Aworkshop was held August 26–28, 2015, by the Earth- Life Science Institute (ELSI) Origins Network (EON, see Appendix I) at the Tokyo Institute of Technology. This meeting gathered a diverse group of around 40 scholars researching the origins of life (OoL) from various perspectives with the intent to find common ground, identify key questions and investigations for progress, and guide EON by suggesting a roadmap of activities. Specific challenges that the attendees were encouraged to address included the following: What key (...) questions, ideas, and investigations should the OoL research community address in the near and long term? How can this community better organize itself and prioritize its efforts? What roles can particular subfields play, and what can ELSI and EON do to facilitate research progress? (See also Appendix II.) The present document is a product of that workshop; a white paper that serves as a record of the discussion that took place and a guide and stimulus to the solution of the most urgent and important issues in the study of the OoL. This paper is not intended to be comprehensive or a balanced representation of the opinions of the entire OoL research community. It is intended to present a number of important position statements that contain many aspirational goals and suggestions as to how progress can be made in understanding the OoL. The key role played in the field by current societies and recurring meetings over the past many decades is fully acknowledged, including the International Society for the Study of the Origin of Life (ISSOL) and its official journal Origins of Life and Evolution of Biospheres, as well as the International Society for Artificial Life (ISAL). (shrink)

In this review, we describe some of the central philosophical issues facing origins-of-life research and provide a targeted history of the developments that have led to the multidisciplinary field of origins-of-life studies. We outline these issues and developments to guide researchers and students from all fields. With respect to philosophy, we provide brief summaries of debates with respect to (1) definitions (or theories) of life, what life is and how research should be conducted in the absence of an accepted theory (...) of life, (2) the distinctions between synthetic, historical, and universal projects in origins-of-life studies, issues with strategies for inferring the origins of life, such as (3) the nature of the first living entities (the “bottom up” approach) and (4) how to infer the nature of the last universal common ancestor (the “top down” approach), and (5) the status of origins of life as a science. Each of these debates influences the others. Although there are clusters of researchers that agree on some answers to these issues, each of these debates is still open. With respect to history, we outline several independent paths that have led to some of the approaches now prevalent in origins-of-life studies. These include one path from early views of life through the scientific revolutions brought about by Linnaeus (von Linn.), Wöhler, Miller, and others. In this approach, new theories, tools, and evidence guide new thoughts about the nature of life and its origin.We also describe another family of paths motivated by a” circularity” approach to life, which is guided by such thinkers as Maturana & Varela, Gánti, Rosen, and others. These views echo ideas developed by Kant and Aristotle, though they do so using modern science in ways that produce exciting avenues of investigation. By exploring the history of these ideas, we can see how many of the issues that currently interest us have been guided by the contexts in which the ideas were developed. The disciplinary backgrounds of each of these scholars has influenced the questions they sought to answer, the experiments they envisioned, and the kinds of data they collected. We conclude by encouraging scientists and scholars in the humanities and social sciences to explore ways in which they can interact to provide a deeper understanding of the conceptual assumptions, structure, and history of origins-of-life research. This may be useful to help frame future research agendas and bring awareness to the multifaceted issues facing this challenging scientific question. (shrink)

In his Posterior Analytics Aristotle confronted a problem that threatened his vision of scientific knowledge as an axiomatic system: if scientific knowledge is demonstrative in character, and if the axioms of a science cannot themselves be demonstrated, then the most basic of all scientific principles will remain unknown. In the famous concluding chapter of this work (II 19), he claimed to solve this problem by distinguishing two kinds of knowledge: we cannot have epistêmê of the first principles, but we can (...) have nous of them. This ‘solution’ has struck many students of his thought as hopelessly ad hoc and unpersuasive. And nowhere is Aristotle less persuasive than when he appeals to a faculty of intuition or a priori insight which arrives on the scene precisely when it is most needed. I defend Aristotle’s account by showing how nous is not properly characterized as a faculty of intuition which operates independently of sense experience. Rather, nous is a kind of knowledge that is available to us whenever our mind advances from the perception of particular individuals to grasp the relevant universal concept or general principle. (shrink)

