Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation

While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-release once-daily tacrolimus formulation (0.20 mg/kg) was administered to 50 Japanese renal transplant patients every 24 h. Stepwise multiple linear regression analysis for tacrolimus dosing was performed each week to determine the effect of patient clinical characteristics. The dose-adjusted trough concentration was approximately 70% higher for patients with the CYP3A5*3/*3 than patients with the CYP3A5*1 allele before the second pre-transplantation tacrolimus dose (0.97 (0.78–1.17) vs. 0.59 (0.45–0.87) ng/mL/mg; p < 0.001). The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively. The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery. Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information.     

Serial Changes of Serum Growth Factor Levels and Liver Regeneration after Partial Hepatectomy in Healthy Humans

This study aimed to investigate the associations of the serial changes of serum levels of various growth factors with liver regeneration after hepatectomy in healthy liver donors. Sixteen healthy liver donors who underwent conventional liver resection were included. Serum levels of various growth factors before hepatectomy and on postoperative day (POD) 1, 3, 5 and 7 were measured. Liver volume data calculated by multi-detector computed tomography using workstation. The ratio of remnant liver volume on POD 0 to liver volume before the operation was 51% ± 20%. The ratio of liver volume on POD 14 to liver volume on POD 0 were inversely correlated with remnant liver volume on POD 0 (r = −0.91). The ratio of liver volume on POD 14 to liver volume on POD 0 were significantly correlated with serum hepatocyte growth factor (HGF) levels on POD 1 (r = 0.54), serum leptin levels on POD 1 (r = 0.54), and serum macrophage colony-stimulating factor (M-CSF) levels on POD 5 (r = 0.76) and POD 7 (r = 0.80). These results suggest that early-phase elevation of serum levels of HGF, leptin and M-CSF may be associated with the acceleration of liver regeneration after hepatectomy in humans.     

Improvement of mechanical properties for PP/PS blends by in situ compatibilization

The effect of the in situ compatibilization on the mechanical properties of PP/PS blends was investigated. The application of Friedel-Crafts alkylation reaction to the PP/PS-blend compatibilization was assessed. Styrene/AlCl₃ was used as catalyst system. The graft copolymer (PP-g-PS) formed at the interphase showed relatively high emulsifying strength. Scission reactions, occurring in parallel with grafting, were verified for PP and PS at high catalyst concentration, but no crosslinking reactions were detected. Tensile tests were performed on dog-bone specimens of the blends. Both elongation at break and toughness increased with catalyst concentration. At 0.7% AlCl₃, a maximum was reached, which amounted to five times the value of the property for the uncompatibilized blend. At higher catalyst concentrations these properties decreased along with the PP molecular weight due to chain-scission reactions. On the other hand, the tensile strength did not change with the catalyst concentration. The in situ compatibilized blends showed considerable improvement in mechanical properties, but were adversely affected by chain scissions at high catalyst contents.     

Molecular simulation for adsorption of chlorinated hydrocarbon in zeolites

Equilibrium and isosteric heat of adsorption for the system of chloroform and USY-type zeolite were studied. The USY-type zeolite (PQ Co., SiO₂/Al₂O₃=70) was used both as a pure crystalline powder and as granulated particles with binder. Chloroform was reagent grade. The adsorption equilibria were measured using a gravimetric method and were expressed as isotherms. A chromatographic method (i.e. pulse response of chloroform through the USY column with helium carrier) was used to get the initial slope of the isotherms. In the simulation, the GCMC method was used to calculate amounts adsorbed for various conditions. FF parameters were confidently applied. And modified structure model was effective for simulation. This paper was presented at The 5th International Symposium on Separation Technology-Korea and Japan held at Seoul between August 19 and 21, 1999.     

Effect of changing groundwater levels caused by land-use changes on greenhouse gas fluxes from tropical peat lands

Monthly measurements of carbon dioxide (CO₂), methane (CH₄) and nitrous oxide (N₂O) fluxes in peat soils were carried out and compared with groundwater level over a year at four sites (drained forest, upland cassava,upland and lowland paddy fields) located in Jambi province, Indonesia. Fluxes from swamp forest soils were also measured once per year as the native state of this investigated area. Land-use change from drained forest to lowland paddy field significantly decreased the CO₂ (from 266 to 30 mg C m^–2 h^–1) and N₂O fluxes (from 25.4 to 3.8 g N m^–2 h^–1), but increased the CH₄ flux (from 0.1 to 4.2 mg C m^–2 h^–1) in the soils. Change from drained forest to cassava field significantly increased N₂O flux (from 25.4 to 62.2 g N m^–2 h^–1), but had no significant influence on CO₂ (from 266 to 200 mg C m^–2 h^–1) and CH₄ fluxes (from 0.1 to 0.3 mg C m^–2 h^–1) in the soils. Averaged CO₂ fluxes in the swamp forests (94 mg C m^–2 h^–1) were estimated to be one-third of that in the drained forest. Groundwater levels of drained forest and upland crop fields had been lowered by drainage ditches while swamp forest and lowland paddy field were flooded, although groundwater levels were also affected by precipitation. Groundwater levels were negatively related to CO₂ flux but positively related to CH₄ flux at all investigation sites. The peak of the N₂O flux was observed at –20 cm of groundwater level. Lowering the groundwater level by 10 cm from the soil surface resulted in a 50 increase in CO₂ emission (from 109.1 to 162.4 mg C m^–2 h^–1) and a 25% decrease in CH₄ emission (from 0.440 to 0.325 mg C m^–2 h^–1) in this study. These results suggest that lowering of groundwater level by the drainage ditches in the peat lands contributes to global warming and devastation of fields. Swamp forest was probably the best land-use management in peat lands to suppress the carbon loss and greenhouse gas emission. Lowland paddy field was a better agricultural system in the peat lands in terms of C sequestration and greenhouse gas emission. Carbon loss from lowland paddy field was one-eighth of that of the other upland crop systems, although the Global Warming Potential was almost the same level as that of the other upland crop systems because of CH₄ emission through rice plants.     

