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)

In lieu of an abstract, here is a brief excerpt of the content:Phenomenology and Modern Behavioral PsychologyLindsay B. Fletcher (bio) and Steven C. Hayes (bio)Keywordsacceptance, contextualism, defusion, relational-frame-theoryPérez-Álvarez and Sass (2008) deserve praise for examining the philosophical roots of clinical psychological science. Modern psychology has moved away from the development of philosophy and theory that is needed to ground scientific investigation within a coherent system. The result is increasingly ill-defined constructs and research programs that each operate within their own divergent (...) paradigm. B.F. Skinner is one of the few modern experimental behavioral psychologists who attempted to build a coherent science of behavior based on observable events with testable hypotheses. Acceptance and Commitment Therapy (ACT; Hayes, Strosahl, and Wilson 1999) and its associated basic science of cognition, Relational Frame Theory (RFT; Hayes, Barnes-Holmes, and Roche 2001), build on Skinner’s work to produce a more progressive science.Psychology and philosophy are different disciplines and how they are approached is defined by the objective. The purpose of philosophy from a scientific point of view is not the same as from a philosophical point of view. It is fine to compare radical behaviorism and phenomenology, but it seems important to ask whether and how this will lead to a more progressive science of behavior.In this commentary, we discuss the philosophy and theory that underlie ACT/RFT and show how they reflect on the relevant points made by the authors regarding the shared features of phenomenology and radical behaviorism. We make two adjustments to the explanation of radical behavioral concepts presented in the current paper to create a more coherent analysis. Finally, we show here how the development of a theory based on applied goals directly informs the methods used in clinical settings.Philosophical AssumptionsThe field of behavior analysis that originated with Skinner has different strands. Some are holistic and pragmatic, whereas others are elementalistic and mechanistic (Hayes, Hayes, and Reese 1988). ACT is based on an a-ontological philosophy termed functional contextualism (Hayes 1993), which views behavior analysis from a holistic and pragmatic perspective. Functional contextualism (AKA radical behaviorism) shares some of the assumptions of phenomenology, as has long been noted (Day 1969). For example, Pérez-Álvarez and Sass (2008) identify a-dualism, or monism, as a common feature. In functional contextualism, the whole is divided into functional units for the purpose of prediction and influence. A three-term contingency (antecedent–behavior–consequence) in behavior analysis is viewed as a [End Page 255] whole event with pragmatically distinguishable aspects, not an assemblage. As the authors point out, this results in a dialectic tension between stimulus control, action, and reinforcer because none are distinct units, and each is defined with reference to the others much as the front of a coin cannot exist without the back. These are not ontological entities, but functional units that are abstracted from the whole for pragmatic purposes. What is “radical” about radical behaviorism is that the philosopher, psychologist, or researcher participates in the event they are observing, and their own acts of scientific observation are identified based on their own functional properties.Behavioral ThinkingIn the service of further developing this philosophical and theoretical foundation and considering it along side phenomenology, we need to examine two aspects of the target article. The first regards the role of the environment in shaping behavior that is central to behavioral and contextual theories. The authors object to behaviorism’s notion of environment and suggest replacing it with the concept of the world, stating that “animals have environment, but man has world.” What is missing is an account of that shift. We believe that modern behavior analysis provides that account.Similarly, the paper argues that “reinforcers are not just things that follow behavior, but also, and above all, values that guide our life.” Again what is missing is an account of the precise behavioral basis for the distinction.In an attempt to do this, the authors incorrectly analyze operant behavior as future oriented, even appealing to final causality. In the three-term contingency, the discriminative stimulus sets the occasion for reinforcement of a particular behavior. The behavior of interest has been reinforced in similar contexts in the past, which gives... (shrink)

