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)

This paper provides a method for characterizing space events using the framework of conceptual spaces. We focus specifically on estimating and ranking the likelihood of collisions between space objects. The objective is to design an approach for anticipatory decision support for space operators who can take preventive actions on the basis of assessments of relative risk. To make this possible our approach draws on the fusion of both hard and soft data within a single decision support framework. Contextual data is (...) also taken into account, for example data about space weather effects, by drawing on the Space Domain Ontologies, a large system of ontologies designed to support all aspects of space situational awareness. The framework is coupled with a mathematical programming scheme that frames a mathematically optimal approach for decision support, providing a quantitative basis for ranking potential for collision across multiple satellite pairs. The goal is to provide the broadest possible information foundation for critical assessments of collision likelihood. (shrink)

Offers a comprehensive nonmathematical treatment regarding the design and analysis of experiments, focusing on basic concepts rather than calculation of technical details. Much of the discussion is in terms of examples drawn from numerous fields of applications. Subjects include the justification and practical difficulties of randomization, various factors occurring in factorial experiments, selecting the size of an experiments, different purposes for which observations may be made and much more.

CHAPTER I INTRODUCTION Relevance was one of the most important concerns in the philosophy of Alfred Schutz. In a sequence of articles dealing with a number ...

Because of the coronavirus pandemic, reminders of death are particularly salient. Although much terror management theory research demonstrates that people engage in defensive tactics to manage mortality awareness, other work shows that existential concerns can motivate growth-oriented actions to improve health. The present study explored the associative link between coronavirus anxieties, fear of death, and participants' well-being. Results, using structural equation modeling, found that increased mortality concerns stemming from COVID-19 were associated with heightened benefit finding from the pandemic. Increased benefit (...) finding, in turn, was related to higher life satisfaction, meaning in life, self-esteem, resilience, and vitality while also correlating negatively with depression and stress scores. There was no evidence for reverse mediation in that fear of mortality did not predict well-being through coronavirus worries. Overall, although many persons have experienced mental health concerns as a function of the COVID-19 pandemic, our findings demonstrate positive benefits that paradoxically follow in terms of an increased appreciation of life, improved relationships, and better health. (shrink)

Computer-based logic proofs are a form of unnatural language in which the process and structure of proof generation can be observed in considerable detail. We have been studying how students respond to multimodal logic teaching, and performance measures have already indicated that students' pre-existing cognitive styles have a significant impact on teaching outcome. Furthermore, a large corpus of proofs has been gathered via automatic logging of proof development. This paper applies a series of techniques, including corpus statistical methods, to the (...) proof logs. The results indicate that students' cognitive styles influence the structure of their logical discourse, via their differing methods of handling abstract information in diagrams, and transferring information between modalities. (shrink)

The overall goal of the approach developed in this paper is to estimate the likelihood of a given kinetic kill scenario between hostile spacebased adversaries using the mathematical framework of Complex Conceptual Spaces Single Observation. Conceptual spaces are a cognitive model that provide a method for systematically and automatically mimicking human decision making. For accurate decisions to be made, the fusion of both hard and soft data into a single decision framework is required. This presents several challenges to this data (...) fusion framework. The first is the challenge involved in handling multiple complex terminologies, which is addressed by drawing on a set of Space Domain Ontologies. Another challenge is the complex combinatorics involved when considering all possible feature combinations. This can be mitigated by using integer linear programming optimization that is outlined by the Complex Conceptual Spaces Single Observation mathematical model framework. A third challenge is the complicated physics that is involved in a spacecraft collision that must be addressed to obtain a better understanding of threat assessment. Overcoming these various challenges allows for a quantitative ranking for the potential of a kinetic kill collision across multiple spacecraft pairs. In addition to overcoming these challenges this paper will break down threat assessment into four domains and identify a ranking of threat both for each individual domain and for the four domains combined. Simulation results are shown to verify the developed concepts. (shrink)

ABSTRACTPeople often use metaphors to discuss their financial prospects – for example, finding a fortune or searching for wealth. The purpose of the present research was to utilize conceptual metap...

