Alzheimer's disease (AD) is the most common cause of dementia, and there is currently no cure. The “β‐amyloid cascade hypothesis” of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three‐dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including (...) β‐amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery. (shrink)
Organizations are increasingly expected by their stakeholders to tackle the “wicked” problems of society. These new pressures have created a highly equivocal corporate social responsibility (CSR) environment whereby firms face competing stakeholder perspectives regarding their CSR strategy. To reduce CSR environmental equivocality and determine a CSR strategy, organizations need to effectively and efficiently identify, evaluate, and exploit CSR initiatives to create financial and social value (i.e., shared value). In this paper, we explain how organizations can optimize their shared value creation (...) and promote the construction of intersubjective agreement, which can reduce CSR environmental equivocality. Theory is put forth that explains how the proper alignment of an organization’s level of CSR environmental equivocality, which is comprised of varying amounts of “unknowingness,” corporate entrepreneurship strategy, which promotes experimentation, and stakeholder engagement process, which facilitates information gathering and dissemination, supports the construction of intersubjective agreement. A typology of organizational shared value creation in equivocal CSR environments with four “ideal types” of organizations—Container, Explorer, Embracer, and Manager—is presented and an organization’s choice among and movement between types discussed. (shrink)
In 1986 Ephraim Fischbach, Sam Aronson, and Carrick Talmadge proposed a modification of Newton’s law of universal gravitation. This modification changed the gravitational potential from V = −Gm1m2∕r to V = [1 + αe−r∕λ] where α, the strength of the interaction, was approximately one percent and the range of the force λ was approximately 100 meters. This additional term was known as the Fifth Force. This suggestion was based on tantalizing evidence provided by a reanalysis of the Eötvös experiment, (...) an early test of the equivalence principle, a difference between the measured value of G, the gravitational constant, as determined by laboratory measurements and those performed in mineshafts, and a small energy dependence in the CP-violating parameters in K0-meson decay. The two initial measurements of the Fifth Force disagreed. One supported its existence and the other did not. How this discrepancy was resolved and the subsequent history of experiments on the Fifth Force will be discussed. By 1990 the consensus was that such a Fifth Force did not exist. Despite that judgment, work continued, and the more recent history of the Fifth Force is also discussed. The consensus remains that there is no Fifth Force. (shrink)
Neste livro Gombrich discute as idéias e as posturas específicas que tiveram influência decisiva na prática da arte renascentista. Todos os estudos aqui reunidos tratam de algo a que se pode chamar clima renascentista de opiniões sobre a arte, além da influência desse clima sobre a prática e a crítica da arte.
In this paper, I analyze George Gaylord Simpson's response to the molecularization of evolutionary biology from his unique perspective as a paleontologist. I do so by exploring his views on early attempts to reconstruct phylogenetic relationships among primates using molecular data. Particular attention is paid to Simpson's role in the evolutionary synthesis of the 1930s and 1940s, as well as his concerns about the rise of molecular biology as a powerful discipline and world-view in the 1960s. I argue that Simpson's (...) belief in the supremacy of natural selection as the primary driving force of evolution, as well as his view that biology was a historical science that seeks ultimate causes and highlights contingency, prevented him from acknowledging that the study of molecular evolution was an inherently valuable part of the life sciences. (shrink)
G.E. Moore, more than either Bertrand Russell or Ludwig Wittgenstein, was chiefly responsible for the rise of the analytic method in twentieth-century philosophy. This selection of his writings shows Moore at his very best. The classic essays are crucial to major philosophical debates that still resonate today. Amongst those included are: * A Defense of Common Sense * Certainty * Sense-Data * External and Internal Relations * Hume's Theory Explained * Is Existence a Predicate? * Proof of an External World (...) In addition, this collection also contains the key early papers in which Moore signals his break with idealism, and three important previously unpublished papers from his later work which illustrate his relationship with Wittgenstein. (shrink)