Complexity in Developmental Systems: Toward an Integrated Understanding of Organ Formation

During animal development, embryonic cells assemble into intricately structured organs by working together in organized groups capable of implementing tightly coordinated collective behaviors, including patterning, morphogenesis and migration. Although many of the molecular components and basic mechanisms underlying such collective phenomena are known, the complexity emerging from their interplay still represents a major challenge for developmental biology. Here, we first clarify the nature of this challenge and outline three key strategies for addressing it: precision perturbation, synthetic developmental biology, and data-driven inference. We then present the results of our effort to develop a set of tools rooted in two of these strategies and to apply them to uncover new mechanisms and principles underlying the coordination of collective cell behaviors during organogenesis, using the zebrafish posterior lateral line primordium as a model system. To enable precision perturbation of migration and morphogenesis, we sought to adapt optogenetic tools to control chemokine and actin signaling. This endeavor proved far from trivial and we were ultimately unable to derive functional optogenetic constructs. However, our work toward this goal led to a useful new way of perturbing cortical contractility, which in turn revealed a potential role for cell surface tension in lateral line organogenesis. Independently, we hypothesized that the lateral line primordium might employ plithotaxis to coordinate organ formation with collective migration. We tested this hypothesis using a novel optical tool that allows targeted arrest of cell migration, finding that contrary to previous assumptions plithotaxis does not substantially contribute to primordium guidance. Finally, we developed a computational framework for automated single-cell segmentation, latent feature extraction and quantitative analysis of cellular architecture. We identified the key factors defining shape heterogeneity across primordium cells and went on to use this shape space as a reference for mapping the results of multiple experiments into a quantitative atlas of primordium cell architecture. We also propose a number of data-driven approaches to help bridge the gap from big data to mechanistic models. Overall, this study presents several conceptual and methodological advances toward an integrated understanding of complex multi-cellular systems

Forecast Performance, Disagreement, and Heterogeneous Signal-to-Noise Ratios

We propose an imperfect information model for the expectations of macroeconomic forecasters that explains differences in average disagreement levels across forecasters by means of cross sectional heterogeneity in the variance of private noise signals. We show that the forecaster-specific signal-to-noise ratios determine both the average individual disagreement level and an individuals' forecast performance: forecasters with very noisy signals deviate strongly from the average forecasts and report forecasts with low accuracy. We take the model to the data by empirically testing for this implied correlation. Evidence based on data from the Surveys of Professional Forecasters for the US and for the Euro Area supports the model for short- and medium-run forecasts but rejects it based on its implications for long-run forecasts

Self-organized collective cell behaviors as design principles for synthetic developmental biology

Over the past two decades, molecular cell biology has graduated from a mostly analytic science to one with substantial synthetic capability. This success is built on a deep understanding of the structure and function of biomolecules and molecular mechanisms. For synthetic biology to achieve similar success at the scale of tissues and organs, an equally deep understanding of the principles of development is required. Here, we review some of the central concepts and recent progress in tissue patterning, morphogenesis and collective cell migration and discuss their value for synthetic developmental biology, emphasizing in particular the power of (guided) self-organization and the role of theoretical advances in making developmental insights applicable in synthesis

An image-based data-driven analysis of cellular architecture in a developing tissue

Quantitative microscopy is becoming increasingly crucial in efforts to disentangle the complexity of organogenesis, yet adoption of the potent new toolbox provided by modern data science has been slow, primarily because it is often not directly applicable to developmental imaging data. We tackle this issue with a newly developed algorithm that uses point cloud-based morphometry to unpack the rich information encoded in 3D image data into a straightforward numerical representation. This enabled us to employ data science tools, including machine learning, to analyze and integrate cell morphology, intracellular organization, gene expression and annotated contextual knowledge. We apply these techniques to construct and explore a quantitative atlas of cellular architecture for the zebrafish posterior lateral line primordium, an experimentally tractable model of complex self-organized organogenesis. In doing so, we are able to retrieve both previously established and novel biologically relevant patterns, demonstrating the potential of our data-driven approach

Dual Use of Liquid Hydrogen in a Next-Generation PEMFC-Powered Regional Aircraft with Superconducting Propulsion

In this paper, we present a comprehensive model framework for a disruptive cryo-electric propulsion system intended for a hydrogen-powered regional aircraft. The main innovation lies in the systematic treatment of all the electrical and thermal components to model the overall system performance. One of the main objectives is to study the feasibility of using the liquid hydrogen (LH2) fuel to provide cryogenic cooling to the cryo-electric propulsion system, and thereby enable ultracompact designs. Another aim has been to identify the optimal working point of the fuel cell to minimize the overall propulsion system’s mass. The full mission profile is evaluated to make the analysis as realistic as possible. Analyses are done for three different 2035 scenarios, where available data from the literature are projected to a baseline, conservative, and optimistic scenario. The results show that the total propulsion system’s power density can be as high as 1.63 kW/kg in the optimistic scenario and 0.79 kW/kg in the baseline scenario. In the optimistic scenario, there is also sufficient cryogenic cooling capacity in the hydrogen to secure proper conditions for all components, whereas the DC/DC converter falls outside the defined limit of 110 K in the baseline scenario.Dual Use of Liquid Hydrogen in a Next-Generation PEMFC-Powered Regional Aircraft with Superconducting PropulsionacceptedVersio

