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Background: Observational studies of intermittent hemodialysis therapy have reported that the excess decrease in K+ concentration in plasma (KP) during treatment is associated with the destabilization of cardiac function. Elucidating the mechanism by which the decrease in KP impairs myocardial excitation is indispensable for a deeper understanding of prescription design. Methods: In this study, by using an electrophysiological mathematical model, we investigated the relationship between KP dynamics and cardiomyocyte excitability for the first time. Results: The excess decrease in KP during treatment destabilized cardiomyocyte excitability through the following events: (1) a decrease in KP led to the prolongation of the depolarization phase of ventricular cells due to the reduced potassium efflux rate of the Kr channel, temporarily enhancing contraction force; (2) an excess decrease in KP activated the transport of K+ and Na+ through the funny channel in sinoatrial nodal cells, disrupting automaticity; (3) the excess decrease in KP also resulted in a significant decrease in the resting membrane potential of ventricular cells, causing contractile dysfunction. Avoiding an excess decrease in KP during treatment contributed to the maintenance of cardiomyocyte excitability. Conclusions: The results of these mathematical analyses showed that it is necessary to implement personal prescription or optimal control of K+ concentration in dialysis fluid based on predialysis KP from the perspective of regulatory science in dialysis treatment.

In this study, we developed a novel method to determine the optimal viewpoint from which an operator could realize faster and more accurate robot teleoperation using reinforcement learning. The reinforcement learning model was trained using images obtained from several candidate viewpoints from scratch, and the viewpoint at which the model achieved the highest rewards was considered the optimal viewpoint. The target robot, task, and environment were modeled using computer simulations and the candidate viewpoint images were obtained using those simulations. We employed the world model as our reinforcement learning model to maximize rewards in the reaching task of a robot arm. The reward function was designed to encourage the robot arm to reach the target position both quickly and accurately. The experimental results validated the choice of the world model as the reinforcement learning model. Moreover, subject experiments wherein subjects operated a robot arm remotely to reach the target position were conducted. The experiments produced results that strongly aligned with the performance obtained through computer simulations, indicating that the proposed method is capable of selecting the optimal viewpoint without handcrafted design and subject experiments.

Neuromodulation techniques for modulating brain activity can affect performance in a variety of behaviors. Techniques including transcranial alternating current stimulation and random noise stimulation can modulate neural oscillations. However, the intervention effect of neuromodulation approaches on motor learning is poor, partly because the electroencephalography (EEG) power spectra associated with the motor learning process has not yet been fully elucidated. Therefore, we investigated the characteristics of EEG power spectra in the process of motor learning in 15 right-handed healthy participants (5 females; mean age = 22.8 ± 3.0 years). The motor task was a ball-rotation task in which participants rotated two balls in the palm of their left hand. Participants performed a pre-test, the motor learning tasks, and a post-test. In the motor learning tasks, twenty 60 s trials were performed in the clockwise (CW) direction. Before and after the motor learning tasks, CW and counterclockwise (CCW; control condition) tasks were performed for 60 s each as pre- and post-tests. Therefore, CW direction was set as a motor learning task, while CCW was a test-only control task. EEG was recorded during the tests and tasks, and the power spectra in the alpha, beta, and gamma oscillations were calculated and compared between pre- and post-tests. The results showed that in the CW post-test, the power of the gamma band in the left parietal areas and the right frontal area was significantly higher than in the pre-test. In the CCW, there was no significant difference in each band at each area between the pre- and post-tests. Our findings reveal the characteristics of the EEG spectra related to the motor learning process. These results may help to establish more effective neuromodulation approaches to modifying neural oscillations in motor learning, including in rehabilitation fields.

Post-stroke patients exhibit distinct muscle activation electromyography (EMG) features in sit-to-stand (STS) due to motor deficiency. Muscle activation amplitude, related to muscle tension and muscle synergy activation levels, is one of the defining EMG features that reflects post-stroke motor functioning and motor impairment. Although some qualitative findings are available, it is not clear if and how muscle activation amplitude-related biomechanical attributes may quantitatively reflect during subacute stroke rehabilitation. To better enable a longitudinal investigation into a patient's muscle activation changes during rehabilitation or an inter-subject comparison, EMG normalization is usually applied. However, current normalization methods using maximum voluntary contraction (MVC) or within-task peak/mean EMG may not be feasible when MVC cannot be obtained from stroke survivors due to motor paralysis and the subject of comparison is EMG amplitude. Here, focusing on the paretic side, we first propose a novel, joint torque-based normalization method that incorporates musculoskeletal modeling, forward dynamics simulation, and mathematical optimization. Next, upon method validation, we apply it to quantify changes in muscle tension and muscle synergy activation levels in STS motor control units for patients in subacute stroke rehabilitation. The novel method was validated against MVC-normalized EMG data from eight healthy participants, and it retained muscle activation amplitude differences for inter- and intra-subject comparisons. The proposed joint torque-based method was also compared with the common static optimization based on squared muscle activation and showed higher simulation accuracy overall. Serial STS measurements were conducted with four post-stroke patients during their subacute rehabilitation stay (137 ± 22 days) in the hospital. Quantitative results of patients suggest that maximum muscle tension and activation level of muscle synergy temporal patterns may reflect the effectiveness of subacute stroke rehabilitation. A quality comparison between muscle synergies computed with the conventional within-task peak/mean EMG normalization and our proposed method showed that the conventional was prone to activation amplitude overestimation and underestimation. The contributed method and findings help recapitulate and understand the post-stroke motor recovery process, which may facilitate developing more effective rehabilitation strategies for future stroke survivors.

