Evidence-Based Network Modelling to Simulate Nucleus Pulposus Multicellular Activity in Different Nutritional and Pro-Inflammatory Environments

Initiation of intervertebral disc degeneration is thought to be biologically driven. This reflects a process, where biochemical and mechanical stimuli affect cell activity (CA) that compromise the tissue strength over time. Experimental research enhanced our understanding about the effect of such stimuli on different CA, such as protein synthesis or mRNA expression. However, it is still unclear how cells respond to their native environment that consists of a “cocktail” of different stimuli that might locally vary. This work presents an interdisciplinary approach of experimental and in silico research to approximate Nucleus Pulposus CA within multifactorial biochemical environments. Thereby, the biochemical key stimuli glucose, pH, and the proinflammatory cytokines TNF-α and IL1β were considered that were experimentally shown to critically affect CA. To this end, a Nucleus Pulposus multicellular system was modelled. It integrated experimental findings from in vitro studies of human or bovine Nucleus Pulposus cells, to relate the individual effects of targeted stimuli to alterations in CA. Unknown stimulus-CA relationships were obtained through own experimental 3D cultures of bovine Nucleus Pulposus cells in alginate beads. Translation of experimental findings into suitable parameters for network modelling approaches was achieved thanks to a new numerical approach to estimate the individual sensitivity of a CA to each stimulus type. Hence, the effect of each stimulus type on a specific CA was assessed and integrated to approximate a multifactorial stimulus environment. Tackled CA were the mRNA expressions of Aggrecan, Collagen types I & II, MMP3, and ADAMTS4. CA was assessed for four different proinflammatory cell states; non-inflamed and inflamed for IL1β, TNF-α or both IL1β&TNF-α. Inflamed cell clusters were eventually predicted in a multicellular 3D agent-based model. Experimental results showed that glucose had no significant impact on proinflammatory cytokine or ADAMTS4 mRNA expression, whereas TNF-α caused a significant catabolic shift in most explored CA. In silico results showed that the presented methodology to estimate the sensitivity of a CA to a stimulus type importantly improved qualitative model predictions. However, more stimuli and/or further experimental knowledge need to be integrated, especially regarding predictions about the possible progression of inflammatory environments under adverse nutritional conditions. Tackling the multicellular level is a new and promising approach to estimate manifold responses of intervertebral disc cells. Such a top-down high-level network modelling approach allows to obtain information about relevant stimulus environments for a specific CA and could be shown to be suitable to tackle complex biological systems, including different proinflammatory cell states. The development of this methodology required a close interaction with experimental research. Thereby, specific experimental needs were derived from systematic in silico approaches and obtained results were directly used to enhance model predictions, which reflects a novelty in this research field. Eventually, the presented methodology provides modelling solutions suitable for multiscale approaches to contribute to a better understanding about dynamics over multiple spatial scales. Future work should focus on an amplification of the stimulus environment by integrating more key relevant stimuli, such as mechanical loading parameters, in order to better approximate native physiological environments.

The impact of socioeconomic and stimulus inequality on human brain physiology

The brain undergoes profound structural and dynamical alteration in response to its stimulus environment. In animal studies, enriched stimulus environments result in numerous structural and dynamical changes along with cognitive enhancements. In human society factors such as education, travel, cell phones and motorized transport dramatically expand the rate and complexity of stimulus experience but diverge in access based on income. Correspondingly, poverty is associated with significant structural and dynamical differences in the brain, but it is unknown how this relates to disparity in stimulus access. Here we studied consumption of major stimulus factors along with measurement of brain signals using EEG in 402 people in India across an income range of $0.82 to $410/day. We show that the complexity of the EEG signal scaled logarithmically with overall stimulus consumption and income and linearly with education and travel. In contrast phone use jumped up at a threshold of $30/day corresponding to a similar jump in key spectral parameters that reflect the signal energy. Our results suggest that key aspects of brain physiology increase in lockstep with stimulus consumption and that we have not fully appreciated the profound way that stimulus expanding aspects of modern life are changing our brain physiology.

Personality-Based Affective Adaptation Methods for Intelligent Systems

In this article, we propose using personality assessment as a way to adapt affective intelligent systems. This psychologically-grounded mechanism will divide users into groups that differ in their reactions to affective stimuli for which the behaviour of the system can be adjusted. In order to verify the hypotheses, we conducted an experiment on 206 people, which consisted of two proof-of-concept demonstrations: a “classical” stimuli presentation part, and affective games that provide a rich and controllable environment for complex emotional stimuli. Several significant links between personality traits and the psychophysiological signals (electrocardiogram (ECG), galvanic skin response (GSR)), which were gathered while using the BITalino (r)evolution kit platform, as well as between personality traits and reactions to complex stimulus environment, are promising results that indicate the potential of the proposed adaptation mechanism.

