+ T cell-mediated autoimmunity: for high dose antigens, it deletes autoreactive T cells, whereas for lower dose antigens, it relies on ignorance.

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Many peripheral solid tumors such as sarcomas and carcinomas express tumor-specific antigens that can serve as targets for immune effector T cells. Nevertheless, overall immune surveillance against such tumors seems relatively inefficient. We studied immune surveillance against a s.c. sarcoma expressing a characterized viral tumor antigen. Surprisingly, the tumor cells were capable of inducing a protective cytotoxic T cell response if transferred as a single-cell suspension. However, if they were transplanted as small tumor pieces, tumors readily grew. Tumor growth correlated strictly with (i) failure of tumor cells to reach the draining lymph nodes and (ii) absence of primed cytotoxic T cells. Cytotoxic T cells were not tolerant or deleted because a tumor antigen-specific cytotoxic T cell response was readily induced in lymphoid tissue by immunization with virus or with tumor cells even in the presence of large tumors. Established tumors were rejected by vaccine-induced effector T cells if effector T cells were maintained by prolonged or repetitive vaccination, but not by single-dose vaccination. Thus, in addition to several other tumor-promoting parameters, some antigenic peripheral sarcomas—and probably carcinomas—may grow not because they anergize or tolerize tumor-specific T cells, but because such tumors are immunologically dealt with as if they were in a so-called immunologically privileged site and are ignored for too long.

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Four variations on Two Envelope Paradox are stated and compared. The variations are employed to provide a diagnosis and an explanation of what has gone awry in the paradoxical modeling of the decision problem that the paradox poses. The canonical formulation of the paradox underdescribes the ways in which one envelope can have twice the amount that is in the other. Some ways one envelope can have twice the amount that is in the other make it rational to prefer the envelope that was originally rejected. Some do not, and it is a mistake to treat them alike. The nature of the mistake is diagnosed by the different roles that rigid designators and definite descriptions play in unproblematic and in untoward formulations of decision tables that are employed in setting out the decision problem that gives rise to the paradox. The decision maker’s knowledge or ignorance of how one envelope came to have twice the amount that is in the other determines which of the different ways of modeling his decision problem is correct. Under this diagnosis, the paradoxical modeling of the Two Envelope problem is incoherent.

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Purpose – The collapse of world economic systems brought the interconnectedness between business and global events sharply into focus. As Starkey points out: “leading business schools need to overcome their fascination with a particular form of finance and economics […] to broaden their intellectual horizons […] (and to) look at the lessons of history and other disciplines”. The purpose of this paper is to provide evidence from three years of research on the Aston MBA suggesting that an emphasis on developing capabilities within a far broader, connected and reflexive business curriculum is what business students and practitioners now recognise as an essential way forward for responsible management education. Design/methodology/approach – This research paper examines the reflective accounts of 300 MBA students undertaking a transdisciplinary Business Ethics, Responsibility and Sustainability core module. Findings – As Klein argues, transdisciplinarity is simultaneously an attitude and a form of action. The student reflections provide powerful discourses of individual learning and report a range of outcomes from finding “the vocabulary or the confidence” to raise issues to acting as “change agents” in the workplace. Originality/value – As responsibility and sustainability requires learners, researchers and educators to engage with real world complexity, uncertainty and risk, conventional disciplinary study, especially within business, often proves inadequate and partial. This paper demonstrates that creative and exploratory frames need to be developed to facilitate the development of more connected knowledge – informed by multiple stakeholders, able to contribute heterogeneous skills, perspectives and expertise.

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Images about Africa in the northern hemisphere are generally negative and pessimistic. In spite of instant global communication, why have these images persisted till date? This contribution shall revisit these perceptions and the images embodying them to unearth the motivations and rationale. The central argument, based on some narratives and experiences, is that ignorance feeds these images and stereotypes. Furthermore, positionality of non-African experts and some groups of African scholars and activists contribute to this culture of ignorance and paternalism. The contribution shall end with an ethical evaluation of the persistence of the images and the extent of moral responsibility of the authors and carriers of the racist stereotypes embedded in the images. (DIPF/Orig.)

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In this thesis I experimentally investigate prosocial and ethical behavior in economic interactions. The thesis consists of three experimental research papers that have a broad range of research questions on social responsibility, ignorance and cheating. With these experiments I aim to better understand when and why people behave ethically and/or prosocially and which consequences it has on their own and other players’ payoffs, and on overall efficiency. The results from the three experimental studies suggest that (i) donations to charity by employees are rewarded in an experimental setting, and the effect is driven by reciprocal concerns; (ii) there is a significant fraction of people who decide not to know about negative consequences of own actions, and the sorting of social agents of a low type into ignorance drives self-interested behavior of ignorant agents; and (iii) if the possibility of being exposed as a liar is small, the tendency to lie increases with incentives, indicating that some people have positive and finite costs of lying. Furthermore, when the participants lie, they lie to the full extent, which suggests that the intrinsic cost of lying is fixed.

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What might early Buddhist teachings offer neuroscience and how might neuroscience inform contemporary Buddhism? Both early Buddhist teachings and cognitive neuroscience suggest that the conditioning of our cognitive apparatus and brain plays a role in agency that may be either efficacious or non-efficacious. Both consider internal time to play a central role in the efficacy of agency. Buddhism offers an approach that promises to increase the efficacy of agency. This approach is found in five early Buddhist teachings that are re-interpreted here with a view to explaining how they might be understood as a dynamic basis for ‘participatory will’ in the context of existing free will debates and the neuroscientific work of Patrick Haggard (et al.). These perspectives offer Buddhism and neuroscience a basis for informing each other as the shared themes of: (1) cognition is dynamic and complex/aggregate based, (2) being dynamic, cognition lacks a fixed basis of efficacy, and (3) efficacy of cognition may be achieved by an understanding of the concept of dynamic: as harmony and efficiency and by means of Buddha-warranted processes that involve internal time.