Mobile Silk Fibroin Electrode for Manipulation and Electrical Stimulation of Adherent Cells

Microfabricated mobile electrodes, nanopallets, designed to provide adherent cells with electrical stimulation are reported. Nanopallets composed of a cross‐linked silk fibroin hydrogel matrix incorporated with poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) are used. The silk fibroin composite is characterized not only by mechanical and electrical conductive properties, but also by its optical transparency in both the visible and ultraviolet regions, and by its biocompatibility with adherent cells. It is demonstrated that the adherent cells, including normal cell‐lined cells and primary neuronal cells, loaded on the nanopallets can be manipulated while faithfully retaining their adhesive properties. By applying voltages via the nanopallets, the voltage‐dependent calcium channels expressed in the cells are selectively stimulated, and this is confirmed by using confocal fluorescent microscopy during manipulation and performing multiangle observations. These features are attributed to both the mobile operation of the transparent nanopallets, and the ability to simultaneously measure electrical signals and perform fluorescent observations.     

Local Controlled Release of Polyphenol Conjugated with Gelatin Facilitates Bone Formation

Catechins are extensively used in health care treatments. Nevertheless, there is scarce information about the feasibility of local administration with polyphenols for bone regeneration therapy, possibly due to lack of effective delivery systems. Here we demonstrated that the epigallocatechin-3-gallate-conjugated gelatin (EGCG/Gel) prepared by an aqueous chemical synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-morpholinium chloride (DMT-MM) gradually disintegrated with time and facilitated bone formation in a critical size defect of a mouse calvaria. Conjugation of EGCG with the Gel generated cross-linking between the two molecules, thereby leading to a retardation of the degradation of the EGCG/Gel and to a delayed release of EGCG. The prepared EGCG/Gels represented significant osteogenic capability compared with that of the uncross-linked Gel and the cross-linked Gel with uncombined-EGCG. In vitro experiments disclosed that the EGCG/Gel induced osteoblastogenesis of a mouse mesenchymal stem cell line (D1 cells) within 14 days. Using fluorescently-labeled EGCG/Gel, we found that the fraction of EGCG/Gel adsorbed onto the cell membrane of the D1 cells possibly via a Gel-cell interaction. The interaction might confer the long-term effects of EGCG on the cells, resulting in a potent osteogenic capability of the EGCG/Gel in vivo. These results should provide insight into local controlled release of polyphenols for bone therapy.     

Mitocryptide-2: Identification of Its Minimum Structure for Specific Activation of FPR2–Possible Receptor Switching from FPR2 to FPR1 by Its Physiological C-terminal Cleavages

Mitocryptides are a novel family of endogenous neutrophil-activating peptides originating from various mitochondrial proteins. Mitocryptide-2 (MCT-2) is one of such neutrophil-activating peptides, and is produced as an N-formylated pentadecapeptide from mitochondrial cytochrome b. Although MCT-2 is a specific endogenous ligand for formyl peptide receptor 2 (FPR2), the chemical structure within MCT-2 that is responsible for FPR2 activation is still obscure. Here, we demonstrate that the N-terminal heptapeptide structure of MCT-2 with an N-formyl group is the minimum structure that specifically activates FPR2. Moreover, the receptor molecule for MCT-2 is suggested to be shifted from FPR2 to its homolog formyl peptide receptor 1 (FPR1) by the physiological cleavages of its C-terminus. Indeed, N-terminal derivatives of MCT-2 with seven amino acid residues or longer caused an increase of intracellular free Ca²⁺ concentration in HEK-293 cells expressing FPR2, but not in those expressing FPR1. Those MCT-2 derivatives also induced β-hexosaminidase secretion in neutrophilic/granulocytic differentiated HL-60 cells via FPR2 activation. In contrast, MCT-2(1–4), an N-terminal tetrapeptide of MCT-2, specifically activated FPR1 to promote those functions. Moreover, MCT-2 was degraded in serum to produce MCT-2(1–4) over time. These findings suggest that MCT-2 is a novel critical factor that not only initiates innate immunity via the specific activation of FPR2, but also promotes delayed responses by the activation of FPR1, which may include resolution and tissue regeneration. The present results also strongly support the necessity of considering the exact chemical structures of activating factors for the investigation of innate immune responses.     

Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model

Systemic injection of a nerve growth factor (NGF) antibody has been proven to have a significant relevance in relieving osteoarthritis (OA) pain, while its adverse effects remain a safety concern for patients. A local low-dose injection is thought to minimize adverse effects. In this study, OA was induced in an 8-week-old male Sprague–Dawley (SD) rat joint by monoiodoacetate (MIA) injection for 2 weeks, and the effect of weekly injections of low-dose (1, 10, and 100 µg) NGF antibody or saline (control) was evaluated. Behavioral tests were performed, and at the end of week 6, all rats were sacrificed and their knee joints were collected for macroscopic and histological evaluations. Results showed that 100 µg NGF antibody injection relieved pain in OA rats, as evidenced from improved weight-bearing performance but not allodynia. In contrast, no significant differences were observed in macroscopic and histological scores between rats from different groups, demonstrating that intra-articular treatment does not worsen OA progression. These results suggest that local administration yielded a low effective NGF antibody dose that may serve as an alternative approach to systemic injection for the treatment of patients with OA.     

Coordinated Setting of Multiple PSSs for Actual Size Power Network

The power system stabilizer (PSS) is a low‐cost method of stabilizing the intertie and local oscillations of a power network. The PSS parameters are usually adjusted based on the one‐machine infinite‐bus system model. In contrast, a real power system consists of multimachine systems. Thus, coordinated setting of the PSS parameters, with the real characteristics of the power system network taken into consideration, is expected to improve stability. For this purpose, the modal performance measure (MPM) method is used to adjust the PSS parameters. The power network mathematical model that is required for this calculation is given by the system identification method. Utilizing the MPM method characteristics, restrictions such as the damping coefficient and maximum gain, which constitute practical design specifications used for conventional controllers, are naturally introduced. Furthermore, radial basis function (RBF) frequency weighing is introduced in order to adjust the frequency responses. The expected favorable results were found in large‐scale power system simulations.     

Mechanical Properties of Woodceramics: A Porous Carbon Material

The mechanical properties of woodceramics, which are new porous carbon materials utilizing the natural structure of wood, were investigated. The effects of burning temperature and amount of impregnated phenol resin on Young's modulus, compressive strength and fracture toughness were measured. The fracture morphology was then observed, and simplified mechanical models of the woodceramics were discussed to explain the mechanical properties. The fracture was initiated at the cell walls that were located in vertical direction against the applied stress. The effect of impregnated phenol resin on the Young's modulus and the compressive strength was reasonably explained by a wall-bending model.     

Characteristics of lithium-ion battery with non-flammable electrolyte

To improve the safety of lithium-ion batteries, we studied non-flammable electrolytes made by adding several types of phosphazene-based flame retardants to conventional electrolytes and evaluated their conductivities, electrochemical characteristics, and the effects of flame retardants in terms of safety. Cell performance tests and abuse tests were also conducted using cylindrical test cells. The conductivity of electrolytes decreased when phosphazene-based flame retardants were added to the conventional electrolytes. The reason for this decrease in conductivity may be the increase in electrolyte viscosity caused by adding flame retardants. The conductivity decrease led to a decrease in cell capacity at high current density and at low temperature. However, the cell capacities at 0.2 CA (CA = 750 mA) and at 25 °C were almost the same as those of cells using conventional electrolytes. Flame tests showed that the electrolytes with flame retardants exhibited flame resistance consistent with UL-94V0. We also carried out several abuse tests to check the safety improvements. Both overcharge tests up to 10 V and heating tests up to 200 °C were completed without any extraordinary heat generation. Heating tests using a burner revealed the self-extinguishing properties of these electrolytes which were gushed out by venting. These results indicate that electrolytes with phosphazene-based flame retardants are effective for making lithium-ion batteries safe.     

A Method for Structuring Service Failure Factors to Realize Highly Reliable Services

As the society matures, customer requirements have become more varied. Services have been attracting increasing attention from industry and academic field as an effective mean to satisfy such varied customer requirements. In order to make a profit, it is important for companies to build and maintain long-term relationships with customers. Therefore, service providers should maintain their service quality and always satisfy their customers. To realize highly reliable product or services, in general, it is an effective approach to prevent failures from occurring in the use phase. Therefore, it is necessary that analysts identify the factors that could cause service failure and take appropriate measures against the target failure factor in advance. However, service failure factors are varied compared to physical products because service failures occur due to uncertainty elements such as human factors. In this study, we aim to enable service analysts to identify the critical failure factor from a number of failure factors. To achieve this, we identify complex failure factors and relationships among them from the viewpoint of the field where the service provided. This paper proposes a method for structuring the causal sequence between service failure factors by using a method of system modeling.