The present study addresses the fluid transport behaviour of the flow of gold -copper /biomagnetic blood hybrid nanofluid in an inclined irregular stenosis artery as a consequence of varying viscosity and Lorentz force. The nonlinear flow equations are transformed into dimensionless form by using nonsimilar variables. The finite-difference technique is involved in computing the nonlinear transport dimensionless equations. The significant parameters like angle parameter, the Hartmann number, changing viscosity, constant heat source, the Reynolds number, and nanoparticle volume fraction on the (...) flow field are exhibited through figures. Present results disclose that the Lorentz force strongly lessens the hybrid nanofluid velocity. Elevating the Grashof number values enhances the rate of blood flow. Growing values of the angle parameter cause to reduce the resistance impedance on the wall. Hybrid nanoparticles have a superior wall shear stress than copper nanoparticles. The heat transfer rate is amplifying at the axial direction with the growing values of nanoparticles concentration. The applied Lorentz force significantly reduces the hybrid and unitary nanofluid flow rate in the axial direction. The hybrid nanoparticles expose a supreme rate of heat transfer than the copper nanoparticles in a blood base fluid. Compared to hybrid and copper nanofluid, the blood base fluid has a lower temperature. (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)

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)

Alzheimer's disease is characterized by amyloid-beta peptide -loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 , which has been shown to be required for the regulation of APP and Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization (...) of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. (shrink)

Alzheimer's disease is characterized by plaques of amyloid-beta peptide, cleaved from amyloid-beta protein precursor . Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 , and the beta amyloid precursor (...) cleaving enzyme . In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. (shrink)

In 'Een handvol filosofen' staan de filosofen centraal die sinds de oprichting van de Vrije Universiteit in 1880 aan deze instelling verbonden zijn geweest. Het gaat hierbij niet alleen om de inhoud van hun werk, maar ook om de personen zelf. Er waren filosofiedocenten die zich met de universiteit identificeerden en zich volledig konden ontplooien. Er waren er echter ook voor wie dit niet gold, die geïsoleerd of in gewetensnood raakten. Veel filosofiestudenten waren actief betrokken bij wat er in hun (...) faculteit gebeurde. Zij namen initiatieven, protesteerden soms tegen de gang van zaken en kozen partij in conflictsituaties. Sinds het eind van de jaren zestig van de twintigste eeuw verloor de Vrije Universiteit geleidelijk haar christelijk karakter. Tegenwoordig werken alle stafleden vanuit hun eigen motivatie mee aan een hoofdzakelijk seculier geworden universiteit, die ruimte biedt voor religieuze en levensbeschouwelijke diversiteit. (shrink)

In this philosophically sophisticated and historically significant work, John H. Zammito reconstructs Kant's composition of The Critique of Judgment and reveals that it underwent three major transformations before publication. He shows that Kant not only made his "cognitive" turn, expanding the project from a "Critique of Taste" to a Critique of Judgment but he also made an "ethical" turn. This "ethical" turn was provoked by controversies in German philosophical and religious culture, in particular the writings of Johann Herder and the (...) Sturm und Drang movement in art and science, as well as the related pantheism controversy. Such topicality made the Third Critique pivotal in creating a "Kantian" movement in the 1790s, leading directly to German Idealism and Romanticism. The austerity and grandeur of Kant's philosophical writings sometimes make it hard to recognize them as the products of a historical individual situated in the particular constellation of his time and society. Here Kant emerges as a concrete historical figure struggling to preserve the achievements of cosmopolitan Aufkl-rung against challenges in natural science, religion, and politics in the late 1780s. More specifically Zammito suggests that Kant's Third Critique was animated throughout by a fierce personal rivalry with Herder and by a strong commitment to traditional Christian ideas of God and human moral freedom. "A work of extraordinary erudition. Zammito's study is both comprehensive and novel, connecting Kant's work with the aesthetic and religious controversies of the late eighteenth century. He seems to have read everything. I know of no comparable historical study of Kant's Third Critique."-Arnulf Zweig, translator and editor of Kant's ;IPhilosophical Correspondence, 1759-1799;X "An intricate, subtle, and exciting explanation of how Kant's thinking developed and adjusted to new challenges over the decade from the first edition of the Critique of Pure Reason to the appearance of the Critique of Judgment. "--John W. Burbidge, Review of Metaphysics "There has been for a long time a serious gap in English commentary on Kant's Critique of Judgment Zammito's book finally fills it. All students and scholars of Kant will want to consult it."--Frederick Beiser, Times Literary Supplement. (shrink)

Introduction: Platonic dramatology -- The political and philosophical problems. Using pre-Socratic philosophy to support political reform: the Athenian stranger ; Plato's Parmenides: Parmenides' critique of Socrates and Plato's critique of Parmenides ; Becoming Socrates ; Socrates interrogates his contemporaries about the noble and good -- Paradigms of philosophy. Socrates' positive teaching ; Timaeus-Critias: completing or challenging Socratic political philosophy? ; Socratic practice -- The trial and death of Socrates. The limits of human intelligence ; The Eleatic challenge ; The trial (...) and death of Socrates -- Conclusion: Why Plato made Socrates his hero. (shrink)

