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The ability to optically interact with cells on both an individual and collective level has applications from wound healing to cancer treatment. Building systems that can facilitate both localised light illumination and visualisation of cells can, however, be challenging and costly. This work takes the Dynamic Optical MicroEnvironment (DOME), an existing platform for the closed-loop optical control of microscale agents, and adapts the design to support live-cell imaging. Through modifications made to the imaging and projection systems within the DOME, a significantly higher resolution, alternative imaging channels and the ability to customise light wavelengths are achieved (Bio-DOME). This is accompanied by an interactive calibration procedure that is robust to changes in the hardware configuration and provides fluorescence imaging (Fluoro-DOME). These alterations to the fundamental design allow for long-term use of the DOME in an environment of higher temperature and humidity. Thus, long-term imaging of living cells in a wound, with closed-loop control of real-time frontier illumination via projected light patterns, is facilitated., Supplementary Information: The online version contains supplementary material available at 10.1007/s12213-024-00165-0., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

In the paper, we are going to show how robotics is undergoing a shift in a bionic direction after a period of emphasis on artificial intelligence and increasing computational efficiency, which included isolation and extreme specialization. We assemble these new developments under the label of the morphological paradigm. The change in its paradigms and the development of alternatives to the principles that dominated robotics for a long time contains a more general epistemological significance. The role of body, material, environment, interaction and the paradigmatic status of biological and evolutionary systems for the principles of control are crucial here. Our focus will be on the introduction of the morphological paradigm in a new type of robotics and to contrast the interests behind this development with the interests shaping former models. The article aims to give a clear account of the changes in principles of orientation and control as well as concluding general observation in terms of historical epistemology, suggesting further political-epistemological analysis., (Copyright © 2023. Published by Elsevier Ltd.)

This paper proposes a new method for real-time terrain recognition-based navigation for mobile robots. Mobile robots performing tasks in unstructured environments need to adapt their trajectories in real-time to achieve safe and efficient navigation in complex terrains. However, current methods largely depend on visual and IMU (inertial measurement units) that demand high computational resources for real-time applications. In this paper, a real-time terrain identification-based navigation method is proposed using an on-board tapered whisker-based reservoir computing system. The nonlinear dynamic response of the tapered whisker was investigated in various analytical and Finite Element Analysis frameworks to demonstrate its reservoir computing capabilities. Numerical simulations and experiments were cross-checked with each other to verify that whisker sensors can separate different frequency signals directly in the time domain and demonstrate the computational superiority of the proposed system, and that different whisker axis locations and motion velocities provide variable dynamical response information. Terrain surface-following experiments demonstrated that our system could accurately identify changes in the terrain in real-time and adjust its trajectory to stay on specific terrain., (© 2023. The Author(s).)

Biological systems are outperforming machines in legged locomoting under almost any conditions. This is partly due to their capability of learning from failure and adapting their control approach and morphological features. This paper proposes an approach that extends the spring-loaded inverted pendulum (SLIP) model with the capability to adapt its attack angle (control) and stiffness (morphology) based on previous locomotion attempts. A set of different update rules, i.e., how this experience is used to adapt, are systematically investigated. The results suggest that modifying either attack angle, or stiffness, or both is beneficial with respect to achieve stable locomotion. Particularly, if the current system configuration (control and morphology) outperforms the previous one, the results suggest that increasing the angle and decreasing the stiffness of the system leads to more stable solutions. Consequently, the basic SLIP model extended by the proposed learning capabilities is able to reach stable locomotion over a much wider range of parameter combinations simply through trial and error., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Various methods based on hyperelastic assumptions have been developed to address the mathematical complexities of modeling motion and deformation of continuum manipulators. In this study, we propose a quasistatic approach for 3D modeling and real-time simulation of a pneumatically actuated soft continuum robotic appendage to estimate the contact force and overall pose. Our model can incorporate external load at any arbitrary point on the body and deliver positional and force propagation information along the entire backbone. In line with the proposed model, the effectiveness of elasticity versus hyperelasticity assumptions (neo-Hookean and Gent) is investigated and compared. Experiments are carried out with and without external load, and simulations are validated across a range of Young's moduli. Results show best conformity with Hooke's model for limited strains with about 6% average normalized error of position; and a mean absolute error of less than 0.08 N for force applied at the tip and on the body, demonstrating high accuracy in estimating the position and the contact force.

