This study examines factors influencing pro-environmental practices for Ganesh idol immersion, a major Hindu religious celebration. The study explores whether environmental consciousness or spiritual beliefs and values are antecedents of pro-environment religious practices adopted for the Ganesh idol immersion. The survey used validated scales to assess spiritual beliefs, spiritual values, environmental consciousness and behaviour, and religious practices. Confirmatory factor analysis and Cronbach alpha ensured spiritual beliefs and values, environmental consciousness and behaviour, and the scale’s reliability and validity. The study has (...) established a positive relationship between spiritual values, environmental consciousness and behaviour and pro-environmental religious practices. Spiritual belief inversely influences pro-environmental religious practices. The two-stage cluster analysis classifies respondents as environmental stewardship, pro-environmentalist, environment and religious neutral, extrinsic religiousness and intrinsic religiousness, aligning with established theory. Segmenting respondents into profiles provides insights to develop focused pro-environmental messaging that resonates across diverse audiences. These findings offer important practical implications for policymakers and environmental agencies seeking to balance religious traditions and ecological impact. Finally, the study advocates religious environmentalism to foster pro-environmental behaviour. (shrink)

This book looks at the affective-cognitive roots of how the human mind inquires into the workings of nature and, more generally, how the mind confronts reality. Reality is an infinitely complex system, in virtue of which the mind can comprehend it only in bits and pieces, by making up interpretations of the myriads of signals received from the world by way of integrating those with information stored from the past. This constitutes a piecemeal interpretation by which we assemble our phenomenal (...) reality. In perceiving the complex world and responding to it, the mind invokes the logic of affect and the logic of reason, the former mostly innate and implicit, and the latter generated consciously in explicit terms with reference to mind-independent relations between entities in nature. It is a strange combination of affect and reason that enables us to make decisions and inferences, --- the latter mostly of the inductive type --- thereby making possible the development of theories. Theories are our tool-kits for explaining and predicting phenomena, guiding us along in our journey in life. Theories, however, are defeasible, and need to be constantly updated, at times even radically. In this, the self and the soul are of enormous relevance. The former is the affect-based psychological engine driving all our mental processes, while the latter is the capacity of the conscious mind to examine and reconstruct the self by modulating repressed conflicts. If the soul remains inoperative, all our theories become misdirected and a rot spreads inexorably all around us. (shrink)

This paper develops an interpretive framework around ethical learning by using qualitative methods to examine the collective impact of Experiential Learning Activity (ELA) and Critical Action Learning (CAL) on student learning of ethics. The aim is to determine not only the effectiveness of two ethical learning theories but also the student “needs” being fulfilled. To understand their perceptions, we collected students’ personal narratives through focus groups and semi-structured interviews post participation on the experiential and action learning activities. Results indicate that (...) teaching through ELAs and CAL in business ethics lead to social benefits and co-creation which portrayed improved engagement with peers, academics and industry. The outcomes suggest that instead of focussing on teaching ethics, the curriculum should provide opportunities for developing interaction with peers, academics and the society and engage students in real time hands on projects to experience and learn about ethics and the consequences of unethical behaviour. (shrink)

Linguists have realised for some time that predicates of the 'know' and 'wonder' classes behave differently in semantic terms with respect to their interrogative complements, but have not so far fully understood how or why. This book seeks to explore and to provide solutions to this and to related problems in explaining the meaning and grammar of embedded interrogatives and the predicates that take interrogative complements.

This paper presents an analysis of negative polarity items (NPIs) in Hindi. It is noted that NPIs in this language are composed of a (weak) indefinite plus a particle bhii meaning ‘even’. It is argued that the compositional semantics of this combination explains their behavior as NPIs as well as their behavior as free choice (FC) items. I assume that weak Hindi indefinites like ek and koi are to be viewed as a predicate that I call one, a predicate that (...) is true of everything that exists. I further assume that bhii exhibits association with focus with the indefinite, and that this leads to contradictory implicatures in positive contexts. The behavior of these phrases in a variety of syntactic contexts is discussed, including constructions like correlatives. Finally, I provide a comparison with analyses of English any, and discuss the relevance of the analysis presented here for that of any. (shrink)

