A virtuous cycle between invertebrate and robotics research: perspective on a decade of Living Machines research.

Many invertebrates are ideal model systems on which to base robot design principles due to their success in solving seemingly complex tasks across domains while possessing smaller nervous systems than vertebrates. Three areas are particularly relevant for robot designers: Research on flying and crawling invertebrates has inspired new materials and geometries from which robot bodies (their morphologies) can be constructed, enabling a new generation of softer, smaller, and lighter robots. Research on walking insects has informed the design of new systems for controlling robot bodies (their motion control) and adapting their motion to their environment without costly computational methods. And research combining wet and computational neuroscience with robotic validation methods has revealed the structure and function of core circuits in the insect brain responsible for the navigation and swarming capabilities (their mental faculties) displayed by foraging insects. The last decade has seen significant progress in the application of principles extracted from invertebrates, as well as the application of biomimetic robots to model and better understand how animals function. This Perspectives paper on the past 10 years of the Living Machines conference outlines some of the most exciting recent advances in each of these fields before outlining lessons gleaned and the outlook for the next decade of invertebrate robotic research.

Adaptive Centipede Walking via Synergetic Coupling Between Decentralized Control and Flexible Body Dynamics.

Multi-legged animals such as myriapods can locomote on unstructured rough terrain using their flexible bodies and legs. This highly adaptive locomotion emerges through the dynamic interactions between an animal's nervous system, its flexible body, and the environment. Previous studies have primarily focused on either adaptive leg control or the passive compliance of the body parts and have shown how each enhanced adaptability to complex terrains in multi-legged locomotion. However, the essential mechanism considering both the adaptive locomotor circuits and bodily flexibility remains unclear. In this study, we focused on centipedes and aimed to understand the well-balanced coupling between the two abovementioned mechanisms for rough terrain walking by building a neuromechanical model based on behavioral findings. In the behavioral experiment, we observed a centipede walking when part of the terrain was temporarily removed and thereafter restored. We found that the ground contact sense of each leg was essential for generating rhythmic leg motions and also for establishing adaptive footfall patterns between adjacent legs. Based on this finding, we proposed decentralized control mechanisms using ground contact sense and implemented them into a physical centipede model with flexible bodies and legs. In the simulations, our model self-organized the typical gait on flat terrain and adaptive walking during gap crossing, which were similar to centipedes. Furthermore, we demonstrated that the locomotor performance deteriorated on rough terrain when adaptive leg control was removed or when the body was rigid, which indicates that both the adaptive leg control and the flexible body are essential for adaptive locomotion. Thus, our model is expected to capture the possible essential mechanisms underlying adaptive centipede walking and pave the way for designing multi-legged robots with high adaptability to irregular terrain.

An agent-based model of the interrelation between the COVID-19 outbreak and economic activities.

As of July 2020, COVID-19 caused by SARS-COV-2 is spreading worldwide, causing severe economic damage. While minimizing human contact is effective in managing outbreaks, it causes severe economic losses. Strategies to solve this dilemma by considering the interrelation between the spread of the virus and economic activities are urgently needed to mitigate the health and economic damage. Here, we propose an abstract agent-based model of the COVID-19 outbreak that accounts for economic activities. The computational simulation of the model recapitulates the trade-off between the health and economic damage associated with voluntary restraint measures. Based on the simulation results, we discuss how the macroscopic dynamics of infection and economics emerge from individuals' behaviours. We believe our model can serve as a platform for discussing solutions to the above-mentioned dilemma.

Wearable Vibration Sensor for Measuring the Wing Flapping of Insects.

In this study, we fabricated a novel wearable vibration sensor for insects and measured their wing flapping. An analysis of insect wing deformation in relation to changes in the environment plays an important role in understanding the underlying mechanism enabling insects to dynamically interact with their surrounding environment. It is common to use a high-speed camera to measure the wing flapping; however, it is difficult to analyze the feedback mechanism caused by the environmental changes caused by the flapping because this method applies an indirect measurement. Therefore, we propose the fabrication of a novel film sensor that is capable of measuring the changes in the wingbeat frequency of an insect. This novel sensor is composed of flat silver particles admixed with a silicone polymer, which changes the value of the resistor when a bending deformation occurs. As a result of attaching this sensor to the wings of a moth and a dragonfly and measuring the flapping of the wings, we were able to measure the frequency of the flapping with high accuracy. In addition, as a result of simultaneously measuring the relationship between the behavior of a moth during its search for an odor source and its wing flapping, it became clear that the frequency of the flapping changed depending on the frequency of the odor reception. From this result, a wearable film sensor for an insect that can measure the displacement of the body during a particular behavior was fabricated.

