It is well established that microRNAs (miRNAs) induce mRNA degradation by binding to 3′ untranslated regions (UTRs). The functionality of sites in the coding domain sequence (CDS), on the other hand, remains under discussion. Such sites have limited impact on target mRNA abundance and recent work suggests that miRNAs bind in the CDS to inhibit translation. What then could be the regulatory benefits of translation inhibition through CDS targeting compared to mRNA degradation following 3′ UTR binding? We propose that these (...) domain‐dependent effects serve to diversify the functional repertoire of post‐transcriptional gene expression control. Possible regulatory benefits may include tuning the time‐scale and magnitude of post‐transcriptional regulation, regulating protein abundance depending on or independently of the cellular state, and regulation of the protein abundance of alternative splice variants. Finally, we review emerging evidence that these ideas may generalize to RNA‐binding proteins beyond miRNAs and Argonaute proteins. (shrink)

The “binding problem” has been a central question in vision science for some 30 years: When encoding multiple objects or maintaining them in working memory, how are we able to represent the correspondence between a specific feature and its corresponding object correctly? In this letter we argue that the boundaries of this research program in fact extend far beyond vision, and we call for coordinated pursuit across the broader cognitive science community of this central question for cognition, which we dub (...) “Binding Problem 2.0”. (shrink)

Chapin reviewed this 1972 ZEITSCHRIFT paper that proves the completeness theorem for the logic of variable-binding-term operators created by Corcoran and his student John Herring in the 1971 LOGIQUE ET ANALYSE paper in which the theorem was conjectured. This leveraging proof extends completeness of ordinary first-order logic to the extension with vbtos. Newton da Costa independently proved the same theorem about the same time using a Henkin-type proof. This 1972 paper builds on the 1971 “Notes on a Semantic Analysis of (...) Variable Binding Term Operators” (Co-author John Herring), Logique et Analyse 55, 646–57. MR0307874 (46 #6989). A variable binding term operator (vbto) is a non-logical constant, say v, which combines with a variable y and a formula F containing y free to form a term (vy:F) whose free variables are exact ly those of F, excluding y. Kalish-Montague 1964 proposed using vbtos to formalize definite descriptions “the x: x+x=2”, set abstracts {x: F}, minimization in recursive function theory “the least x: x+x>2”, etc. However, they gave no semantics for vbtos. Hatcher 1968 gave a semantics but one that has flaws described in the 1971 paper and admitted by Hatcher. In 1971 we give a correct semantic analysis of vbtos. We also give axioms for using them in deductions. And we conjecture strong completeness for the deductions with respect to the semantics. The conjecture, proved in this paper with Hatcher’s help, was proved independently about the same time by Newton da Costa. (shrink)

Temporal binding via 40-Hz synchronization of neuronal discharges in sensory cortices has been hypothesized to be a necessary condition for the rapid selection of perceptually relevant information for further processing in working memory. Binocular rivalry experiments have shown that late stage visual processing associated with the recognition of a stimulus object is highly correlated with discharge rates in inferotemporal cortex. The hippocampus is the primary recipient of inferotemporal outputs and is known to be the substrate for the consolidation of working (...) memories to long-term, episodic memories. The prefrontal cortex, on the other hand, is widely thought to mediate working memory processes, per se. This article reviews accumulated evidence for the role of a subcortical matrix in linking frontal and hippocampal systems to select and ''stream'' conscious episodes across time (hundreds of milliseconds to several seconds). ''Streaming'' is hypothesized to be mediated by the selective gating of reentrant flows of information between these cortical systems and the subcortical matrix. The physiological mechanism proposed for this temporally extended form of binding is synchronous oscillations in the slower EEG spectrum (< 8 Hz). (shrink)

Combinatory logic (Curry and Feys 1958) is a “variable-free” alternative to the lambda calculus. The two have the same expressive power but build their expressions differently. “Variable-free” semantics is, more precisely, “free of variable binding”: it has no operation like abstraction that turns a free variable into a bound one; it uses combinators—operations on functions—instead. For the general linguistic motivation of this approach, see the works of Steedman, Szabolcsi, and Jacobson, among others. The standard view in linguistics is that reflexive (...) and personal pronouns are free variables that get bound by an antecedent through some coindexing mechanism. In variable free semantics the same task is performed by some combinator that identifies two arguments of the function it operates on (a duplicator). This combinator may be built into the lexical semantics of the pronoun, into that of the antecedent, or it may be a free-floating operation applicable to predicates or larger chunks of texts, i.e. a typeshifter. This note is concerned with the case of cross-sentential anaphora. It adopts Hepple’s and Jacobson’s interpretation of pronouns as identity maps and asks how this can be extended to the cross-sentential case, assuming the dynamic semantic view of anaphora. It first outlines the possibility of interpreting indefinites that antecede non-ccommanded pronouns as existential quantifiers enriched with a duplicator. Then it argues that it is preferable to use the duplicator as a type-shifter that applies “on the fly”. The proposal has consequences for two central ingredients of the classical dynamic semantic treatment: it does away with abstraction over assignments and with treating indefinites as inherently existentially quantified. However, cross-sentential anaphora remains a matter of binding, and the idea of propositions as context change potentials is retained. (shrink)

