Fin-Bayes: A Multi-Objective Bayesian Optimization Framework for Soft Robotic Fingers.

Computational design is a critical tool to realize the full potential of Soft Robotics, maximizing their inherent benefits of high performance, flexibility, robustness, and safe interaction. Practically, computational design entails a rapid iterative search process over a parameterized design space, with assessment using (frequently) computational modeling and (more rarely) physical experimentation. Bayesian approaches work well for these expensive-to-analyze systems and can lead to efficient exploration of design space than comparative algorithms. However, such computational design typically entails weaknesses related to a lack of fidelity in assessment, a lack of sufficient iterations, and/or optimizing to a singular objective function. Our work directly addresses these shortcomings. First, we harness a sophisticated nonlinear Finite Element Modeling suite that explicitly considers geometry, material, and contact nonlinearity to perform rapid accurate characterization. We validate this through extensive physical testing using an automated test rig and printed robotic fingers, providing far more experimental data than that reported in the literature. Second, we explore a significantly larger design space than comparative approaches, with more free variables and more opportunity to discover novel, high performance designs. Finally, we use a multiobjective Bayesian optimizer that allows for the identification of promising trade-offs between two critical objectives, compliance and contact force. We test our framework on optimizing Fin Ray grippers, which are ubiquitous throughout research and industry due to their passive compliance and durability. Results demonstrate the benefits of our approach, allowing for the optimization and identification of promising gripper designs within an extensive design space, which are then 3D printed and usable in reality.

Erratum: Dynamic 13C Flux Analysis Captures the Reorganization of Adipocyte Glucose Metabolism in Response to Insulin.

[This corrects the article DOI: 10.1016/j.isci.2020.100855.].

Insulin signaling requires glucose to promote lipid anabolism in adipocytes.

Adipose tissue is essential for metabolic homeostasis, balancing lipid storage and mobilization based on nutritional status. This is coordinated by insulin, which triggers kinase signaling cascades to modulate numerous metabolic proteins, leading to increased glucose uptake and anabolic processes like lipogenesis. Given recent evidence that glucose is dispensable for adipocyte respiration, we sought to test whether glucose is necessary for insulin-stimulated anabolism. Examining lipogenesis in cultured adipocytes, glucose was essential for insulin to stimulate the synthesis of fatty acids and glyceride-glycerol. Importantly, glucose was dispensable for lipogenesis in the absence of insulin, suggesting that distinct carbon sources are used with or without insulin. Metabolic tracing studies revealed that glucose was required for insulin to stimulate pathways providing carbon substrate, NADPH, and glycerol 3-phosphate for lipid synthesis and storage. Glucose also displaced leucine as a lipogenic substrate and was necessary to suppress fatty acid oxidation. Together, glucose provided substrates and metabolic control for insulin to promote lipogenesis in adipocytes. This contrasted with the suppression of lipolysis by insulin signaling, which occurred independently of glucose. Given previous observations that signal transduction acts primarily before glucose uptake in adipocytes, these data are consistent with a model whereby insulin initially utilizes protein phosphorylation to stimulate lipid anabolism, which is sustained by subsequent glucose metabolism. Consequently, lipid abundance was sensitive to glucose availability, both during adipogenesis and in Drosophila flies in vivo Together, these data highlight the importance of glucose metabolism to support insulin action, providing a complementary regulatory mechanism to signal transduction to stimulate adipose anabolism.

Dynamic 13C Flux Analysis Captures the Reorganization of Adipocyte Glucose Metabolism in Response to Insulin.

Cellular metabolism is dynamic, but quantifying non-steady metabolic fluxes by stable isotope tracers presents unique computational challenges. Here, we developed an efficient 13C-tracer dynamic metabolic flux analysis (13C-DMFA) framework for modeling central carbon fluxes that vary over time. We used B-splines to generalize the flux parameterization system and to improve the stability of the optimization algorithm. As proof of concept, we investigated how 3T3-L1 cultured adipocytes acutely metabolize glucose in response to insulin. Insulin rapidly stimulates glucose uptake, but intracellular pathways responded with differing speeds and magnitudes. Fluxes in lower glycolysis increased faster than those in upper glycolysis. Glycolysis fluxes rose disproportionally larger and faster than the tricarboxylic acid cycle, with lactate a primary glucose end product. The uncovered array of flux dynamics suggests that glucose catabolism is additionally regulated beyond uptake to help shunt glucose into appropriate pathways. This work demonstrates the value of using dynamic intracellular fluxes to understand metabolic function and pathway regulation.

Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism.

Insulin triggers an extensive signaling cascade to coordinate adipocyte glucose metabolism. It is considered that the major role of insulin is to provide anabolic substrates by activating GLUT4-dependent glucose uptake. However, insulin stimulates phosphorylation of many metabolic proteins. To examine the implications of this on glucose metabolism, we performed dynamic tracer metabolomics in cultured adipocytes treated with insulin. Temporal analysis of metabolite concentrations and tracer labeling revealed rapid and distinct changes in glucose metabolism, favoring specific glycolytic branch points and pyruvate anaplerosis. Integrating dynamic metabolomics and phosphoproteomics data revealed that insulin-dependent phosphorylation of anabolic enzymes occurred prior to substrate accumulation. Indeed, glycogen synthesis was activated independently of glucose supply. We refer to this phenomenon as metabolic priming, whereby insulin signaling creates a demand-driven system to "pull" glucose into specific anabolic pathways. This complements the supply-driven regulation of anabolism by substrate accumulation and highlights an additional role for insulin action in adipocyte glucose metabolism.

