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With the deterioration of bridges as social infrastructure, appropriate maintenance and life extension are required. However, aging degradation of individual bridges is not the same. Since traffic volume and bridge environment are different for each bridge, the degree of deterioration of the bridge is also different. Therefore, it is necessary to identify and eliminate the cause of individual deterioration and to take appropriate measures. This paper focuses on weathering steel bridge that the formation of dense rust is greatly influenced by the environment. The purpose of this study is to clarify the effect of anticorrosion by the environmental improvement which covers the whole steel girder with the metal sandwich panel for weathering steel bridge. Since the space in the girder covered with the metal sandwich panel cannot be expected to have the effect of washing by rainwater or drying and wetting by the flow of wind, the adoption of the metal sandwich panel for weatherproof steel bridge has not been judged until now. In this thesis, the corrosion behavior of weathering steel and the effectiveness of corrosion protection are shown by exposure test, and the corrosion protection effect of environmental improvement by metal sandwich panel is clarified. In addition, this study examines the economical advantages by the metal sandwich panel installation by calculating the life cycle cost. This paper consists of six chapters. Chapter 1 describes the background and purpose of this research. Chapter 2 summarizes previous studies on corrosion protection methods used in steel bridges. In Chapter 3, exposure tests were conducted inside and outside the metal sandwich panel and the following finding were obtained. 1) In the girder covered with the metal sandwich panel, fluctuation range of temperature and humidity is small throughout the year, and it does not follow the sudden weather change of outside of the panel. Since the difference between the temperature and dew point in the panel is large, the wet time in the panel is suppressed to 1/5 or less of the wet time of outside the panel. 2) At the structure which has thin floor slab and low height girder, the temperature rise in the panel may be unavoidable depending on season. However, since the humidity in the panel is low and the wet time is also greatly reduced, the anticorrosive effect can be expected in the steel bridge including the weathering steel bridge. 3) Amount of air born salt into the panel after the metal sandwich panel installation was not detected. In Chapter 4, a small test specimen was placed in the inside space of the steel girder, and the transition of corrosion, anticorrosion effect by environmental improvement and inner surface painting were examined. 1) The untreated steel and the uncoated steel in the ingrown rust region evaluated by the ion permeation resistance method are kept almost same condition after five years. 2) It is also conceivable that the initial salinity of the steel material subjected to the substrate adjustment by blasting exists even after the substrate adjustment, and that the adhering salinity penetrates into the inside of the steel plate at the time of rust formation. However, the increase rate of rust thickness due to aging is slow, and a method of installing a metal sandwich panel after blasting is also effective. 3) Although the effect of environmental isolation from outside the girder was confirmed, it became clear that it was difficult to completely suppress the progress of rust. Chapter 5 examined the economic effects of installing metal sandwich panels on new girders from the beginning and installing them on overbridges 50 years after the star of service. 1) If repainting is required even 1 time during the during the design service period of 100 years, the anticorrosion method by environmental improvement of the metal sandwich panel is economically superior. 2) Accumulating the cost of close visual inspection (for 50 years) of the overbridge that has been in service for 50 years increases the maintenance cost. Chapter 6 summarizes this research and describes future issues.

ダイアモンド・ブラックファン貧血 (Diamond–Blackfan anemia : DBA) は, リボゾーム蛋白異常によって生じる赤芽球癆で, 新生児期の貧血および一部で身体奇形を合併する. 臨床的特徴が多様で, 原因となるリボゾーム蛋白遺伝子も多数存在するため, 新生児期にDBAと確定診断し, 適切な治療を行うことが困難である. 本研究では, 全エクソーム解析 (whole-exome sequencing; WES) を用いて最終診断した3組の母子例について報告する. 貧血の重症度や治療反応性は各母子間で異なり, 低身長, 翼状頸, 母指球形成不全などの特徴的な身体奇形を認めた症例は, 母1名のみだった. この母はRPL11 (exon 2, c.58_59del) のフレームシフト変異があり, 子は一過性の新生児貧血を認めたがリボゾーム蛋白遺伝子の変異はなかった. 他の2組の母子では, それぞれRPS19 (exon 4, c.185G>A) のミスセンス変異とRPS7のスプライシング変異 (exon 3, c.76-1G>T) を同定した. それぞれの変異と別に, 貧血を来し得る遺伝子変異はなかった. 本研究は, WESがヒトリボゾーム病の迅速かつ正確な診断を得るために有用であることを示唆した.

