Using mouse models to explore genotype-phenotype relationship in Down syndrome

Down Syndrome (DS) caused by trisomy 21 is characterized by a variety of phenotypes and involves multiple organs. Sequencing of human chromosome 21 (HSA21) and subsequently of its orthologues on mouse chromosome 16 have created an unprecedented opportunity to explore the complex relationship between various DS phenotypes and the extra copy of approximately 300 genes on HSA21. Advances in genetics together with the ability to generate genetically well-defined mouse models have been instrumental in understanding the relationships between genotype and phenotype in DS. Indeed, elucidation of these relationships will play an important role in understanding the pathophysiological basis of this disorder and helping to develop therapeutic interventions. A successful example of using such a strategy is our recent studies exploring the relationship between failed nerve growth factor (NGF) transport and amyloid precursor protein (App) overexpression. We found that increased dosage of the gene for App is linked to failed NGF signaling and cholinergic neurodegeneration in a mouse model of DS. Herein, we discuss several mouse models of DS and explore the emergence of exciting new insights into genotype-phenotype relationships, particularly those related to nervous system abnormalities. An important conclusion is that uncovering these relationships is enhanced by working from carefully defined phenotypes to the genes responsible.     

Four dimensions of self-defining memories (specificity, meaning, content, and affect) and their relationships to self-restraint, distress, and repressive defensiveness

This study examines four dimensions of self-defining memory (specificity, meaning, content, and affect) and their relationship to self-restraint, distress, and defensiveness. The development and validation of a protocol for measuring specificity, meaning, and affect in self-defining memories is discussed. Specificity is operationalized as the temporal and detailed specificity of the narrative. Meaning refers to the participant's stepping back from the narrative to derive higher personal meaning or a life lesson. Affect reflects subjective emotion upon recall. Agreement between two raters scoring 1040 memories was kappa=.83 for specificity and kappa=.72 for meaning. The protocol is compatible with Thorne and McLean's scoring system for content (the types of events in memories). The current study compared individual differences in the four dimensions of 10 self-defining memories collected from 103 undergraduates to scores of self-restraint, distress, and repressive defensiveness, as measured by the Weinberger Adjustment Inventory. Memory specificity was inversely related to repressive defensiveness, while greater memory meaning was linked to moderate and high levels of self-restraint. Memory content and affect predicted individuals' degree of subjective distress. Based on these findings, the authors discuss the place of self-defining memories in Conway and Pleydell-Pearce's Self-Memory System model of autobiographical memory and personality, more generally.     

On interchangeability of Nash equilibria in multi-player strategic games

The article studies properties of interchangeability of pure, mixed, strict, and strict mixed Nash equilibria. The main result is a sound and complete axiomatic system that describes properties of interchangeability in all four settings. It has been previously shown that the same axiomatic system also describes properties of independence in probability theory, nondeducibility in information flow, and non-interference in concurrency theory.     

Independence in Information Spaces

Three different types of interdependence between pieces of information, or ??secrets??, are discussed and compared. Two of them, functional dependence and nondeducibility, have been studied and axiomatized before. This article introduces a third type of interdependence and provides a complete and decidable axiomatization of this new relation.     

Making history philosophical: Kant,Maimon, and the evolution of the historiography of philosophy in the critical period

ABSTRACT

In this article I explore Maimon’s role in the evolution of Kant’s understanding of the function of the history of philosophy in philosophical enquiry. Kant is often viewed as holding an ambivalent relation to the history of philosophy. On the one hand, he dismisses past philosophers as victims of transcendental illusion and downplays the value of the historiography of philosophy. On the other hand, by framing his project as a synthesis of several philosophical traditions, Kant embeds the critical philosophy into a sweeping historical narrative in a manner that highlights the importance of the past for present philosophical aims. In this article, I argue that for most of his career Kant held a position reflective of the former view, but that the publication of Maimon’s response to a prize question announced by the Royal Academy led Kant to develop an understanding of the history of philosophy more in line with the latter view. The result is a distinctively post-Kantian model for a ‘philosophical history of philosophy’ that is both methodologically nuanced and potentially relevant to contemporary debates.