Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

Trope theory is the view that the world consists (wholly or partly) of particular qualities, or tropes. This admittedly thin core assumption leaves plenty of room for variation. Still, most trope theorists agree that their theory is best developed as a one-category theory according to which there is nothing but tropes. Most hold that ‘sameness of property’ should be explained in terms of resembling tropes. And most hold that concrete particulars are made up from tropes in compresence (for an overview, (...) including an introduction to some alternative versions of the view, cf. Maurin, 2014). D. M. Armstrong disagrees. He thinks the world is a world of immanent universals, the thin particulars in which those universals are instantiated, and the states of affairs that—thereby—exist. He holds that ‘sameness of property’ should be explained in terms of numerically identical universals or—if the resembling things are the universals themselves—in terms of partially identical universals. And he believes that concrete particulars are made up from ‘thin particulars’ in which a (sufficient) number of universals are instantiated. In spite of their disagreements, proponents of tropes owe Armstrong a debt of gratitude. First, for being one of the theory’s earliest, most serious, and—not least—most prominent, critics (Armstrong for the first time considers, and rejects, what he then labels ‘particularism’, in his 1978a). But also for being one of the theory’s most ardent champions. Already in his 1989a, Armstrong regrets his 1978-rejection of the view. Equivalence classes of exactly resembling tropes, he now admits, for most purposes “serve as an excellent substitute for universals” (Armstrong 1989a, 122). But then why isn’t Armstrong a trope theorist? In this paper, Armstrong’s main reasons for rejecting the trope view are critically scrutinized. All of them, it is maintained, fail to convince. If this argument is accepted, Armstrong seems to have no—or, at least, no good—reason for not accepting the existence of tropes. But, then, ought Armstrong to have been a trope theorist? If the ‘best’ version of the trope view turns out to be ontologically more parsimonious than Armstrong’s own theory of universals, then, yes. That there is a version of the trope view, a version that is not (or, at least not seriously) considered by Armstrong, that is ontologically more parsimonious than the universals view, is argued in the next section. Why none of Armstrong’s reasons for preferring universals to tropes manage to convince, is explained in the section after that. First, however, and in order to avoid a common misunderstanding of the trope view and, as a consequence, of why one ought to reject it, a few more words about the core-difference between tropes and universals, and about how this difference matters (as well as does not matter) to what—and how well—these theories explain. (shrink)

Machine generated contents note: Part I -- Doctors -- Dr. Joseph Messer -- Dr. Sharon Sandell -- ER -- Dr. John Barrett -- Marc and Noreen Levison, a paramedic and a nurse -- Lloyd (Pete) Haywood, a former gangbanger -- Claire Hellstern, a nurse -- Ed Reardon, a paramedic -- Law and Order -- Robert Soreghan, a homicide detective -- Delbert Lee Tibbs, a former death-row inmate -- War -- Dr. Frank Raila -- Haskell Wexler, a cinematographer -- Tammy Snider, (...) a Hiroshima survivor (hibakusha) -- Mothers and Sons -- V.I.M. (Victor Israel Marquez), a Vietnam vet -- Angelina Rossi, his mother -- Guadalupe Reyes, a mother -- God's Shepherds -- Rev. Willie T. Barrow -- Father Leonard Dubi -- Rabbi Robert Marx -- Pastor Tom Kok -- Rev. Ed Townley -- The Stranger -- Rick Rundle, a city sanitation worker -- Part II -- Seeing Things -- Randy Buescher, an associate architect -- Chaz Ebert, a lawyer -- Antoinette Korotko-Hatch, a church worker -- Karen Thompson, a student -- Dimitri Mihalas, an astronomer and physicist -- A View from the Bridge -- Hank Oettinger, a retired printer -- Ira Glass, a radio journalist -- Kid Pharaoh, a retired "collector" -- Quinn Brisben, a retired teacher -- Kurt Vonnegut, a writer -- The Boomer -- Bruce Bendinger, an advertising executive and writer -- Part III -- Fathers and Sons -- Doc Watson, a folksinger -- Vernon Jarrett, a journalist -- Country Women -- Peggy Terry, a retired mountain woman -- Bessie Jones, a Georgia Sea Island Singer (1972) -- Rosalie Sorrels, a traveling folksinger -- The Plague I -- Tico Valle, a young man -- Lori Cannon, "curator" of the Open Hand Society -- Brian Matthews, an ex-bartender, writer for a gay weekly -- Jewell Jenkins, a hospital aide -- Justin Hayford, a journalist, musician -- Matta Kelly, a case manager -- The Old Guy -- Jim Hapgood -- The Plague II -- Nancy Lanoue -- Out There -- Dr. Gary Slutkin -- Day of the Dead -- Carlos Cortez, a painter and poet -- Vine Deloria, a writer and teacher -- Helen Sclair, a cemetery familiar -- The Other Son -- Steve Young, a father -- Maurine Young, a mother -- The Job -- William Herdegen, an undertaker -- Rory Moina, a hospice nurse -- The End and the Beginning -- Mamie Mobley, a mother -- Dr. Marvin Jackson, a son -- Epilogue -- Kathy Fagan and Linda Gagnon, mothers. (shrink)