Soft materials are increasingly utilized for various purposes in many engineering applications. These materials have been shown to perform a number of functions that were previously difficult to implement using rigid materials. Here, we argue that the diverse dynamics generated by actuating soft materials can be effectively used for machine learning purposes. This is demonstrated using a soft silicone arm through a technique of multiplexing, which enables the rich transient dynamics of the soft materials to be fully exploited as a computational resource. The computational performance of the soft silicone arm is examined through two standard benchmark tasks. Results show that the soft arm compares well to or even outperforms conventional machine learning techniques under multiple conditions. We then demonstrate that this system can be used for the sensory time series prediction problem for the soft arm itself, which suggests its immediate applicability to a real-world machine learning problem. Our approach, on the one hand, represents a radical departure from traditional computational methods, whereas on the other hand, it fits nicely into a more general perspective of computation by way of exploiting the properties of physical materials in the real world.

Soft machines have recently gained prominence due to their inherent softness and the resulting safety and resilience in applications. However, these machines also have disadvantages, as they respond with complex body dynamics when stimulated. These dynamics exhibit a variety of properties, including nonlinearity, memory, and potentially infinitely many degrees of freedom, which are often difficult to control. Here, we demonstrate that these seemingly undesirable properties can in fact be assets that can be exploited for real-time computation. Using body dynamics generated from a soft silicone arm, we show that they can be employed to emulate desired nonlinear dynamical systems. First, by using benchmark tasks, we demonstrate that the nonlinearity and memory within the body dynamics can increase the computational performance. Second, we characterize our system's computational capability by comparing its task performance with a standard machine learning technique and identify its range of validity and limitation. Our results suggest that soft bodies are not only impressive in their deformability and flexibility but can also be potentially used as computational resources on top and for free.

Morphological computation can be loosely defined as the exploitation of the shape, material properties, and physical dynamics of a physical system to improve the efficiency of a computation. Morphological control is the application of morphological computing to a control task. In its theoretical part, this article sharpens and extends these definitions by suggesting new formalized definitions and identifying areas in which the definitions we propose are still inadequate. We go on to describe three ongoing studies, in which we are applying morphological control to problems in medicine and in chemistry. The first involves an inflatable support system for patients with impaired movement, and is based on macroscopic physics and concepts already tested in robotics. The two other case studies (self-assembly of chemical microreactors; models of induced cell repair in radio-oncology) describe processes and devices on the micrometer scale, in which the emergent dynamics of the underlying physical system (e.g., phase transitions) are dominated by stochastic processes such as diffusion.

The behaviors of the animals or embodied agents are characterized by the dynamic coupling between the brain, the body, and the environment. This implies that control, which is conventionally thought to be handled by the brain or a controller, can partially be outsourced to the physical body and the interaction with the environment. This idea has been demonstrated in a number of recently constructed robots, in particular from the field of "soft robotics". Soft robots are made of a soft material introducing high-dimensionality, non-linearity, and elasticity, which often makes the robots difficult to control. Biological systems such as the octopus are mastering their complex bodies in highly sophisticated manners by capitalizing on their body dynamics. We will demonstrate that the structure of the octopus arm cannot only be exploited for generating behavior but also, in a sense, as a computational resource. By using a soft robotic arm inspired by the octopus we show in a number of experiments how control is partially incorporated into the physical arm's dynamics and how the arm's dynamics can be exploited to approximate non-linear dynamical systems and embed non-linear limit cycles. Future application scenarios as well as the implications of the results for the octopus biology are also discussed.