Decoding the essential interplay between central and peripheral control in adaptive locomotion of amphibious centipedes.

Amphibious animals adapt their body coordination to compensate for changing substrate properties as they transition between terrestrial and aquatic environments. Using behavioural experiments and mathematical modelling of the amphibious centipede Scolopendra subspinipes mutilans, we reveal an interplay between descending command (brain), local pattern generation, and sensory feedback that controls the leg and body motion during swimming and walking. The elongated and segmented centipede body exhibits a gradual transition in the locomotor patterns as the animal crosses between land and water. Changing environmental conditions elicit a mechano-sensory feedback mechanism, inducing a gait change at the local segment level. The body segments operating downstream of a severed nerve cord (no descending control) can generate walking with mechano-sensory inputs alone while swimming behaviour is not recovered. Integrating the descending control for swimming initiation with the sensory feedback control for walking in a mathematical model successfully generates the adaptive behaviour of centipede locomotion, capturing the possible mechanism for flexible motor control in animals.

Novel contrast-injection protocol for high-resolution abdominal CT-angiography: vascular visualization improvement with vasodilator.

PURPOSE: To evaluate the usefulness of a novel contrast-injection protocol for high-resolution abdominal computed tomography angiography (CTA) using nitroglycerin (NTG). METHODS: Abdominal CTA was performed in 80 patients using two 64-detector-row CT scanners. Forty patients were examined after administration of sublingual NTG (NTG group), while 40 were examined without NTG administration (non-NTG group). Arterial phase images were acquired with maximum intensity projection and volume rendering. Reduction rates: vessel cross-sectional areas ratio of 10 cm distal to origin at the superior mesenteric artery, contrast enhancements, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were assessed. Three reviewers evaluated degree of depiction of the peripancreatic vasculature using a four-point scale (1 = poor, 4 = excellent). RESULTS: Reduction rates were significantly lower in the NTG group (P < 0.001), while there were no significant differences in contrast enhancements, SNR, or CNR between groups. Visual evaluation results of the NTG group were significantly better than those of the non-NTG group (P < 0.01). CONCLUSION: Abdominal CTA using NTG improved visualization of the abdominal peripheral vessels. This improved arterial view may be beneficial for preoperative evaluation of the arterial anatomy.

Decentralized control mechanism underlying interlimb coordination of millipedes.

Legged animals exhibit adaptive and resilient locomotion through interlimb coordination. The long-term goal of this study is to clarify the relationship between the number of legs and the inherent decentralized control mechanism for interlimb coordination. As a preliminary step, the study focuses on millipedes as they represent the species with the greatest number of legs among various animal species. A decentralized control mechanism involving local force feedback was proposed based on the qualitative findings of behavioural experiments in which responses to the removal of part of the terrain and leg amputation were observed. The proposed mechanism was implemented in a developed millipede-like robot to demonstrate that the robot can adapt to the removal of the part of the terrain and leg amputation in a manner similar to that in behavioural experiments.

Decentralized control scheme for myriapod robot inspired by adaptive and resilient centipede locomotion.

Recently, myriapods have attracted the attention of engineers because mobile robots that mimic them potentially have the capability of producing highly stable, adaptive, and resilient behaviors. The major challenge here is to develop a control scheme that can coordinate their numerous legs in real time, and an autonomous decentralized control could be the key to solve this problem. Therefore, we focus on real centipedes and aim to design a decentralized control scheme for myriapod robots by drawing inspiration from behavioral experiments on centipede locomotion under unusual conditions. In the behavioral experiments, we observed the response to the removal of a part of the terrain and to amputation of several legs. Further, we determined that the ground reaction force is significant for generating rhythmic leg movements; the motion of each leg is likely affected by a sensory input from its neighboring legs. Thus, we constructed a two-dimensional model wherein a simple local reflexive mechanism was implemented in each leg. We performed simulations by using this model and demonstrated that the myriapod robot could move adaptively to changes in the environment and body properties. Our findings will shed new light on designing adaptive and resilient myriapod robots that can function under various circumstances.

Risk factors for systemic air embolism as a complication of percutaneous CT-guided lung biopsy: multicenter case-control study.