We previously developed the biochemical reaction simulator WinBEST-KIT. In recent years, research interest has shifted from analysis of individual biochemical reactions to analysis of metabolic pathways as systems. These large-scale and complicated metabolic pathways can be considered as characteristic multi-layered structures, which, for convenience, are separated from whole biological systems according to their specific roles. These pathways include reactants having the same name but with unique stoichiometric coefficients arranged across many different places and connected between arbitrary layers. Accordingly, in this study, we have developed a new version of WinBEST-KIT that allows users (1) to utilize shortcut symbols that can be arranged with multiple reactants having the same name but with unique stoichiometric coefficients, thereby providing a layout that is similar to metabolic pathways depicted in biochemical textbooks; (2) to create layers that divide large-scale and complicated metabolic pathways according to their specific roles; (3) to connect the layers by using shortcut symbols; and (4) to analyze the interactions between these layers. These new and existing features allow users to create and analyze such multi-layered metabolic pathways efficiently. Furthermore, WinBEST-KIT supports SBML, making it possible for users to utilize these new and existing features to create and publish SBML models.

Abstract Background Production directly from carbon dioxide by engineered cyanobacteria is one of the promising technologies for sustainable future. Previously, we have successfully achieved 1,3-propanediol (1,3-PDO) production using Synechococcus elongatus PCC 7942 with a synthetic metabolic pathway. The strain into which the synthetic metabolic pathway was introduced produced 3.48 mM (0.265 g/L) 1,3-PDO and 14.3 mM (1.32 g/L) glycerol during 20 days of incubation. In this study, the productivities of 1,3-PDO were improved by gene disruption selected by screening with in silico simulation. Methods First, a stoichiometric metabolic model was applied to prediction of cellular metabolic flux distribution in a 1,3-PDO-producing strain of S. elongatus PCC 7942. A genome-scale model of S. elongatus PCC 7942 constructed by Knoop was modified by the addition of a synthetic metabolic pathway for 1,3-PDO production. Next, the metabolic flux distribution predicted by metabolic flux balance analysis (FBA) was used for in silico simulation of gene disruption. As a result of gene disruption simulation, NADPH dehydrogenase 1 (NDH-1) complexes were found by screening to be the most promising candidates for disruption to improve 1,3-PDO production. The effect of disruption of the gene encoding a subunit of the NDH-1 complex was evaluated in the 1,3-PDO-producing strain. Results and Conclusions During 20 days of incubation, the ndhF1-null 1,3-PDO-producing strain showed the highest titers: 4.44 mM (0.338 g/L) 1,3-PDO and 30.3 mM (2.79 g/L) glycerol. In this study, we successfully improved 1,3-PDO productivity on the basis of in silico simulation of gene disruption.

In this study, the skill of automotive engineers in sheet metal repair is analyzed. Because no two damage situations are identical, every damage is reconsidered on a case-to-case basis, and flexible responses are required. This work requires considerable human technical skill and relies on experienced workers. When the skills depend on experience, human resource development is essential to impart such skills. The overall objective of this research is to propose a personnel training tool. The fender of an automobile was repaired by workers by a sheet metal working technique. The work was recorded using a video camera and a three-dimensional motion measurement system. Then, the results were analyzed. Experts and non-experts were recorded when performing the task, and the differences in the process behaviors and hammer-strike positions were examined. The results showed that the experts initiated their strikes in the peripheral part of the dents. Thereafter, they applied several broad strike patterns in their repairs: for example, avoiding striking the peripheral part of the dent; striking the central part while avoiding the press line, followed by striking both the peripheral and central parts; and applying many strikes on the press line in the central part of the dent.