We introduce the notion of complexity, first at an intuitive level and then in relatively more concrete terms, explaining the various characteristic features of complex systems with examples. There exists a vast literature on complexity, and our exposition is intended to be an elementary introduction, meant for a broad audience. -/- Briefly, a complex system is one whose description involves a hierarchy of levels, where each level is made of a large number of components interacting among themselves. The time evolution (...) of such a system is of a complex nature, depending on the interactions among subsystems in the next level below the one under consideration and, at the same time, conditioned by the level above, where the latter sets the context for the evolution. Generally speaking, the interactions among the constituents of the various levels lead to a dynamics characterized by numerous characteristic scales, each level having its own set of scales. What is more, a level commonly exhibits ‘emergent properties’ that cannot be derived from considerations relating to its component systems taken in isolation or to those in a different contextual setting. In the dynamic evolution of some particular level, there occurs a self-organized emergence of a higher level and the process is repeated at still higher levels. -/- The interaction and self-organization of the components of a complex system follow the principle commonly expressed by saying that the ‘whole is different from the sum of the parts’. In the case of systems whose behavior can be expressed mathematically in terms of differential equations this means that the interactions are nonlinear in nature. -/- While all of the above features are not universally exhibited by complex systems, these are nevertheless indicative of a broad commonness relative to which individual systems can be described and analyzed. There exist measures of complexity which, once again, are not of universal applicability, being more heuristic than exact. The present state of knowledge and understanding of complex systems is itself an emerging one. Still, a large number of results on various systems can be related to their complex character, making complexity an immensely fertile concept in the study of natural, biological, and social phenomena. -/- All this puts a very definite limitation on the complete description of a complex system as a whole since such a system can be precisely described only contextually, relative to some particular level, where emergent properties rule out an exact description of more than one levels within a common framework. -/- We discuss the implications of these observations in the context of our conception of the so-called noumenal reality that has a mind-independent existence and is perceived by us in the form of the phenomenal reality. The latter is derived from the former by means of our perceptions and interpretations, and our efforts at sorting out and making sense of the bewildering complexity of reality takes the form of incessant processes of inference that lead to theories. Strictly speaking, theories apply to models that are constructed as idealized versions of parts of reality, within which inferences and abstractions can be carried out meaningfully, enabling us to construct the theories. -/- There exists a correspondence between the phenomenal and the noumenal realities in terms of events and their correlations, where these are experienced as the complex behavior of systems or entities of various descriptions. The infinite diversity of behavior of systems in the phenomenal world are explained within specified contexts by theories. The latter are constructs generated in our ceaseless attempts at interpreting the world, and the question arises as to whether these are reflections of `laws of nature' residing in the noumenal world. This is a fundamental concern of scientific realism, within the fold of which there exists a trend towards the assumption that theories express truths about the noumenal reality. We examine this assumption (referred to as a ‘point of view’ in the present essay) closely and indicate that an alternative point of view is also consistent within the broad framework of scientific realism. This is the view that theories are domain-specific and contextual, and that these are arrived at by independent processes of inference and abstractions in the various domains of experience. Theories in contiguous domains of experience dovetail and interpenetrate with one another, and bear the responsibility of correctly explaining our observations within these domains. -/- With accumulating experience, theories get revised and the network of our theories of the world acquires a complex structure, exhibiting a complex evolution. There exists a tendency within the fold of scientific realism of interpreting this complex evolution in rather simple terms, where one assumes (this, again, is a point of view) that theories tend more and more closely to truths about Nature and, what is more, progress towards an all-embracing ‘ultimate theory’ -- a foundational one in respect of all our inquiries into nature. We examine this point of view closely and outline the alternative view -- one broadly consistent with scientific realism -- that there is no ‘ultimate’ law of nature, that theories do not correspond to truths inherent in reality, and that successive revisions in theory do not lead monotonically to some ultimate truth. Instead, the theories generated in succession are incommensurate with each other, testifying to the fact that a theory gives us a perspective view of some part of reality, arrived at contextually. Instead of resembling a monotonically converging series successive theories are analogous to asymptotic series. -/- Before we summarize all the above considerations, we briefly address the issue of the complexity of the {\it human mind} -- one as pervasive as the complexity of Nature at large. The complexity of the mind is related to the complexity of the underlying neuronal organization in the brain, which operates within a larger biological context, its activities being modulated by other physiological systems, notably the one involving a host of chemical messengers. The mind, with no materiality of its own, is nevertheless emergent from the activity of interacting neuronal assemblies in the brain. As in the case of reality at large, there can be no ultimate theory of the mind, from which one can explain and predict the entire spectrum of human behavior, which is an infinitely rich and diverse one. (shrink)