PURPOSE: To determine risk factors for systemic air embolism by percutaneous computed tomography (CT)-guided lung biopsy. METHODS: This case-control study used data from 2216 percutaneous lung biopsy procedures performed over 11 years at 12 institutions in Japan. Systemic air embolism was identified by retrospective review of CT images obtained during and immediately after the procedures. To fulfill our objective, multiple variables were compared between cases and controls with univariate analyses by using Student's t test and Fisher's exact test for numerical and categorical values, respectively. Multivariate logistic regression analysis was then performed using selected variables. RESULTS: Ten cases of systemic air embolism and 2,206 controls were identified. Univariate analyses showed that the lesions in the lower lobe (P = 0.025) and occurrence of parenchymal hemorrhage (P = 0.019) were significant risk factors. Multivariate analysis showed that the use of a larger biopsy needle was a significant risk factor (P = 0.014). CONCLUSION: Parenchymal hemorrhage during the procedure, lesions in the lower lobe, and the use of larger biopsy needles may be risk factors for systemic air embolism by percutaneous CT-guided lung biopsy. Our findings may provide clues toward minimizing the risk of this complication.

Radiofrequency ablation of lung cancer at Okayama University Hospital: a review of 10 years of experience.

The application of radiofrequency ablation for the treatment of lung cancer by our group at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences began in June 2001, and in the present report, we review our 10-year experience with this treatment modality at Okayama University Hospital. The local efficacy of radiofrequency ablation for the treatment of lung cancer depends on tumor size and the type of electrode used, but not on tumor type. An important factor for the prevention of local failure may be the acquisition of an adequate ablative margin. The combination of embolization and radiation therapy enhances the local efficacy. Local failure may be salvaged by repeating the radiofrequency ablation, particularly in small tumors. Survival rates after radiofrequency ablation are quite promising for patients with clinical stage I non-small cell lung cancer and pulmonary metastasis from colorectal cancer, hepatocellular carcinoma, and renal cell carcinoma. The complications caused by radiofrequency ablation can be treated conservatively in the majority of cases. However, attention should be paid to rare but serious complications. This review shows that radiofrequency ablation is a promising treatment for patients with lung cancer.

Polidocanol sclerotherapy for painful venous malformations: evaluation of safety and efficacy in pain relief.

The aim of this study was to retrospectively evaluate the safety and efficacy of polidocanol sclerotherapy in pain relief for painful venous malformations (VMs). Thirty-one patients with painful VMs underwent polidocanol sclerotherapy. Pain intensity was assessed with an 11-point verbal numerical rating scale. Sclerotherapy was technically successful in 58 (98.3%) of 59 sessions. Twenty-six (89.7%) out of 29 patients experienced an improvement in pain after sclerotherapy at follow-up, a mean of 46 months after treatment. The mean pain score improved from 6.6 + or - 2.5 before treatment to 2.4 + or - 2.9 after treatment (P <.001). The factors that significantly influenced the therapeutic effect were size of lesion (P = .008), margin of lesion (P = .006), and stasis of sclerosant (P = .032). Adverse events included hypotension and bradycardia during the procedure. No major complication occurred. Polidocanol sclerotherapy is safe and most efficacious in providing pain relief for patients with small VMs (equal to or less than 10 cm in diameter), VMs with a well-defined margin, and VMs with good stasis of sclerosant during sclerotherapy.

Radiofrequency ablation followed by radiation therapy for large primary lung tumors.

We report the clinical experience of radiofrequency ablation followed by radiation therapy for large primary lung tumors. Two patients with large primary lung tumors were treated with combined radiofrequency ablation and radiation therapy, and good local control was observed. Combined radiofrequency ablation and radiation therapy that involves minimally invasive techniques appears to be promising for the treatment of large lung tumors.

Percutaneous radiofrequency ablation of lung tumors close to the heart or aorta: evaluation of safety and effectiveness.

PURPOSE: The authors retrospectively evaluated the safety and effectiveness of percutaneous radiofrequency ablation of lung tumors close to the heart or aorta. MATERIALS AND METHODS: Forty-two tumors (mean diameter, 25 mm +/- 16; range, 5-73 mm) located less than 10 mm from the heart or aorta were treated with radiofrequency ablation in 47 sessions. Lung tumors were classified into two groups according to their distance from the heart or aorta: group A (n = 27) comprised tumors at a distance of 1-9 mm; group B (n = 15) comprised contiguous tumors (distance, 0 mm). The safety and technique effectiveness of the procedure, defined as no evidence of local tumor progression, were evaluated. RESULTS: Radiofrequency ablation was feasible for all the 42 tumors. Procedural complications included asymptomatic pleural effusion (n = 5), small pneumothorax (n = 11), pneumothorax that necessitated chest tube placement (n = 4), and lung abscess (n = 1). No complications related to the specific tumor location, such as the accidental insertion of the electrode into the heart or aorta, pericardial effusion, arrhythmia, or cardiac infarction, occurred. The overall primary technique effectiveness rate was 75.8%, 45.9%, and 45.9% at 6, 12, and 24 months, respectively. This rate in group A (94.7%, 69.3%, and 69.3% at 6, 12, and 24 months, respectively) was significantly (P < .001) higher than that in group B (42.9% and 8.6% at 6 and 12 months, respectively). CONCLUSIONS: Radiofrequency ablation of lung tumors close to the heart or aorta was safely performed. The local control of tumors contiguous to the heart or aorta was considerably lower compared with the tumors that were close but not contiguous to these structures.

