Variations in levels of apolipoprotein E have been tied to the risk and progression of Alzheimer's disease . Our group has previously compared and contrasted the promoters of the mouse and human ApoE gene promoter sequences and found notable similarities and significant differences that suggest the importance of the APOE promoter's role in the human disease. We examine here three specific single-nucleotide polymorphisms within the human APOE promoter region, specifically at -491 , -427 , and at -219 upstream from the (...) +1 transcription start site. The -219 and -491 polymorphic variations have significant association with instance of AD, and -491AA has significant risk even when stratified for the APOEepsilon4 allele. We also show significant effects on reporter gene expression in neuronal cell cultures, and, notably, these effects are modified by species origin of the cells. The -491 and -219 polymorphisms may have an interactive effect in addition to any independent activity. DNA-protein interactions differ between each polymorphic state. We propose SP1 and GATA as candidates for regulatory control of the -491 and -219 polymorphic sites. This work's significance lies in drawing connection among APOE promoter polymorphisms' associations with AD to functional promoter activity differences and specific changes in DNA-protein interactions in cell culture-based assays. Taken together, these results suggest that APOE expression levels are a risk factor for AD irrespective of APOEepsilon4 allele status. (shrink)

We apply an online optimization process based on machine learning to the production of Bose-Einstein condensates. BEC is typically created with an exponential evaporation ramp that is optimal for ergodic dynamics with two-body s-wave interactions and no other loss rates, but likely sub-optimal for real experiments. Through repeated machine-controlled scientific experimentation and observations our ’learner’ discovers an optimal evaporation ramp for BEC production. In contrast to previous work, our learner uses a Gaussian process to develop a statistical model of the (...) relationship between the parameters it controls and the quality of the BEC produced. We demonstrate that the Gaussian process machine learner is able to discover a ramp that produces high quality BECs in 10 times fewer iterations than a previously used online optimization technique. Furthermore, we show the internal model developed can be used to determine which parameters are essential in BEC creation and which are unimportant, providing insight into the optimization process of the system. (shrink)

This unique collection of essays, published together for the first time, not only elucidates the complexity of ancient Greek thought, but also reveals Karl Popper's engagement with Presocratic philosophy and the enlightenment he experienced in his reading of Parmenides. As Karl Popper himself states himself in his introduction, he was inspired to write about Presocratic philosophy for two reasons - firstly to illustrate the thesis that all history is the history of problem situations and secondly, to show the greatness of (...) the early Greek philosophers, who gave Europe its philosophy, its science and its humanism. (shrink)

This unique collection of essays not only explores the complexity of ancient Greek thought, but also reveals Popper's engagement with Presocratic philosophy and the enlightenment he experienced in reading Parmenides. It includes writings on Greek science, philosophy and history, and demonstrates Popper's lifelong fascination and admiration of the Presocratic philosophers, in particular Parmenides, Xenophanes and Heraclitus.

This unique collection of essays, published together for the first time, not only elucidates the complexity of ancient Greek thought, but also reveals Karl Popper's engagement with Presocratic philosophy and the enlightenment he experienced in his reading of Parmenides. As Karl Popper himself states himself in his introduction, he was inspired to write about Presocratic philosophy for two reasons - firstly to illustrate the thesis that all history is the history of problem situations and secondly, to show the greatness of (...) the early Greek philosophers, who gave Europe its philosophy, its science and its humanism. (shrink)