Despite the concern with oppressive systems and practices there have been few attempts to analyse the general concept of oppression. Recently, Iris Marion Young has argued that it is not possible to analyse oppression as a unitary moral category. Rather, the term ‘oppression’ refers to several distinct structures, namely, exploitation, marginalisation, powerlessness, cultural imperialism, and violence. This paper rejects Young's claim and advances a general theory of oppression. Drawing insight from American chattel slavery and the situation of the German Jews (...) during the 1930's, I argue that to be oppressed is to be unjustly denied the opportunity for what I call ‘resilient autonomy’. I argue that all instances of oppression can usefully be analysed in these terms. I test my analysis against each of Young's five structures of oppression, concluding that in each case they are captured by my analysis. (shrink)

Biography of ʻAbd Allāh ibn Muḥammad ʻAyn al-Quḍāh al-Hamadhānī, d. 1131, a Muslim saint from Iran.

The attempts at introducing so called "value neutrality" into social sciences did not approve to be the sufficient means against their ideological deformations, which still are a challenge requiring a new complex system of the critique of new ideologies. A more detailed examination of the ancient philosophy could be useful in resolving this task. The works of Eric Voegelin and Leo Strauss represent a specific approach to the study of ancient philosophical systems, They both emphasize, though from different points of (...) view, the complexity in classical philosophers in their examination of human nature. The paper focuses on those doctrines of the above mentioned modern philosophers, which might be useful not only in considering not only the political crisis in the West in the 20th century, but also in creating a better means for the critical analysis of the current problems of global politics. It also introduces examples of practical consequences of modern rejecting the "classical model" and points out several simplifications occurring in contemporary approaches to classical political philosophy. (shrink)

We analyze the back-action of nonlinear atomic homodyning measurements on steady-state “macroscopic superpositions” that can be generated in high-Q microwave cavities. We show that a full characterization of the state requires measurements such that the macroscopic superposition is irreversibly destroyed, that is, it cannot be reconstructed by using the scheme that was used to generate it in the first place.

Logic; Islamic philosophy; Islam--doctrines.

First Published in 1999. Routledge is an imprint of Taylor & Francis, an informa company.

A perennial problem in the philosophy of love has centered around what it is to love persons qua persons. Plato has usually been interpreted as believing that when we love we are attaching ourselves to qualities that inhere in the objects of our love and that these qualities transcend the objects. Vlastos has argued, along with Nussbaum, Price and many others that such an account tells against a true love of persons as unique and irreplaceable individuals. I argue that Plato’s (...) account of love as present in the Lysis and Symposium is not so easily rejected. My concern is to show both that Plato can meet the objections and that his theory can still offer helpful insights into the understanding of love in our lives. In particular, I will identify two manners of loving persons; one which is context and individual specific, and another which might be termed metaphysical, thereby preserving aspects of the Platonic ascent of love. I will further argue that the two aspects are often non-controversially linked, and that such linking helps explain something of the mysterious nature of love. (shrink)