This essay presents a point of view for looking at `free will', with the purpose of interpreting where exactly the freedom lies. For, freedom is what we mean by it. It compares the exercise of free will with the making of inferences, which usually is predominantly inductive in nature. The making of inference and the exercise of free will, both draw upon psychological resources that define our ‘selves’. I examine the constitution of the self of an individual, especially the involvement (...) of personal beliefs, personal memories, affects, emotions, and the hugely important psychological value-system, all of which distinguish the self of one individual from that of another. The foundational position that adopted in this essay is that all psychological processes are correlated with corresponding ones involving large scale neural aggregates in the brain, communicating with one another through wavelike modes of excitation and de-excitation. Of central relevance is the value-network around which the affect system is organized, the latter, in turn, being the axis around which is assembled the self, with all its emotional correlates. The self is a complex system. I include a brief outline of what complexity consists of. In reality all systems are complex, for complexity is ubiquitous, and certain parts of nature appear to us to be ‘simple’ only in certain specific contexts. It is in this background that the issue of determinism is viewed in this essay. Instead of looking at determinism as a grand principle entrenched in nature independent of our interpretation of it, I look at our ability to explain and to predict events and phenomena around us, which is made possible by the existence of causal links running in a complex course that set up correlations between diverse parts of nature, in this way putting the stamp of necessity on these events. However, the complexity of systems limits our ability to explain and to predict to within certain horizons defined by contexts. Our ability to explain and predict in matters relating to acts of free will is similarly limited by the operations of the self that remain hidden from our own awareness. The aspects of necessity and determinism appear to us in the form of reason and rationality that explain and predict only within a limited horizon, while the rest depends on the complex operation of self-linked psychological resources, where the latter appear as contingent in the context of the exercise of free will. The hallmark of complex systems is the existence of amplifying factors that operate as destabilizing ones, along with inhibiting or stabilizing factors as well that generally limit the destabilizing influences to local occurrences, while preserving the global integrity of a system. This complex interplay of destabilizing and stabilizing influences lead to the possibility of an enormous number of distinct modes of behavior that appear as emergent phenomena in complex systems. Looking at the particular case of the self of an individual that guide her actions and thoughts, it is the operation of our emotions, built around the psychological value-system, that provide for the amplifying and inhibiting factors mentioned above. The operation of these self-linked factors stamps our actions and thoughts as contingent ones that do not fit with our concepts of reason and rationality. And this is what provides the basis of our idea of free will. Free will is not ‘free’ in virtue of exemption from causal links running through all our self-based processes - ones that remain hidden from our awareness, but is free of what is perceived to be ‘reason and rationality’ based on knowledge and the common pool of beliefs and principles associated with a shared world-view. When we speak of the choice involved in an act of exercise of free will what we actually refer to is the commonly observed fact that various different individuals of a similar disposition respond differently when placed under similar circumstances. In other words, free will is ‘free’ precisely because it is not subject to constraints of a commonly accepted and shared set of principles, beliefs, and values. While it is possible that, in an exercise of free will, the self-linked psychological resources are brought into action when a number of alternatives are presented to the self by the operation of the ingredients of a commonly shared world-view, it seems likely that, that set of alternatives is not of primary relevance in the final response that the mind produces, since the latter is primarily a product of the operation of the self-based psychological resources. What is of greater relevance here is the operation of emotion-driven processes, guided by the psychological value-system based on the activity of the so-called reward-punishment network in the brain. These processes lead the individual to a response that appears to be free from the shackles of determinism precisely because their mechanisms, which are hidden from us, do not conform to commonly accepted and shared rules and principles. In contrast, inductive inference is a process that is based on the ‘cognitive face’ of self, where the self-based psychological resources play a supportive role to the commonly shared world-view of an individual. There is never any freedom from the all-pervading causal links representing correlations among all objects, entities, and events in nature. In the midst of all this, the closest thing to freedom that we can have in our life comes with self-examination and self-improvement. The possibility of self-examination appears in the form of specific conjunctions between our complex self-processes and the ceaseless changes of scenario in our external world. This actually makes the emergent phenomenon of self-examination a matter of chance, but one that keeps on appearing again and again in our life. Once realized, self examination creates possibilities that would not be there in the absence of it, and these possibilities include the enhancement of further self-enrichment and further diversity in the exercise of our free will. (shrink)

