Human agents draw a variety of inferences effortlessly, spontaneously, and with remarkable efficiency – as though these inferences were a reflexive response of their cognitive apparatus. Furthermore, these inferences are drawn with reference to a large body of background knowledge. This remarkable human ability seems paradoxical given the complexity of reasoning reported by researchers in artificial intelligence. It also poses a challenge for cognitive science and computational neuroscience: How can a system of simple and slow neuronlike elements represent a large (...) body of systemic knowledge and perform a range of inferences with such speed? We describe a computational model that takes a step toward addressing the cognitive science challenge and resolving the artificial intelligence paradox. We show how a connectionist network can encode millions of facts and rules involving n-ary predicates and variables and perform a class of inferences in a few hundred milliseconds. Efficient reasoning requires the rapid representation and propagation of dynamic bindings. Our model (which we refer to as SHRUTI) achieves this by representing (1) dynamic bindings as the synchronous firing of appropriate nodes, (2) rules as interconnection patterns that direct the propagation of rhythmic activity, and (3) long-term facts as temporal pattern-matching subnetworks. The model is consistent with recent neurophysiological evidence that synchronous activity occurs in the brain and may play a representational role in neural information processing. The model also makes specific psychologically significant predictions about the nature of reflexive reasoning. It identifies constraints on the form of rules that may participate in such reasoning and relates the capacity of the working memory underlying reflexive reasoning to biological parameters such as the lowest frequency at which nodes can sustain synchronous oscillations and the coarseness of synchronization. (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)

A central issue of cognitive neuroscience is to understand how a large collection of coupled neurons combines external signals with internal memories into new coherent patterns of meaning. An external stimulus localized at some input spreads over a large assembly of coupled neurons, building up a collective state univocally corresponding to the stimulus. Thus, the synchronization of spike trains of many individual neurons is the basis of a coherent perception. Based on recent investigations of homoclinic chaotic systems and their synchronization, (...) a novel conjecture for the dynamics of single neurons and, consequently, for neuron assemblies is formulated. Homoclinic chaos is proposed as a suitable way to code information in time by trains of equal spikes occurring at apparently erratic times. In order to classify the set of different perceptions, the percept space can be given a metric structure by introducing a distance measure between distinct percepts. The distance in percept space is conjugate to the duration of the perception in the sense that an uncertainty relation in percept space is associated with time-limited perceptions. This coding of different percepts by synchronized spike trains entails fundamental quantum features which are not restricted to microscopic phenomena. It is conjectured that they are related to the details of the perceptual chain rather than depending on Planck's action. (shrink)

A central issue of cognitive neuroscience is to understand how a large collection of coupled neurons combines external signals with internal memories into new coherent patterns of meaning. An external stimulus localized at some input spreads over a large assembly of coupled neurons, building up a collective state univocally corresponding to the stimulus. Thus, the synchronization of spike trains of many individual neurons is the basis of a coherent perception. Based on recent investigations of homoclinic chaotic systems and their synchronization, (...) a novel conjecture for the dynamics of single neurons and, consequently, for neuron assemblies is formulated. Homoclinic chaos is proposed as a suitable way to code information in time by trains of equal spikes occurring at apparently erratic times. In order to classify the set of different perceptions, the percept space can be given a metric structure by introducing a distance measure between distinct percepts. The distance in percept space is conjugate to the duration of the perception in the sense that an uncertainty relation in percept space is associated with time-limited perceptions. This coding of different percepts by synchronized spike trains entails fundamental quantum features which are not restricted to microscopic phenomena. It is conjectured that they are related to the details of the perceptual chain rather than depending on Planck's action. (shrink)

A new system of dynamic logic is introduced and motivated, witha novel approach to variable binding for incremental interpretation. Thesystem is shown to be equivalent to first order logic and complete.The new logic combines the dynamic binding idea from DynamicPredicate Logic with De Bruijn style variable free indexing. Quantifiersbind the next available variable register; the indexing mechanismguarantees that active registers are never overwritten by newquantifiers actions. Apart from its interest in its own right, theresulting system has (...) certain advantages over Dynamic Predicate Logic orDiscourse Representation Theory. It comes with a more well behaved(i.e., transitive) consequence relation, it gives a more explicitaccount of how anaphoric context grows as text gets processed, and ityields new insight into the dynamics of anaphoric linking in reasoning.Incremental dynamics also points to a new way of handling contextdynamically in Montague grammar. (shrink)

Binding relations are fimdamentally semantic in nature. They arise as relations that are established with an interpretation. This is most apparent with dynamic binding, of the kind found in Dynamic Predicate Logic. Here it is the runtime of the evaluation that may permit a binding relation, in..