Среди выдающихся латиноамериканских философов, которые так или иначе занимаются аксиологическими nроблемами, находится месиканец Эдуардo Гарсия Майнез. По мнению Майнеза, каnитальные проблемы аксиологии могут быть сведены к четырем: а) проблема существования ценности; б) nроблема оценочного nознания; в) проблема реализации ценности; д) проблема свободы выбора личностью ценности. В данной работе анализируется в основном те идеи этого автора, которые касаются nервой из этих больших nроблем - вопроса о существовании ценностей. Entre los más destacados filósofos mexicanos que trabajan la problemática axiológica se encuentra el (...) mexicano Eduardo García Maynez. En opinión de Maynez los problemas capitales de la axiología son cuatro: a) el problema de la existencia del valor; b) el problema del conocimiento valorativo; c) el problema de la realización del valor; d) el problema de la libertad del hombre en la elección del valor. En este trabajo se analiza, en los fundamental, las ideas de este autor referidas al primero de estos grandes problemas: el tema de la existencia de los valores. (shrink)

The aim of this paper is to review the controversy concerning the nature of nonconceptual content, and its philosophical implications. I will focus the presentation on three topics: (a) the different motivations behind the postulation of nonconceptual content, (b) the arguments for nonconceptual content, and (c) the different characterizations offered of nonconceptual content (and the problem these definitions pose). In the last section of the paper I will mention the presuppositions behind this notion and analyze a couple of paradoxical theses (...) that emerged from this discussion. (shrink)

This study sets out the main points in Leonardo Polo’s theory of moral development, which systematically articulates goods, norms, and virtues. To make them easier to understand, each point has been compared with Kohlberg’s theory of moral development, which is well known to specialists and radically different to it. We have chosen three aspects of Kohlberg’s theory of moral development to highlight the uniqueness of Polo’s theory: a) Kohlberg does not account for the specificity of voluntary acts, particularly the act (...) of deciding; b) The options that solve Kohlberg’s dilemmas are isolated from potential prior and subsequent decisions, so his moral development ignores any internal biographical storyline to the decisions themselves; and c) The Kohlbergian morality is an ethics of justice and duty, thereby relegating the friendship, which to Polo is the culmination of ethics, to a morally irrelevant level. (shrink)

Frente a la imagen de un Vico ajeno a las exigencias del rigor metódico, este trabajo se propone plantear: a) Que la preocupación por el problema del método es una constante en el pesamiento de Vico. b) Que su aportación debe considerarse especialmente relevante en lo que atañe a los actuales empeños rehabilitadores de la racionalidad práctica y, en particular, para las más recientes teorias de la argumentación jurídica. c) Que, no obstante lo anterior, la actitud metódico jurídica de Vico (...) no puede ser calificada de meramente "retórica", más bien, entraña un intento de proyectar principios de justificación racional a los tópicos argumentativos del Derecho; o a propiciar un esfuerzo integrador de los topoi retóricos de las controversias jurídicas con las exigencias justificatorias de la razón práctica. Para explicitar este enfoque se procederá a abordar, por aproximación sucesiva, tres cuestiones: 1ª) Los aspectos básicos del actual debate sobre la racionalidad juridica y la teoría de la argumentación en el Derecho. 2ª) La apelación a Vico como punto de partida del nuevo interés por la revalorización de la tópica jurídica. 3ª) El significado de la argumentación en el "interior" de la reflexión metódica viquiana y en sus proyecciones "externas" al presente. (shrink)