We look into the ontology of quantum theory as distinct from that of the classical theory in the sciences. Theories carry with them their own ontology while the metaphysics may remain the same in the background. We follow a broadly Kantian tradition, distinguishing between the noumenal and phenomenal realities where the former is independent of our perception while the latter is assembled from the former by means of fragmentary bits of interpretation. Theories do not tell us how the noumenal world (...) is constituted but are conceptual constructs applying to models generated in the phenomenal world within limited contexts. -/- The ontology of quantum theory principally rests on the view that entities in the world are pervasively correlated with one another not by means of probabilities as in the case of the classical theory, but by means of probability amplitudes involving finely tuned phases characterising the oscillatory behaviour of quantum mechanical states. -/- The amplitude-dependent correlations (quantum entanglement) exist over and above the classical ones expressed in terms of probabilities. While the classical correlations are essentially local in nature, quantum correlations are shared globally in the process of environment-induced decoherence. The decoherence is an effectively random process that removes local correlations in the course of global sharing of entanglement—the removal being especially manifest in the case of systems that appear as classical ones. It is this aspect of the decoherence process that makes the so-called measurement postulate (one relating to wave function collapse) cohere with the rest of the principles of quantum theory where the latter implies a Schrodinger type time evolution of quantum mechanical systems. -/- The mathematical basis of the quantum correlations consists of the description of pure states of a system in terms of vectors in a linear vector space (a mixed state appears as an admixture of pure states with some probability distribution associated with it) and, in addition, the description of (pure) states of composite systems as vectors in the product space arising from the component sub-systems. -/- The crucial aspect of the decoherence process, of significance in the context of the apparent incompatibility of the measurement postulate with the unitary Schrodinger evolution, relates to the fact that it is almost instantaneous in the case of a classical object (one that is nevertheless amenable to a quantum description). Indeed, the decoherence time is, in all likelihood, of the order of the Planck scale, being driven by field fluctuations in the Planck regime. This points to factors of an unknown nature determining the finest details of the decoherence process since Planck scale physics remains an obscure terrain. -/- In other words, quantum theory is, to all intents and purposes, in the need of a radical revision, in keeping with the fact that all theories are defeasible and need revision as our domains of experience expand and get realigned in a complex manner. The context within which quantum theory (and quantum field theory too) is defined is set precisely by the Planck scale, across which a novel theoretical framework is likely to emerge. However, as in the case of theory revisions in general, that emerging theory will stand in an asymmetric relation of incommensurability with the present-day quantum theory, where the concepts of the latter will be comprehensible in terms of those of the former, but the converse will not hold. (shrink)

This paper explores changing production relations in agriculture in context of increasingly widespread and longer-duration male outmigration, as against previous, short-duration and seasonal migration. It investigates how de facto women-heads of households (WHHs) are changing a resilient crop-sharing system in absence of adequate access to productive assets, formal training or experience in farming, and while contributing labour to farming and coping with gendered demands on their time. Based on qualitative inquiry in one of the poorest parts of South Asia, the (...) Eastern Gangetic Plains, the paper shows that a section of WHHs are replacing sharecropping arrangements with fixed-value rental arrangements that resemble commercial contracts. The paper ends with a discussion on the implications of this emerging development. (shrink)

Menstruation leave for women workers brings into the public domain of mining ongoing debates around protective legislation for women. It brings into focus the presumed tensions between gender equity and gender difference with regard to women's economic citizenship. Large-scale mining in East Kalimantan in Indonesia has offered some opportunities to poor and unskilled rural women to find formal jobs in the mines as truck and heavy equipment operators. This paper presents a case study of women in mining occupations, considers the (...) implications of current menstruation leave provisions on the employment of women in the mines and raises serious issues related to gender equity in the workplace. The involvement of women in a non-conventional workplace such as the mine pits, providing a novel site for contestation over the rights of women workers, illuminates a less-debated area in feminist studies, especially in view of the significant ongoing changes in the Indonesian framework for industrial relations. (shrink)