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)

As a result of the increasing economical exploitation of outer space, humanity faces a new challenge that, as well as having economic advantages, also entails a great many ecological hazards. At present, the human race is encroaching on outer space, particularly in the form of almost 5000 active satellites and the corresponding space debris they produce. For the large part, this debris burns up on entering the Earth’s atmosphere, yet time and again it still does cause damage. However, this could (...) change dramatically if, as is now foreseeable, further uses of outer space, such as tourism, so-called satellite mega-constellations, regular transport flights to the moon or even Mars and the extraction of water and valuable rocks from celestial bodies, are expanded. There is a danger that ecological damage like that of the earlier phases of economic development will become externalised and ultimately pose a threat to the whole of humanity. Sautter’s ‘global “sustainability trilemma”’ remains unresolved. This trilemma consists in the fact that, in political resolutions, ‘the growth of resource-intensive prosperity is weighted far more highly than the conservation of functioning ecosystems and the implementation of inter- and intragenerational “justice”’ and that there are ‘up until now no efficient and ethically acceptable solutions’ for this problem. In this situation, it is therefore more important that rules for the sustainable use of outer space be established and enshrined as legally binding so that it becomes possible to minimise or even to preclude negative ecological consequences.Contribution: Although the commercial use of outer space does not seem to be a crucial point, it marks a new step of the dynamics of modern economics that has to be identified as an important ethical challenge. The article discusses aspects of ethics, law, religion and economy in a multidisciplinary way. (shrink)

A new formalism for predicate logic is introduced, with a non-standard method of binding variables, which allows a compositional formalization of certain anaphoric constructions, including donkey sentences and cross-sentential anaphora. A proof system in natural deduction format is provided, and the formalism is compared with other accounts of this type of anaphora, in particular Dynamic Predicate Logic.

Visual perception requires parallel processing of distributed information. To achieve true parallelism, in which multiple patterns can be processed simultaneously, dynamic synchronization in ongoing, oscillatory brain activity plays a crucial role. On a large time scale, it can help create and maintain an optimal brain connectivity structure that is clustered, modular, and connected. Over a range of shorter time scales, dynamic synchrony is instrumental in coordinating and controlling the flow of information in the brain. Dynamic synchronization modulates (...) in a pulsed manner the receptivity of sensory systems, the effectivity of neural communication and the binding of visual stimulus information. Collectively, these processes control communication in the brain and determine what we experience. (shrink)

The recognition of extracellular molecules by cell surface receptors is the principal mechanism used by cells to sense their environment. Consequently, signals transduced as a result of these interactions make a major contribution to the regulation of cellular phenotype. Historically, particular emphasis has been placed on elucidating the intracellular consequences of growth factor and cytokine binding to cells. In addition to these interactions, however, cells are usually in intimate contact with a further source of complex structural and functional information, (...) namely immobilised extracellular matrix and/or cell surface adhesion proteins. A key question in recent years has been whether cells use the myriad of adhesion protein‐receptor interactions purely for structural and migratory function, or whether these interactions also make a more varied contribution to cell phenotype. Here we review dynamic aspects of the function of one major class of adhesion receptor, the integrins. In particular, we focus on the evidence for shape changes in integrin molecules, the mechanisms responsible for regulating ligand binding, and the signals transduced following integrin occupancy. (shrink)