Frente a la imagen de un Vico ajeno a las exigencias del rigor metódico, este trabajo se propone plantear: a) Que la preocupación por el problema del método es una constante en el pesamiento de Vico. b) Que su aportación debe considerarse especialmente relevante en lo que atañe a los actuales empeños rehabilitadores de la racionalidad práctica y, en particular, para las más recientes teorias de la argumentación jurídica. c) Que, no obstante lo anterior, la actitud metódico jurídica de Vico (...) no puede ser calificada de meramente "retórica", más bien, entraña un intento de proyectar principios de justificación racional a los tópicos argumentativos del Derecho; o a propiciar un esfuerzo integrador de los topoi retóricos de las controversias jurídicas con las exigencias justificatorias de la razón práctica. Para explicitar este enfoque se procederá a abordar, por aproximación sucesiva, tres cuestiones: 1ª) Los aspectos básicos del actual debate sobre la racionalidad juridica y la teoría de la argumentación en el Derecho. 2ª) La apelación a Vico como punto de partida del nuevo interés por la revalorización de la tópica jurídica. 3ª) El significado de la argumentación en el "interior" de la reflexión metódica viquiana y en sus proyecciones "externas" al presente.Contrarily to the images purporting Vico as a thinker who paid little attention to methodological rigor, this paper aims to show: a) that there is a through concern along the Vichian thought with problems related with methodology; b) that Vico’s philosophical contributions should be acknowledged particularly relevant in those subjects connected both with practical rationality and recent theories about legal reasonings; c) that Vico’s methodological and legal approach can, nonetheless, hardly be labelled merely as "rhetoric", rather it entails a serious attempt to cast rational justifying pnnciples onto the topic related with legal reasonings. In order to accomplish the above claims, three related questions should be addressed: 1) the basic elements underlying the recent discussion on legal rationality and theories about patterns of reasonings in law; 2) the claim that Vico is to be regarded as a starting point in the new assessment of legal topic; 3) the meaning of the arguments inside the limits of the Vichian methodological reflections and the extemal connections they still keep with contemporary discussions. (shrink)

Williamson defiende la regla del conocimiento, RK, sobre las aseveraciones: debemos aseverar que p sólo si sabemos que p. En este trabajo exploro algunas consecuencias interesantes de RK: (a) en ocasiones, al hacer una aseveración correcta transmitimos (como implicatura) un significado no literal verdadero, que \sin embargo\ no podría ser correctamente aseverado; (b) ese tipo de implicatura se da, entre otros casos, en una cierta subclase de las implicaturas: las implicaturas argumentativas; (c) RK y la noción de implicatura argumentativa permiten (...) explicar la tendencia a tratar de forma equivalente diferentes tipos de argumentos antiescépticos inspirados en Moore.Williamson defends the knowledge rule, KR, about assertions: one must: assert p only if one knows p. In this work I explore some interesting consequences of KR: (a) sometimes, when making a correct assertion we transmit (as an implicature) a true non-literal meaning which \nevertheless\ could not be rightly asserted; (b) this kind of implicatures are present, for instance, in a certain subclass of implicatures: argumentative implicatures; (c) KR and the notion of argumentative implicature allow for an explanation of the tendency to treat different kinds of Moore-like antiskeptical arguments as if they were equivalent. (shrink)

Originally motivated by a sophism, Pardo's discussion about the unity of mental propositions allows him to elaborate on his ideas about the nature of propositions. His option for a non-composite character of mental propositions is grounded in an original view about syncategorems: propositions have a syncategorematic signification, which allows them to signify aliquid aliqualiter, just by virtue of the mental copula, without the need of any added categorematic element. Pardo's general claim about the simplicity of mental propositions is developed into (...) several specific thesis about mental propositions: a) it is not judgement which gives its unity to mental propositions, but judicative acts always follow some previous apprehensive act that is simple in its own right; b) this simplicity is compatible with a certain kind of complexity, that can be explained in terms of the "causal history" of the acts of knowing; c) traditional conceptions about subject and predicate must be recast, while keeping their usual explicative power concerning logical properties; d) of course, the traditional conception about the copula has been modified, giving rise to a fully innovative conception of the nature of mental propositions. Nevertheless, this innovative conception of mental language seems still infected by certain "common sense" prejudices, which lead Pardo to propose also a provocative conception of vocal language, which I consider unnecessary. (shrink)