In this essay we collect and put together a number of ideas relevant to the under- standing of the phenomenon of creativity, confining our considerations mostly to the domain of cognitive psychology while we will, on a few occasions, hint at neuropsy- chological underpinnings as well. In this, we will mostly focus on creativity in science, since creativity in other domains of human endeavor have common links with scientific creativity while differing in numerous other specific respects. We begin by briefly (...) introducing a few basic notions relating to cognition, among which the notion of ‘concepts’ is of basic relevance. The myriads of concepts lodged in our mind constitute a ‘conceptual space’ of an enormously complex structure, where con- cepts are correlated by beliefs that are themselves made up of concepts and are as- sociated with emotions. The conceptual space, moreover, is perpetually in a state of dynamic evolution that is once again of a complex nature. A major component of the dynamic evolution is made up of incessant acts of inference, where an inference occurs essentially by means of a succession of correlations among concepts set up with beliefs and heuristics, the latter being beliefs of a special kind, namely, ones relatively free of emotional associations and possessed of a relatively greater degree of justification. Beliefs, along with heuristics, have been described as the ‘mind’s software’, and con- stitute important cognitive components of the self-linked psychological resources of an individual. The self is the psychological engine driving all our mental and physical activity, and is in a state of ceaseless dynamics resulting from one’s most intimate ex- periences of the world accumulating in the course of one’s journey through life. Many of our psychological resources are of a dual character, having both a self-linked and a shared character, the latter being held in common with larger groups of people and imbibed from cultural inputs. We focus on the privately held self-linked beliefs of an individual, since these are presumably of central relevance in making possible inductive inferences – ones in which there arises a fundamental need of adopting a choice or making a decision. Beliefs, decisions, and inferences, all have the common link to the self of an individual and, in this, are fundamentally analogous to free will, where all of these have an aspect of non-determinism inherent in them. Creativity involves a major restructuring of the conceptual space where a sustained inferential process eventually links remote conceptual domains, thereby opening up the possibility of a large number of new correlations between remote concepts by a cascading process. Since the process of inductive inference depends crucially on de- cisions at critical junctures of the inferential chain, it becomes necessary to examine the basic mechanism underlying the making of decisions. In the framework that we attempt to build up for the understanding of scientific creativity, this role of decision making in the inferential process assumes central relevance. With this background in place, we briefly sketch the affect theory of decisions. Affect is an innate system of response to perceptual inputs received either from the exter- nal world or from the internal physiological and psychological environment whereby a positive or negative valence gets associated with a perceptual input. Almost every sit- uation faced by an individual, even one experienced tacitly, i.e., without overt aware-ness, elicits an affective response from him, carrying a positive or negative valence that underlies all sorts of decision making, including ones carried out unconsciously in inferential processes. Referring to the process of inferential exploration of the conceptual space that gener- ates the possibility of correlations being established between remote conceptual do- mains, such exploration is guided and steered at every stage by the affect system, analogous to the way a complex computer program proceeds through junctures where the program ascertains whether specified conditions are met with by way of generating appropriate numerical values – for instance, the program takes different routes, depending on whether some particular numerical value turns out to be positive or negative. The valence generated by the affect system in the process of adoption of a choice plays a similar role which therefore is of crucial relevance in inferential processes, especially in the exploration of the conceptual space where remote domains need to be linked up – the affect system produces a response along a single value dimension, resembling a number with a sign and a magnitude. While the affect system plays a guiding role in the exploration of the conceptual space, the process of exploration itself consists of the establishment of correlations between concepts by means of beliefs and heuristics, the self-linked ones among the latter having a special role in making possible the inferential journey along alternative routes whenever the shared rules of inference become inadequate. A successful access to a remote conceptual domain, necessary for the creative solution of a standing problem or anomaly – one that could not be solved within the limited domain hitherto accessed – requires a phase of relatively slow cumulative search and then, at some stage, a rapid cascading process when a solution is in sight. Representing the conceptual space in the form of a complex network, the overall process can be likened to one of self-organized criticality commonly observed in the dynamical evolution of complex systems. In order that inferential access to remote domains may actually be possible, it is necessary that restrictions on the exploration process – necessary for setting the context in ordinary instances of inductive inference – be relaxed and a relatively free exploration in a larger conceptual terrain be made possible. This is achieved by the mind going into the default mode, where external constraints – ones imposed by shared beliefs and modes of exploration – are made inoperative. While explaining all these various aspects of the creative process, we underline the supremely important role that analogy plays in it. Broadly speaking, analogy is in the nature of a heuristic, establishing correlations between concepts. However, analo- gies are very special in that these are particularly effective in establishing correlations among remote concepts, since analogy works without regard to the contiguity of the concepts in the conceptual space. In establishing links between concepts, analogies have the power to light up entire terrains in the conceptual space when a rapid cas- cading of fresh correlations becomes possible. The creative process occurs within the mind of a single individual or of a few closely collaborating individuals, but is then continued by an entire epistemic community, eventually resulting in a conceptual revolution. Such conceptual revolutions make pos- sible the radical revision of scientific theories whereby the scope of an extant theory is broadened and a new theoretical framework makes its appearance. The emerging theory is characterized by a certain degree of incommensurability when compared with the earlier one – a feature that may appear strange at first sight. But incommen- surability does not mean incompatibility and the apparently contrary features of the relation between the successive theories may be traced to the multi-layered structureof the conceptual space where concepts are correlated not by means of single links but by multiple ones, thereby generating multiple layers of correlation, among which some are retained and some created afresh in a conceptual restructuring. We conclude with the observation that creativity occurs on all scales. Analogous to correlations being set up across domains in the conceptual space and new domains being generated, processes with similar features can occur within the confines of a domain where a new layer of inferential links may be generated, connecting up sub- domains. In this context, insight can be looked upon as an instance of creativity within the confines of a domain of a relatively limited extent. (shrink)