Cytoplasmic male sterility (CMS) is a plant trait that involves interactions between nuclear- and mitochondrial genomes. In CMS, the nuclear restorer-of-fertility gene (Rf), a suppressor of male-sterility inducing mitochondria, is one of the best known genetic factors. Other unidentified genetic factors may exist but have not been well characterized. In sugar beet (Beta vulgaris L.), CMS is used for hybrid seed production, but few male-sterility inducing nuclear genotypes exist. Such genotypes could be introduced from a closely related plant such as leaf beet, but first the fertility restoring genotype of the related plant must be characterized. Here, we report the discovery of a Japanese leaf beet accession 'Fukkoku-ouba' that has both male-sterility inducing and fertility restoring genotypes. We crossed the leaf beet accession with a sugar beet CMS line, developed succeeding generations, and examined the segregation of two DNA markers that are linked to two sugar beet Rfs, Rf1 and Rf2. Only the Rf2 marker co-segregated with fertility restoration in every generation, implying that the Rf1 locus in leaf beet is occupied by a non-restoring allele. Fertility restoration was incomplete without a genetic factor closely linked to Rf1, leading to the assumption that the Rf1 locus encodes a modifier that cannot restore fertility by itself but perhaps strengthens another Rf. We sequenced the apparently non-restoring 'Fukkoku-ouba' rf1 gene-coding region and found that it closely resembles a restoring allele. The protein product demonstrated its potential to suppress CMS in transgenic suspension cells. In contrast, 'Fukkoku-ouba' rf1 transcript abundance was highly reduced compared to that of the restoring Rf1. Consistently, changes in protein complexes containing CMS-associated mitochondrial protein in anthers were very minor. Accordingly, we concluded that 'Fukkoku-ouba' rf1 is a hypomorph that acts as a non-restoring allele but has the potential to support another Rf, i.e. it is a modifier candidate.

In recent years, due to its high specific stiffness and strength, fiber reinforced plastics (FRP) are being used in aerospace components, automobile components, sports equipment, and in various other applications. Especially since composite laminates have superior mechanical properties, there is a high demand for their use as structural materials. However, mechanical properties in the out-of-plane direction of composite laminates, specifically the interlaminar strength and fracture toughness, are much weaker than those in the in-plane direction. This study focuses on the needle punch techniques that aim to improve composite properties in the out-of-plane direction. This technique is typically used for fabricating non-woven fabrics. Fiber webs were punched by a plate containing many special needles with many barbs. A portion of fibers in the in-plane direction were aligned in the out-of-plane direction. In this study, the needle punch process is applied on chopped strand mats. Static tensile tests, fatigue loading tests, and residual strength tests are performed. Tensile properties, residual strength properties and fracture mechanisms of FRPs with needle-punched chopped strand mats are investigated.

Carbon Capture and Storage (CCS) is regarded as a countermeasure for global warming, but introduction of conventional CCS system deteriorates thermal efficiency of power station. To find out its solution, a project has started by NEDO to develop the High-efficiency Oxy-fuel IGCC system, which can keep high efficiency even after capturing CO2. In this system, gasifying agent and combustion air is substituted by oxygen diluted by exhaust gas recirculated from gas turbine combustor. The target of this project was set as to achieve net thermal efficiency more than 42% at HHV basis, which is equivalent to state of the art coal-fired power station. Various approaches were done to confirm the concept of this system and to develop fundamental technologies necessary for the system since 2008 to 2014 under the support by NEDO. As good achievements were obtained till 2014, the project made another step for developing high efficiency oxy-fuel IGCC since 2015 as a 5 year joint project with MHI and MHPS under the support by NEDO. This paper introduces the latest status of this project executed by CRIEPI by referring several related papers.

Hybrid composites of fillers and/or fibers reinforced polymer was generally produced by masterbatch dilution technique. In this work, the simplified preparation was introduced for the large volume production of 30 wt % short-fiber and talcum reinforced polymer hybrid composite by direct feeding into twin-screw extruder. Multifunctional epoxide-based terpolymer and/or maleic anhydride were selected as in situ reactive compatibilizers. The influence of fiber and talcum ratios and in situ reactive compatibilizers on mechanical, dynamic mechanical, morphological and thermal properties of hybrid composites were investigated. The morphological results showed the strong interfacial adhesion between fiber or talcum and Poly(lactic acid) (PLA) matrix due to a better compatibility by reaction of in situ compatibilizer. The reactive PLA hybrid composite showed the higher tensile strength and the elongation at break than non-compatibilized hybrid composite without sacrificing the tensile modulus. Upon increasing the talcum contents, the modulus and storage modulus of hybrid composites were also increased while the tensile strength and elongation at break were slightly decreased compared to PLA/fiber composite. Talcum was able to induce the crystallization of PLA hybrid composites.