Increasingly open to question are the efficacies and timing of some traditional, conventional and current meditative techniques. Recent brain research emphasizes that it is important to distinguish between the Self-centred (egocentric) and other-centred (allocentric) streams of processing. It also proves useful to view as complementary the assets of the concentrative and receptive styles of meditation, especially when one's practices cultivate an appropriate balance between their top-down and bottom-up systems of attentive processing. From this neural perspective, Part I ventures a small (...) sample of empirical suggestions. Some of these could help practitioners engage in more open, effortless, choiceless, varieties of receptive meditation?indoors and outdoors. Part II discusses recent research that illuminates issues arising at the interface between Self and other. The evidence suggests how a balanced attentiveness might enable long-term meditators to enhance mindfulness of the present moment, while simultaneously becoming much less fearful and, ultimately, freer to openly express their most objective, innate instincts of selfless compassion. The art of Progress is to preserve order amid change and to preserve change amid order. (Alfred North Whitehead 1861?1947). (shrink)

Putnam and others have argued that an examination of structures arising in quantum mechanics can lead to a non-classical propositional logic, quantum logic. In this paper it is argued that the procedure by which quantum logic is said to be discovered, a process called reading off, is fundamentally flawed. A parody fable shows that reading off leads to absurd consequences. The fable also leads one to cast doubt on the following claims central to the quantum logic program: (i) logic can (...) be reformed locally; (ii) classical logic is read off classical physics; and (iii) reading off is a justifiable process because quantum logic resolves quantum paradoxes. (shrink)

Part I of the present work outlined the rigorous application of information theory to a quantum mechanical system in a thermodynamic equilibrium state. The general formula developed there for the best-guess density operator $\hat \rho$ was indeterminate because it involved in an essential way an unspecified prior probability distribution over the continuumD H of strong equilibrium density operators. In Part II mathematical evaluation of $\hat \rho$ is completed after an epistemological analysis which leads first to the discretization ofD H and (...) then to the adoption of a suitable indifference axiom to delimit the set of admissible prior distributions. Finally, quantal formulas for information-theoretic and thermodynamic entropies are contrasted, and the entire work is summarized. (shrink)

Machine generated contents note: 1. Introducing persons and the psychology of personhood Jack Martin and Mark H. Bickhard; Part I. Philosophical, Conceptual Perspectives: 2. The person concept and the ontology of persons Michael A. Tissaw; 3. Achieving personhood: the perspective of hermeneutic phenomenology Charles Guignon; Part II. Historical Perspectives: 4. Historical psychology of persons: categories and practice Kurt Danziger; 5. Persons and historical ontology Jeff Sugarman; 6. Critical personalism: on its tenets, its historical obscurity, and its future prospects James (...) T. Lamiell; Part III. Social-Developmental Perspectives: 7. Conceiving of self and others as persons: evolution and development John Barresi, Chris Moore and Raymond Martin; 8. Position exchange theory and personhood: moving between positions and perspectives within physical, sociocultural and psychological space and time Jack Martin and Alex Gillespie; 9. The emergent ontology of persons Mark H. Bickhard; 10. Theorising personhood for the world in transition and change: reflections from a transformative activist stance on human development Anna Stetsenko; Part IV. Narrative Perspectives: 11. Identity and narrative as root metaphors of personhood Amia Lieblich and Ruthellen Josselson; 12. Storied persons: the double triad of narrative identity Mark Freeman. (shrink)