Complex functions of the central nervous system such as learning and memory are believed to result from the modulation of the synaptic transmission between neurons. The sequence of events leading to the fusion of synaptic vesicles at the presynaptic active zone and the detection of this signal at the postsynaptic density involve the activity of ion channels and neurotransmitter receptors. Their accumulation and dynamic exchange at synapses are dependent on their interaction with synaptic scaffolds. These are synaptic structures composed (...) of adaptor proteins that provide binding sites for receptors and channels as well as other synaptic proteins. While in its entirety the synaptic scaffold is a relatively stable structure, individual adaptor proteins exchange at a fast time scale. These properties of scaffolds help to ensure the stability of synaptic transmission while permitting the modulation of synaptic strength. Here, we review the dynamics of the synaptic scaffold and of adaptor proteins in relation to their roles in the organisation of the synapse as well as in the clustering and trafficking of receptor proteins. BioEssays 30:1062–1074, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Most readings of Kierkegaard’s Fear and Trembling take its account of the Abraham and Isaac story to imply fairly obviously that duty towards God is absolutely distinct from, and therefore capable of superseding, duty towards neighbor or son. This paper will argue, however, that the Akedah, or ‘binding’ of Isaac, as Kierkegaard’s pseudonym, Johannes de Silentio, depicts it, binds Abraham to Isaac in a revitalized neighbor relation that is not at all subordinate, in any simple way, to Abraham’s God-relation. (...) The two relations are defined by an intimate mutual tension, a dynamic of passionate inwardness that responds to the immediate demands of the neighbor as fully as the ethics that Levinas notoriously accuses Kierkegaard of having ignored. It is also the dynamic of time consciousness, which for Levinas is fundamentally ethical. I show that Kierkegaardian faith can be viewed as the dynamic of time-consciousness transformed by passionate inwardness into one’s God-relation—that is, converted into a certain religious mode of life. The ethics corresponding to this—an ethics of neighbor love superseding the ‘social morality’ that Silentio, following Hegel, calls the ‘ethical’—would then be the same dynamic of time-consciousness transformed by passionate inwardness into one’s neighbor-relation. The key to the argument is seeing the need to substitute for the spatial dichotomy ‘interior/exterior,’ which results in so much trouble when comparing Levinas and Kierkegaard, the temporal contraries ‘giving up’ and ‘getting back.’. (shrink)

The dark matter problem in astrophysics exposes an underappreciated weakness in the evidential warrant for General Relativity (GR). The "dark matter double bind" entails that GR gets no differential evidential support from dynamical phenomena occurring at scales larger than our solar system, as compared to members of a significant class of rival gravitation theories. These rivals are each empirically indistinguishable from GR for phenomena taking place at solar system scales, but make predictions that may differ radically from GR's at larger (...) scales. Thus the typical confidence in the universal applicability of GR is insufficiently warranted in the present evidential context. (shrink)

A general conceptual framework for large-scale neocortical dynamics based on data from many laboratories is applied to a variety of experimental designs, spatial scales, and brain states. Partly distinct, but interacting local processes (e.g., neural networks) arise from functional segregation. Global processes arise from functional integration and can facilitate (top down) synchronous activity in remote cell groups that function simultaneously at several different spatial scales. Simultaneous local processes may help drive (bottom up) macroscopic global dynamics observed with electroencephalography (EEG) or (...) magnetoencephalography (MEG). A local/global dynamic theory that is consistent with EEG data and the proposed conceptual framework is outlined. This theory is neutral about properties of neural networks embedded in macroscopic fields, but its global component makes several qualitative and semiquantitative predictions about EEG measures of traveling and standing wave phenomena. A more general “metatheory” suggests what large-scale quantitative theories of neocortical dynamics may be like when more accurate treatment of local and nonlinear effects is achieved. The theory describes the dynamics of excitatory and inhibitory synaptic action fields. EEG and MEG provide large-scale estimates of modulation of these synaptic fields around background levels. Brain states are determined by neuromodulatory control parameters. Purely local states are dominated by local feedback gains and rise and decay times of postsynaptic potentials. Dominant local frequencies vary with brain region. Other states are purely global, with moderate to high coherence over large distances. Multiple global mode frequencies arise from a combination of delays in corticocortical axons and neocortical boundary conditions. Global frequencies are identical in all cortical regions, but most states involve dynamic interactions between local networks and the global system. EEG frequencies may involve a “matching” of local resonant frequencies with one or more of the many, closely spaced global frequencies. Key Words: binding problem; cell assemblies; coherence; EEG; limit cycles; neocortical dynamics; pacemakers; phase locking; spatial scale; standing waves; synchronization. Footnotes1 The relationship between the synaptic action fields proposed in the target article and cell assemblies is clarified with Figure R1 (p. 416) of the Response. (This figure was not available to Commentators. (shrink)

