Alzheimer's disease is characterized by plaques of amyloid-beta peptide, cleaved from amyloid-beta protein precursor . Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 , and the beta amyloid precursor (...) cleaving enzyme . In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. (shrink)

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

Alzheimer's disease is characterized by amyloid-beta peptide -loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 , which has been shown to be required for the regulation of APP and Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization (...) of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. (shrink)

R. S. Woolhouse; IV*—Leibniz's Reaction to Cartesian Interaction, Proceedings of the Aristotelian Society, Volume 86, Issue 1, 1 June 1986, Pages 69–82, https:/.

A comparative study of business related values among business students was conducted over the last 10 years in two neighbouring countries. Although Estonia and Finland are culturally related, according to an empirical study of managerial values, including the ethical values of business students, the two countries display significant differences. During the last decade, Estonia has changed from being a country characterised by an authoritarian, centralized, totalitarian state socialism, to a democratic country with a free market economy and different attitudes and (...) values. At the same time Finland has experienced almost a century of capitalism and democracy. It is argued that the differences in values exhibited by these two countries could be explained by using the institutional and historical context. The authors propose a model of value hierarchies in relation to institutionalism. (shrink)

„My sole purpose in this paper is to try and correct what I take to be a common misinterpretation of Hume’s opinions on mathematics. I shall not enquire whether he was right or wrong in holding these opinions. Nor shall I offer opinions of my own.“.

If educators are to educate they must be accorded some level of trust. Anthony Giddens claims that because trust is not easily created, it is now being replaced with ‘confidence’ because this latter disposition is much easier to give and is more convenient. It is argued in this paper that this shift from trust to confidence stifles education because emphasis is placed solely upon qualifications and competence, and is neglectful of disclosing one’s motives and desires—which are considered to be essential (...) elements for relationships and communities which depend upon trust. Therefore, educators ought to seek to become more trustworthy by going beyond evidence-based practices and codes of ethics, towards articulating a developed personal philosophy of education outlining the ultimate end-purposes to which they aspire. Through such a philosophy, educators identify their ultimate desires and commitments and this self-disclosure can make trust-giving more likely. Demonstrated evidence of achievements and qualifications encourage confidence and this has some value. In addition to these artefacts of evidence, it is argued here that educators must also articulate what they actually desire. This can be understood as John Dewey’s virtue of ‘genuine interest’ which he characterises as being wholehearted, persistent and impartial. For educators, this is often represented in our personal philosophy of education and because it is personal, it is also existential in the sense that it pertains to giving sense, meaning and purpose to all of our activities and way of life for which we are individually responsible and passionately committed to as professionals. As a consequence of being existential, our philosophy and our commitment to it has an intellectual and moral aspect and because it reaches to the very depths of our raison d’être, it pertains to our passion as described by Søren Kierkegaard. This paper shall draw upon Dewey’s notion of wholeheartedness and Kierkegaard’s notion of purity of heart, to make the case that if educators embrace these in their practices, we may become more trustworthy. (shrink)

Deficits in social cognition and more specifically in communication have an important impact on the real-life functioning of people with schizophrenia. In particular, patients have severe problems in communicative-pragmatics, for example, in correctly inferring the speaker’s communicative intention in everyday conversational interactions. This limit is associated with morphological and functional alteration of the left middle temporal gyrus, a cerebral area involved in various communicative processes, in particular in the distinction of ironic communicative intention from sincere and deceitful ones. We performed (...) an fMRI study on 20 patients with SZ and 20 matched healthy controls while performing a pragmatic task testing the comprehension of sincere, deceitful, and ironic communicative intentions. We considered the L-MTG as the region of interest. SZ patients showed difficulties in the correct comprehension of all types of communicative intentions and, when correctly answering to the task, they exhibited a higher activation of the L-MTG, as compared to HC, under all experimental conditions. This greater involvement of the L-MTG in the group of patients could depend on different factors, such as the increasing inferential effort required in correctly understanding the speaker’s communicative intentions, and the higher integrative semantic processes involved in sentence processing. Future studies with a larger sample size and functional connectivity analysis are needed to study deeper the specific role of the L-MTG in pragmatic processes in SZ, also in relation to other brain areas. (shrink)

R. A. Duff; III*—Socratic Suicide?, Proceedings of the Aristotelian Society, Volume 83, Issue 1, 1 June 1983, Pages 35–48, https://doi.org/10.1093/aristotelian/.