From its ornamental and often bookish exterior to its use as an exegetical tool for understanding the Book of Nature, the 18th-century microscope was socialized as an instrument of letters as well as of science. This essay proposes a reading of the microscope as a literary artifact by examining its bindings, its texts and its illustrations. While the instrument promised to extend human sense perception and to give its user access to invisible worlds, it simultaneously threatened to alter received views (...) concerning both aesthetics and social hierarchy. Nevertheless, the destabilizing effects of the microscopic message entered polite society cloaked in a veil of familiarity in the binding of a good book. The nostalgia-encrusted instrument absorbed the shock of the new. (shrink)

In this paper I inquire into the methodological status of one of the arguments that have figured prominently in contemporary debates about the semantics of a variety of expressions, the so-called “Binding Argument”. My inquiry is limited to the case of meteorological sentences like “It is raining”, but my conclusion can be extended to other types of sentences as well. Following Jason Stanley, I distinguish between three interpretations of the argument. My focus is on the third, weakest interpretation, according to (...) which postulating variables for locations in the logical form of meteorological sentences is the best available explanation of the binding phenomena that such sentences give rise to. My aim is to show that even in this weak interpretation, the argument cannot be reasonably taken to hold. I accomplish this by showcasing several alternative ways to account for the binding data that have not been, as of yet, ruled out as flawed. (shrink)

Recent research suggests that the subjective feeling of conscious recollection is uniquely characterized by joint memory for several context features while merely familiar memories lack this property . In the present research we took the novel approach of extending the dual task paradigm to the simultaneous study of subjective retrieval experience and joint memory for two orthogonal context features. While dual task load during encoding lead to reductions in the frequency of the subjective experience of conscious recollection and reductions in (...) overall context memory, joint context memory was not affected. Furthermore, the relation of higher overall context memory for consciously recollected items than for familiar items was preserved even under dual task load. These results have import implications for theories of long-term feature binding and the processes involved in producing the experience of conscious recollection. (shrink)

Lange & Dyer misunderstand what is meant by an “entity” and confuse a medium of representation with the content being represented. This leads them to the erroneous conclusion that SHRUTI will run out of phases and that its representation of bindings lacks semantic content. It is argued that the limit on the number of phases suffices, and SHRUTI can be interpreted as using “dynamic signatures” that offer significant advantages over fixed preexisting signatures. Bonatti refers to three levels of commitment to (...) a representational theory of the mind and states that SHRUTI is committed to RTM at levels 1 and 2. He acknowledges that SHRUTI is not committed at level 3, but argues that an extended SHRUTI would have to make such a commitment. We agree that SHRUTI is committed to RTM at level 1 and, in a sense, also at level 2. SHRUTI, however, is not committed to RTM at level 3 and, even though it has been extended in several ways, it has retained its original representational character. (shrink)

Our daily lives unfold continuously, yet our memories are organised into distinct events, situated in a specific context of space and time, and chunked when this context changes (at event boundaries). Previous research showed that this process, termed event segmentation, enhances object-context binding but impairs temporal order memory. Physiologically, peaks in pupil dilation index event segmentation, similar to emotion-induced bursts of autonomic arousal. Emotional arousal also modulates object-context binding and temporal order memory. Yet, these two critical factors have not been (...) systematically studied together. To address this gap, we ran a behavioural experiment using a paradigm validated to study event segmentation and extended it with emotion manipulation. During encoding, we sequentially presented greyscale objects embedded in coloured frames (colour changes defining events), with a neutral or aversive sound. During retrieval, we tested participants’ memory of temporal order memory and object-colour binding. We found opposite effects of emotion and event segmentation on episodic memory. While event segmentation enhanced object-context binding, emotion impaired it. On the contrary, event segmentation impaired temporal order memory, but emotion enhanced it. These findings increase our understanding of episodic memory organisation in laboratory settings, and potentially in real life with perceptual changes and emotion fluctuations constantly interacting. (shrink)

What follows is the elaboration of a series of discussions held by the two authors at a seminar during which we tried to “read” Wim Wenders's Lisbon Story starting from Gregory Bateson's double bind theory. These discussions then developed into writings that were intertwined, hybridized, corrected, extended, and cut. We experimented directly with the game of relationships, the “mess that works” of the difficult distinction between map and territory, between epistemology and cinematography. Emerging from general considerations on cinema is the (...) double bind of the “crisis” of images, a prelude to a renewed faith in the creative and constructive possibilities of art: image not as a replica but as the experience of a relationship. (shrink)

Does nostalgia for one’s time at university predict current intentions to engage with the university? In Study 1, United States participants’ nostalgia for their university experience (university nostalgia) at a southern public university predicted stronger intentions to socialize with fellow alumni, attend a future reunion, volunteer for their university, and donate money to their university. Study 2 replicated these findings with alumni from a northeastern private university, and extended them by finding that the links between university nostalgia and university engagement (...) emerged even when controlling for the positivity of university experience. In both studies, feelings of university belonging mediated most of the associations between university nostalgia and university engagement. In Study 2, the positivity of the university experience moderated the relation between university nostalgia and two indices of university engagement. Specifically, university nostalgia was more strongly associated with intentions to attend a reunion and donate money among those who had a relatively negative university experience. Nostalgia for one’s university past predicts future engagement with the university as well as its members. (shrink)

