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)

In this paper we compare the propositional logic of Frege’s Grundgesetze der Arithmetik to modern propositional systems, and show that Frege does not have a separable propositional logic, definable in terms of primitives of Grundgesetze, that corresponds to modern formulations of the logic of “not”, “and”, “or”, and “if…then…”. Along the way we prove a number of novel results about the system of propositional logic found in Grundgesetze, and the broader system obtained by including identity. In particular, we show that (...) the propositional connectives that are definable in terms of Frege’s horizontal, negation, and conditional are exactly the connectives that fuse with the horizontal, and we show that the logical operators that are definable in terms of the horizontal, negation, the conditional, and identity are exactly the operators that are invariant with respect to permutations on the domain that leave the truth-values fixed. We conclude with some general observations regarding how Frege understood his logic, and how this understanding differs from modern views. (shrink)

Self-applied portable polysomnography is considered a promising tool to assess sleep architecture in field studies. However, no findings have been published regarding the appearance of a first-night effect within a sport-specific setting. Its absence, however, would allow for a single night sleep monitoring and hence minimize the burden on athletes while still obtaining the most important variables. For this reason, the aim of the study was to assess whether the effect appears in home-based sleep monitoring of elite athletes.The study sample (...) included eight male and 12 female German elite athletes from five different sports. Participants slept with a portable polysomnography for two nights, which they self-applied at night before going to bed. Time in bed and wake-up time in the morning were freely chosen by each individual athlete without any restrictions regarding time or sleeping environment. Participants were asked to keep the same location and time frame during the two days of monitoring and stick to their usual sleeping schedules. Sleep stages were manually scored using 30-s epochs. Sleep parameters and stages were later compared with the help of linear mixed models to investigate the factor time.Significant differences between the two nights were found for percentage of Non-REM sleep [T = −2,10, p < 0.05, d = −0.47, 95%-CI ] with small effect size, Total Wake Time [T = 2.30, p = 0.03, d = 0.51, 95%-CI ], Sleep Efficiency [T = −2.48, p = 0.02, d = −0.55, 95%-CI ], and Wake percentage [T = 2.47, p = 0.02, d = 0.55, 95%-CI ] with moderate effect sizes, and N3 Sleep Onset Latency [T = 3.37, p < 0.01, d = 0.75, 95%-CI ] with large effect size. Confidence Intervals for all other indices range from negative to positive values and hence specify, that parameters were not systematically negatively affected in the first night.Findings suggest that some individuals are more affected by the first-night effect than others. Yet, in order to keep the measurement uncertainties to a minimum, a more conservative approach with at least two monitoring nights should be used whenever possible, if no other supporting information on the athletes says otherwise. (shrink)

SummaryThe apparent conflict between first person authority and externalism arises only from needlessly thinking of first person authority in terms of “knowing what.”.

Pain may appear to undermine the radically intentionalist view that the phenomenal character of any experience is entirely constituted by its representational content. That appearance is illusory. After categorizing versions of pain intentionalism along two dimensions, I argue that an 'objectivist' and 'non-mentalist' version is the most promising, if it can withstand two objections concerning what we say when in pain, and the distinctiveness of pain. I rebut these objections, in a way available to both opponents of and adherents to (...) the view that experiential content is entirely conceptual. (shrink)

In this paper, I attempt to explain one of the most controversial views attributed to the Stoic Chrysippus: that the impossible can follow from the possible. My solution finds in Chrysippus a distinction later made by the medieval logician John Buridan: that between being possible (there being a state of affairs that may occur) and being possibly-true (there being some proposition whose truth-conditions are that state of affairs). Buridan and Chrysippus have radically opposing views on the nature of propositions. What (...) their conceptions share is the conclusion that at least some propositions must be contingent beings. They argue for this while maintaining a rigorous commitment to the view that propositions are strictly bivalent. In 2. I explain the Chrysippean passage in terms of a distinction Buridan makes explicitly. In 3. I show how the distinction follows implicitly from the Stoic theory of quantification. In 4. I compare the modality with other aspects of Stoic logic. In 5. I discuss how the distinction behaves in the future tense. (shrink)

The papers in this volume bring together a number of scholars working on topics ranging from contemporary ethics to the history of philosophy. This wide scope reflects the comprehensive nature of Dietrich von Hildebrand's philosophic vision. His career includes foundational works on such subjects as ethics, philosophical method, aesthetics, and the nature of love. One struggles to imagine how Hildebrand managed to fit all this into a life that also includes extensive anti-Nazi political activism during World War II. Within this (...) broad scope of Hildebrand's work, one finds a number of important philosophical problems that beg for further development, such as his conception of personal existence, his rich and pluralistic conception of beauty, or his distinction between person and personality. In several places, however, the development of Hildebrand's thought must involve a correction or even an outright challenge to his reasoning. Each of these papers does just this, applying the insights of Hildebrand to a number of diverse philosophical problems, while also advancing and challenging his thought in various ways. Despite this wide diversity, three central issues appear again and again in these papers, and represent some of Hildebrand's most important contributions to philosophy: (i) his method of phenomenological realism, (ii) his conception of value and value-response, and (iii) his personalism. I want to provide here a brief sketch of these three areas to orient the reader before approaching the more technical details of each essay. (shrink)