Michael Polanyi names Augustine as inaugurates of his “postcritical”philosophy. To understand what this means by exploring creation in the Confessions will clarify complex problems in Augustine and articulate theological implications in Polanyi. Specifically, it will show why an autobiographical account of conversion ends speaking of creation; how creation can thus be understood as “personal” language; how creation can be recovered in a time preoccupied with conversion; how conversion and creation are linked with incarnation, hermeneutics, and confessional rhetoric; and it will (...) suggest a contemporary use of creation language that connects the scientific and the religious. (shrink)

The article studies two related issues. First, it introduces the notion of the contraposition of quantifiers which is a “dual” notion of symmetry and has similar relations to co-intersectivity as symmetry has to intersectivity. Second, it shows how symmetry and contraposition can be generalised to higher order type quantifiers, while preserving their relations with other notions from generalized quantifiers theory.

Kur’an’ın kendine has birbiriyle irtibatlı kelimeler dünyası bulunmakta-dır. Doğru bir Allah tasavvuru, Allah-âlem, Allah-kul, âlem-kul ilişkisinin nasıl olması gerektiği bu kelime dünyası tarafından anlatılmaktadır. Bu nok-tada Kur’an’da herhangi bir konu anlatılırken aralarında sıkı irtibat olan kelime grupları kullanılmıştır. Örneğin Allah Kur’ân’da kendisini, Rakîb, Alîm, Basîr, Habîr, Latîf vb. lafızlarla insanın idrakine yansıtmakta ve böylece doğru bir Allah Tasavvuru oluşmasını amaçlamaktadır. Bu çalışmada, öncelikle ra-ka-be /رقب kökünün etimolojisi üzerinde durulacaktır. Zira bir kelimenin dildeki asli anlamı ve türevleriyle beraber sonradan kazandığı anlamların (...) tespiti, ilgili kelimenin anlam sahasını keşfetme ile mümkündür. Akabinde bu kökün türevlerinden “Rakîb” kelimesi ile anlam ilişkisi olan ve Yüce Allah’ın Kur’ân’da kendisine nispet ettiği sıfatlarından, Alîm, Basîr, Habîr, Şehîd kelimeler tahlil edilecektir. Bu bağlamda doğrudan olmasa da dolaylı olarak Allah’ın görmesini ve gözetlemesini ifade eden kelimelere ve ilgili âyetlere yer verilecektir. Böylece ra-ka-be kökünün Kur’an siyakındaki anlam sahası ortaya konulmuş olacaktır. (shrink)

The present work is substantially a dissertation presented to the Faculty of the Graduate School of the University of Toronto. While aware of the numerous imperfections of the work I have decided, on the urging of many colleagues, to publish it at this time because of the current relevance of the subject-matter and especially of the collection of texts. I am happy to acknowledge my indebtedness to the faculty of the Pontifical Mediaeval Institute of Toronto and especially to the Reverend (...) Ignatius Eschmann, O.P., who first suggested the idea of this study and whose encouragement and assistance brought it to completion. My thanks are due also to the Reverend George Klubertanz, S.J., and Mr. Paul Mathews, both of the Department of Philosophy of Saint Louis University, and" for invaluable secretarial assistance, to Mrs. Savina Tonella and Miss Agnes Kutz. R. J. HENLE, S.j. Saint Louis December, 1954 TABLE OF CONTENTS GENERAL INTRODUCTION... (shrink)