Oxidative damage to DNA has been associated with neurodegenerative diseases. Developmental exposure to lead has been shown to elevate the Alzheimer's disease related beta-amyloid peptide , which is known to generate reactive oxygen species in the aging brain. This study measures the lifetime cerebral 8-hydroxy-2'-deoxyguanosine levels and the activity of the DNA repair enzyme 8-oxoguanine DNA glycosylase in rats developmentally exposed to Pb. Oxo8dG was transiently modulated early in life , but was later elevated 20 months after exposure to Pb (...) had ceased, while Ogg1 activity was not altered. Furthermore, an age-dependent loss in the inverse correlation between Ogg1 activity and oxo8dG accumulation was observed. The effect of Pb on oxo8dG levels did not occur if animals were exposed to Pb in old age. These increases in DNA damage occurred in the absence of any Pb-induced changes in copper/zinc-superoxide dismutase , manganese-SOD , and reduced-form glutathion . These data suggest that oxidative damage and neurodegeneration in the aging brain could be impacted by the developmental disturbances. (shrink)

Achieving space situational awareness requires, at a minimum, the identification, characterization, and tracking of space objects. Leveraging the resultant space object data for purposes such as hostile threat assessment, object identification, and conjunction assessment presents major challenges. This is in part because in characterizing space objects we reference a variety of identifiers, components, subsystems, capabilities, vulnerabilities, origins, missions, orbital elements, patterns of life, operational processes, operational statuses, and so forth, which tend to be defined in highly heterogeneous and sometimes inconsistent (...) ways. The Space Domain Ontologies are designed to provide a consensus-based realist framework for formulating such characterizations in a way that is both consistent and computable. Space object data are aligned with classes and relations in a suite of ontologies built around the existing Space Object Ontology. They are stored in a dynamically updated Resource Description Framework triple store, which can be queried to support space situational awareness and the needs of spacecraft operators and analysts. This paper provides an overview of the Space Domain Ontologies and their development and use. It presents the motivation for and advantages of the Space Domain Ontologies, including the benefits they provide for enhancing and maintaining long-term space situational awareness. (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)

Neuroscientists are searching for the engram within the conceptual framework established by John Locke's theory of mind. This framework was elaborated before the development of information theory, before the development of information processing machines and the science of computation, before the discovery that molecules carry hereditary information, before the discovery of the codon code and the molecular machinery for editing the messages written in this code and translating it into transcription factors that mark abstract features of organic structure such as (...) anterior and distal. The search for the engram needs to abandon Locke's conceptual framework and work within a framework informed by these developments. The engram is the medium by which information extracted from past experience is transmitted to the computations that inform future behavior. The information-conveying symbols in the engram are rapidly generated in the course of computations, which implies that they are molecules. (shrink)

Professor Austin explores four main areas in this paper. First of all he outlines the physical development of sex differentiation in the embryo. He develops this by describing the clinical manifestations of abnormality which can appear at that stage. Professor Austin points out that there are relatively few people with abnormalities and that those who do show homosexual tendencies are not noticeably different from the norm in terms of their sexual equipment and hormone levels. It is much more likely that (...) their psychological and social development has a greater influence in differentiating them sexually. The last section of the paper is a synopsis of society's reactions to homosexuality or bisexuality which term in Professor Austin's opinion is more accurate and descriptive of the condition. (shrink)

Recent reports published by the United Nations and the World Health Organization suggest that the brain drain of healthcare professionals from the developing to the developed world is decimating the provision of healthcare in poor countries. The migration of these key workers is driven by a combination of economic inequalities and the recruitment policies of governments in the rich world. This article assesses the impact of the healthcare brain drain and argues that wealthy countries have a moral obligation to reduce (...) the flow of healthcare workers from the developing to the developed world. (shrink)

This paper, which gives continuity to another article, analyzes the content of I Dialogus V, 14-22 and, in an appendix, presents our Portuguese translation of this excerpt. In these chapters, the Inceptor Venerabilis discusses whether St. Peter and the Roman Church possess primacy over all other apostles and churches; andwhether this primacy is granted by God himself. Ockham first presents, not ad litteram, the opinion of those who refute the thesis that Christ did not give primacy to Peter and the (...) Roman Church. Then, because this thesis fully deflates papal power, he proposes a contrary thesis based on five proofs. We conclude that Ockham’s unnamed opponent is Marsilius of Padua, whose opinions are in his Defensor Pacis. (shrink)

Recent research on the relations of personality to well-being shows that the people who are most healthy, happy and fulfilled are those who are high in all three of the character traits of self-directedness, cooperativeness, and self-transcendence as measured by the Temperament and Character Inventory. In the past, the healthy personality has often been considered to require only high self-directedness and high cooperativeness. However, now the self-centred behaviour of people who are low in self-transcendence is degrading the conditions needed for (...) sustainable life by all human beings. Consequently, human beings need to and can develop their capacity for self-transcendence in order to maintain their individual and collective well-being. (shrink)

The title may be understood in three ways. Firstly, the truth under study is the truth about freedom. We speak of the truth of something, in as much as we presume that there are many misconceptions about that something, and it stands in need of clarification. Thus, the many misconceptions about freedom will have to be divested, if freedom is to be rightly grasped. Secondly, in the sense that there is a truth in the core of freedom, indeed, truth is (...) the essence of freedom. If truth is to be rightly grasped, its core has to be penetrated. Thirdly, there is a deeper relation between truth and freedom. Freedom cannot be understood, much less rightly practised, if we do not comprehend the necessary relation that freedom bears to truth. This essay purports to study all three senses, not quite generally, but with special reference to Ratzinger, the German theologian-cum-phenomenologist of religion, who also happens to be the current pope Benedict XVI of the Catholic Christianity. The study proceeds in three stages. First of all, I will give the statement of the problem. Secondly, I will briefly dwell on the modern Western history of freedom. Thirdly, I will study the interface between freedom and truth, highlighting the nature of human freedom, the relation between freedom and responsibility, and the relation between freedom and the truth of human existence itself. The essay is more interpretive than evaluative, with an eye to be as close to the insightful thoughts of Ratzinger as possible. (shrink)