Previous studies have shown that zinc deficiency leads to apoptosis of neuronal precursor cells in vivo and in vitro. In addition to the role of p53 as a nuclear transcription factor in zinc deficient cultured human neuronal precursors (NT-2), we have now identified the translocation of phosphorylated p53 to the mitochondria and p53-dependent increases in the pro-apoptotic mitochondrial protein BAX leading to a loss of mitochondrial membrane potential as demonstrated by a 25% decrease in JC-1 red:green fluorescence ratio. Disruption of (...) mitochondrial membrane integrity was accompanied by efflux of the apoptosis inducing factor (AIF) from the mitochondria and translocation to the nucleus with a significant increase in reactive oxygen species (ROS) after 24 h of zinc deficiency. Measurement of caspase cleavage, mRNA, and treatment with caspase inhibitors revealed the involvement of caspases 2, 3, 6, and 7 in zinc deficiency-mediated apoptosis. Down-stream targets of caspase activation, including the nuclear structure protein lamin and polyADP ribose polymerase (PARP), which participates in DNA repair, were also cleaved. Transfection with a dominant-negative p53 construct and use of the p53 inhibitor, pifithrin- ␮, established that these alterations were largely dependent on p53. Together these data identify a cascade of events involving mitochondrial p53 as well as p53-dependent caspase-mediated mechanisms leading to apoptosis during zinc deficiency. (shrink)

The contributions to the Special Issue on Multiple Belief Change, Iterated Belief Change and Preference Aggregation are divided into three parts. Four contributions are grouped under the heading "multiple belief change" (Part I, with authors M. Falappa, E. Fermé, G. Kern-Isberner, P. Peppas, M. Reis, and G. Simari), five contributions under the heading "iterated belief change" (Part II, with authors G. Bonanno, S.O. Hansson, A. Nayak, M. Orgun, R. Ramachandran, H. Rott, and E. Weydert). These papers do not only pick (...) up the particular questions raised, but also extend and modify the framework of Alchourrón, Gärdenfors and Makinson. Part III deals with preference aggregation and consists of one contribution (by F. Herzberg and D. Eckert). (shrink)

This is a well-written analysis of the interpreters and interpretations of the Buddhist nirvana from the West. The first chapter treats the West's encounters with Buddhism before 1800, Marco Polo, etc. The remainder of the book deals with the interpretations of nirvana by Eugène Burnouf, Friedrich Max Müller, James D'Alwis, Robert Caesar Childres, Schopenhauer, Wagner, Nietzsche, Hermann Oldenberg, the Rhys Davidses, La Vallée Poussin, and Stcherbatsky. The author's own opinion is given in a few pages at the end of (...) the book; however, his opinion is not so much an exposition of nirvana but a short essay on the methodology of a study of nirvana. He quotes Richard Robinson to bring home his point that this long array of scholars could not forsake their cultural bias and that one needs therefore to approach non-Western ideas from the inside of a non-Western culture. Welbon's intention is to present an outline of the history of Western discussions on the meaning of the Buddhist nirvana. His research is thorough; his presentation is clear; this is a chronicle of heroic but club-footed attempts to learn about a non-Western idea. The book should be read by all aspiring Buddhologists, for it will convince them of the absolute necessity of learning the language of a Buddhist culture and of searching out qualified native informants. Its value for non-Buddhologists is not to learn more about nirvana but to learn the history of this burgeoning study. Welbon has admirably succeeded in his aim; he has concisely presented Western opinion on nirvana up to World War II.--P. J. H. (shrink)

"With a strong interdisciplinary approach to a subject that does not lend itself easily to the reference format, this work may not seem to support directly academic programs beyond general research, but it is a more thorough and up-to-date ...

Professor H. James Birx shows how the never-ending controversy of human evolution came to be. He details the events that caused thinkers like Charles Darwin to develop his theory of evolution, and what ideas caused some people to reconcile a somewhat mystical theology with a concrete model of the universe. He tells you how Darwin's work infuriated everybody from "God-fearing" Christians to the church heirarchies. Birx explains how scientific advances and philosophical arguments have made beliefs about divine intervention as (...) the origin of man a moot point. He shows how creationism ignores proven scientific facts, and how human evolution remains a much sounder truth. You'll read how some western religions are starting to accept evolution as the process which creates life on earth. You'll also learn why scientific evolution and creationism have not been accepted together and how bold attempts to merge the two ideas have failed miserably. (shrink)

Alzheimer's disease is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-beta peptide . The rate-limiting step in the production of Abeta is the processing of Abeta precursor protein by beta-site APP-cleaving enzyme . Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Abeta within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 was (...) suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of beta-galactoside alpha-2,6-sialyltransferase I . In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future. (shrink)