A massive integrative mathematical model of DNA double-strand break (DSB) generation, DSB repair system, p53 signaling network, and apoptosis induction pathway was constructed to explore the dominant factors of unknown criteria of cell fate decision. In the proposed model, intranuclear reactions were modeled as stochastic processes and cytoplasmic reactions as deterministic processes, and both reaction sets were simulated simultaneously. The simulated results at the single-cell level showed that the model generated several sustained oscillations (pulses) of p53, Mdm2, ATM, and Wip1, and cell-to-cell variability in the number of p53 pulses depended on IR intensity. In cell populations, the model generated damped p53 oscillations, and IR intensity affected the amplitude of the first p53 oscillation. Cells were then subjected to the same IR dose exhibiting apoptosis induction variability. These simulated results are in quantitative agreement with major biological findings observed in human breast cancer epithelial MCF7, NIH3T3, and fibrosarcoma cells, demonstrating that the proposed model was concededly biologically appropriate. Statistical analysis of the simulated results shows that the generation of multiple p53 pulses is a prerequisite for apoptosis induction. Furthermore, cells exhibited considerable individual variability in p53 dynamics, which correlated with intrinsic apoptosis induction. The simulated results based on the proposed model demonstrated that the stochasticity of intranuclear biochemical reaction processes controls the final decision of cell fate associated with DNA damage. Applying stochastic simulation to an exploration of intranuclear biochemical reaction processes is indispensable in enhancing the understanding of the dynamic characteristics of biological multi-layered systems of higher organisms.

Continuous natural fiber reinforced thermoplastic materials are expected to replace inorganic fiber reinforced thermosetting materials. However, in the process of fabricating the composite, it is difficult to impregnate the thermoplastic resin into reinforcement fiber because of the high melt viscosity. Therefore, intermediate material, which allows high impregnation during molding, has been investigated for fabricating continuous fiber reinforced thermoplastic composite by aligning resin fiber alongside reinforcing fiber with braiding technique. This intermediate material has been called “microbraid yarn (MBY.)” Moreover, it is well known that the interfacial properties between natural fiber and resin are low; therefore, surface treatment on continuous natural fiber was performed by using polyurethane (PU) and flexible epoxy (FLEX) to improve the interfacial properties. The effect of surface treatment on the mechanical properties of continuous natural fiber reinforced thermoplastic composites was examined. From these results, it was suggested that surface treatment by PU with low content could produce composites with better mechanical properties.

Recycled needle punched jute fiber mats as a first natural fiber reinforcement system and these jute mats used as a core needle punched with recycled jute fabric cloths as skin layers as a second natural fiber reinforcement system were used for unsaturated polyester matrix composites via modifying the hand lay-up technique with resin preimpregnation into the jute fiber in vacuum. The effect of skin jute fabric on the tensile and bending properties of jute mat composites was investigated for different fiber weight contents. Moreover, the notch sensitivity of these composites was also compared by using the characteristic distance d o calculated by Finite Element Method (FEM). The results showed that the tensile and flexural properties of jute mat composites increased by increasing the fiber weight content and by adding the jute fabric as skin layers. On the other hand, by adding the skins, the characteristic distance decreased and, therefore, the notch sensitivity of the composites increased. The fracture behavior investigated by SEM showed that extensive fiber pull-out mechanism was revealed at the tension side of jute mat composites under the bending load and by adding the jute cloth, the failure mode of jute mat was changed to fiber bridge mechanism.

The tumor suppressor, p53, regulates several gene expressions that are related to the DNA repair protein, cell cycle arrest and apoptosis induction, which activates the implementation of both cell cycle arrest and induction of apoptosis. However, it is not clear how p53 specifically regulates the implementation of these functions. By applying several well-known kinetic mathematical models, we constructed a novel model that described the influence that DNA damage has on the implementation of both the G2/M phase cell cycle arrest and the intrinsic apoptosis induction via its activation of the p53 synthesis process. The model, which consisted of 32 dependent variables and 115 kinetic parameters, was used to examine interference by DNA damage in the implementation of both G2/M phase cell cycle arrest and intrinsic apoptosis induction. A low DNA damage promoted slightly the synthesis of p53, which showed a sigmoidal behavior with time. In contrast, in the case of a high DNA damage, the p53 showed an oscillation behavior with time. Regardless of the DNA damage level, there were delays in the G2/M progression. The intrinsic apoptosis was only induced in situations where grave DNA damage produced an oscillation of p53. In addition, to wreck the equilibrium between Bcl-2 and Bax the induction of apoptosis required an extreme activation of p53 produced by the oscillation dynamics, and was only implemented after the release of the G2/M phase arrest. When the p53 oscillation is observed, there is possibility that the cell implements the apoptosis induction. Moreover, in contrast to the cell cycle arrest system, the apoptosis induction system is responsible for safeguarding the system that suppresses malignant transformations. The results of these experiments will be useful in the future for elucidating of the dominant factors that determine the cell fate such as normal cell cycles, cell cycle arrest and apoptosis.