Intractable pneumothorax due to bronchopleural fistula after radiofrequency ablation of lung tumors.

We describe two cases of intractable pneumothorax that were attributed to a bronchopleural fistula (BPF) after radiofrequency ablation of lung tumors. In both cases, radiofrequency ablation induced necrosis of the lung tissue between the pleural space and the bronchus. The bronchopleural fistula formed after sloughing of the necrotic tissue. Management of the bronchopleural fistula was quite challenging, requiring frequent treatments, including pleurodesis, endobronchial management, and/or surgical repair. In one of the patients, air leakage persisted despite these efforts, and the patient died of acute pneumonia 52 days after the procedure. Although it is rare, with an incidence of 0.6% (2/334) at our institution, intractable pneumothorax due to bronchopleural fistula should be recognized as a risk associated with radiofrequency ablation of lung tumors.

Pneumothorax, pleural effusion, and chest tube placement after radiofrequency ablation of lung tumors: incidence and risk factors.

PURPOSE: To retrospectively evaluate the incidence of and risk factors for pneumothorax, pleural effusion, and chest tube placement for pneumothorax after radiofrequency (RF) ablation of lung tumors. MATERIALS AND METHODS: Institutional review board approval was obtained, with waiver of informed consent. This retrospective study comprised 224 ablation sessions for 392 tumors in 142 patients (92 men, 50 women; mean age, 64.0 years). Multiple variables were analyzed by using the Student t test or the Mann-Whitney U test for numerical values and by using the chi(2) test or the Fisher exact test for categorical values in order to assess risk factors for pneumothorax, pleural effusion, and chest tube placement for pneumothorax. RESULTS: The incidence of pneumothorax, pleural effusion, and chest tube placement for pneumothorax was 52% (117 of 224 sessions), 19% (42 of 224 sessions), and 21% (24 of 117 sessions), respectively. For pneumothorax, risk factors included male sex (P = .030), no history of pulmonary surgery (P < .001), a greater number of tumors ablated (P < .001), involvement of the middle or lower lobe (P = .008), and increased length of the aerated lung traversed by the electrode (P = .014). For pleural effusion, risk factors included the use of a cluster electrode (P = .008), decreased distance to the nearest pleura (P = .040), and decreased length of the aerated lung traversed by the electrode (P = .019). For chest tube placement for pneumothorax, risk factors included no history of pulmonary surgery (P = .002), the use of a cluster electrode (P < .001), and involvement of the upper lobe (P < .001). CONCLUSION: Pneumothorax and pleural effusion can occur after RF ablation in patients with lung tumors, and chest tube placement for pneumothorax is sometimes required.

Effects of radiofrequency ablation on individual renal function: assessment by technetium-99m mercaptoacetyltriglycine renal scintigraphy.

We quantitatively evaluated total and individual renal function by technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3) renal scintigraphy before and after radiofrequency ablation (RFA) of renal tumors. Eleven patients who underwent Tc-99m MAG3 renal scintigraphy 1 week before and after RFA were evaluated (7 men and 4 women; age range: 23-83 years; mean age: 60.6 years). Five patients had solitary kidneys, and five had normally or minimally functioning contralateral kidneys. One patient had a renal cell carcinoma in the contralateral kidney. One patient with a solitary kidney underwent RFA a second time for a residual tumor. In patients with a solitary kidney, MAG3 clearance decreased after 5 of 6 RFAs, and in patients with a normally functioning contralateral kidney, MAG3 clearance decreased after 4 of 5 RFAs, but no significant differences were observed between before and after treatments. In addition to the total MAG3 clearance, the split MAG3 clearance was evaluated in patients with a normally functioning contralateral kidney. MAG3 clearance decreased in 4 of 5 treated kidneys, while it adversely increased in the contralateral kidneys after 4 of 5 RFAs. No significant differences, however, were observed between before and after treatments. The results of our study revealed no significant differences in sCr, BUN, CCr, or MAG3 clearance between pre- and post-RFA values. These results support data regarding the functional impact and safety of renal RFA in published reports. We evaluated total and individual renal function quantitatively using Tc-99m MAG3 renal scintigraphy before and after treatment. This scintigraphy was very useful in assessing the effects of RFA on renal function.