The Influence of Situational Cues on Children’s Creativity in an Alternative Uses Task and the Moderating Effect of Selective Attention

Taking a perception-action perspective, we investigated how the presence of different real objects in children’s immediate situation affected their creativity and whether this effect was moderated by their selective attention. Seventy children between ages 9 and 12 years old participated. Verbal responses on a visual Alternative Uses Task with a low stimulus and high stimulus condition were coded on fluency, flexibility, and originality. Selective attention was measured with a visual search task. Results showed that fluency was not affected by stimulus condition and was unrelated to selective attention. Flexibility was positively associated with selective attention. Originality, net of fluency and flexibility, showed a main effect of stimulus condition in an unexpected direction, as children gave more original responses in the low stimulus condition compared to the high stimulus condition. A significant moderation effect revealed that children with better selective attention skills benefitted from a low stimulus environment, whereas children with weaker selective attention performed better in a high stimulus environment. The findings demonstrate differential effects of the immediate situation and selective attention, and support the hypothesis that creativity is impacted by immediate situation and selective attention, yet in unexpected ways.

Системные и ситуационные детерминанты вовлеченности морского судового экипажа в трудовую деятельность

В статье определены факторы, оказывающие существенное влияние на эффективность деятельности моряков, пребывающих на судне на протяжении длительного времени Рассмотрены условия труда моряков на судне, требующие волевых усилий, психологической готовности к ситуативному физическому, интеллектуальному и эмоциональному напряжению, сопровождающемуся периодами монотонии. Цель исследования заключалась в проверке гипотезы о том, что члены экипажа, отличающиеся высоким уровнем включенности в свою трудовую деятельность и ситуацию на судне в целом, менее подвержены влиянию обеднённой стимульной среды, провоцирующей развитие деривационных процессов.In this article the organizational and psychological factors that have a significant impact on the effectiveness of the work of seafarers staying on the ship for a long time are identifies. The conditions in which crew members live and work are examined from a psychological point of view. Among the many factors that can destructively affect for the psycho-emotional state, sensory, cognitive, emotional and social types of deprivation are considered in detail. The working conditions of seafarers on the ship, requiring volitional efforts, psychological readiness for situational physical, intellectual and emotional stress, accompanied by periods of monotony, are considered. The purpose of the study is to test the hypothesis that crewmembers who are distinguished by a high level of involvement in their work activity and the situation on the ship as a whole are less susceptible to the effect of a depleted stimulus environment that provokes the development of diversion processes.

Supporting Creativity with Virtual Reality Technology

This contribution includes the development and validation of a Virtual Reality (VR) supported creativity technique: “Sensory Stimulus Environment Technique”. Key elements of this technique are the creativity process, a VR tool and the support of the tool (Virtual Creative Environments). The creativity process consists of phases for individual and group-based work. The VR tool “Virtual Creativity” includes functions to support the preparation of Virtual Creative Environments (VCE), the generation and evaluation of new ideas. For the generation of VCE, the tool possesses an environment configurator. Users of this function are supported by Design Rules for VCE.For the validation of the creativity technique, it was used in a product engineering project. The project members procedure two phases of the creativity process (Preparation and Individual Idea Generation) and used “Virtual Creativity” to generate VCEs and ideas to solve their tasks. By questionnaires, functions of “Virtual Creativity” were assessed for generating VCEs and ideas.

Phasic and tonic neuron ensemble codes for stimulus-environment conjunctions in the lateral entorhinal cortex

The lateral entorhinal cortex (LEC) is thought to bind sensory events with the environment where they took place. To compare the relative influence of transient events and temporally stable environmental stimuli on the firing of LEC cells, we recorded neuron spiking patterns in the region during blocks of a trace eyeblink conditioning paradigm performed in two environments and with different conditioning stimuli. Firing rates of some neurons were phasically selective for conditioned stimuli in a way that depended on which room the rat was in; nearly all neurons were tonically selective for environments in a way that depended on which stimuli had been presented in those environments. As rats moved from one environment to another, tonic neuron ensemble activity exhibited prospective information about the conditioned stimulus associated with the environment. Thus, the LEC formed phasic and tonic codes for event-environment associations, thereby accurately differentiating multiple experiences with overlapping features.