Recent advances in genomic and imaging techniques have revealed the complex manner of organizing billions of base pairs of DNA necessary for maintaining their functionality and ensuring the proper expression of genetic information. The SMC proteins and cohesin complex primarily contribute to forming higher‐order chromatin structures, such as chromosomal territories, compartments, topologically associating domains (TADs) and chromatin loops anchored by CCCTC‐binding factor (CTCF) protein or other genome organizers. Cohesin plays a fundamental role in chromatin organization, gene expression and regulation. (...) This review aims to describe the current understanding of the dynamic nature of the cohesin‐DNA complex and its dependence on cohesin for genome maintenance. We discuss the current 3C technique and numerous bioinformatics pipelines used to comprehend structural genomics and epigenetics focusing on the analysis of Cohesin‐centred interactions. We also incorporate our present comprehension of Loop Extrusion (LE) and insights from stochastic modelling. (shrink)

Linguistics and philosophy have provided distinct views on the nature of reference to individuals in language. In philosophy, in particular in the tradition of direct reference, the distinction is between reference and description. In linguistics, in particular in the tradition of generative grammar, the distinction is between pronouns and R-expressions. I argue for a third conception, grounded in dynamic semantics, in which the main watershed is between definites, which trigger presuppositions that want to be bound, and indefinites, which set (...) up new discourse referents. On this view, proper names, indexicals, and definite descriptions are all analyzed as presupposition triggers. (shrink)

Describing actions entails that relations between objects are discovered. A pervasively neural account of this process requires that fundamental problems are solved: the neural pointer problem, the binding problem, and the problem of generating discrete processing steps from time-continuous neural processes. We present a prototypical solution to these problems in a neural dynamic model that comprises dynamic neural fields holding representations close to sensorimotor surfaces as well as dynamic neural nodes holding discrete, language-like representations. Making the (...) connection between these two types of representations enables the model to describe actions as well as to perceptually ground movement phrases—all based on real visual input. We demonstrate how the dynamic neural processes autonomously generate the processing steps required to describe or ground object-oriented actions. By solving the fundamental problems of neural pointing, binding, and emergent discrete processing, the model may be a first but critical step toward a systematic neural processing account of higher cognition. (shrink)

We propose that the missing link from nonhuman to human cognition lies with our ability to form, modify, and re-form dynamic bindings between internal representations of world-states. This capacity goes beyond dynamic feature binding in perception and involves a new conception of working memory. We propose two tests for structured knowledge that might alleviate the impasse in empirical research in nonhuman animal cognition.

Over the past few years, there have been a series of attempts Zee89, GS90, EK95, Mus94, KKP95] to combine the Montagovian type theoretic framework Mon74] with dynamic approaches, such as DRT Kam81]. The motivation for these developments is to obtain a general logical framework for discourse semantics that combines compositionality and dynamic binding.

Transcription factor (TF) signaling regulates gene transcription and requires a complex network of proteins. This network includes co‐activators, co‐repressors, multiple TFs, histone‐modifying complexes, and the basal transcription machinery. It has been widely appreciated that pioneer factors, such as FoxA1 and GATA1, play an important role in opening closed chromatin regions, thereby allowing binding of a secondary factor. In this review we will focus on a newly proposed model wherein multiple TFs, such as steroid receptors (SRs), can function in a (...) pioneering role. This model, termed dynamic assisted loading, integrates data from widely divergent methodologies, including genome wide ChIP‐Seq, digital genomic footprinting, DHS‐Seq, live cell protein dynamics, and biochemical studies of ATP‐dependent remodeling complexes, to present a real time view of TF chromatin interactions. Under this view, many TFs can act as initiating factors for chromatin landscape programming. Furthermore, enhancer and promoter states are more accurately described as energy‐dependent, non‐equilibrium steady states. (shrink)

While the prevailing perspective on executive leadership has emphasized the effectiveness of a unified command structure, family firms frequently adopt shared leadership structures, such as dyads, triads, or larger co-CEO constellations. Given the widespread use of such structures in family firms, it becomes imperative to understand how family involvement in the firm shapes the dynamics of co-CEO constellations and their implications for firm outcomes. Drawing upon the socioemotional wealth (SEW) perspective, we propose that the salience of extended SEW concerns increases (...) the costs associated with a shared leadership structure. These elevated costs, in turn, result in adverse environmental, social, and governance (ESG) outcomes. Our empirical analysis, based on panel data from 76 Italian firms listed on the Milan Stock Exchange during 2003–2020, suggests that family firms employing a co-CEO structure tend to exhibit lower ESG performance, while a positive relationship emerges in nonfamily firms. We theorize and find empirical support that the negative effect for family firms stems from family-induced cognitive diversity, manifested via the inclusion of both family and nonfamily members or family members from different generations in the co-CEO constellation. Importantly, we identify a key mitigating factor: when one of the co-CEOs also holds the position of the board chair, the negative impact of the co-CEO structure on ESG performance is mitigated and even turns positive. These findings advance our understanding of how family involvement in the shared leadership structure shapes a firm’s ethical orientation, having important implications for the governance of family firms. (shrink)