Contour adaptation is a recently described paradigm that renders otherwise salient visual stimuli temporarily perceptually invisible. Here we investigate whether this illusion can be exploited to study visual awareness. We found that CA can induce seconds of sustained invisibility following similarly long periods of uninterrupted adaptation. Furthermore, even fragmented adaptors are capable of producing CA, with the strength of CA increasing monotonically as the adaptors encompass a greater fraction of the stimulus outline. However, different types of adaptor patterns, such as (...) distinctive shapes or illusory contours, produce equivalent levels of CA suggesting that the main determinants of CA are low-level stimulus characteristics, with minimal modulation by higher-order visual processes. Taken together, our results indicate that CA has desirable properties for studying visual awareness, including the production of prolonged periods of perceptual dissociation from stimulation as well as parametric dependencies of that dissociation on a host of stimulus parameters. (shrink)

This article seeks to explore utilitarian conceptions of personhood which for a long time have been employed as part of a rational moral justification for the termination of pregnancy. Michael Tooley's desires-based rights approach to personhood presented in his work Abortion and Infanticide is considered and, it is argued, is found wanting when one considers unconscious adults and their ability to desire life. This article will offer that unconscious sleeping individuals only have the potential to regain the capacity to value (...) their own life and, as such, under Tooley's formula for personhood, temporarily lose their status as a person. Following this, John Harris's utilitarian views on the status of the sleeping adult will be considered and deconstructed to show that, like Tooley, his ascription for personhood falls down at the sleeping adult. This article illustrates that utilitarian conceptions of personhood leave the sleeping adult human devoid of the rights of a person and hence render the value of this consquentialist theory, with regard to the idea of personhood, in severe doubt. The paper argues that utilitarian conceptions of personhood do little more than obstruct the worthy debate over the morality of abortion. (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)

Through the analysis of forty ethical dilemmas drawn from real-life situations, _Ethics in Action_ guides the reader through a process of moral deliberation that leads to the resolution of a variety of moral dilemmas. Fosters critical thinking by evaluating the reasons people give to support their choices and actions Challenges the paradigm of moral relativism that often impedes efforts to resolve moral dilemmas Incorporates international perspectives often lacking in texts published for a U.S. audience.

The rapid rise of international collaborative science has enabled access to genomic data. In this article, it is argued that to move beyond mapping genomic variation to understanding its role in complex disease aetiology and treatment will require extending data sharing for the purposes of clinical research translation and implementation.

The focus on translational research in clinical trials has the potential to generate clinically relevant genetic data that could have importance to patients. This raises challenging questions about communicating relevant genetic research results to individual patients. An exploratory pharmacogenetic analysis was conducted in the international ovarian cancer phase III trial, AGO-OVAR 16, which found that patients with clinically important germ-line BRCA1/2 mutations had improved progression-free survival prognosis. Mechanisms to communicate BRCA results were evaluated, because these findings may be beneficial to (...) patients and their families. Communicating individual BRCA results was not anticipated during clinical trial design. Consequently, options were not available for patients to indicate their preference for receiving their individual results when they signed pharmacogenetic informed consent. Differences in local requirements, clinical practice, and opinion regarding the ethical aspects of how to convey genetic results to patients are all potential barriers to returning individual BRCA results to patients. Communicating the aggregate BRCA result from this study provided clinical investigators with a mechanism to disseminate the overall study finding to patients while taking individual circumstances, local guidelines and clinical practice into account. This study illustrates the importance of increasing the clarity and scope of informed consent and the need for patient engagement to ensure clinical trial participants can indicate their preference regarding receipt of potentially important individual pharmacogenetic results. This study was registered in the NCT Clinical Trial Registry under NCT00866697 on March 19, 2009, following approval from participating ethics committees. (shrink)