Till D. Frank

Order parameter dynamics of body-scaled hysteresis and mode transitions in grasping behavior.

Several experimental studies have shown that human grasping behavior exhibits a transition from one-handed to two-handed grasping when to-be-grasped objects become larger and larger. The transition point depends on the relative size of objects measured in terms of human body-scales. Most strikingly, the transitions between the two different behavioral ‘modes’ of grasping exhibit hysteresis. That is, one-to-two hand transitions and two-to-one hand transitions occur at different relative object sizes when objects are scaled up or down in size. In our study we approach body-scaled hysteresis and mode transitions in grasping by exploiting the notion that human behavior in general results from self-organization and satisfies appropriately-defined order parameter equations. To this end, grasping transitions and grasping hysteresis are discussed from a theoretical perspective in analogy to cognitive processes defined by Haken’s neural network model for pattern recognition. In doing so, issues such as the exclusivity of grasping modes, biomechanical constraints, mode-mode interactions, single subject behavior and population behavior are explored.

NFκB and HIF display synergistic behaviour during hypoxic inflammation

The oxygen-sensitive transcription factor hypoxia inducible factor (HIF) is a key regulator of gene expression during adaptation to hypoxia. Crucially, inflamed tissue often displays regions of prominent hypoxia. Recent studies have shown HIF signalling is intricately linked to that of the pro-inflammatory transcription factor nuclear factor kappa B (NFκB) during hypoxic inflammation. We describe the relative temporal contributions of each to hypoxia-induced inflammatory gene expression and investigate the level of crosstalk between the two pathways using a novel Gaussia princeps luciferase (Gluc) reporter system. Under the control of an active promoter, Gluc is expressed and secreted into the cell culture media, where it can be sampled and measured over time. Thus, Gluc constructs under the control of either HIF or NFκB were used to resolve their temporal transcriptional dynamics in response to hypoxia and to cytokine stimuli, respectively. We also investigated the interactions between HIF and NFκB activities using a construct containing the sequence from the promoter of the inflammatory gene cyclooxygenase 2 (COX-2), which includes functionally active binding sites for both HIF and NFκB. Finally, based on our experimental data, we constructed a mathematical model of the binding affinities of HIF and NFκB to their respective response elements to analyse transcriptional crosstalk. Taken together, these data reveal distinct temporal HIF and NFκB transcriptional activities in response to hypoxic inflammation. Furthermore, we demonstrate synergistic activity between these two transcription factors on the regulation of the COX-2 promoter, implicating a co-ordinated role for both HIF and NFκB in the expression of COX-2 in hypoxic inflammation.

Behavioral dynamics of the affordance "graspable".

On a daily basis, one perceives whether an object affords grasping with one hand or with both hands. In experiments in which differently sized objects of a fixed type have been presented, the transition from using one manual mode to the other has depended on both the ratio of object size to hand span and the presentation sequence—that is, size increasing versus decreasing. The transitions and their observed hysteresis (i.e., a transition ratio larger for the increasing sequence) can be accommodated by the order parameter dynamics typifying self-organizing systems. Here, we show that hysteresis magnitude depends on (a) the interaction between the attractors (one hand vs. two hands) and (b) the strength of the two-hands attractor. Through modeling and experimental results, we extend the investigation of affordance perception within dynamical-systems theory.

Negative hysteresis in the behavioral dynamics of the affordance “graspable”

One commonly perceives whether a visible object will afford grasping with one hand or with both hands. In experiments in which differently sized objects of a fixed type are presented, the transition from using one of these manual modes to the other depends on the ratio of object size to hand span and on the presentation sequence, with size increasing versus decreasing. Conventional positive hysteresis (i.e., a larger transition ratio for the increasing sequence) can be accommodated by the order parameter dynamics that typify self-organizing systems (Lopresti-Goodman, Turvey, and Frank, Attention, Perception, & Psychophysics 73:1948–1965, 2011). Here we identified and addressed conditions of unconventional negative hysteresis (i.e., a larger transition ratio for the decreasing sequence). They suggest a second control parameter in the self-organization of affordance perception, one that is seemingly regulated by inhibitory dynamics occurring in the agent–task–environment system. Our experimental results and modeling extend the investigation of affordance perception within dynamical systems theory.

Deterministic and Stochastic Postural Processes: Effects of Task, Environment, and Age

ABSTRACT Upright standing is always environmentally embedded and typically co-occurs with another (suprapostural) activity. In the present study, the authors investigate how these facts affect postural dynamics in an experiment in which younger (M age = 20.23 years, SD = 2.02 years) and older (M age = 75.26 years, SD = 4.87 years) participants performed a task of detecting letters in text or maintaining gaze within a target while standing upright in a structured or nonstructured stationary environment. They extracted the coefficients of drift (indexing attractor strength) and diffusion (indexing noise strength) from the center of pressure (COP) time series in anteroposterior (AP) and mediolateral (ML) axes. COP standard deviation decreased with drift and increased with diffusion. The authors found that structure reduced AP diffusion for both groups and that letter detection reduced younger SD AP (primarily by diffusion decrease) and increased older SD ML (primarily by drift decrease). For older and younger participants, ML drift was lower during letter detection. Further, in older letter detection, larger visual contrast sensitivity was associated with larger ML drift and smaller SD ML, raising the hypotheses that ML sway helps information detection and reflects neurophysiological age.