In order to handle presuppositions in the scope of attitude verbs, the binding theory allows presuppositions triggered in a subject's beliefs to be bound at the matrix level; and it allows presuppositions triggered in non-doxastic attitudes to be bound in the subject's beliefs (Geurts, 1999; Maier, 2015). However, we argue that this leads to serious overgeneration, for example it predicts that the unacceptable `Sue will come to the party, but Bill is sure that she won't and that only Sue (...) will come to the party' should be equivalent to the acceptable `Sue will come to the party, but Bill is sure that nobody will come to the party'. This is because the presupposition triggered by `only Sue will come to the party' should be able to be bound at the matrix level. We discuss some responses to this problem, but argue that they all have shortcomings. (shrink)

Post‐transcriptional regulation faces a distinctive challenge in gametes. Transcription is limited when the germ cells enter the division phase due to condensed chromatin, while gene expression during gamete maturation, fertilization, and early cleavage depends on existing mRNA post‐transcriptional coordination. The dynamics of the 3ʹ‐poly(A) tail play crucial roles in defining mRNA fate. The 3ʹ‐poly(A) tail is covered with poly(A)‐binding proteins (PABPs) that help to mediate mRNA metabolism and recent work has shed light on the number and function of germ (...) cell‐specific expressed PABPs. There are two structurally different PABP groups distinguished by their cytoplasmic and nuclear localization. Both lack catalytic activity but are coupled with various roles through their interaction with multifunctional partners during mRNA metabolism. Here, we present a synopsis of PABP function during gametogenesis and early embryogenesis and describe both conventional and current models of the functions and regulation of PABPs, with an emphasis on the physiological significance of how germ cell‐specific PABPs potentially affect human fertility. (shrink)

This paper advances recent efforts to re-integrate Tourette Syndrome (TS) with phenomenological psychiatry by centring discussions on the ticcing person as an agent interacting with her world. To achieve this, I will draw on a concept which rarely appears in the literature on tic disorders, but which is central to phenomenological psychiatry: the self and, more specifically, the notion of agency. First, I will present emerging experimental evidence for altered agency dynamics in TS, as expressed by both heightened attributions of (...) agency (AA) and a weakened pre-reflective sense of agency (SA). I will explore possible explanations for these agency dynamics by drawing on contemporary neuroscientific experiments on perception–action binding in TS and suggest that there is a person-level “phenomenological correlate” to the strong binding effect observed between perception and action in the experimental literature. Next, I will ask how hypo-SA and hyper-AA may be interrelated, and what other factors might influence agency dynamics in TS. In conclusion, I call for more nuanced phenomenological research into Tourettic experiences of agency and their implications and opportunities for research and care. (shrink)

Agnes Heller was one of the first critical theorists to turn her attention to a contemporary theory of modernity. Yet her many writings on this topic remained fragments until the publication of her A Theory of Modernity (1999). This article focuses on the structural elements of this account. It traces the evolution of Heller's ideas in regard to logics, dynamic and social arrangement of modernity. It explains how these fit into her own development towards the standpoint she describes as (...) postmodern resignation and her notions of the `double bind' and `pendulum of modernity'. It argues that while Heller has modified her conception of the multiple logics of modernity to keep faith with a critical brief and an open-ended vision, some theoretical tensions remain. In particular, it explores the idea of modernity as a `steamroller' in conjunction with the question of its survival. It also questions whether Heller's emphatic normative vision of cultural modernity can easily be reconciled with the empirical trends of globalization that promise an increasing diversity of modernities. (shrink)

Rho/Rac proteins constitute a subgroup of the Ras superfamily of GTP hydrolases. Although originally implicated in the control of cytoskeletal events, it is currently known that these GTPases coordinate diverse cellular functions, including cell polarity, vesicular trafficking, the cell cycle and transcriptomal dynamics. In this review, we will provide an overview on the recent advances in this field regarding the mechanism of regulation and signaling, and the roles in vivo of this important GTPase family. BioEssays 29:356–370, 2007. © 2007 Wiley (...) Periodicals, Inc. (shrink)

