Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.     

Chemical reaction kinetics dataset of Cs-I-B-Mo-O-H system for evaluation of fission product chemistry under LWR severe accident conditions

In order to improve LWR source term under severe accident conditions, the first version of a fission product chemistry database named ‘ECUME’ was developed. The ECUME is intended to include several datasets of major chemical reactions and their effective kinetic constants for representative severe accident sequences. It is expected that the ECUME can serve as a fundamental basis from which fission product chemical models can be elaborated for use in the severe accident analysis codes. The implemented chemical reactions in the first version were those for representative gas species in Cs-I-B-Mo-O-H system from 300 to 3000 K. The chemical reaction kinetic constants were evaluated from either literature data or calculated values using ab-initio calculations. The sample chemical reaction calculation using the presently constructed dataset showed meaningful kinetics effects at 1000 K. Comparison of the chemical equilibrium compositions by using the dataset with those by chemical equilibrium calculations has shown rather good consistency for the representative Cs-I-B-Mo-O-H species. From these results, it was concluded that the present dataset should be useful to evaluate fission product chemistry in Cs-I-B-Mo-O-H system under LWR severe accident conditions, where kinetics effects should be considered.     

Mechanisms of orientational and photoelastic birefringence generation of methacrylates for the design of zero–zero‐birefringence polymers

The intrinsic birefringence Δn⁰ and photoelastic coefficient C of poly(methyl methacrylate), poly(2,2,2‐trifluroethyl methacrylate), poly(phenyl methacrylate), and poly(2,2,3,3,3‐pentafluorophenyl methacrylate) were determined. We categorized these methacrylate polymers into four birefringence‐types, even though their molecular structures differed only by the substituents on the side chains. Based on the results of Δn⁰ and C, novel polymers that exhibit neither orientational nor photoelastic birefringence, i.e., zero–zero‐birefringence polymers, were designed and synthesized by quaternary copolymerization system. Furthermore, we confirmed that the mechanisms of orientational birefringence and photoelastic birefringence generation were different in these methacrylate polymers. The conformation of the repeat unit of the polymers was nearly constant during the generation of orientational birefringence. In contrast, the conformation of the repeat unit of the polymers changed during the generation of photoelastic birefringence in the glassy state. These findings demonstrated the reasonability of evaluating orientational and photoelastic birefringence separately, as well as the adequacy of the classification of polymers into four birefringence‐types. Given these results and the fact that zero–zero‐birefringence polymers could be prepared successfully by four‐birefringence type monomers, we demonstrated the reasonability of the method for designing the zero–zero‐birefringence polymers. POLYM. ENG. SCI., 55:1330–1338, 2015. © 2015 Society of Plastics Engineers     

Preparation of Polymer-Based Nanocomposites Composed of Sustainable Organo-Modified Needlelike Nanoparticles and Their Particle Dispersion States in the Matrix

Polymer-based nanohybrid materials were created using sustainable sepiolite clay composed from ubiquitous elements. Although sepiolite is generally recognized as a fibrous natural clay mineral, it turned out to be an acicular microcrystal because of the organo-modification of the outermost surface. Surface modification was performed using phosphonic acid derivatives containing hydrocarbon chains or fluorocarbon chains. Formation of a bidentate bond enhanced the desorption temperature and made nanocomposite preparation possible by melt compounding with polymers having a high melting point. As a result of organo-modification, amphiphilic sepiolite was obtained, and nanodispersion in an organic solvent was achieved. This technology was useful for detailed evaluation of sepiolite morphology. The nanocomposite of crystalline polymers/organo-modified sepiolites achieved uniform dispersion of these nanofillers in the matrix polymer. The introduction of 1 wt% nanofillers did not impair the transparency of the matrix polymer. As a result, a lamellae structure of the polymer developed, the crystallinity increased, and the mechanical properties improved. In addition, the crystallization temperature was improved, indicating that organo-modified sepiolites may act as a nucleating agent. It was found that sepiolite nanofiller with a highly aggregated tendency can achieve a well-nanodispersed state, even in phase-separable fluoropolymers, by applying fluorocarbon modification. POLYM. ENG. SCI., 60:541–552, 2020. © 2019 Society of Plastics Engineers     

Direct Growth of Germanene at Interfaces between Van der Waals Materials and Ag(111)

Germanene, a 2D honeycomb germanium crystal, is grown at graphene/Ag(111) and hexagonal boron nitride (h-BN)/Ag(111) interfaces by segregating germanium atoms. A simple annealing process in N₂ or H₂/Ar at ambient pressure leads to the formation of germanene, indicating that an ultrahigh-vacuum condition is not necessary. The grown germanene is stable in air and uniform over the entire area covered with a van der Waals (vdW) material. As an important finding, it is necessary to use a vdW material as a cap layer for the present germanene growth method since the use of an Al₂O₃ cap layer results in no germanene formation. The present study also proves that Raman spectroscopy in air is a powerful tool for characterizing germanene at the interfaces, which is concluded by multiple analyses including first-principles density functional theory calculations. The direct growth of h-BN-capped germanene on Ag(111), which is demonstrated in the present study, is considered to be a promising technique for the fabrication of future germanene-based electronic devices.     