The reduction of excessive discharge of phosphate into water bodies is a dominant theme to combat the critical eutrophication issue and requires the development of high-performance materials for effective phosphate treatment. In this study, rice straw was used as a raw material for the synthesis of biochar functionalized with layered double hydroxides (BC-LDHs) as efficacious phosphate adsorbents, and their successful synthesis was corroborated via characterization analysis. Experimental investigations, including pH, coexisting anion, reaction time, and initial phosphate concentration effects were systematically performed with selected BC-LDHs 6 and pure LDHs. An optimum pH of 3.0 was observed in both samples. Kinetic and isotherm studies indicated that phosphate adsorption on these samples was controlled by the pseudo-second-order model and the Freundlich model. Comparative kinetic tests also demonstrated that BC-LDHs 6 and pure LDHs reached the equilibrium within 24 h and 3 h, respectively. Nonetheless, the maximum adsorption capacity of the composite was 192 mg/g, which was higher than that of pure LDHs (166 mg/g). The coexistence of various anions negligibly affected the removal efficiency of the composite; however, fluoride was the most competitive anion for adsorption on pure LDHs. The adsorption mechanisms of the composite involved electrostatic interaction, inner-sphere complexation, pore diffusion, precipitation, and reconstruction. Furthermore, phosphate adsorbed on both materials could be easily recovered by 0.1 M NaOH solution owing to the displacement reaction between phosphate and hydroxyl ions. Additional evidence from reusability experiments exhibited that the composite could maintain its good adsorption performance even after three adsorption-desorption cycles. The transformation of BC-LDHs 6 after its usage in phosphate treatment (P-BC-LDHs 6) into a fertilizer was further explored by using seed germination and early growth assays of lettuce through a comparison with phosphate-loaded LDHs (P-LDHs). Lettuce seeds germinated in all P-BC-LDH 6 treatments showed undesirable growth characteristics compared with the controls, while total germination failure was observed under high concentrations of P-LDHs. In the latter experiments, the optimal application rates for plant growth were 2.5% for P-BC-LDHs 6 and 1.0% for P-LDHs. The considerably greater biomass development and length of lettuce were visible in samples delivered from P-BC-LDHs 6 compared to those from P-LDHs. The results obtained suggest that BC-LDHs 6 is a promising adsorbent for phosphate treatment and post-adsorption BC-LDHs 6 has the application potential to serve as a fertilizer for horticultural crop production.

Chromatography is considered as a key operation in the downstream process (DSP) of biopharmaceuticals, including proteins. Therapeutic proteins such as monoclonal antibodies (mAbs) with high economic values in the global market require immediate innovation in the purification step to adapt to the increased throughput from upstream. Authorities have also initiated changes toward a more modernized pharmaceutical manufacturing platform which is agile and flexible without extensive oversight. Instead of the conventional batch operation and empirical models, the design and application of in silico modeling and simulation for integrated multi-column processes to improve their performance in capture chromatography steps have been explored in the dissertation. Due to the fact that mechanistic models can reveal adsorption and mass transfer behaviors better in the chromatography compared to statistical models, mechanistic frameworks were applied in the study. Ion-exchange and protein A chromatography, the main categories of therapeutic protein chromatography were examined. With an example of oligonucleotides, the mass transfer phenomenon of biomolecules in different types of ion-exchange resins was explored by mechanistic models. The results demonstrate the effectiveness of modeling approaches to understand the chromatography process of biopharmaceuticals. By focusing on the DSP of mAbs, multi-column continuous chromatography was examined with IgG samples. The study covered the repeating batch to 4-column settings in the continuous periodic counter-current (PCC) chromatography, with development in modeling and simulation tools for process quantification and evaluation. Process performances including productivity, capacity utilization, and buffer consumption were investigated by simulations with the aim to increase productivities and lower buffer consumptions, which are the main bottleneck in the current DSP. The critical operation parameter, breakthrough percent (BT%) for column switching in PCC processes, requires the information from binding capacity, mass transfer, and non-loading operations. To obtain the optimal BT% under synchronized conditions, numerical solvers developed from mechanistic models were employed. It was found that over 20% improvement in buffer consumption and resin utilization can be observed in PCC processes while the same productivity as batch operation is maintained. Furthermore, regressive relations were developed for predictions of process performances and BT% based on the findings from PCC simulations. With high coherence in R2 over 0.95, the linear regression function can act as an accelerated method in the PCC process design. Finally, a new strategy of linear flow-velocity gradient (LFG) in the loading step was explored as a supplement to increase process efficiency. The method controls the total column capacity and the loaded amount as functions of time. Based on the relationship between the dynamic binding capacity and residence time, the gradient time of LFG was obtained. The optimal flow velocities and time gradients were examined by scanning through the range of applicable residence times. A case study of the 4-column PCC process is presented. By integrating a linear decreasing flow gradient in the PCC loading operation, the productivity has 1.4 times enhancement along with a 13% reduction in the cost of resin per amount of processed mAbs compared to constant flows. Undoubtedly, the next generation of DSP platform technology is directed toward continuous and integrated systems. Regarding the advantages in process performances and regulation perspectives, continuous manufacturing can advance development and manufacturing while assuring the product quality. The evolution in modeling and simulation enables faster development of in silico process prediction and evaluation. With the support from models, process design and optimization in chromatography can rise to the challenge.