On one reading, twentieth century Christian personalists such as Max Scheler, Dietrich von Hildebrand, or Edith Stein merely translate into Christian terms a set of modern concerns that arise apart from and are at odds with the historical Christian tradition. According to this reading, modern philosophy makes a fundamental break with previous thinking when it turns inward to examine the interior, personal dimension of existence. A person who favors this inward turn will see the Christian personalists as vainly attempting to (...) salvage traditional Christian categories while trying to keep up with the times. For example, someone who favors twentieth century existentialism or psychoanalysis may sympathize with a Christian personalist account of the interiority and irreplaceable uniqueness of each person but despise the larger religious framework of grace and salvation. Someone who favors traditional metaphysics, by contrast, may see these personalists as falling prey to modern errors when they should have kept the faith. Such a traditionalist may think, for example, that an emphasis on the personal is an infiltration into Christianity from secular political philosophies of individualism and that this has been thinly covered over with traditional Christian language. -/- Both perspectives, however, ignore the historical roots of personalism much further back in the history of philosophy than Descartes and Kant. Central to this history is the idea that each person uniquely realizes an incommunicable dimension of his existence, irreducible to the category of nature or essence. While we are in nature and while we *are* a nature, our nature as nature remains purely general, describing *what* we are in common with every other member of our species. As particular persons exercising our freedom and spiritual existence, however, each of us concretizes that purely general nature in a unique, personal way. For many centuries, Christians have called the dimension that concretizes nature ὑπόστασις: each ὑπόστασις is a distinct realization of a general nature. When this notion is first introduced into Christian discourse during the second half of the fourth century, the uniqueness of persons as opposed to the uniqueness of individual pebbles or horses does not come fully into focus. Nevertheless, a thick conception of ὑπόστασις develops in order to speak precisely about Trinitarian and Christological theology, and this context gives it a distinctly personalist character, especially when it is translated into Latin as *persona*. In order to speak of God as three ὑποστάσεις or *personae* in one essence and to speak of Christ as one ὑπόστασις or *persona* in two natures, the category of ὑπόστασις must be irreducible to the category of nature. Along this irreducible dimension persons are irreplaceable *someones* in relationship with other someones rather than merely *somethings*, specimens of a kind more or less interchangeable with any other such specimen. (shrink)

Contemporary bioethical theory relies upon the concept of informed consent to protect against abuses of patient autonomy. Due to the complexity of the informed consent process, however, many patients rely more on their trust in their health care providers than they do upon their own ability to decide whether or not to give informed consent. Reformation theologian John Calvin placed a strong emphasis on the decision-maker's duty to respect the trust that others repose in the decision-maker. In keeping with Calvin's (...) concept of the duty to honor that trust, bioethics would do well to complement its current emphasis on informed consent with an emphasis on the protection of patient trust. (shrink)

Routledge is now re-issuing this prestigious series of 204 volumes originally published between 1910 and 1965. The titles include works by key figures such as C.G. Jung, Sigmund Freud, Jean Piaget, Otto Rank, James Hillman, Erich Fromm, Karen Horney and Susan Isaacs. Each volume is available on its own, as part of a themed mini-set, or as part of a specially-priced 204-volume set.

The self seems to be a unitary entity remaining stable across time. Nevertheless, current theorizing conceptualizes the self as a number of interacting sub-systems involving perception, intention and action (self-model). One important function of such a self-model is to distinguish between events occurring as a result of one's own actions and events occurring as the result of somebody else's actions. We conducted an fMRI experiment that compared brain activation after an abrupt mismatch between one's own movement and its visual consequences (...) with an abrupt mismatch between one's own movement and somebody else's visually perceived hand movement. A right fronto-parietal network was selectively active during a sudden mismatch between one's own observed and performed hand action. (shrink)

In this paper, I argue for an extension of relational accounts of the imago Dei which includes a kind of priestly relation to the created order. In this relation, humanity is intended to ensure the independent flourishing of creation in a way reflective of the kind of communion we ought to have with one another. Through an analysis of the brokenness of these relationships, I argue human oppression of other humans and ravaging of creation are born of the same brokenness (...) in such a way that they contribute to one another as distortions of human teleological communion. By drawing on Social Identity Approach in group psychology, I can offer an account of shared human identity out of which humanity acts in distorted ways as a group. By describing oppression and ravaging in terms of broken communal telos and group action, I offer a way forward for relating humanity to the created order in a way that neither instrumentalizes creation, nor flattens the distinctiveness of human creation in the image of God. (shrink)