Bottom-up synthesis of oxygen-containing carbon materials using a Lewis acid catalyst

Oxygen-containing carbon materials have been studied extensively because of their excellent dispersibility, absorptivity, separability, and supportability of catalysts. However, structural control by existing top-down methods is almost impossible. Our group has demonstrated that phloroglucinol (PG, 1,3,5-trihydroxybenzene) can be a promising raw material to synthesize structurally controlled oxygen-containing carbon materials. In this study, in addition to PG, hexahydroxybenzene (HHB), which has more oxygen and high symmetry, was used as the raw material, and a Lewis acid catalyst, tris (pentafluorophenyl) borane (TPB), was used to enhance the structural control rate and the removability of catalysts from the carbonized samples. The solubility of heat-treated HHB was lower than that of heat-treated PG, but the oxygen content of heat-treated HHB was higher than that of heat-treated PG even at 673 K. By adding TPB to PG, dibenzofuran-like structures formed, and the structural control rate increased up to 93.6%. Besides, the content of fluorine in the catalyst was reduced to 0%, indicating that TPB can be a promising recyclable catalyst to promote the structural control rate of carbonized PG.

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Importance of Kupffer Cells in the Development of Acute Liver Injuries in Mice

Kupffer cells reside within the liver sinusoid and serve as gatekeepers. They produce pro- and anti-inflammatory cytokines and other biologically important molecules upon the engagement of pattern recognition receptors such as Toll-like receptors. Kupffer cell-ablated mice established by in vivo treatment with clodronate liposomes have revealed many important features of Kupffer cells. In this paper, we review the importance of Kupffer cells in murine acute liver injuries and focus on the following two models: lipopolysaccharide (LPS)-induced liver injury, which is induced by priming with Propionibacterium acnes and subsequent challenge with LPS, and hypercoagulability-mediated acute liver failure such as that in concanavalin A (Con A)-induced hepatitis. Kupffer cells are required for LPS sensitization induced by P. acnes and are a major cellular source of interleukin-18, which induces acute liver injury following LPS challenge. Kupffer cells contribute to Con A-induced acute liver failure by initiating pathogenic, intrasinusoidal thrombosis in collaboration with sinusoidal endothelial cells. The mechanisms underlying these models may shed light on human liver injuries induced by various etiologies such as viral infection and/or abnormal metabolism.     

Evaluation of cost reduction potential for 1 kW class SOFC stack production: Implications for SOFC technology scenario

Recently, a commercial version of a residential solid oxide fuel cell (SOFC) system with a flat tubular cell has been developed. However, the system cost still remains very high, which is a barrier to its widespread use. In this study, the potential for cost reductions in SOFC stack production was investigated in order to contribute to the viability of the widespread use of such residential SOFC systems in future. A cost analysis of 700 W SOFC stack production based on a process integration modeling was conducted. The present bottom–up approach enabled us to perform a sensitivity analysis with a variety of parameters in terms of cell design, the production process and cell performance. This allowed us to investigate the effects of these factors on the production cost, thereby revealing the quantitative impact of each technological improvement on the cost reduction potential. The present analysis also revealed innovation pathways which could result in technology scenarios where residential SOFC systems could reach a break-even point in comparison with the baseload electricity cost. The analysis of the cost reduction potential presented here provides a useful viewpoint for developing a research strategy for state-of-the-art SOFC technology.     

Precise disturbance modeling for improvement of positioning performance

This paper presents a modeling methodology for unknown disturbances in mechatronics systems, based on disturbance estimation using an iterative learning process. In disturbance modeling, nonlinear frictions are specially handled as disturbances in the mechanisms, which mainly degrade trajectory control performance. Friction can be mathematically modeled by using learned estimation data as a function of the displacement, velocity. acceleration, and jerk of the actuator. This model has the distinctive feature that friction compensation can be achieved with a generalization capability for different conditions. The proposed positioning control approach with disturbance modeling and compensation has been verified by experiments using a table drive system on a machine stand. © 2010 Wiley Periodicals, Inc. Electr Eng Jpn, 171(2): 31–39, 2010; Published online in Wiley InterScience ( www. interscience.wiley.com ). DOI 10.1002/eej.20928