Retrotransposon-derived elements (RDEs) can disrupt gene expression, but are nevertheless widespread in metazoan genomes. This review presents a hypothesis that repressive RNA-binding proteins (RBPs) facilitate the large-scale accumulation of RDEs. Many RBPs bind RDEs in pre-mRNAs to repress the effects of RDEs on RNA processing, or the formation of inverted repeat RNA structures. RDE-binding RBPs often assemble on extended, multivalent binding sites across the RDE, which ensures repression of cryptic splice or polyA sites. RBPs thereby minimize the effects of RDEs (...) on gene expression, which likely reduces the negative selection against RDEs. While mutations that change splice sites in RDEs act as an off-on switch in exon formation, mutations that decrease the multivalency of RBP binding sites resemble a rheostat that enables a more gradual evolution of new RDE-derived exons. RBPs might also repress aberrant processing of active retrotransposons, thus increasing the chance that full-length copies are made. Taken together, in this review, it is proposed that RBPs facilitate the widespread accumulation of intronic RDEs by repressing RNA processing while chaperoning their potential to gradually evolve into new exons. (shrink)

The work of Donaldson and Dunfee offers an example of how normative and descriptive approaches to business ethics can be integrated. We suggest that to be truly integrative, however, the theory should explore the processes by which such integration happens. We, therefore, sketch some preliminary thoughts that extend Integrative Social Contracts Theory by beginning to consider the process by which microsocial contracts are connected to hypernorms.

Wegner and colleagues have offered an explanation of the sense of agency over one’s bodily actions. If the orthodox view is correct and there is a sense of agency deficit associated with delusions of alien control, then Wegner and colleagues’ model ought to extend to an explanation of this deficit. Data from intentional binding studies opens up the possibility that an abnormality in representing the timing of mental events leads to a violation of the principle of priority in those suffering (...) from delusions of alien control. However, the model ultimately fails as it is unable to accommodate action monitoring deficits associated with delusions of alien control, in particular the theory of mind deficiencies predicted by such accounts have not materialised. There are theory of mind problems associated with schizophrenia but they are not associated with delusions of alien control. Such accounts thereby fail to adequately explain delusions of alien control. (shrink)

This Dissertation argues for a care-centrically grounded account of relational personhood and widely realized diachronic personal identity. The moral distinction between persons and non-persons is arguably one of the most salient ethical lines we can draw since many of our most fundamental rights are delineated via the bounds of personhood. The problem with drawing such morally salient lines is that the orthodox, rationalistic definition of personhood, which is widespread within philosophical, medical, and colloquial spheres, excludes, and thereby de-personifies, a large (...) number and a great variety of human beings such as neonates, young children, the elderly who suffer from dementia, individuals with severe cognitive disabilities, and patients in vegetative states. The reconceptualization of personhood necessary for a more inclusive definition ought to originate with an appropriate moral grounding. To this end, this Dissertation grounds the notion of personhood in the care ethical sphere, thereby emphasizing the role of care relations in the maintenance of the moral consideration of vulnerable individuals. This Dissertation argues that grounding the concept of a person in care relations entails a relational account of personhood, which, along with the insights of the Extended Mind and Social Manifestation Theses, leads to an extended and externalized understanding of diachronic identity, which allows fragile people to be held in their personal identities even if they themselves lack the capacities usually associated with moral personhood. As we trace a person’s identity through time, we track the various relational properties, which constitute personal narratives and thus act as a glue that binds such dynamic and often unique properties into stable, trackable narratives. Since care relations are morally relevant on a care-centric account of personhood, what is lost in cases where such care relating ceases is not merely of sentimental value, but of great moral importance as well. Morally meaningful care relations are not replaceable, and, by extension, neither are the narratives that are constituted by such unique and irreplaceable instances of relating. This Dissertation argues that the constitutive care relational nature of personal narratives makes such narratives irreplaceable and is precisely what makes persons so morally precious. (shrink)

The desire to understand the mathematics of living systems is increasing. The widely held presupposition that the mathematics developed for modeling of physical systems as continuous functions can be extended to the discrete chemical reactions of genetic systems is viewed with skepticism. The skepticism is grounded in the issue of scientific invariance and the role of the International System of Units in representing the realities of the apodictic sciences. Various formal logics contribute to the theories of biochemistry and molecular biology (...) and genetics. Various paths of extension are invoked in these formal logics in order to express the information of biological apodicticism. Symbolizing the appropriate notations for invariant relations and for biological extensions of relations is fundamental to the exact generating functions of discrete algebraic biology. Aspects of philosophical perspectives of the relation scientific number systems are contrasted. The deep distinction between physical motion and biological motion is expressed in terms the roles of Aristotelian causes. The interior motion within perplex numbers is contrasted with the exterior motion of physical systems. The need for a new mathematics for biology is suggested. (shrink)

