The apolipoprotein E gene plays an important role in the pathogenesis of Alzheimer's disease , and amyloid plaque comprised mostly of the amyloid-beta peptide ) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly understood. We examined how A treatment affects APOE expression in cultured cells and tested the role of the transcription factor NF-B in APOE gene regulation. To delineate NF-B's role, we have characterized a 1098 nucleotide segment containing the (...) 5'-flanking region of the human APOE gene . Sequence analysis of this region suggests the presence of two potential NF-B elements. To demonstrate promoter activity, the region was cloned upstream of a promoterless luciferase gene. This segment was able to drive expression of luciferase in transient transfections of human fetal glial cells. Promoter activity was stimulated twofold by A treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against NF-B reduced A stimulation. Deletion and mutagenetic analyses demonstrated that the distal NF-B element was functional and showed a strong DNA-protein complex band in gel shift analysis, similar to that from control NF-B consensus element. An anti-inflammatory and anti-NF-B drug, sodium salicylate, significantly blocked A-induced APOE promoter function. Our data provide evidence that upregulation of APOE by A in astroglial cells is mediated by an NF-B-element present in the 5'-flanking region of the APOE gene. (shrink)
The eight relatively short papers in this volume were first presented at the International Institute of Philosophy Entretiens held at Helsinki in 1970. Four main topics are considered: the definition of knowledge, memory, Wittgenstein’s theory of knowledge, and evidence. Representing the first topic, B. A. O. Williams’ paper "Knowledge and Reasons" is chiefly directed toward examining the role of reasons in knowledge. His main thesis is that when speaking in general about knowledge, it is not necessary either that "the knower (...) be able to support or ground his true belief by reference to other propositions" or "that he be in any special state" concerning his belief. Yet it is necessary that, "given the truth of p, it is no accident that A believes p rather than not-p." The author is quick to indicate that this formula is highly schematic and, as an analysis of knowledge, insufficient. A. J. Ayer, as commentator on Williams’ paper, tends to concur with and further amplify a number of Williams’ ideas. However, he does take issue with Williams on two main points: his remarks on the possibility of "radically impersonal knowledge" and his formula that true belief should not be accidental. Concerning the latter, Ayer, while aware of the outline form of Williams’ argument, is "sceptical of its power to yield a precise formula which would differentiate between knowledge and true belief" in a satisfactory manner. (shrink)
In many research studies, tumor biopsies are an unavoidable requirement for achieving key scientific aims. Yet some commentators view mandatory research biopsies as coercive and suggest they should be optional, or at least optional until further data are obtained regarding their scientific usefulness. Further complicating the ethical picture is the fact that some research biopsies offer a potential for clinical benefit to trial participants. We interviewed and surveyed a convenience sample of participants in phase I clinical trials at a single (...) institution. Our primary aim was to describe phase I participants’ understanding of whether a research biopsy offered them the prospect of medical benefit. We also endeavored to describe participants’ views about biopsies—specifically, the benefits of biopsies, if any, and whether biopsies were acceptable, risky, or discouraged trial participation. Finally, we collected data on demographics and attitudes to see if any strong correlations with misunderstanding, acceptability, or riskiness existed. Overall, the respondents tended to view research biopsies as acceptable, though they did not succeed in identifying the lack of benefit of a research biopsy. These findings call for renewed efforts in consent conversations and documents to carefully describe the benefits, or lack thereof, of research biopsies. (shrink)
Behaving ethically depends on the ability to recognize that ethical issues exist, to see from an ethical point of view. This ability to see and respond ethically may be related more to attributes of corporate culture than to attributes of individual employees. Efforts to increase ethical standards and decrease pressure to behave unethically should therefore concentrate on the organization and its culture. The purpose of this paper is to discuss how total quality (TQ) techniques can facilitate the development of a (...) cooperative corporate culture that promotes and encourages ethical behavior throughout an organization. (shrink)
In previous work we gave a new proof-theoretical method for establishing upper-bounds on the space complexity of the provability problem of modal and other propositional non-classical logics. Here we extend and refine these results to give an O -space decision procedure for the basic positive relevance logic B+. We compute this upper-bound by first giving a sound and complete, cut-free, labelled sequent system for B+, and then establishing bounds on the application of the rules of this system.
Odon Lottin, O.S.B. was an historian and a moral theologian. As an historian, he studied the scholastic attention to human psychology and morality. As a theologian, he studied the roles that thought and action play in the development of the moral agent. His influence in historical and moral theology has been significant. Nonetheless, moralists and medievalists independently have appropriated his insights. No one has yet studied the relationship between his historical investigations and his moral theology. This work accomplishes that study. (...) ;This dissertation considers Lottin's contributions to both historical and moral theology. Lottin studies the medieval history and understanding of free choice, moral action, the acquired virtues and conscience. He traces this history to uncover specific ideas, expose the development of thought, recognize the emergence of consensus, and find whether satisfying resolutions were achieved. Many of his contemporaries in the manual tradition misinterpreted this history. This misinterpretation was due to their inaccurate or undeveloped historical method. And, just as there was deficiency in their method, there were significant shortcomings in the scope of their theological investigations. Thus, by looking back to history, Lottin presents a moral theology more substantive than the manuals. Each of the first four chapters of this dissertation presents Lottin's historical studies of the major debates, examines his incorporation of that material into his own contribution to the debates' resolutions, and concludes with how his work has been appropriated and where it may yet lead. The final chapter considers Lottin's contribution to the discipline of moral theology. ;Moral theology can neither be ahistorical nor impersonal. Lottin's work demonstrates the necessity of accurate history for interpretation and of critical reflection on the cause of human action. His return to medieval moral theology is a return to human agency. His agent-centered moral theology retrieves prudence and the moral virtues as dynamic means for rightly forming consciences and determining action. Historical and agent-centered moral theology is concerned with theory and practice. The theory of the moral life looks at human intentionality, the practice is its free expression; together they comprise the meaning of self-determination. (shrink)
At any given time, an individual has certain beliefs and certain procedures or methods for modifying those beliefs. In The Realm of Reason, as in his previous book, Being Known (1999), Christopher Peacocke is concerned with the elusive question of what it is for someone to be “entitled” to a given belief or procedure.1..
A referente resenha busca fazer uma análise mais detalhada acerca do livro: "O Movimento Sofista" de George Kerferd. Objetivamos explicitar os pontos basilares ressaltados pelo autor em contrapartida a análise tradicional dos sofistas ao decorrer da história.
The paper is an attempt to reconstruct difficult and problematic, but on the same time vital and crucial, links between liberalism and eurocentrism. That relationship is considered as a result of mutual self-seeking and profit-seeking with the process of colonization as historical and formational “epicenter” of European Modernity. Colonization, the “expansion of Europe” demanded an ideological background and backup which in reverse were fostered and strengthened by the opportunity of belonging to the extensive “colonial space-time”. “Rise of the west” together (...) with “technologies of colonization”, refined and perfectioned during the era of “the long sixteenth century”, would have been inconceivable without a presence of specific “ontology” – the possessive individualism conceptualized and analyzed by C.B. Macpherson in his works on liberal (liberal-democratic) political theory. (shrink)