Species differential regulation of COX2 can be described by an NFκB-dependent logic AND gate

Cyclooxygenase 2 (COX2), a key regulatory enzyme of the prostaglandin/eicosanoid pathway, is an important target for anti-inflammatory therapy. It is highly induced by pro-inflammatory cytokines in a Nuclear factor kappa B (NFκB)-dependent manner. However, the mechanisms determining the amplitude and dynamics of this important pro-inflammatory event are poorly understood. Furthermore, there is significant difference between human and mouse COX2 expression in response to the inflammatory stimulus tumor necrosis factor alpha (TNFα). Here, we report the presence of a molecular logic AND gate composed of two NFκB response elements (NREs) which controls the expression of human COX2 in a switch-like manner. Combining quantitative kinetic modeling and thermostatistical analysis followed by experimental validation in iterative cycles, we show that the human COX2 expression machinery regulated by NFκB displays features of a logic AND gate. We propose that this provides a digital, noise-filtering mechanism for a tighter control of expression in response to TNFα, such that a threshold level of NFκB activation is required before the promoter becomes active and initiates transcription. This NFκB-regulated AND gate is absent in the mouse COX2 promoter, most likely contributing to its differential graded response in promoter activity and protein expression to TNFα. Our data suggest that the NFκB-regulated AND gate acts as a novel mechanism for controlling the expression of human COX2 to TNFα, and its absence in the mouse COX2 provides the foundation for further studies on understanding species-specific differential gene regulation.

CONJUGATE MIRROR DESIGN AND SIMULATION USING A NONLINEAR COUPLING MICRORING CIRCUIT

This paper presents the use of a nonlinear microring resonator device known as a modified add-drop filter for small scale conjugate mirror, which is a basic device for 3D image construction and reconstruction system. It can also be useful for real time 3D image display applications. By using the modified add-drop filter, the 3D image can be constructed and reconstructed within the microring circuit. In this circuit, the object and reference beams can be formed by the reflected signals from through and drop ports of the add-drop filter respectively, where the conjugate mirror concept is obtained by the nonlinear coupling effects via the two nonlinear side rings, in which the four-wave mixing of those signals can be introduced. Finally, the interference of those two beams can be constructed and seen by the whispering gallery mode (WGM) at the center ring, while the interference signals can be seen by the add port output. The WGMs of waves are simulated and discussed, where the 3D image construction and reconstruction can be seen by using the microring circuit as the conjugate mirror, in which the use of large volume display using a new type of conjugate mirror can be realized.

Multistable Pattern Formation Systems: Candidates for Physical Intelligence?

We argue that multistable physical pattern formation systems of the inanimate world, such as fluids and gases producing convection rolls, are promising candidate systems for physical intelligence. The reason for this is that the principles that govern intelligent behavior of humans and animals and have been used to construct certain numerical algorithms in the field of artificial intelligence are quite similar to the principles that underlie pattern formation in physical systems. In order to support this claim we demonstrate that the emergence of convection rolls in fluid and gas layers, human “intelligent” behavior as revealed in grasping transitions, and certain pattern recognition processes of “intelligent” engineered algorithms satisfy the same underlying self-organization principles when expressing them mathematically in terms of amplitude equations. The implications are at least two-fold. First, we support the hypothesis of the existence of smart physical systems. Second, we demonstrate the possibility indicated previously by Haken (1991) to map smart engineered algorithms to physical systems such that physical systems possess the ability to solve problems in the field of artificial intelligence.

Catching transcriptional regulation by thermostatistical modeling

Gene expression is frequently regulated by multiple transcription factors (TFs). Thermostatistical methods allow for a quantitative description of interactions between TFs, RNA polymerase and DNA, and their impact on the transcription rates. We illustrate three different scales of the thermostatistical approach: the microscale of TF molecules, the mesoscale of promoter energy levels and the macroscale of transcriptionally active and inactive cells in a cell population. We demonstrate versatility of combinatorial transcriptional activation by exemplifying logic functions, such as AND and OR gates. We discuss a metric for cell-to-cell transcriptional activation variability known as Fermi entropy. Suitability of thermostatistical modeling is illustrated by describing the experimental data on transcriptional induction of NFκB and the c-Fos protein.

Versatility of Cooperative Transcriptional Activation: A Thermodynamical Modeling Analysis for Greater-Than-Additive and Less-Than-Additive Effects

We derive a statistical model of transcriptional activation using equilibrium thermodynamics of chemical reactions. We examine to what extent this statistical model predicts synergy effects of cooperative activation of gene expression. We determine parameter domains in which greater-than-additive and less-than-additive effects are predicted for cooperative regulation by two activators. We show that the statistical approach can be used to identify different causes of synergistic greater-than-additive effects: nonlinearities of the thermostatistical transcriptional machinery and three-body interactions between RNA polymerase and two activators. In particular, our model-based analysis suggests that at low transcription factor concentrations cooperative activation cannot yield synergistic greater-than-additive effects, i.e., DNA transcription can only exhibit less-than-additive effects. Accordingly, transcriptional activity turns from synergistic greater-than-additive responses at relatively high transcription factor concentrations into less-than-additive responses at relatively low concentrations. In addition, two types of re-entrant phenomena are predicted. First, our analysis predicts that under particular circumstances transcriptional activity will feature a sequence of less-than-additive, greater-than-additive, and eventually less-than-additive effects when for fixed activator concentrations the regulatory impact of activators on the binding of RNA polymerase to the promoter increases from weak, to moderate, to strong. Second, for appropriate promoter conditions when activator concentrations are increased then the aforementioned re-entrant sequence of less-than-additive, greater-than-additive, and less-than-additive effects is predicted as well. Finally, our model-based analysis suggests that even for weak activators that individually induce only negligible increases in promoter activity, promoter activity can exhibit greater-than-additive responses when transcription factors and RNA polymerase interact by means of three-body interactions. Overall, we show that versatility of transcriptional activation is brought about by nonlinearities of transcriptional response functions and interactions between transcription factors, RNA polymerase and DNA.