Radiofrequency ablation of metastatic mediastinal lymph nodes during cooling and temperature monitoring of the tracheal mucosa to prevent thermal tracheal damage: initial experience.

Institutional review board approval and patient informed consent were obtained. Radiofrequency ablation in a total of 10 sessions was performed for each mediastinal lymph node metastasis from esophageal cancer that had a mean largest diameter of 2.2 cm +/- 0.6 (standard deviation) in seven male patients (mean age, 59 years). During ablation, cooling and temperature of the tracheal mucosa were monitored in the proper position in eight of the 10 sessions; in the other two sessions, monitoring was not done because of tracheal stenosis (perforation resulted). Three of the four lymph nodes that were 2.0 cm or smaller in largest diameter showed no evidence of local progression for at least 1 year since ablation; all three of the nodes greater than 2.0 cm in largest diameter progressed within 6 months. The 1-year survival rate was 60%; the median survival time was 13 months. Radiofrequency ablation may be effective for local control of small metastatic mediastinal lymph nodes, and cooling and temperature monitoring of the tracheal mucosa in the proper position may prevent thermal tracheal damage.

Characterization of the E-138 (Glu/Lys) mutation in Japanese encephalitis virus by using a stable, full-length, infectious cDNA clone.

A stable plasmid DNA, pMWJEAT, was constructed by using full-length Japanese encephalitis virus (JEV) cDNA isolated from the wild-type strain JEV AT31. Recombinant JEV was obtained by synthetic RNA transfection into Vero cells and designated rAT virus. JEV rAT exhibited similar large-plaque morphology and antigenicity to the parental AT31 strain. Mutant clone pMWJEAT-E138K, containing a single Glu-to-Lys mutation at aa 138 of the envelope (E) protein, was also constructed to analyse the mechanisms of viral attenuation arising from this mutation. Recombinant JEV rAT-E138K was also recovered and displayed a smaller-plaque morphology and lower neurovirulence and neuroinvasiveness than either AT31 virus or rAT virus. JEV rAT-E138K exhibited greater plaque formation than rAT virus in virus-cell interactions under acidic conditions. Heparin or heparinase III treatment inhibited binding to Vero cells more efficiently for JEV rAT-E138K than for rAT virus. Inhibition of virus-cell interactions by using wheatgerm agglutinin was more effective for JEV rAT than for rAT-E138K on Vero cells. About 20 % of macropinoendocytosis of JEV rAT for Vero cells was inhibited by cytochalasin D treatment, but no such inhibition occurred for rAT-E138K virus. Furthermore, JEV rAT was predominantly secreted from infected cells, whereas rAT-E138K was more likely to be retained in infected cells. This study demonstrates clearly that a single Glu-to-Lys mutation at aa 138 of the envelope protein affects multiple steps of the viral life cycle. These multiple changes may induce substantial attenuation of JEV.

Nuclear localization of Japanese encephalitis virus core protein enhances viral replication.

Japanese encephalitis virus (JEV) core protein was detected in both the nucleoli and cytoplasm of mammalian and insect cell lines infected with JEV or transfected with the expression plasmid of the core protein. Mutation analysis revealed that Gly(42) and Pro(43) in the core protein are essential for the nuclear and nucleolar localization. A mutant M4243 virus in which both Gly(42) and Pro(43) were replaced by Ala was recovered by plasmid-based reverse genetics. In C6/36 mosquito cells, the M4243 virus exhibited RNA replication and protein synthesis comparable to wild-type JEV, whereas propagation in Vero cells was impaired. The mutant core protein was detected in the cytoplasm but not in the nucleus of either C6/36 or Vero cell lines infected with the M4243 virus. The impaired propagation of M4243 in mammalian cells was recovered by the expression of wild-type core protein in trans but not by that of the mutant core protein. Although M4243 mutant virus exhibited a high level of neurovirulence comparable to wild-type JEV in spite of the approximately 100-fold-lower viral propagation after intracerebral inoculation to 3-week-old mice of strain Jcl:ICR, no virus was recovered from the brain after intraperitoneal inoculation of the mutant. These results indicate that nuclear localization of JEV core protein plays crucial roles not only in the replication in mammalian cells in vitro but also in the pathogenesis of encephalitis induced by JEV in vivo.