The dimensional structure of phenomenal space and its relation to the brain have not been widely focused on in brain and consciousness studies. This paper postulates that focusing on the dimensional structures displayed in the relation between phenomenal space and the brain is necessary for understanding the integration of distributed brain events in binding. A related issue is why items and events of phenomenal space and consciousness as they appear in experience seem to be beyond the reach of natural scientific (...) empirical observation. The proposed solution to these issues is postulated to require a fourth spatial dimension. A transcendence principle of detection (TPD) is introduced, which states that transcendent degrees of freedom of an n+1 dimension are a necessary condition for experiencing or detecting an n-dimensionally extended physical structure as an n-dimensionally extended phenomenal structure. It is postulated that the phenomenal outcome of binding, i.e. the threedimensionally distributed and extended phenomenal structure of human experience, is the expected first-person outcome of threedimensionally distributed neurophysical structures being monitored at the domain of a fourth spatial dimension. (shrink)

Consistent with Ruchkin and colleagues' proceduralist account, recent research on grouping and verbal-spatial binding in immediate memory shows continuity across short- and long-term retention, and activation of classes of information extending beyond those typically allowed in modular models. However, Ruchkin et al.'s account lacks well-specified mechanisms for the retention of serial order, binding, and the control of activation through attention.

Analyses of singular causation often make use of the idea that a cause increases the probability of its effect. Of particular salience in such accounts are the values of the probability function of the effect, conditional on the presence and absence of the putative cause, analysed around the times of the events in question: causes are characterized by the effect’s probability function being greater when conditionalized upon them. Put this way, it becomes clearer that the ‘behaviour’ of probability functions in (...) small intervals about the times in question ought to be of concern. In this article, I make an extended case that causal theorists employing the ‘probability raising’ idea should pay attention to the continuity question. Specifically, if the probability functions are ‘jumping about’ in ways typical of discontinuous functions, then the stability of the relevant probability increase is called into question. The rub, however, is that sweeping requirements for either continuity or discontinuity are problematic and, as I argue, this constitutes a ‘continuity bind’. Hence more subtle considerations and constraints are needed, two of which I consider: utilizing discontinuous first derivatives of continuous probability functions, and abandoning point probability for imprecise probability. _1_ Introduction _2_ Probability Trajectories and Continuity _2.1_ Probability trajectories _2.2_ Causation as discontinuous jumps _2.3_ Against systematic discontinuity _3_ Broader Discontinuity Concerns _4_ The Continuity Bind _4.1_ Retaining continuity with discontinuous first derivatives _4.2_ Imprecise probability trajectories _5_ Concluding Remarks Appendix. (shrink)

ABSTRACT Does genetic relatedness define who is a mother or father and who incurs obligations towards or entitlements over children? While once the answer to this question may have been obvious, advances in reproductive technologies have complicated our understanding of what makes a parent. In a recent publication Bayne and Kolers argue for a pluralistic account of parenthood on the basis that genetic derivation, gestation, extended custody and sometimes intention to parent are sufficient (but not necessary) grounds for parenthood.1 Bayne (...) and Kolers further suggest that definitions of parenthood are underpinned by the assumption that ‘being causally implicated in the creation of a child is the key basis for being its parent’.2 This paper examines the claim that genetic relatedness is sufficient grounds for parenthood based on a causal connection between genetic parents and their offspring. I argue that parental obligations are about moral responsibility and not causal responsibility because we are not morally accountable for every consequence to which we causally contribute. My account includes the conditions generally held to apply to moral responsibility, i.e. freedom and foreseeability. I argue that parental responsibilities are generated whenever the birth of a child is a reasonably foreseeable consequence of voluntary actions. I consider the implications of this account for third parties involved in reproductive technologies. I argue that under some conditions the obligations generated by freely and foreseeably causing a child to exist can be justifiably transferred to others. (shrink)

Vision is the main entrance for environmental input to the human brain. Even if vision is our most used sensory modality, its importance is not limited to environmental exploration. Rather it has strong links to motor competences, further extending to cognitive and social aspects of human life. These multifaceted relationships are particularly important in developmental age and become dramatically evident in presence of complex deficits originating from visual aberrancies. The present review summarizes the available neuropsychological evidence on the development of (...) visual competences, with a particular focus on the associated visuo-motor integration skills in health and disease. With the aim of supporting future research and interventional settings, the goal of the present review is to constitute a solid base to help the translation of neuropsychological hypotheses into straightforward empirical investigations and rehabilitation/training protocols. This approach will further increase the impact, ameliorate the acceptance, and ease the use and implementation of lab-derived intervention protocols in real-life situations. (shrink)

This volume brings together about 50 scientists and researchers from the four corners of the world to redefine and anticipate tomorrow's values, and reflect on ...