Moral reasoning traditionally distinguishes two types of evil:moral and natural. The standard view is that ME is the product of human agency and so includes phenomena such as war, torture and psychological cruelty; that NE is the product of nonhuman agency, and so includes natural disasters such as earthquakes, floods, disease and famine; and finally, that more complex cases are appropriately analysed as a combination of ME and NE. Recently, as a result of developments in autonomousagents in cyberspace, a new (...) class of interesting and importantexamples of hybrid evil has come to light. In this paper, it is called artificial evil and a case is made for considering it to complement ME and NE to produce a more adequate taxonomy. By isolating the features that have led to the appearance of AE, cyberspace is characterised as a self-contained environment that forms the essential component in any foundation of the emerging field of Computer Ethics. It is argued that this goes someway towards providing a methodological explanation of whycyberspace is central to so many of CE's concerns; and it isshown how notions of good and evil can be formulated incyberspace. Of considerable interest is how the propensity for anagent's action to be morally good or evil can be determined evenin the absence of biologically sentient participants and thusallows artificial agents not only to perpetrate evil but conversely to `receive' or `suffer from'it. The thesis defended is that the notion of entropy structure,which encapsulates human value judgement concerning cyberspace ina formal mathematical definition, is sufficient to achieve thispurpose and, moreover, that the concept of AE can be determinedformally, by mathematical methods. A consequence of this approachis that the debate on whether CE should be considered unique, andhence developed as a Macroethics, may be viewed, constructively,in an alternative manner. The case is made that whilst CE issues are not uncontroversially unique, they are sufficiently novel to render inadequate the approach of standard Macroethics such as Utilitarianism and Deontologism and hence to prompt the search for a robust ethical theory that can deal with them successfully. The name Information Ethics is proposed for that theory. Itis argued that the uniqueness of IE is justified by its beingnon-biologically biased and patient-oriented: IE is anEnvironmental Macroethics based on the concept of data entityrather than life. It follows that the novelty of CE issues suchas AE can be appreciated properly because IE provides a newperspective. In light of the discussion provided in this paper, it is concluded that Computer Ethics is worthy of independent study because it requires its own application-specific knowledge and is capable of supporting a methodological foundation, Information Ethics. (shrink)

The purpose of this brief introduction is to describe the origin of the papers here presented and to acknowledge the help of some of the many individuals who were involved in the preparation of this volume. Of the eighteen papers, nine stem from the annual fall colloquium of the Depart ment of Philosophy at the University of Western Ontario held in London, Ontario from November 10 to November 12, 1967. The colloquium was entitled 'Philosophical Logic'. After some discussion, the editors (...) decided to retain that title for this volume. Von Wright's paper 'On the Logic and Ontology of Norms' is printed here after some revision. A. R. Anderson commented on the paper at the colloquium, but his comments here are based upon the revised version of the von Wright paper. The chairman of the session at which von Wright's paper was read and discussed was T. A. Goudge. Aqvist's paper 'Scattered Topics in Interrogative Logic', and Belnap's comments, 'Aqvist's Cor rections-Accumulating Question-Sequences', are printed as delivered. The chairman of the Aqvist-Belnap session was R. E. Butts. Wilfrid Sellars' paper 'Some Problems about Belief' is printed as delivered at the col loquium, but 'Quantifiers, Beliefs, and Sellars' by Ernest Sosa is a revision of his comments at the colloquium. That session was chaired by G. D. W. Berry. Ackermann's paper 'Some Problems oflnductive Logic', as well as Skyrms' comments, are printed as delivered. (shrink)

This presentation of the main phases and features of political thought in the sixteenth century is based on an exhaustive study of contemporary writings in Latin, English, French, German and Italian. The book is divided into four parts. The first part deals with the new thought of Protestantism. The rest describes special ideas that emerged in England, France and Italy.

Biobanking of patient-derived materials is routine in health care, research, and public health emergencies. Ethical guidelines for biobanking address concerns including some about genetic materials, informed consent, confidentiality, regulatory environments, and standards of governance. This chapter identifies some limitations of existing guidelines that were apparent to one author during an Ebola outbreak, and specifies five ethical concerns about biobanking that warrant additional attention: misconceptions about biobanking, unknown consequences for donors, socioeconomic inequities that compound vulnerabilities, lasting and proportional benefits in North-South (...) research, and contextual challenges to disclosure and understanding. These affect patients, donors, health systems, research, and policy, and are amplified during public health emergencies. (shrink)

Is logic normative for reasoning? In the wake of work by Gilbert Harman and John MacFarlane, this question has been reduced to: are there any adequate bridge principles which link logical facts to normative constraints on reasoning? Hitherto, defenders of the normativity of logic have exclusively focussed on identifying adequate validity bridge principles: principles linking validity facts—facts of the form 'gamma entails phi'—to normative constraints on reasoning. This paper argues for two claims. First, for the time being at least, Harman’s (...) challenge cannot be surmounted by articulating validity bridge principles. Second, Harman’s challenge can be met by articulating invalidity bridge principles: principles linking invalidity facts of the form 'gamma does not entail phi' to normative constraints on reasoning. In doing so, I provide a novel defence of the normativity of logic. (shrink)