Commercial Seed Lots Exhibit Reduced Seed Dormancy in Comparison to Wild Seed Lots of Echinacea purpurea.

Seed germination patterns were studied in E. purpurea (L.) Moench grouped by seed source, one group of seven lots from commercially cultivated populations and a second group of nine lots regenerated from ex situ conserved wild populations. Germination tests were conducted in a growth chamber in light (40 µmol·m(-2)·s(-1)) or darkness at 25 °C for 20 days after soaking the seeds in water for 10 minutes. Except for two seed lots from wild populations, better germination was observed for commercially cultivated populations in light (90% mean among seed lots, ranging from 82% to 95%) and in darkness (88% mean among seed lots, ranging from 82% to 97%) than for wild populations in light (56% mean among seed lots, ranging from 9% to 92%) or in darkness (37% mean among seed lots, ranging from 4% to 78%). No germination difference was measured between treatments in light and darkness in the commercially cultivated populations, but significant differences were noted for treatments among wild populations. These results suggest that repeated cycles of sowing seeds during cultivation without treatments for dormancy release resulted in reduced seed dormancy in E. purpurea.

Patterns of Variation in Alkamides and Cichoric Acid in Roots and Aboveground Parts of Echinacea purpurea (L.) Moench.

We investigated patterns of variation in alkamides and cichoric acid accumulation in the roots and aboveground parts of Echinacea purpurea (L.) Moench. These phytochemicals were extracted from fresh plant parts with 60% ethanol and quantified by high performance liquid chromatography (HPLC) analysis. Concentrations of alkamides and cichoric acid were measured on a dry-weight basis (mg·g(-1)). For total alkamides, concentrations among individual plants varied from 5.02 to 27.67 (mean = 14.4%) in roots, from 0.62 to 3.42 (mean = 1.54) in nearly matured seed heads (NMSH), and 0.22 to 5.25 (mean = 0.77) in young tops (about ½ flower heads, » leaves, and » stems). For cichoric acid, concentrations among individual plants varied from 2.65 to 37.52 (mean = 8.95), from 2.03 to 31.58 (mean = 10.9), and from 4.79 to 38.55 (mean = 18.88) in the roots, the NMSH, and the tops, respectively. Dodeca-2E, 4E, 8Z, 10E-tetraenoic acid isobutylamide and dodeca-2E, 4E, 8Z, 10Z-tetraenoic acid isobutylamide (alkamides 8/9) accounted for only 9.4% of the total alkamides in roots, but comprised 87.9% in the NMSH, and 76.6% in the young tops. Correlations of concentrations of alkamides or cichoric acid between those of roots and those of the NMSH were not statistically significant, and either within the roots, the NMSH, and the young tops. However, a significant negative correlation was observed between the concentration of cichoric acid in the roots and in young tops, and a significant positive correlation was observed between total alkamide concentration in the roots and cichoric acid concentration in the young tops. These results may be useful in the genetic improvement of E. purpurea for medicinal use.

Ethephon Promotes Germination of Echinacea angustifolia and E. pallida in Darkness.

Seeds from five lots each of Echinacea angustifolia DC, and E. pallida (Nutt.) Nutt. were germinated in a growth chamber in light (40 µmol·m(-2)· s(-1)) or darkness at 25 °C for 16 to 20 d after soaking in 1 mM ethephon or water for 10 min, or moist stratification at 4 - 6 °C for two weeks. Either light or ethephon promoted seed germination of E. angustifolia and E. pallida, in comparison with darkness in nine of ten lots. Ethephon in the dark had similar or greater germination percentages than water with light. Ethephon with light improved germination in three of ten lots compared with ethephon in the dark. The effect of cold, moist stratification in comparison with darkness varied by seed lot. Five lots of E. purpurea (L.) Moench were tested; however, no treatment differences were measured. The finding that ethethon promoted E. angustifolia and E. pallida seed germination in darkness could be useful in the cultivation of these two species. Chemical name used: 2-chloroethylphosphonic acid (ethephon).

Chromosome Karyotypes of Echinacea angustifolia var. angustifolia and E. purpurea.

Chromosome karyotypes of the most commonly cultivated and medicinally used Echinacea taxa, E. angustifolia DC. var. angustifolia and E. purpurea (L.) Moench., were analyzed. The chromosomes of both taxa are medium in length, ranging from 4.12 to 5.83 µm in E. angustifolia var. angustifolia and 3.99 to 6.08 µm in E. purpurea. No abrupt length changes in the chromosomes were noted. The karyotypes of the two species are generally similar, but a distinguishable feature exists in one pair of chromosomes. The centromere of chromosome pair 10 is subterminally located in E. purpurea, but terminally located in E. angustifolia var. angustifolia, which can be readily recognized in mitotic metaphase cell plates. This finding may provide useful information for Echinacea evolutionary, genetic, and breeding studies.