El presente trabajo reflexiona críticamente en torno a la inclusión educativa sobre la base de: a) la labor investigativa desarrollada acerca del derecho a la educación a partir de narrativas de jóvenes con discapacidad en la educación superior, como también de b) diferentes encuentros con estudiantes y docentes de distintos niveles educativos y c) las actividades desarrolladas en el marco de distintas redes en las que confluyen el activismo y el campo académic. Presenta los temas de modo espiralado, es decir, (...) con la intención de desarrollar reflexiones que permitan avanzar en un posicionamiento crítico-activo, pero volviendo permanentemente sobre algunos nudos centrales que tensan el devenir de la inclusión educativa y la discapacidad: la ideología de la normalidad, la lógica binaria, el capacitismo, la colonialidad, los procesos de identificación y la necesidad de promover un giro epistémico para el trabajo institucional cotidiano, tanto en el terreno macro como micropolítico. Se destacan tanto las responsabilidades ineludibles del Estado y de sus sistemas educativos como también de todas las partes que los conformamos. (shrink)

El presente trabajo describe los diferentes significados que la forma ychakat, en sus diversas combinatorias, tiene en la obra de Valdivia (1607) sobre la lengua allentiac. Más específicamente, se propone que esta forma puede: a) ocurrir postpuesta a (pro)nombres con significados intensificador y reflexivo; b) antepuesta a verbos con un significado reflexivo y c) sufijada a verbos con significados reflexivo y pasivo. A partir de la identificación de dichos significados, se propone una reconstrucción de dos procesos diacrónicos experimentado por esta (...) forma, examinando para dicha propuesta los diferentes caminos que se han propuesto en perspectiva tipológica sobre el tema. Finalmente, se propone que es posible que la tendencia de cambios hacia la sufijación tenga que ver con el contacto con otras lenguas del área andina; sin embargo, el camino semántico seguido es exclusivo del allentiac y no se comparte con otras lenguas del área, por lo que es probable que sea un cambio de naturaleza interna. (shrink)

What are the most fundamental features of the world? Do minds stand outside the natural order? Is a unified picture of mental and physical reality possible? The Mind in Nature provides a staunchly realist account of the world as a unified system incorporating both the mental and the physical.

Background:The first wave of the COVID-19 pandemic caused a shortage of qualified nurses in Spain. As a result, the government authorized the hiring of senior students.Objectives:To explore the ethical dilemmas and ethical conflicts experienced by final-year nursing students who worked during the first outbreak of the COVID-19 pandemic in Spain.Research design:A qualitative exploratory study was conducted using purposive sampling. Semi-structured interviews were carried out using a question guide. Interviews took place via a private video chat room platform. A thematic, inductive (...) analysis was performed of the information gathered.Participants and research context:Eighteen nursing students were recruited from two universities of Madrid, aged between 18 and 65 years old, enrolled in the fourth year of nursing studies and who were hired under a relief contract for health professionals during the pandemic.Ethical considerations:The present study was carried out in accordance with the Declaration of Helsinki, and the study was approved by the Local Ethics Committee of Universidad Rey Juan Carlos.Results:Three specific themes emerged: (a) coping with patient triage, (b) difficulties in providing end-of-life care, and (c) coping with patient death. Nursing students participated in the process of patient selection for resource allocation and ICU bed occupancy. They were shown how to care for patients who were not admitted to the ICU, in their last moments and were faced with the difficulties of applying end-of-life care. Finally, the nursing students were confronted with the death of their patients, in overwhelming numbers and under adverse conditions.Conclusions:These findings can help shed light on the ethical dilemmas and ethical conflicts faced by novice nursing students, incorporated into the workforce during the COVID-19 pandemic. Moreover, it was described that students may normalize the death due to the exhaustion and overwhelmed routine. (shrink)