The generation of robust periodic movements of complex nonlinear robotic systems is inherently difficult, especially, if parts of the robots are compliant. It has previously been proposed that complex nonlinear features of a robot, similarly as in biological organisms, might possibly facilitate its control. This bold hypothesis, commonly referred to as morphological computation, has recently received some theoretical support by Hauser et al. (Biol Cybern 105:355-370, doi: 10.1007/s00422-012-0471-0 , 2012). We show in this article that this theoretical support can be extended to cover not only the case of fading memory responses to external signals, but also the essential case of autonomous generation of adaptive periodic patterns, as, e.g., needed for locomotion. The theory predicts that feedback into the morphological computing system is necessary and sufficient for such tasks, for which a fading memory is insufficient. We demonstrate the viability of this theoretical analysis through computer simulations of complex nonlinear mass-spring systems that are trained to generate a large diversity of periodic movements by adapting the weights of a simple linear feedback device. Hence, the results of this article substantially enlarge the theoretically tractable application domain of morphological computation in robotics, and also provide new paradigms for understanding control principles of biological organisms.

The control of compliant robots is, due to their often nonlinear and complex dynamics, inherently difficult.The vision of morphological computation proposes to view these aspects not only as problems, but rather also as parts of the solution. Non-rigid body parts are not seen anymore as imperfect realizations of rigid body parts, but rather as potential computational resources. The applicability of this vision has already been demonstrated for a variety of complex robot control problems. Nevertheless, a theoretical basis for understanding the capabilities and limitations of morphological computation has been missing so far. We present a model for morphological computation with compliant bodies, where a precise mathematical characterization oft he potential computational contribution of a complex physical body is feasible. The theory suggests that complexity and nonlinearity, typically unwanted properties of robots, are desired features in order to provide computational power. We demonstrate that simple generic models of physical bodies,based on mass-spring systems, can be used to implement complex nonlinear operators. By adding a simple readout(which is static and linear) to the morphology, such devices are able to emulate complex mappings of input to output streams in continuous time. Hence, by outsourcing parts of the computation to the physical body, the difficult problem of learning to control a complex body, could be reduced to a simple and perspicuous learning task, which can not get stuck in local minima of an error function.

Despite many efforts, balance control of humanoid robots in the presence of unforeseen external or internal forces has remained an unsolved problem. The difficulty of this problem is a consequence of the high dimensionality of the action space of a humanoid robot, due to its large number of degrees of freedom (joints), and of non-linearities in its kinematic chains. Biped biological organisms face similar difficulties, but have nevertheless solved this problem. Experimental data reveal that many biological organisms reduce the high dimensionality of their action space by generating movements through linear superposition of a rather small number of stereotypical combinations of simultaneous movements of many joints, to which we refer as kinematic synergies in this paper. We show that by constructing two suitable non-linear kinematic synergies for the lower part of the body of a humanoid robot, balance control can in fact be reduced to a linear control problem, at least in the case of relatively slow movements. We demonstrate for a variety of tasks that the humanoid robot HOAP-2 acquires through this approach the capability to balance dynamically against unforeseen disturbances that may arise from external forces or from manipulating unknown loads.

Echo state networks (ESNs) are a novel approach to recurrent neural network training with the advantage of a very simple and linear learning algorithm. It has been demonstrated that ESNs outperform other methods on a number of benchmark tasks. Although the approach is appealing, there are still some inherent limitations in the original formulation. Here we suggest two enhancements of this network model. First, the previously proposed idea of filters in neurons is extended to arbitrary infinite impulse response (IIR) filter neurons. This enables such networks to learn multiple attractors and signals at different timescales, which is especially important for modeling real-world time series. Second, a delay&sum readout is introduced, which adds trainable delays in the synaptic connections of output neurons and therefore vastly improves the memory capacity of echo state networks. It is shown in commonly used benchmark tasks and real-world examples, that this new structure is able to significantly outperform standard ESNs and other state-of-the-art models for nonlinear dynamical system modeling., (Copyright 2009 Elsevier Ltd. All rights reserved.)

To learn more about how the step of cholesterol uptake into the brush border membrane (BBM) of enterocytes influences overall cholesterol absorption, we measured cholesterol absorption 4 and 24 h after administration of an intragastric bolus of radioactive cholesterol in mice with scavenger receptor class B, type 1 (SR-BI) and/or cluster determinant 36 (CD36) deleted. The cholesterol absorption efficiency is unaltered by deletion of either one or both of the receptors. In vitro determinations of the cholesterol uptake specific activity of the BBM from the mice reveal that the scavenger receptors facilitate cholesterol uptake into the proximal BBM. It follows that cholesterol uptake into the BBM is not normally rate-limiting for the cholesterol absorption process in vivo; a subsequent step, such as NPC1L1-mediated transfer from the BBM into the interior of the enterocyte, is rate-limiting. The absorption of dietary cholesterol after 4 h in mice lacking SR-BI and/or CD36 and fed a high-fat/high-cholesterol diet is delayed to more distal regions of the small intestine. This effect probably arises because ATP binding cassette half transporters G5 and G8-mediated back flux of cholesterol from the BBM to the lumen of the small intestine limits absorption and causes the local cholesterol uptake facilitated by SR-BI and CD36 to become rate-limiting under this dietary condition.