In his preface to Human, Too Human Nietzsche wrote: ‘My books have been labelled the school of suspicion … ‘ Predicted and desired by Nietzsche, the age of suspicion does seem to be one of the labels that best characterize the century that has just closed. And symptomatically it was used a few decades later in France to describe writers’ interrogations about the novel as a literary genre, its facilities and conventions, its easy determinisms, as well as the exorbitant power (...) of the novelist-demiurge. Is it necessary to recall that the forerunner to the nouveau roman, written by Nathalie Sarraute in the 1930s, was in fact entitled L’Ère du soupçon? It is impossible to emphasize enough this close concordance between philosophical questioning and aesthetic interrogations, particularly in the notion of avant-garde, which is indispensable for thinking about intellectual and political renewal. It is true that the 20th century was the century of the universal declaration of human rights, but also the century of rejection of norms inherited from philosophical, literary, cultural, religious or scientific traditions, which came to be suspected of providing only off-the-peg elements for thought and action at a time when the world was changing and required new forms of thinking. (shrink)

Résumé Le cheminement de la pensée occidentale, depuis plus d’un siècle, a vu : la mort de Dieu, la chute des idéologies politiques qui semblaient avoir pris le relais des valeurs « divines », la solitude de l’individu désorienté. Le malaise de l’individu serait le symptôme d’une remise en question de la notion même d’être humain. En reprenant la critiques de l’humanisme introduite par Nietzsche, Sloterdijk fait ressortir que l’homme aurait échappé à la bestialité par les moyens mêmes qu’il emploie (...) pour apprivoiser les animaux et les mettre à son service. Que dire de ce que la recherche permet actuellement de faire sur l’être humain? La manipulation du vivant a fait émerger la possibilité d’une fabrique de l’être humain. Les choix que nous avons à faire quant au devenir de l’humain restent éminemment politiques. Le terme d’humanisme est complexe : il est deux types d’humanisme. Celui qui conçoit l’humain comme une essence. La seconde forme considère qu’il n’y a pas de nature humaine, que l’on devient humain. Le monde humain est ouvert à la création, mais fragilisé parce que placé sous notre responsabilité. (shrink)

In his preface to Human, Too Human Nietzsche wrote: ‘My books have been labelled the school of suspicion … ‘ Predicted and desired by Nietzsche, the age of suspicion does seem to be one of the labels that best characterize the century that has just closed. And symptomatically it was used a few decades later in France to describe writers’ interrogations about the novel as a literary genre, its facilities and conventions, its easy determinisms, as well as the exorbitant power (...) of the novelist-demiurge. Is it necessary to recall that the forerunner to the nouveau roman, written by Nathalie Sarraute in the 1930s, was in fact entitled L’Ère du soupçon? It is impossible to emphasize enough this close concordance between philosophical questioning and aesthetic interrogations, particularly in the notion of avant-garde, which is indispensable for thinking about intellectual and political renewal. It is true that the 20th century was the century of the universal declaration of human rights, but also the century of rejection of norms inherited from philosophical, literary, cultural, religious or scientific traditions, which came to be suspected of providing only off-the-peg elements for thought and action at a time when the world was changing and required new forms of thinking. (shrink)

The basic elements of faceted thesauri are described, together with a review of their origins and some prominent examples. Their use in browsing and searching applications is discussed. Faceted thesauri are distinguished from faceted classification schemes, while acknowledging the close similarities. The paper concludes by comparing faceted thesauri and related knowledge organization systems to ontologies and discussing appropriate areas of use.

This work gives an extended presentation of the treatment of variable-binding operators adumbrated in [3:1993d]. Illustrative examples include elementary languages with quantifiers and lambda-equipped categorial languages. Some remarks are also offered to illustrate the philosophical import of the resulting picture. Particularly, a certain conception of logic emerges from the account: the view that logics are true theories in the model-theoretic sense, i.e. the result of selecting a certain class of models as the only “admissible” interpretation structures (for a given language).

This chapter argues that Hegel is a major (albeit unrecognized) epistemologist: Hegel’s Introduction provides the key to his phenomenological method by showing that the Pyrrhonian Dilemma of the Criterion refutes traditional coherentist and foundationalist theories of justification. Hegel then solves this Dilemma by analyzing the possibility of constructive self- and mutual criticism. ‘Sense Certainty’ provides a sound internal critique of ‘knowledge by acquaintance’, thus undermining a key tenet of Concept Empiricism, a view Hegel further undermines by showing that a series (...) of non-logical a priori concepts must be used to identify any particular object of experience. Most importantly, Hegel justifies a semantics of singular cognitive reference with important anti-skeptical implications. ‘Perception’ extends Hegel’s criticism Concept Empiricism by exposing the inadequacy of Modern theories of perception (and also sense data theories) which lack a tenable concept of the identity of perceptible things. Hegel demonstrates that this concept is a priori and integrates two counterposed sub-concepts, ‘unity’ and ‘plurality’. Hegel’s examination of this concept reveals his clear awareness of what is now called the ‘binding problem’ in neurophysiology of perception, a problem only very recently noticed by epistemologists. ‘Force and Understanding’ exposes a fatal equivocation in the traditional concept of substance which thwarts our understanding of force and causal interaction. Hegel’s disambiguation of that concept enables us to comprehend how relations can be essential to physical particulars. Hegel contends that Newtonian universal gravitation shows that gravitational relations are essential to physical particulars, and he criticizes a series of attempts—including the infamous ‘inverted world’—to avoid this conclusion. Hegel’s cognitive semantics supports Newton’s Fourth Rule of philosophizing, which rejects mere logical possibilities as counter-examples to empirical hypotheses. This is an important anti-Cartesian, also anti-empiricist, insight. Finally, Hegel’s cognitive semantics reveals a previously unnoticed link between Pyrrhonian and Cartesian skepticism and empiricist anti-realism about causality within philosophy of science: all three appeal to premises, hypotheses, or counter-examples which, as mere logical possibilities, lack in principle fully determinate, cognitively legitimate meaning. ‘Consciousness’ thus establishes basic principles and features of human cognition to which Hegel returns throughout the Phenomenology. The chapter concludes by summarizing Hegel’s over-arching epistemological analysis in the Phenomenology. (shrink)