Awareness of, and respect for differences of gender, race, religion, language, and culture have liberated many oppressed groups from the hegemony of white, Western males. However, respect for previously denigrated collective identities should not be allowed to confine individuals to identities constructed around one main component used for political mobilisation, or to identities that depend on a priority of properties that are not optional, like race, gender, and language. In this article I want to sketch an approach for accommodating different (...) kinds of identity within a multicultural constitutional democracy. From a vantage point provided by a definition and explanation of personal identity, I want to show how people define, construct and change their personal identities to make themselves into unique individuals. Next I show how democratic political institutions and the personal identities of individuals reciprocally influence one another. In the final section I sketch ways in which diverse personal identities ought to be accommodated in multicultural constitutional democracies. The conclusion is that a society which gives its members the liberty, space, and opportunity to freely construct their own identities might avoid the formation of closed groups committed exclusively to their own sectional interests. (shrink)

A promise to do some action seems to create a binding obligation to do that action. And yet, paradoxically, an obligation seems not to be a fact that we can create or bring into existence; we can create an obligation only by creating or bringing into existence something else. The only way to avoid the paradox is to show that the act of promising creates something other than an obligation, which nonetheless binds us to perform the action in question. After (...) considering and rejecting various options such as the promisee's expectation and the promisor's resolve, Prichard locates the bindingness of a promise in a prior general promise, which allows the noises we make when promising to generate an obligation to perform the promised action. (shrink)

This article presents a response to Richard Rorty's paper "Is Philosophy Relevant to Business Ethics?" The author questions Rorty's views on the depreciation of the role of philosophy in applied ethics, and outlines four reasons why philosophy retains its relevance. The author addresses the role of moral reasoning in the development of the moral imagination. The author also concludes that humans have the means necessary to make moral progress and are capable of moral reasoning, and need only to develop a (...) strong moral imagination. (shrink)

I bogen "Den store humor" undersøger Harald Høffding humoren som livsanskuelse. "Den store humor" er ifølge Høffding en etisk livsholdning, som et menneske kan leve sit liv efter. Inspireret af filosoffen Søren Kierkegaards stadieteori karakteriserer Harald Høffding humoren som et etisk standpunkt, der nægter at anerkende den kristnes tragiske syn på livet. I stedet formår humoristen, at balancere livets lyse og skyggefulde sider. Humoristen lever sit liv med åbne øjne og har derfor blik for såvel verdens komik som tragik. Harald (...) Høffding (1843-1931) var teolog og filosof og virkede gennem 30 år som professor ved Københavns Universitet. I løbet af sin karriere opnåede han en central position i det danske videns- og kulturliv og nød stor anerkendelse både i og udenfor Danmark. Høffding var yderst virksom hele sit liv, og tankegodset i hans bøger er stadig relevant i dag. Udover værkerne om etik, filosofihistorie og psykologi kendes han for monografier om Søren Kierkegaard, Jean-Jacques Rousseau og Baruch Spinoza. (shrink)

This groundbreaking volume casts light on the long shadow of naturalistic monism in modern thought and culture. When monism's philosophical proposition - the unity of all matter and thought in a single, universal substance - fused with scientific empiricism and Darwinism in the mid-nineteenth century, it led to the formation of a powerful worldview articulated in the work of figures such as Ernst Haeckel. The compelling essays collected here, written by leading international scholars, investigate the articulation of monism in science, (...) philosophy, and religion and its impact on a range of social movements, from socialism and early feminism to imperialism and eugenics. The result is a broad and comprehensive chronological, disciplinary, and geographic map of a century of monism, as well as a bellwether for innovative new directions in the interdisciplinary study of science, religion, philosophy, and culture. (shrink)

Many people are worried about the harmful effects of climate change but nevertheless enjoy some activities that contribute to the emission of greenhouse gas (driving, flying, eating meat, etc.), the main cause of climate change. How should such people make choices between engaging in and refraining from enjoyable greenhouse-gas-emitting activities? In this chapter, we look at the answer provided by decision theory. Some scholars think that the right answer is given by interactive decision theory, or game theory; and moreover think (...) that since private climate decisions are instances of the prisoner’s dilemma, one rationally should engage in these activities provided that one enjoys them. Others think that the right answer is given by expected utility theory, the best-known version of individual decision theory under risk and uncertainty. In this chapter, we review these different answers, with a special focus on the latter answer and the debate it has generated. (shrink)

The article examines philosophical conceptions of responsibility found in the contributions of Martin Buber, Hans Jonas and Emmanuel Levinas. It argues that, despite the significant differences of these contributions, they all share important goals, significant structural features, and corresponding challenges. All three thinkers try to overcome the solipsistic limitations of Edmund Husserl’s phenomenology as well as the egocentrism of Heidegger’s concept of "solicitude" or "self-care." All three try to overcome the Kantian subject-object dichotomy. All three understand responsibility as a bipolar (...) relation only. In consequence, all of them face similar challenges resulting from new forms of dichotomies and the exclusion of “thirdness” that are the result of their conceptual decisions. (shrink)

Classical treatise on the fundamentals of Nyaya philosophy with commentaries; critical edition.