We compared cholesterol uptake into brush border membrane vesicles (BBMV) made from the small intestines of either wild-type or Niemann-Pick C1-like 1 (NPC1L1) knockout mice to elucidate the contribution of NPC1L1 to facilitated uptake; this uptake involves cholesterol transport from lipid donor particles into the BBM of enterocytes. The lack of NPC1L1 in the BBM of the knockout mice had no effect on the rate of cholesterol uptake. It follows that NPC1L1 cannot be the putative high-affinity, ezetimibe-sensitive cholesterol transporter in the brush border membrane (BBM) as has been proposed by others. The following findings substantiate this conclusion: (I) NPC1L1 is not a brush border membrane protein but very likely localized to intracellular membranes; (II) the cholesterol absorption inhibitor ezetimibe and its analogues reduce cholesterol uptake to the same extent in wild-type and NPC1L1 knockout mouse BBMV. These findings indicate that the prevailing belief that NPC1L1 facilitates intestinal cholesterol uptake into the BBM and its interaction with ezetimibe is responsible for the inhibition of this process can no longer be sustained.

Enantio- and diastereoselective syntheses of a substituted oxazolidinone, isoxazoline and pyrazoline as beta-lactam surrogates are described. The substituted heterocycles were designed to incorporate side chains closely resembling those found in the beta-lactam cholesterol absorption inhibitor ezetimibe (1). Additionally, the in vitro inhibitory efficacy of the novel compounds as cholesterol absorption inhibitors is reported using a brush border membrane vesicle assay.

We have utilized our recently developed in vitro assay to address two key questions in the design of small-molecule cholesterol absorption inhibitors using ezetimibe, the only drug yet approved for the inhibition of cholesterol absorption in the small intestine, as a starting point: (1) the role of glycosylation and (2) the importance of the beta-lactam scaffold of ezetimibe for inhibitory activity. A wide range of nonhydrolyzable phenolic glycosides of ezetimibe were synthesized and demonstrated to be active inhibitors of cholesterol absorption using the brush border membrane vesicle assay. The analogous azetidines provided access to a variety of inhibitors in vitro, suggesting that the beta-lactam of ezetimibe merely serves as a ring scaffold to appropriately position the required substituents. Our findings highlight several promising strategies for the design of alternative small-molecule cholesterol absorption inhibitors that could ultimately be useful in preventing cardiovascular disease by lowering blood cholesterol levels.

Fibres with a range of abilities to perturb cholesterol homeostasis were used to investigate how the serum cholesterol-lowering effects of insoluble dietary fibres are related to parameters of intestinal cholesterol absorption and hepatic cholesterol homeostasis in mice. Cholestyramine, chitosan and cellulose were used as examples of fibres with high, intermediate and low bile acid-binding capacities, respectively. The serum cholesterol levels in a control group of mice fed a high fat/high cholesterol (HFHC) diet for 3 weeks increased about 2-fold to 4.3 mm and inclusion of any of these fibres at 7.5 % of the diet prevented this increase from occurring. In addition, the amount of cholesterol accumulated in hepatic stores due to the HFHC diet was reduced by treatment with these fibres. The three kinds of fibres showed similar hypocholesterolaemic activity; however, cholesterol depletion of liver tissue was greatest with cholestyramine. The mechanisms underlying the cholesterol-lowering effect of cholestyramine were (1) decreased cholesterol (food) intake, (2) decreased cholesterol absorption efficiency, and (3) increased faecal bile acid and cholesterol excretion. The latter effects can be attributed to the high bile acid-binding capacity of cholestyramine. In contrast, incorporation of chitosan or cellulose in the diet reduced cholesterol (food) intake, but did not affect either intestinal cholesterol absorption or faecal sterol output. The present study provides strong evidence that above all satiation and satiety effects underlie the cholesterol-lowering properties of insoluble dietary fibres with moderate or low bile acid-binding capabilities.