An ontology's theory of ontic predication has implications for the concomitant predicate logic. Remarkable in its analytic power for both ontology and logic is the here developed Particularized Predicate Logic (PPL), the logic inherent in the realist version of the doctrine of unit or individuated predicates. PPL, as axiomatized and proven consistent below, is a three-sorted impredicative intensional logic with identity, having variables ranging over individuals x, intensions R, and instances of intensions $R_{i}$ . The power of PPL is illustrated (...) by its clarification of the self-referential nature of impredicative definitions and its distinguishing between legitimate and illegitimate forms. With a wellmotivated refinement on the axiom of comprehension, PPL is, in effect, a higher-order logic without a forced stratification of predicates into types or the use of other ad hoc restrictions. The Russell-Priest characterization of the classic self-referential paradoxes is used to show how PPL diagnosis and solves these antimonies. A direct application of PPL is made to Grelling's Paradox. Also shown is how PPL can distinguish between identity and indiscernibility. (shrink)

This article considers categorical perception (CP) as a crucial process involved in all sort of communication throughout the biological hierarchy, i.e. in all of biosemiosis. Until now, there has been consideration of CP exclusively within the functional cycle of perception–cognition–action and it has not been considered the possibility to extend this kind of phenomena to the mere physiological level. To generalise the notion of CP in this sense, I have proposed to distinguish between categorical perception (CP) and categorical sensing (CS) (...) in order to extend the CP framework to all communication processes in living systems, including intracellular, intercellular, metabolic, physiological, cognitive and ecological levels. The main idea is to provide an account that considers the heterarchical embeddedness of many instances of CP and CS. This will take me to relate the hierarchical nature of categorical sensing and perception with the equally hierarchical issues of the “binding problem”, “triadic causality”, the “emergent interpretant” and the increasing semiotic freedom observed in biological and cognitive systems. (shrink)

The binding group theorem for stable theories is partially extended to the simple context. Some results concerning internality are proved. We also introduce a ‘small’ normal subgroup G0+ of the automorphism group and show that if p is Q-internal then it has a finite exponent and G/G0+ is interpretable.

Alternative cleavage and polyadenylation (APA) can diversify coding and non‐coding regions, but has particular impact on increasing 3′ UTR diversity. Through the gain or loss of regulatory elements such as RNA binding protein and microRNA sites, APA can influence transcript stability, localization, and translational efficiency. Strikingly, the central nervous systems of invertebrate and vertebrate species express a broad range of transcript isoforms bearing extended 3′ UTRs. The molecular mechanism that permits proximal 3′ end bypass in neurons is mysterious, and only (...) beginning to be elucidated. This landscape of neural 3′ UTR extensions, many reaching unprecedented lengths, may help service the unique post‐transcriptional regulatory needs of neurons. A combination of approaches, including transcriptome‐wide profiling, genetic screening to identify APA factors, biochemical dissection of alternative 3′ end formation, and manipulation of individual neural APA targets, will be necessary to gain fuller perspectives on the mechanism and biology of neural‐specific 3′ UTR lengthening. (shrink)

The article deals with the origin and formation of debating positions in American criticism and philosophy. It analyzes “Intentional Fallacy” by W. Wimsatt and M. Beardsley. as well as E.D. Hirsch’s texts concerning the idea of objective interpretation which initiated this discussion. In fact, both positions are limited because of their normative and ahistorical character. Both sides try to regulate interpretation. Wimsatt and Beardsley lose the historical place of a text, whereas Hirsch reduces the historical place of an interpreter. Anti-intentionalism (...) of Wimsatt and Beardsley relies on interpretative practice of American New Criticism with its principle of work’s autonomy. Despite the article’s empirical character, its important outcome is negation of subjectivity of meaning, and formulation of premises of its intersubjective understanding. Hirsch affirms the invariability of work’s meaning and with this purpose identifies it with the author’s intention binding it with the notion of intentionality and author’s horizoncontext, introduces the distinction between meaning and significance. Despite the contradictions of Hirsch’s positions both in understanding these ideas and in his own conclusions, his merit is the statement of the problem of meaning in general and extending the discussion into the territory of hermeneutics and philosophy of literature. (shrink)

Animate vision systems have gaze control mechanisms that can actively position the camera coordinate system in response to physical stimuli. Compared to passive systems, animate systems show that visual computation can be vastly less expensive when considered in the larger context of behavior. The most important visual behavior is the ability to control the direction of gaze. This allows the use of very low resolution imaging that has a high virtual resolution. Using such a system in a controlled way provides (...) additional constraints that dramatically simplify the computations of early vision. Another important behavior is the way the environment “behaves‘. Animate systems under real-time constraints can further reduce their computational burden by using environmental cues that are perspicuous in the local context. A third source of economy is introduced when behaviors are learned. Because errors are rarely fatal, systems using learning algorithms can amortize computational cost over extended periods. Further economies can be achieved when the learning system uses indexical reference, which is a form of dynamic variable binding. Animate vision is a natural way of implementing this dynamic binding. (shrink)