The development of a compositional model shows the incoherence of such notions as levels of being and both bottom-up and top-down causality. The mathematization of nature through the partial considerations of physics qua quantities is seen to lead to Pythagoreanism, if what is not included in the partial consideration is denied. An ontology of only probabilities, if not Pythagoreanism, is equivalent to a world of primitive dispositionalities. Problems are found with each. There is a need for properties as well as (...) quantities and these properties must be qualitative as well as dispositional. So there is a need for physical qualia (qualities) for the depiction of the intrinsic character of the finest interstices of nature. (shrink)

Current views of the control of complex, purposeful movements acknowledge that organizational processes must reconcile multiple concerns. The central priority is of course accomplishing the actor's goal. But in specifying the manner in which this occurs, the action plan must accommodate such factors as the interaction of mechanical forces associated with the motion of a multilinked system (classical mechanics) and, in many cases, intrinsic bias toward preferred movement patterns, characterized by so-called “coordination dynamics.” The most familiar example of the latter (...) is the symmetry constraint, where spatial trajectories and/or temporal landmarks (e.g., reversal points) of concurrentlymoving body segments (limbs, digits, etc.) exhibit mutual attraction. The natural coordination tendencies that emerge through these constraints can facilitate or hinder motor control, depending on the degree of congruency with the desired movement pattern. Motor control theorists have long recognized the role of classical mechanics in theories of movement organization, but an appreciation of the importance of intrinsic interlimb bias has been gained only recently.Although detailed descriptions of temporal coordination dynamics have been provided, systematic attempts to identify additional salient dimensions of interlimb constraint have been lacking. We develop and implement here a novel method for examining this problem by exploiting two robust principles of psychomotor behavior, the symmetry constraint and the Two-Thirds Power Law. Empirical evidence is provided that the relative spatial patterns of concurrently moving limbs are naturally constrained in much the same manner as previously identified temporal constraints and, further, that apparent velocity interference is an indirect, secondary consequence of primary spatial assimilation. The theoretical implications of spatial interference are elaborated with respect to movement organization and motor learning. The need to carefully consider the appropriate dimensions with which to characterize coordination dynamics is also discussed. (shrink)

IT IS SHOWN IN DETAIL THAT RECENT ACCOUNTS FAIL TO DISTINGUISH BETWEEN INTENTIONALITY AND MERELY CAUSALLY DISPOSITIONAL STATES OF INORGANIC PHYSICAL OBJECTS—A QUICK ROAD TO PANPSYCHISM. THE CLEAR NEED TO MAKE SUCH A DISTINCTION GIVES DIRECTION FOR FUTURE WORK. A BEGINNING IS MADE TOWARD PROVIDING SUCH AN ACCOUNT.

This work provides an interesting, though sometimes rather sweeping, demonstration that the metaphysical problem of the same and the other is also the central problem of literature and literary criticism. The author defends the analogical imagination as the symbolic counterpart of participation in Platonic metaphysics.--D. C. B.

After an exceedingly short treatment of six theories of tragedy, the author concludes that while each has emphasized a necessary component of the tragic, none has really come to grips with its basic "paradox": the fact that while the art of tragedy attempts to explain the mystery of human suffering, such an attempt is doomed to failure.--D. C. B.

The aim of this paper is to set out some of the ontologies amongst which some forms of anti-realism must select. This provides the appropriate setting for presenting an alternative realist ontology. The argument is that the choice between the varieties of anti-realism and realism is inevitably a choice between ontologies.

Corporate social responsibility (CSR) continues to gain attention atop the corporate agenda and is by now an important component of the dialogue between companies and their stakeholders. Nevertheless, there is still little guidance as to how companies can implement CSR activity in order to maximize returns to CSR investment. Theorists have identified many company-favoring outcomes of CSR; yet there is a dearth of research on the psychological mechanisms that drive stakeholder responses to CSR activity. Borrowing from the literatures on meansend (...) chains and relationship marketing, we propose a conceptual model that explains how CSR provides individual stakeholders with numerous benefits (functional, psychosocial, and values) and how the type and extent to which a stakeholder derives these benefits from CSR initiatives influences the quality of the relationship between the stakeholder and the company. The paper discusses the implications of these insights and highlights a number of areas for future research. (shrink)