Alpha Rhythms in Audition: Cognitive and Clinical Perspectives

Like the visual and the sensorimotor systems, the auditory system exhibits pronounced alpha-like resting oscillatory activity. Due to the relatively small spatial extent of auditory cortical areas, this rhythmic activity is less obvious and frequently masked by non-auditory alpha-generators when recording non-invasively using magnetoencephalography (MEG) or electroencephalography (EEG). Following stimulation with sounds, marked desynchronizations can be observed between 6 and 12 Hz, which can be localized to the auditory cortex. However knowledge about the functional relevance of the auditory alpha rhythm has remained scarce so far. Results from the visual and sensorimotor system have fuelled the hypothesis of alpha activity reflecting a state of functional inhibition. The current article pursues several intentions: (1) Firstly we review and present own evidence (MEG, EEG, sEEG) for the existence of an auditory alpha-like rhythm independent of visual or motor generators, something that is occasionally met with skepticism. (2) In a second part we will discuss tinnitus and how this audiological symptom may relate to reduced background alpha. The clinical part will give an introduction into a method which aims to modulate neurophysiological activity hypothesized to underlie this distressing disorder. Using neurofeedback, one is able to directly target relevant oscillatory activity. Preliminary data point to a high potential of this approach for treating tinnitus. (3) Finally, in a cognitive neuroscientific part we will show that auditory alpha is modulated by anticipation/expectations with and without auditory stimulation. We will also introduce ideas and initial evidence that alpha oscillations are involved in the most complex capability of the auditory system, namely speech perception. The evidence presented in this article corroborates findings from other modalities, indicating that alpha-like activity functionally has an universal inhibitory role across sensory modalities

Design of a Power-Dense Aviation Motor With a Low-Loss Superconducting Slotted Armature

This article describes the design and analysis of a 2.5-MW, 5000-rpm electric motor with a slotted armature employing REBCO high-temperature superconductors (HTS). The alternating current and field in the armature induces AC losses in the superconductors, requiring cryogenic cooling. Therefore, the aim is to design a machine with sufficiently low losses to make this cooling realistic, which simultaneously outperforms the state-of-the-art. The reasoning behind the key design choices is presented before the model used for two-dimensional (2-D) finite element analysis (FEA) is described. Then, HTS AC losses are studied with the T-A-formulation, examining the impact of various operating conditions. Aligning the HTS tapes with the field was found to successfully reduce AC losses, while filamentization was only successful for more than 10 filaments. The final design had an active torque density of 50.9 Nm/kg and an estimated efficiency of 99.8% when the HTS are operated at 40 K.Design of a Power-Dense Aviation Motor With a Low-Loss Superconducting Slotted ArmaturepublishedVersio

High‐Temperature Annealing and Patterned AlN/Sapphire Interfaces

Using the example of epitaxial lateral overgrowth of AlN on trench-patterned AlN/sapphire templates, the impact of introducing a high-temperature annealing step into the process chain is investigated. Covering the open surfaces of sapphire trench sidewalls with a thin layer of AlN is found to be necessary to preserve the trench shape during annealing. Both the influence of annealing temperature and annealing duration are investigated. To avoid the deformation of the AlN/sapphire interface during annealing, the annealing duration or annealing temperature must be low enough. Annealing for 1 h at 1730 °C is found to allow for the lowest threading dislocation density of 3.5 × 108 cm−2 in the subsequently grown AlN, while maintaining an uncracked smooth surface over the entire 2 in. wafer. Transmission electron microscopy study confirms the defect reduction by high-temperature annealing and reveals an additional strain relaxation mechanism by accumulation of horizontal dislocation lines at the interface between annealed and nonannealed AlN. By applying a second annealing step, the dislocation density can be further reduced to 2.5 × 108 cm−2

Increasing awareness of climate change with immersive virtual reality

Previous research has shown that immersive virtual reality (VR) is a suitable tool for visualizing the consequences of climate change. The aim of the present study was to investigate whether visualization in VR has a stronger influence on climate change awareness and environmental attitudes compared to traditional media. Furthermore, it was examined how realistic a VR experience has to be in order to have an effect. The VR experience consisted of a model of the Aletsch glacier (Switzerland) melting over the course of 220 years. Explicit measurements (new environmental paradigm NEP, climate change scepticism, and nature relatedness) and an implicit measurement (implicit association test) were collected before and after the VR intervention and compared to three different non-VR control conditions (video, images with text, and plain text). In addition, the VR environment was varied in terms of degrees of realism and sophistication (3 conditions: abstract visualization, less sophisticated realistic visualization, more sophisticated realistic visualization). The six experimental conditions (3 VR conditions, three control conditions) were modeled as mixed effects, with VR versus control used as a fixed effect in a mixed effects modeling framework. Across all six conditions, environmental awareness (NEP) was higher after the participants (N = 142) had been confronted with the glacier melting, while no differences were found for nature relatedness and climate change scepticism before and after the interventions. There was no significant difference between VR and control conditions for any of the four measurements. Nevertheless, contrast analyses revealed that environmental awareness increased significantly only for the VR but not for the control conditions, suggesting that VR is more likely to lead to attitude change. Our results show that exposure to VR environments successfully increased environmental awareness independently of the design choices, suggesting that even abstract and less sophisticated VR environment designs may be sufficient to increase pro-environmental attitudes