Color-motion asynchrony (CMA) refers to an apparent lag of direction of motion when a dynamic stimulus changes both color and direction at the same time. The subjective order of simultaneous events, however, is not only perceptual but also subject to illusions during voluntary actions. Self-initiated actions, for example, seem to precede their sensory outcomes following an adaptation to a delay between the action and the sensory feedback. Here, we demonstrate that the extent of the apparent asynchrony can be substantially (...) reduced when direction change is induced by a voluntary key press following a delay adaptation regime. We also show that the reduced color-motion asynchrony effect size following a motor-sensory recalibration is not a result of a change in the onset of perceived direction change relative to that of the color. This is particularly important as it implies, for the first time in the literature, that voluntary action is not only important in forming action-sensory outcome associations but may also act as a binding factor between the two perceptual features of a sensory event. (shrink)

We present a neural dynamic model that perceptually grounds nested noun phrases, that is, noun phrases that contain further (possibly also nested) noun phrases as parts. The model receives input from the visual array and a representation of a noun phrase from language processing. It organizes a search for the denoted object in the visual scene. The model is a neural dynamic architecture of interacting neural populations which has clear interfaces with perceptual processes. It solves a set of (...) theoretical challenges, including the problem of keeping a nested structure in short-term memory in a way that solves the problem of 2 and massive binding problem emphasized by Jackendoff. The model organizes a search for the objects that are referenced in that structure. We motivate the model, demonstrate simulation results, and discuss how it differs from related models. (shrink)

The Streptococcus pyogenes CRISPR‐Cas system has gained widespread application as a genome editing and gene regulation tool as simultaneous cellular delivery of the Cas9 protein and guide RNAs enables recognition of specific DNA sequences. The recent discovery that Cas9 can also bind and cleave RNA in an RNA‐programmable manner indicates the potential utility of this system as a universal nucleic acid‐recognition technology. RNA‐targeted Cas9 (RCas9) could allow identification and manipulation of RNA substrates in live cells, empowering the study of cellular (...) gene expression, and could ultimately spawn patient‐ and disease‐specific diagnostic and therapeutic tools. Here we describe the development of RCas9 and compare it to previous methods for RNA targeting, including engineered RNA‐binding proteins and other types of CRISPR‐Cas systems. We discuss potential uses ranging from live imaging of transcriptional dynamics to patient‐specific therapies and applications in synthetic biology. (shrink)

We address the biological dynamics problem of the persistence of several species in conditions of non-existence of an equilibrium, including an example of stabilization by predation and the very controversial “competitive exclusion”. We give normal forms for various examples of such persistence and comments on the involved topology, which implies the presence of exceptional heteroclinic connections binding equilibria on the boundary.

The preceding five years have brought remarkable advances in our understanding of the primary structure of drug receptors. The roles of certain amino acid residues in binding drugs and effecting receptor function have been proposed. As even more detailed structures become available, the goal of rational design of drug molecules based on predicted fits between the drug and its receptor will be near at hand. Although none of the classical receptors has yet yielded to X‐ray crystallographic analysis, the methods (...) of molecular biology facilitate the production of the large amounts of these rare proteins necessary for crystallization. Receptor proteins share one fundamental characteristic with allosterically regulated enzymes. Both have the structural flexibility that allows information to be transmitted to distant parts of the molecule. We will discuss recent observations about receptor structure and the dynamic nature of drug receptors, and pose questions about the significance of receptor dynamics for drug design. (shrink)

Shows that both anaphoricity and egocentric em de se binding play a crucial role in the interpretation of tense in discourse. Uses the English backwards shifted reading of the past tense in a mistaken time scenario to bring out the tension between these two features. Provides a suitable representational framework for the observed clash in the form of an extension of DRT in which updates of the common ground are accompanied by updates of each relevant agent's complex attitudinal state.