This article, written in Bengali ('Gonit Dorshon' means `philosophy of mathematics' ), briefly reviews a few of the major points of view toward mathematics and the world of mathematical entities, and interprets the philosophy of mathematics as an interaction between these. The existence of these different points of view is indicative that mathematics, in spite of being of universal validity, can nevertheless accommodate alternatives. In particular, I review the alternative viewpoints of Platonism and Intuitionism and present the case that in (...) spite of their great differences, they are not mutually exclusive - that both can be accommodated within the infinite edifice of mathematics. This, in turn, is argued to be consistent with the viewpoint of Category Theory that holds the promise of an entirely new interpretation of the world of mathematics and the relation of that world to the world of our concepts and ideas: mathematics is a human enterprise and mathematical logic is a reflection of how our ideas and concepts are formed and combined with one another. I venture that this, perhaps, is the view of mathematics that Ludwig Wittgenstein would espouse. (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)

[A revised and updated version of an earlier article 'Understanding Creativity: Affect Decision and Inference' (unpublished), posted at PhilArchive in 2021.] -/- This book looks at the creative process in the human mind. -/- Creativity involves a major restructuring of the conceptual space where a sustained inferential process eventually links remote conceptual domains, thereby opening up the possibility of a large number of new correlations between remote concepts by a cascading process. Since the process of inductive inference depends crucially on (...) decisions at critical junctures of the inferential chain, it becomes necessary to examine the basic mechanism underlying the making of decisions. In the framework that we attempt to build up for the understanding of scientific creativity, this role of decision making in the inferential process assumes central relevance. -/- Referring to the process of inferential exploration of the conceptual space that generates the possibility of correlations being established between remote conceptual domains, such exploration is guided and steered at every stage by the affect system, -/- While the affect system plays a guiding role in the exploration of the conceptual space, the process of exploration itself consists of the establishment of correlations between concepts by means of beliefs and heuristics, the self-linked ones among the latter having a special role in making possible the inferential journey along alternative routes whenever the shared rules of inference become inadequate. -/- Representing the conceptual space in the form of a complex network, the overall process can be likened to one of self-organised criticality commonly observed in the dynamical evolution of complex systems. An instance of self-organised criticality is found in the avalanche set up in a slowly growing sand-pile. (shrink)

This monograph is an in-depth and engaging discourse on the deeply cognitive roots of human scientific quest. The process of making scientific inferences is continuous with the day-to-day inferential activity of individuals, and is predominantly inductive in nature. Inductive inference, which is fallible, exploratory, and open-ended, is of essential relevance in our incessant efforts at making sense of a complex and uncertain world around us, and covers a vast range of cognitive activities, among which scientific exploration constitutes the pinnacle. Inductive (...) inference has a personal aspect to it, being rooted in the cognitive unconscious of individuals, which has recently been found to be of paramount importance in a wide range of complex cognitive processes. One other major aspect of the process of inference making, including the making of scientific inferences, is the role of a vast web of beliefs lodged in the human mind, as also of a huge repertoire of heuristics, that constitute an important component of ‘unconscious intelligence’. Finally, human cognitive activity is dependent in a large measure on emotions and affects, that operate mostly at an unconscious level. Of special importance in scientific inferential activity is the process of hypothesis making, which is examined in this book, along with the above aspects of inductive inference, at considerable depth. The book focuses on the inadequacy of the viewpoint of naive realism in understanding the contextual nature of scientific theories, where a cumulative progress towards an ultimate truth about Nature appears to be too simplistic a generalization. It poses a critique to the commonly perceived image of science which is seen as the last word in logic and objectivity, the latter in the double sense of being independent of individual psychological propensities and, at the same time, approaching a correct understanding of the workings of a mind-independent nature. Adopting the naturalist point of view, it examines the essential tension between the cognitive endeavours of individuals and scientific communities, immersed in belief systems and cultures, on the one hand, and the engagement with a mind-independent reality on the other. In the end, science emerges as an interpretation of nature, which is perceived by us only contextually, as successively emerging cross-sections of limited scope and extent. Successive waves of theory building in science appear as episodic and kaleidoscopic changes in perspective as certain in-built borders are crossed, rather than as a cumulative progress towards some ultimate truth. While written in an informal and conversational style, the book raises a number of deep and intriguing questions located at the interface of cognitive psychology and philosophy of science, meant for both the general lay reader and the specialist. Of particular interest is the way it explores the role of belief (aided by emotions and affects) in making the process of inductive inference possible since belief is a subtle though all-pervasive cognitive factor not adequately investigated in the current literature. (shrink)