Phillips & Singer (P&S) extend ideas derived from the observation eight years ago that the coherence (synchronization) of cortical oscillations can be modulated by the structure of visual stimuli. As described in the target article, a large part of the continued interest in this finding is related to independent theoretical work suggesting that synchronized cell firing could help solve the problem of binding together within cortex neuronal activity associated with different attributes of visual stimuli. The authors present an abstract “proof (...) of concept” model describing how their cortical processing scheme could work, but our biologically realistic models of cortical relationships suggest that the proposal is biologically implausible. Our realistic models lead to a very different interpretation of the significance of cortical oscillations. (shrink)

Nominal terms extend first-order terms with binding. They lack some properties of first- and higher-order terms: Terms must be reasoned about in a context of ‘freshness assumptions’; it is not always possible to ‘choose a fresh variable symbol’ for a nominal term; it is not always possible to ‘α-convert a bound variable symbol’ or to ‘quotient by α-equivalence’; the notion of unifier is not based just on substitution.Permissive nominal terms closely resemble nominal terms but they recover these properties, and in (...) particular the ‘always fresh’ and ‘always rename’ properties. In the permissive world, freshness contexts are elided, equality is fixed, and the notion of unifier is based on substitution alone rather than on nominal terms’ notion of unification based on substitution plus extra freshness conditions.We prove that expressivity is not lost moving to the permissive case and provide an injection of nominal terms unification problems and their solutions into permissive nominal terms problems and their solutions.We investigate the relation between permissive nominal unification and higher-order pattern unification. We show how to translate permissive nominal unification problems and solutions in a sound, complete, and optimal manner, in suitable senses which we make formal. (shrink)

Building on the success of the bestselling first edition, the second edition of this textbook provides a comprehensive and accessible introduction to the major issues in Principles and Parameters syntactic theory, including phrase structure, the lexicon, case theory, movement, and locality conditions. Includes new and extended problem sets in every chapter, all of which have been annotated for level and skill type. Features three new chapters on advanced topics including vP shells, object shells, control, gapping and ellipsis and an additional (...) chapter on advanced topics in binding. Offers a brief survey of both Lexical-Functional Grammar and Head-Driven Phrase Structure Grammar. Succeeds in strengthening the reader's foundational knowledge, and prepares them for more advanced study. Supported by an instructor's manual and online resources for students and instructors, available at www.blackwellpublishing.com/carnie. (shrink)

Current models of insulin binding to the insulin receptor (IR) propose (i) that there are two binding sites on the surface of insulin which engage with two binding sites on the receptor and (ii) that ligand binding involves structural changes in both the ligand and the receptor. Many of the features of insulin binding to its receptor, namely B‐chain helix interactions with the leucine‐rich repeat domain and A‐chain residue interactions with peptide loops from another part of the receptor, are also (...) seen in models of relaxin and insulin‐like peptide 3 binding to their receptors. We show that these principles can likely be extended to the group of mimetic peptides described by Schäffer and coworkers, which are reported to have no sequence identity with insulin. This review summarizes our current understanding of ligand‐induced activation of the IR and highlights the key issues that remain to be addressed. (shrink)

Predicting the binding mode of flexible polypeptides to proteins is an important task that falls outside the domain of applicability of most small molecule and protein-protein docking tools. Here, we test the small molecule flexible ligand docking program Glide on a set of 19 non-α-helical peptides and systematically improve pose prediction accuracy by enhancing Glide sampling for flexible polypeptides. In addition, scoring of the poses was improved by post-processing with physics-based implicit solvent MM- GBSA calculations. Using the best RMSD among (...) the top 10 scoring poses as a metric, the success rate (RMSD ≤ 2.0 \textbackslash AA for the interface backbone atoms) increased from 21 with default Glide SP settings to 58 with the enhanced peptide sampling and scoring protocol in the case of redocking to the native protein structure. This approaches the accuracy of the recently developed Rosetta FlexPepDock method (63 success for these 19 peptides) while being over 100 times faster. Cross-docking was performed for a subset of cases where an unbound receptor structure was available, and in that case, 40 of peptides were docked successfully. We analyze the results and find that the optimized polypeptide protocol is most accurate for extended peptides of limited size and number of formal charges, defining a domain of applicability for this approach. (shrink)