It is worthwhile to search for forms of coding, processing, and learning common to various cortical regions and cognitive functions. Local cortical processors may coordinate their activity by maximizing the transmission of information coherently related to the context in which it occurs, thus forming synchronized population codes. This coordination involves contextual field (CF) connections that link processors within and between cortical regions. The effects of CF connections are distinguished from those mediating receptive field (RF) input; it is shown how CFs (...) can guide both learning and processing without becoming confused with the transmission of RF information. Simulations explore the capabilities of networks built from local processors with both RF and CF connections. Physiological evidence for synchronization, CFs, and plasticity of the RF and CF connections is described. Coordination via CFs is related to perceptual grouping, the effects of context on contrast sensitivity, amblyopia, implicit influences of color in achromotopsia, object and word perception, and the discovery of distal environmental variables and their interactions through self-organization. Cortical computation could thus involve the flexible evaluation of relations between input signals by locally specialized but adaptive processors whose activity is dynamically associated and coordinated within and between regions through specialized contextual connections. Key Words: cell assemblies; cerebral cortex; context; coordination; dynamic binding; epistemology; functional specialization; learning; neural coding; neural computation; neuropsychology; object recognition; perception; reading; self-organization; synaptic plasticity; synchronization. (shrink)

Microtubules form a highly dynamic filament network in all eukaryotic cells. Individual microtubules grow by tubulin dimer subunit addition and frequently switch between phases of growth and shortening. These unique dynamics are powered by GTP hydrolysis and drive microtubule network remodeling, which is central to eukaryotic cell biology and morphogenesis. Yet, our knowledge of the molecular events at growing microtubule ends remains incomplete. Here, recent ultrastructural, biochemical and cell biological data are integrated to develop a realistic model of growing (...) microtubule ends comprised of structurally distinct but biochemically overlapping zones. Proteins that recognize microtubule lattice conformations associated with specific tubulin guanosine nucleotide states may independently control major structural transitions at growing microtubule ends. A model is proposed in which tubulin dimer addition and subsequent closure of the MT wall are optimized in cells to achieve rapid physiological microtubule growth. (shrink)

We suggest a common ground for alternative proposals In different domains of cognitive science which have previously seemed to have little in common. The underlying common theme is associated with a redefinition of the basic unit of analysis in each domain of thought. Our framework suggests a definition of unity which is based not on inherent properties of the elements constituting the unit, but rather on dynamic patterns of correlation across the elements. We introduce a set of features that (...) characterize the new dynamic units, and distinguish them from traditional units of analysis. A conceptual connection is made with the identification of elementary units in modern physics theories, as well as with concepts and structures in the study of complex dynamical systems and connectionism. The paper analyses the evolution of the concept of unit in different domains of thought in cognitive science, and examines the proposed framework of “dynamic unity” with regard to various theoretical problems within each domain. The particular cognitive science issues discussed in the paper include: (1) the binding problem in the brain; (2) the mental unit of conceptual organization; (3) defining ‘wordhood’ in linguistics; and (4) identifying the unit of cognition in the natural environment. (shrink)

The BTB domain is a protein–protein interaction motif that is found throughout eukaryotes. It determines a unique tri‐dimensional fold with a large interaction surface. The exposed residues are highly variable and can permit dimerization and oligomerization, as well as interaction with a number of other proteins. BTB‐containing proteins are numerous and control cellular processes that range from actin dynamics to cell‐cycle regulation. Here, we review findings in the field of transcriptional regulation to illustrate how the high variability of the BTB (...) has allowed related transcription factors to evolve different functional abilities. We then report how recent work has showed that, in spite of their high sequence divergence and apparently unrelated functions, many BTB‐containing proteins have at least one shared role: the recruitment of degradation targets to E3 ubiquitin ligase complexes. Taken together, these findings illustrate diverse and convergent functions of a versatile protein–protein interaction domain. BioEssays 28: 1194–1202, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

In a recent paper, Pickel and Rabern (2016) argue that a dynamic Tarskian semantics resolves Fine’s antinomy of the variable without the radical consequences for semantics proposed by Fine (2003, 2007). While Pickel and Rabern’s basic insight—a parameter of discourse context that tracks occurrences of variable-binding expressions—is important, I will argue that their own Tarskian theory faces a destructive dilemma: either their theory does not resolve Fine’s antinomy as they propose, or their theory does not reflect the intuitive (...) motivation for what they call structured meanings. I suggest that in response to this dilemma we should reject one of the principles that generates Pickel and Rabern’s version of the antinomy. Here Pickel and Rabern’s insight has surprising, but salutary, foundational consequences for semantics. (shrink)