The Cambridge History of Renaissance Philosophy, published in 1988, offers a balanced and comprehensive account of philosophical thought from the middle of the fourteenth century to the emergence of modern philosophy. This was the first volume in English to synthesise for a wider audience the substantial and sophisticated research now available. The volume is organised by branch of philosophy rather than by individual philosopher or school, and the intention has been to present the internal development of different aspects of the (...) subject in their own historical context. The structure also naturally emphasises the international nature of philosophy in the Renaissance. (shrink)

The _Second Treatise_ is one of the most important political treatises ever written and one of the most far-reaching in its influence. In his provocative 15-page introduction to this edition, the late eminent political theorist C. B. Macpherson examines Locke's arguments for limited, conditional government, private property, and right of revolution and suggests reasons for the appeal of these arguments in Locke's time and since.

In answering the question, “How is the concept of a person possible?”, Strawson lays great stress upon a particular class of predicate.He says, “They are predicates, roughly, which involve doing something, which clearly imply intention or a state of mind or at least consciousness in general, and which indicate a characteristic pattern, or range of patterns, of bodily movement, while not indicating at all precisely any very definite sensation or experience …. Such predicates have the interesting characteristic of many P-predicates, (...) that one does not, in general, ascribe them to oneself on the strength of observation, whereas one does ascribe them to others on the strength of observations. But, in the case of these predicates, one feels minimal reluctance to concede that what is ascribed in these two different ways is the same. This is because of the marked dominance of a fairly definite pattern of bodily movement in what they describe, and the marked absence of any distinctive experience. (shrink)

John Dewey expresses repeatedly that the significance of democracy is more than political discourse. He invites us to realize that democracy is primarily moral idea that animates a process of living and should be actualized continuously. He underlines that the idea of liberty, equality and fraternity, which is the democratic trinity, is ethical ideal of humanity in which personality is at the centre of reflection. Every human individual is free to actualize its self-realization. His liberty is based on the belief (...) that every human individual has a right to equal opportunity with every other person to develop whatever endowment he has. Then, democracy indicates fraternity as an ethical value, which every human individual is able to actualize his capacities only in actively cooperative relationship with other. Political and social democracy presenting in a real association of life will be effectively sustained if its values of ideal hu-manity becomes an animating force of life. In other words, he envisions that democracy becomes a personal way of life. Keywords: values of democracy, social responsibility, culture of democracy, transformation of life, peaceful life. Absrak: John Dewey menyatakan berulangkali bahwa demokrasi lebih dari sekedar persoalan politik. Ia menunjukkan bahwa demokrasi pertama-tama merupakan sebuah gagasan etis yang menjiwai proses hidup secara terus-menerus. Kebebasan, kesederajatan, dan persaudaraan yang menjadi inti demokrasi merupakan nilai-nilai etis kemanusiaan yang menjadi arah hidup manusia di dalam kehidupan bersama di tengah masyarakat. Setiap individu adalah bebas untuk mewujudkan dirinya. Kebebasannya didasarkan pada keyakinan bahwa setiap individu mempunyai hak dan kesempatan yang sama untuk mengembangkan diri sesuai dengan potensi yang dianugerahkan kepadanya. Persaudaraan merupakan nilai etis yang menegaskan bahwa setiap individu hanya mampu mewujudkan diri di dalam relasi dan kerjasama dengan sesamanya. Ketiga nilai etis tersebut seharusnya menjiwai tata hidup bersama. Dengan kata lain, demokrasi seharusnya menjadi pola hidup setiap pribadi sebagai anggota masyarakat. Kata-kata Kunci: nilai-nilai demokrasi, tanggung jawab sosial, budaya demo-krasi, transformasi hidup, hidup damai. (shrink)