The introduction of novel diagnostic techniques in clinical domains such as genomics and radiology has led to a rich ethical debate on how to handle unsolicited findings that result from these innovations. Yet while unsolicited findings arise in both genomics and radiology, most of the relevant literature to date has tended to focus on only one of these domains. In this article, we synthesize and critically assess similarities and differences between “scanning the body” and “sequencing the genome” from an ethical (...) perspective. After briefly describing the novel diagnostic contexts leading to unsolicited findings, we synthesize and reflect on six core ethical issues that relate to both specialties: terminology; benefits and risks; autonomy; disclosure of unsolicited findings to children; uncertainty; and filters and routine screening. We identify ethical rationales that pertain to both fields and may contribute to more ethically sound policies. Considerations of preserving public trust and ensuring that people perceive healthcare policies as fair also support the need for a combined debate. (shrink)

This is the first sustained, whole-Bible treatment on the theme of meeting God face to face. Starting with Genesis and ending with Revelation, the author systematically covers the major events in salvation history, all of which reveal the beauty of encountering God's grace in abundance.

In this book, Phillip Wiebe examines religious, spiritual, and mystical experiences, assessing how these experiences appear to implicate a spiritual order. Despite the current prevalence of naturalism and atheism, he argues that experiences purporting to have a religious or spiritual significance deserve close empirical investigation. Wiebe surveys the broad scope of religious experience and considers different types of evidence that might give rise to a belief in phenomena such as spirits, paranormal events, God, and an afterlife. He demonstrates that there (...) are different explanations and interpretations of religious experiences, both because they are typically personal accounts, and they suggest a reality that is often unobservable. Wiebe also addresses how to evaluate evidence for theories that postulate unobservables in general, and a Theory of Spirits in particular. Calling for more rigorous investigation of these phenomena, Wiebe frames the study of religious experience among other accepted social sciences that seek to understand religion. (shrink)

The impact of digital media and technology on performance arts is evident when digital visual effects (VFX) filming techniques are introduced on a film set. Digital technologies influence the film actor’s approach to be congruent to and authentic within the circumstances of the scene. Actors require an effective skillset and strategies to successfully deliver an embodied performance aligning with the various digital VFX techniques. Focusing on imagination, action and emotion that would facilitate such an embodied performance, we drew on relevant (...) neuroscientific notions such as neuron reactivation, conceptual blending, as-if body states and affordances. Additionally, we incorporated relevant embodied performance concepts from Stanislavski, Laban/Bartenieff Movement Studies, Effector Patterns including the Emotional Body Approach and Lessac Kinesensics to the development of a digital acting programme, advancing the actor’s required skills and providing on-set digital acting strategies to support congruency with digital VFX and authenticity within the diegetic reality. The efficacy of this programme was determined by assessing pre- and post-intervention recordings of both a control and an experimental group of trained actors. Reflection-on-action journals from participants supplemented the assessment. The assessments and journals indicate that the acquired skillset and on-set digital acting strategies effectively improve the actor’s performance with digital VFX filming technology. (shrink)

Background: The factors influencing parents’ willingness to enroll their children in biobanks are poorly understood. This study sought to assess parents’ willingness to enroll their children, and their perceived benefits, concerns, and information needs under different consent and data-sharing scenarios, and to identify factors associated with willingness. Methods: This large, experimental survey of patients at the 11 eMERGE Network sites used a disproportionate stratified sampling scheme to enrich the sample with historically underrepresented groups. Participants were randomized to receive one of (...) three consent and data-sharing scenarios. Results: In total, 90,000 surveys were mailed and 13,000 individuals responded (15.8% response rate). 5737 respondents were parents of minor children. Overall, 55% (95% confidence interval 50–59%) of parents were willing to enroll their youngest minor child in a hypothetical biobank; willingness did not differ between consent and data-sharing scenarios. Lower educational attainment, higher religiosity, lower trust, worries about privacy, and attitudes about benefits, concerns, and information needs were independently associated with less willingness to allow their child to participate. Of parents who were willing to participate themselves, 25% were not willing to allow their child to participate. Being willing to participate but not willing to allow one’s child to participate was independently associated with multiple factors, including race, lower educational attainment, lower annual household income, public health care insurance, and higher religiosity. Conclusions: Fifty-five percent of parents were willing to allow their youngest minor child to participate in a hypothetical biobank. Building trust, protecting privacy, and addressing attitudes may increase enrollment and diversity in pediatric biobanks. (shrink)

It has been a decade since the phrase virtue argumentation was introduced, and while it would be an exaggeration to say that it burst onto the scene, it would be just as much of an understatement to say that it has gone unnoticed. Trying to strike the virtuous mean between the extremes of hyperbole and litotes, then, we can fairly characterize it as a way of thinking about arguments and argumentation that has steadily attracted more and more attention from argumentation (...) theorists. We hope it is neither too late for an introduction to the field nor too soon for some retrospective assessment of where things stand. (shrink)