BACKGROUND: Alzheimer's disease is intimately tied to amyloid-beta peptide. Extraneuronal brain plaques consisting primarily of Abeta aggregates are a hallmark of AD. Intraneuronal Abeta subunits are strongly implicated in disease progression. Protein sequence mutations of the Abeta precursor protein account for a small proportion of AD cases, suggesting that regulation of the associated gene may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or "proximal regulatory element" , at -76/-47, from the (...) +1 transcription start site that confers cell type specificity. This PRE contains sequences that make it vulnerable to epigenetic modification and may present a viable target for drug studies. We examined PRE-nuclear protein interaction by gel electrophoretic mobility shift assay and PRE mutant EMSA. This was followed by functional studies of PRE mutant/reporter gene fusion clones. RESULTS: EMSA probed with the PRE showed DNA-protein interaction in multiple nuclear extracts and in human brain tissue nuclear extract in a tissue-type specific manner. We identified transcription factors that are likely to bind the PRE, using competition gel shift and gel supershift: Activator protein 2 , nm23 nucleoside diphosphate kinase/metastatic inhibitory protein , and specificity protein 1 . These sites crossed a known single nucleotide polymorphism . EMSA with PRE mutants and promoter/reporter clone transfection analysis further implicated PuF in cells and extracts. Functional assays of mutant/reporter clone transfections were evaluated by ELISA of reporter protein levels. EMSA and ELISA results correlated by meta-analysis. CONCLUSIONS: We propose that PuF may regulate the APP gene promoter and that AD risk may be increased by interference with PuF regulation at the PRE. PuF is targeted by calcium/calmodulin-dependent protein kinase II inhibitor 1, which also interacts with the integrins. These proteins are connected to vital cellular and neurological functions. In addition, the transcription factor PuF is a known inhibitor of metastasis and regulates cell growth during development. Given that APP is a known cell adhesion protein and ferroxidase, this suggests biochemical links among cell signaling, the cell cycle, iron metabolism in cancer, and AD in the context of overall aging. (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)

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)

Amyloid-beta peptide plaque in the brain is the primary diagnostic criterion of Alzheimer's disease . The physiological role of Abeta are poorly understood. We have previously determined an Abeta interacting domain in the promoters of AD-associated genes . This AbetaID interacts in a DNA sequence-specific manner with Abeta. We now demonstrate novel Abeta activity as a possible transcription factor. Herein, we detected Abeta-chromatin interaction in cell culture by ChIP assay. We observed that human neuroblastoma cells treated with FITC conjugated Abeta1-40 (...) localized Abeta to the nucleus in the presence of H2O2-mediated oxidative stress. Furthermore, primary rat fetal cerebrocortical cultures were transfected with APP and BACE1 promoter-luciferase fusions, and rat PC12 cultures were transfected with polymorphic APP promoter-CAT fusion clones. Transfected cells were treated with different Abeta peptides and/or H2O2. Abeta treatment of cell cultures produced a DNA sequence-specific response in cells transfected with polymorphic APP clones. Our results suggest the Abeta peptide may regulate its own production through feedback on its precursor protein and BACE1, leading to amyloidogenesis in AD. (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)

OBJECTIVES: Early-emerging, temperamental differences in fear-related traits may be a heritable vulnerability factor for anxiety disorders. Previous research indicates that the serotonin transporter promoter region polymorphism is a candidate gene for such traits. METHODS: Associations between 5-HTTLPR genotype and indices of fearful child temperament, derived from maternal report and standardized laboratory observations, were examined in a community sample of 95 preschool-aged children. RESULTS: Children with one or more long alleles of the 5-HTTLPR gene were rated as significantly more nervous during (...) standardized laboratory tasks than children who were homozygous for the short alleles. Children homozygous for the short alleles were also rated as significantly shyer, by maternal report, than those with at least one copy of the long allele of the 5-HTTLPR gene. CONCLUSIONS: This study extends the literature linking the short alleles of the serotonin transporter promoter region polymorphism to fear and anxiety-related traits in early childhood and adulthood, and is one of very few studies to examine the molecular genetics of preschoolers' temperament using multiple measures of traits in a normative sample. (shrink)