Because little is known about the human trait of affiliation, we provide a novel neurobehavioral model of affiliative bonding. Discussion is organized around processes of reward and memory formation that occur during approach and consummatory phases of affiliation. Appetitive and consummatory reward processes are mediated independently by the activity of the ventral tegmental area (VTA) dopamine (DA)–nucleus accumbens shell (NAS) pathway and the central corticolimbic projections of the u-opiate system of the medial basal arcuate nucleus, respectively, although these two projection (...) systems functionally interact across time. We next explicate the manner in which DA and glutamate interact in both the VTA and NAS to form incentive-encoded contextual memory ensembles that are predictive of reward derived from affiliative objects. Affiliative stimuli, in particular, are incorporated within contextual ensembles predictive of affiliative reward via: (a) the binding of affiliative stimuli in the rostral circuit of the medial extended amygdala and subsequent transmission to the NAS shell; (b) affiliative stimulus-induced opiate potentiation of DA processes in the VTA and NAS; and (c) permissive or facilitatory effects of gonadal steroids, oxytocin (in interaction with DA), and vasopressin on (i) sensory, perceptual, and attentional processing of affiliative stimuli and (ii) formation of social memories. Among these various processes, we propose that the capacity to experience affiliative reward via opiate functioning has a disproportionate weight in determining individual differences in affiliation. We delineate sources of these individual differences, and provide the first human data that support an association between opiate functioning and variation in trait affiliation. Key Words: affiliation corticolimbic-striatal networks; appetitive and consummatory reward; dopamine; oxytocin; personality; social bonds; social memory; u-opiates. (shrink)

Methyl CpG binding protein 2 (MeCP2) was initially isolated as an exclusive reader of DNA methylated at CpG. This recognition site, was subsequently extended to other DNA methylated residues and it has been the persisting dogma that binding to methylated DNA constitutes its physiologically relevant role. As we review here, two very recent papers fundamentally change our understanding of the interactions of this protein with chromatin, as well as its functional attributes. In the first one, the protein has been shown (...) to bind to tri‐methylated histone H3 (H3K27me3), providing a hint for what might turn out to be the first described chromodomain‐containing protein reader in the animal kingdom, and unequivocally demonstrates the ability of MeCP2 to bind to nonmethylated CpG regions of the genome. The second paper reports how the protein dynamically participates in the formation of constitutive heterochromatin condensates. Histone H3K27me3 is a critical component of this form of chromatin. (shrink)

An introductory text in linguistic semantics, uniquely balancing empirical coverage and formalism with development of intuition and methodology. -/- This introductory textbook in linguistic semantics for undergraduates features a unique balance between empirical coverage and formalism on the one hand and development of intuition and methodology on the other. It will equip students to form intuitions about a set of data, explain how well an analysis of the data accords with their intuitions, and extend the analysis or seek an alternative. (...) No prior knowledge of linguistics is required. After mastering the material, students will be able to tackle some of the most difficult questions in the field even if they have never taken a linguistics course before. -/- After introducing such concepts as truth conditions and compositionality, the book presents a basic symbolic logic with negation, conjunction, and generalized quantifiers, to serve as the basis for translation throughout the book. It then develops a detailed compositional semantics, covering quantification (scope and binding), adverbial modification, relative clauses, event semantics, tense and aspect, as well as pragmatic phenomena, notably deictic pronouns and narrative progression. -/- A Course in Semantics offers a large and diverse set of exercises, interspersed throughout the text; those labeled “Important practice and looking ahead” prepare students for material to come; those labeled “Thinking about ” invite students to think beyond the content of the book. (shrink)

Brian Hedden defends a radical view about the relationship between rationality, personal identity, and time. On the standard view, personal identity over time plays a central role in thinking about rationality, because there are rational norms for how a person's attitudes and actions at one time should fit with her attitudes and actions at other times. But these norms are problematic. They make what you rationally ought to believe or do depend on facts about your past that aren't part of (...) your current perspective on the world, and they make rationality depend on controversial, murky metaphysical facts about what binds different instantaneous snapshots into a single person extended in time. Hedden takes a different approach, treating the relationship between different time-slices of the same person as no different from the relationship between different people. On his account, the locus of rationality is the time-slice rather than the temporally extended agent. This impersonal, time-slice-centric approach to rationality yields a unified approach to the rationality of beliefs, preferences, and actions where what rationality demands of you is solely determined by your evidence, with no special weight given to your past beliefs or actions. (shrink)

According to most accounts of trust, you can only trust other people (or groups of people). To trust is to think that another has goodwill, or something to that effect. I sketch a different form of trust: the unquestioning attitude. What it is to trust, in this sense, is to settle one’s mind about something, to stop questioning it. To trust is to rely on a resource while suspending deliberation over its reliability. Trust lowers the barrier of monitoring, challenging, checking, (...) and questioning. Trust sets up open pipelines between yourself and parts of the external world. Trust permits external resources to have a similar relationship to one as one’s internal cognitive faculties. This creates efficiency, but at the price of exquisite vulnerability. We must trust in this way because we are cognitively limited beings in a cognitively overwhelming world. Crucially, we can hold the unquestioning attitude towards objects and technologies. When I trust my climbing rope, I stop worrying about its reliability. When I trust my online calendaring system, I simply go to the events indicated, without question. But, one might worry, how could one ever hold such a normatively loaded attitude as trust towards mere objects? How could it ever make sense to feel betrayed by an object? Trust is our engine for expanding and outsourcing our agency — for binding external processes into our practical selves. Thus, we can be betrayed by our smartphones in the same way that we can be betrayed by our memory. When we trust, we try to make something a part of our agency, and we are betrayed when our part lets us down. To unquestioningly trust something is to let it in—to attempt to bring it inside one’s practical functioning. This suggests a new form of gullibility: agential gullibility, which occurs when agents too hastily and carelessly integrate external resources into their own agency. (shrink)