From segment to somite: segmentation to epithelialization analyzed within quantitative frameworks

One of the most visually striking patterns in the early developing embryo is somite segmentation. Somites form as repeated, periodic structures in pairs along nearly the entire caudal vertebrate axis. The morphological process involves short- and long-range signals that drive cell rearrangements and cell shaping to create discrete, epithelialized segments. Key to developing novel strategies to prevent somite birth defects that involve axial bone and skeletal muscle development is understanding how the molecular choreography is coordinated across multiple spatial scales and in a repeating temporal manner. Mathematical models have emerged as useful tools to integrate spatiotemporal data and simulate model mechanisms to provide unique insights into somite pattern formation. In this short review, we present two quantitative frameworks that address the morphogenesis from segment to somite and discuss recent data of segmentation and epithelialization

MODELLING OF MATERIAL PHENOMENA OF STEEL IN CONSTITUTIVE RELATIONS IN CONTEXT OF WELDING

The application of partly decoupled approach by means of continuum mechanics facilitates the calculation of structural responses due to welding. The numerical results demonstrate the ability of a qualitative prediction of welded connections. As it is intended to integrate the local effects of a joint in structural analysis of steel constructions, it is necessary to meet higher approaches towards quality. The wide array of material parameters are presented, which are affecting the thermal, metallurgical and mechanical behavior, and which have to be identified. For that purpose further investigations are necessary to analyze the sensitivity of the models towards different material properties. The experimental determination of every material parameter is not possible due to the extraordinary laborious efforts needed. Besides that, experimentally identified parameters can be applied only for the tested steel quality for measured temperature-time regimes. For that reason alternative approaches for identification of material parameters, such as optimization strategies, have to be applied. After a definition of material parameters a quantitative prediction of welded connections will also be possible. Numerical results show the effect of phase transformation, activated by welding process, on residual stress state. As these phenomena occur in local areas in the range of crystal and grain sizes, the description of microscopic phenomena and their propagation on a macroscopic level due to approaches of homogenization might be expedient. Nevertheless, one should bear in mind, the increasing number of material parameters as well as the complexity of their experimental determination. Thus the microscopic approach should always be investigated under the scope of ability and efficiency of a required prediction. Under certain circumstances a step backwards, adopting a phenomenological approach, also can be beneficial

A Compositionality Machine Realized by a Hierarchic Architecture of Synfire Chains

The composition of complex behavior is thought to rely on the concurrent and sequential activation of simpler action components, or primitives. Systems of synfire chains have previously been proposed to account for either the simultaneous or the sequential aspects of compositionality; however, the compatibility of the two aspects has so far not been addressed. Moreover, the simultaneous activation of primitives has up until now only been investigated in the context of reactive computations, i.e., the perception of stimuli. In this study we demonstrate how a hierarchical organization of synfire chains is capable of generating both aspects of compositionality for proactive computations such as the generation of complex and ongoing action. To this end, we develop a network model consisting of two layers of synfire chains. Using simple drawing strokes as a visualization of abstract primitives, we map the feed-forward activity of the upper level synfire chains to motion in two-dimensional space. Our model is capable of producing drawing strokes that are combinations of primitive strokes by binding together the corresponding chains. Moreover, when the lower layer of the network is constructed in a closed-loop fashion, drawing strokes are generated sequentially. The generated pattern can be random or deterministic, depending on the connection pattern between the lower level chains. We propose quantitative measures for simultaneity and sequentiality, revealing a wide parameter range in which both aspects are fulfilled. Finally, we investigate the spiking activity of our model to propose candidate signatures of synfire chain computation in measurements of neural activity during action execution

Border forces and friction control epithelial closure dynamics

Epithelization, the process whereby an epithelium covers a cell-free surface, is not only central to wound healing but also pivotal in embryonic morphogenesis, regeneration, and cancer. In the context of wound healing, the epithelization mechanisms differ depending on the sizes and geometries of the wounds as well as on the cell type while a unified theoretical decription is still lacking. Here, we used a barrier-based protocol that allows for making large arrays of well-controlled circular model wounds within an epithelium at confluence, without injuring any cells. We propose a physical model that takes into account border forces, friction with the substrate, and tissue rheology. Despite the presence of a contractile actomyosin cable at the periphery of the wound, epithelization was mostly driven by border protrusive activity. Closure dynamics was quantified by an epithelization coefficient $D = \sigma_p/\xi$ defined as the ratio of the border protrusive stress $\sigma_p$ to the friction coefficient $\xi$ between epithelium and substrate. The same assay and model showed a high sensitivity to the RasV12 mutation on human epithelial cells, demonstrating the general applicability of the approach and its potential to quantitatively characterize metastatic transformations.Comment: 44 pages, 17 figure

Motor potentials evoked by transcranial magnetic stimulation: interpreting a simple measure of a complex system

Transcranial magnetic stimulation (TMS) is a non‐invasive technique that is increasingly used to study the human brain. One of the principal outcome measures is the motor‐evoked potential (MEP) elicited in a muscle following TMS over the primary motor cortex (M1), where it is used to estimate changes in corticospinal excitability. However, multiple elements play a role in MEP generation, so even apparently simple measures such as peak‐to‐peak amplitude have a complex interpretation. Here, we summarize what is currently known regarding the neural pathways and circuits that contribute to the MEP and discuss the factors that should be considered when interpreting MEP amplitude measured at rest in the context of motor processing and patients with neurological conditions. In the last part of this work, we also discuss how emerging technological approaches can be combined with TMS to improve our understanding of neural substrates that can influence MEPs. Overall, this review aims to highlight the capabilities and limitations of TMS that are important to recognize when attempting to disentangle sources that contribute to the physiological state‐related changes in corticomotor excitability