In the present study, we examine the interactive effect of vowels on Mandarin fricative sibilants using a passive oddball paradigm to determine whether the HEIGHT features of vowels can spread on the surface and influence preceding consonants with unspecified features. The stimuli are two pairs of Mandarin words contrasting in vowel HEIGHT. Each word in the same pair was presented both as standard and deviant, resulting in four conditions. In line with the Featurally Underspecified Lexicon model, asymmetric patterns of processing (...) were found in the [su] ∼ [ʂu] word pair where both the MMN and LDN components were more negative in /su/[ʂu] than in /ʂu/[su], suggesting the spreading of the feature [HIGH] from the vowel [u] to [ʂ] on the surface. In the [sa] ∼ [ʂa] pair, however, symmetric negativities were observed as there is no conflict between the surface feature [LOW] from [a] to [ʂ] and the underlying specified feature [LOW] of [s]. These results confirm that not all features are fully specified in the mental lexicon: features of vowels can spread on the surface and influence surrounding unspecified segments. (shrink)

BACKGROUND: Serotonin transporter promoter genotype appears to increase risk for depression in the context of stressful life events. However, the effects of this genotype on measures of stress sensitivity are poorly understood. Therefore, this study examined whether 5-HTTLPR genotype was associated with negative information processing biases in early childhood. METHOD: Thirty-nine unselected seven-year-old children completed a negative mood induction procedure and a Self-Referent Encoding Task designed to measure positive and negative schematic processing. Children were also genotyped for the 5-HTTLPR gene. (...) RESULTS: Children who were homozygous for the short allele of the 5-HTTLPR gene showed greater negative schematic processing following a negative mood prime than those with other genotypes. 5-HTTLPR genotype was not significantly associated with positive schematic processing. LIMITATIONS: The sample size for this study was small. We did not analyze more recently reported variants of the 5-HTTLPR long alleles. CONCLUSIONS: 5-HTTLPR genotype is associated with negative information processing styles following a negative mood prime in a non-clinical sample of young children. Such cognitive styles are thought to be activated in response to stressful life events, leading to depressive symptoms; thus, cognitive styles may index the "stress-sensitivity" conferred by this genotype. (shrink)

Major hallmarks of Alzheimer's disease include brain deposition of the amyloid-beta peptide , which is proteolytically cleaved from a large Abeta precursor protein by beta and gamma- secretases. A transmembrane aspartyl protease, beta-APP cleaving enzyme , has been recognized as the beta-secretase. We review the structure and function of the BACE1 protein, and of 4129 bp of the 5'-flanking region sequence of the BACE1 gene and its interaction with various transcription factors involved in cell signaling. The promoter region and 5'-untranslated (...) region contain multiple transcription factor binding sites, such as AP-1, CREB and MEF2. A 91 bp fragment is the shortest region with significant reporter gene activity and constitutes the minimal promoter element for BACE1. The BACE1 promoter contains six unique functional domains and three structural domains of increasing sequence complexity as the "ATG" start codon is approached. Notably, the BACE1 gene promoter contains basal regulatory elements, inducible features and sites for regulation by various important transcription factors. Herein, we also discuss and speculate how the interaction of these transcription factors with the BACE1 promoter can modulate synaptic plasticity, neuronal apoptosis and oxidative stress, which are pertinent to the pathogenesis and progression of AD. (shrink)

The apolipoprotein E gene plays an important role in the pathogenesis of Alzheimer's disease , and amyloid plaque comprised mostly of the amyloid-beta peptide ) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly understood. We examined how A treatment affects APOE expression in cultured cells and tested the role of the transcription factor NF-B in APOE gene regulation. To delineate NF-B's role, we have characterized a 1098 nucleotide segment containing the (...) 5'-flanking region of the human APOE gene . Sequence analysis of this region suggests the presence of two potential NF-B elements. To demonstrate promoter activity, the region was cloned upstream of a promoterless luciferase gene. This segment was able to drive expression of luciferase in transient transfections of human fetal glial cells. Promoter activity was stimulated twofold by A treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against NF-B reduced A stimulation. Deletion and mutagenetic analyses demonstrated that the distal NF-B element was functional and showed a strong DNA-protein complex band in gel shift analysis, similar to that from control NF-B consensus element. An anti-inflammatory and anti-NF-B drug, sodium salicylate, significantly blocked A-induced APOE promoter function. Our data provide evidence that upregulation of APOE by A in astroglial cells is mediated by an NF-B-element present in the 5'-flanking region of the APOE gene. (shrink)

The present review highlights an association between autism, Alzheimer disease , and fragile X syndrome . We propose a conceptual framework involving the amyloid-beta peptide , Abeta precursor protein , and fragile X mental retardation protein based on experimental evidence. The anabolic effect of the secreted alpha form of the amyloid-beta precursor protein may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPalpha levels associate with more severe symptoms of (...) autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 . Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPalpha level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPalpha and production of insoluble Abeta would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism. (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)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)