There is now a general consensus that the intestinal absorption of water-insoluble, dietary lipids is protein-mediated, but the assignment of protein(s) to this function is still a matter of debate. To address this issue, we measured beta-carotene and cholesterol absorption in wild-type and SR-BI knockout mice and the uptake of these lipids in vitro using brush border membrane (BBM) vesicles. From the comparison of the in vivo and in vitro results we conclude that both BBM-resident class B scavenger receptors, SR-BI and CD36, can facilitate the absorption of beta-carotene and cholesterol. SR-BI is essential for beta-carotene absorption, at least in mice on a high fat diet. This is due to the fact that the absorption of beta-carotene is restricted to the duodenum and SR-BI is the predominant receptor in the mouse duodenum. In contrast, SR-BI may be involved but is not essential for cholesterol absorption in the small intestine. The question of whether SR-BI contributes to cholesterol absorption in vivo is still unresolved. Transfection of COS-7 cells with SR-BI or CD36 confers on these cells lipid uptake properties closely resembling those of enterocytes and BBM vesicles. Both scavenger receptors facilitate the uptake of dietary lipids such as beta-carotene, free and esterified cholesterol, phospholipids, and fatty acids into COS-7 cells. This lipid uptake is effected from three different lipid donor particles: mixed bile salt micelles, phospholipid small unilamellar vesicles, and trioleoylglycerol emulsions which are all likely to be present in the small intestine. Ezetimibe, a representative of a new class of drugs that inhibit intestinal cholesterol absorption, blocks SR-BI- and CD36-facilitated uptake of cholesterol into COS-7 cells.

[reaction: see text] The use of carbohydrate sulfonyl chlorides is introduced as a new, facile glycoconjugation method which could find broad applications. We demonstrate the approach by synthesizing a number of glycosylated cholesterol absorption inhibitors which display high inhibitory efficacies in our recently established in vitro assay. Furthermore, we highlight an advantage of the electron-withdrawing nature of the sulfonyl linkage which allowed the synthesis of otherwise unstable azetidine conjugates.

The kinetics of long-chain fatty acid (FA) transfer from three different donor systems to unilamellar egg phosphatidylcholine (EPC) vesicles containing the pH-sensitive fluorophore pyranine in the vesicle cavity were determined. The transfer of long-chain FA from three FA donors, FA vesicles, unilamellar EPC vesicles containing FA, and bovine serum albumin-FA complexes to pyranine-containing EPC vesicles is a true first-order process, indicating that the FA transfer proceeds through the aqueous phase and not through collisional contacts between the donor and acceptor. A collisional mechanism would be at least bimolecular, giving rise to second-order kinetics. Evidence from stopped-flow fluorescence spectroscopy using the pyranine assay (as developed by Kamp, F., and Hamilton, J. A. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 11367-11370) shows that the transverse or flip-flop motion of long-chain FA (from 14 to 22 C atoms) is immeasurably fast in both small and large unilamellar EPC vesicles and characterized by half-times t(1/2) < 5 ms. The rate-limiting step of FA transfer from these different donor systems to pyranine-containing EPC vesicles is the dissociation or desorption of the FA molecule from the donor. The desorption of the FA molecule is chain-length-dependent, confirming published data (Zhang et al. (1996) Biochemistry 35, 16055-16060): the first-order rate constant k(1) decreases by a factor of about 10 with elongation of the FA chain by two CH(2) groups. Similar rates of desorption are observed for the transfer of oleic acid from the three donors to pyranine-containing EPC vesicles with rate constants k(1) ranging from 0.4 to 1.3 s(-1). We also show that osmotically stressed, pyranine-containing EPC vesicles can give rise to artifacts. In the presence of a chemical potential gradient across the lipid bilayer of these vesicles, fast kinetic processes are observed with stopped-flow fluorescence spectroscopy which are probably due to electrostatic and/or osmotic effects.ne