Role of Cu film texture in grain growth correlated with twin boundary formation

To understand the role of Cu film texture in grain growth at room temperature (RT) in relation to twin boundary formation Cu films were deposited on various barrier materials and the Cu film texture was investigated by X-ray diffraction. Cu grain growth was rapid on a barrierless SiO₂/Si substrate and very slow on a Ta barrier due to strong (1 1 1) texture. The growth rate and the average grain diameter after being kept at RT for up to ∼60 days were maximum at a (2 0 0)_Cu peak to (2 2 2)_Cu peak area ratio of ∼1.0, where {1 1 1}, {1 0 0} and {5 1 1} grains coexisted. Such coexistence of three or more orientations of grains is essential in facilitating Cu grain growth at RT. Similarly, the average twin boundary (TB) density was maximum when Cu grain growth was facilitated. TB formation in nano-sized Cu grains was not controlled by grain size, but due to grain growth. The TB could be annealing twins caused by irregularities in the stacking sequence during relatively fast grain growth. The Cu film texture is concluded to be determined at the beginning of deposition, and the wettability of various barrier materials by the Cu films plays a key role in determining the film texture.     

Processing of Oriented K(Ta,Nb)O3 Films Using Chemical Solution Deposition

K(Ta,Nb)O₃ (KTN) thin films have been prepared by the chemical solution deposition method. KTN precursors consisted of a uniform mixture of K[Ta(OC₂H₅)₆] and K[Nb(OC₂H₅)₆] with interaction at the molecular level. Perovskite KTN thin films with the desired composition (Ta/Nb = 65/35, 50/50, and 35/65) were synthesized from the precursor solutions by the dip coating method. KTN thin films with (100) preferred orientation were successfully synthesized on MgO(100) and Pt(100)/MgO(100) substrates. X-ray pole figure measurements showed that grains of KTN films had a prominent three-dimensional regularity on MgO(100) and Pt(100)/MgO(100) surfaces. The Curie temperatures of KTN films decreased with increasing Ta/Nb ratio. Typical P-E hysteresis loops were observed for KTN thin films of three compositions on Pt(100)/MgO(100) substrates. The values of remanent polarization ( P _r) of KTN films increased as the Ta/Nb ratio changed from 65/35 to 35/65.     

Preparation of mesoporous silica replica using ordered mesoporous carbon by vapor phase transport of silica source

A new vapor phase transport (VPT) technique to prepare an inverse silica replica of an ordered mesoporous carbon was developed. Tetraethyl orthosilicate (TEOS) was infiltrated in mesoporous carbon CMK-3 as the hard template at 180 °C for 48 h under an autogenous pressure in an autoclave in the presence of water. The samples obtained by removal of CMK-3 retained structural regularity of CMK-3 with little shrinkage of framework, which were characterized by SAXRD, N₂ adsorption, TG-DTA, and SEM. Influence of preparation temperature on the loading amount of silica was investigated. The multi-step replication process was monitored by characterizing the replicated materials as well as intermediate composites.     

Thermal Feasibility Analyses for the 1356MWe High Conversion-Type Innovative Water Reactor for Flexible Fuel Cycle

A new reactor concept of innovative water reactor for flexible fuel cycle (FLWR) is under development at Japan Atomic Energy Agency in cooperation with Japanese reactor suppliers. A design of 1,356 MWe high conversion boiling water reactor-type FLWR core, which has an instantaneous conversion ratio of 1.04, negative void coefficient, high burnup of 65 GWd/t, and 15-month operational cycle length, has been constructed. So far, studies on thermal-hydraulic characteristics have been performed for tight lattice core. Evaluation methods for the critical power and the pressure drop under both the steady and the transient states have been established, and a modified TRAC-BF1 code has been developed for the thermal-hydraulic design of the FLWR. In this paper, the thermal feasibility of the designed 1356MWe FLWR core is analyzed by using the modified TRAC-BF1 code. The analysis is first carried out for the current core design. It is confirmed that no boiling transition (BT) occurs under the steady state. However, the minimum critical power ratio (MCPR) is only about 1.08, and the BT is confirmed occurring under the postulated abnormal transient processes. Therefore, concretizations of the conditions that ensure the thermal feasibility of a natural circulation-type FLWR and a forced circulation-type FLWR are performed. As for the results, for a forced circulation-type FLWR, the operation-limited MCPR (OLMCPR) is 1.32, and the necessary minimum core coolant flow rate is 640 kg/(m²s). For a natural circulation-type FLWR, the OLMCPR is 1.19, and the necessary minimum core coolant flow rate is 560 kg/(m²s).     

Surface modification of an organosilane self-assembled monolayer on silicon substrates using atomic force microscopy: scanning probe electrochemistry toward nanolithography

Organosilane self-assembled monolayers (SAMs) have been applied to resist materials for nanolithography based on scanning probe microscopy. An organosilane SAM was prepared on Si substrates from a precursor, that is octadecyltrimethoxysilane. Using an atomic force microscope with a conductive probe, current was injected from the probe into the SAM-covered Si substrate so that the SAM was locally degraded at the probe-contacting point. Nanoscale patterns drawn on the SAM was clearly imaged by lateral force microscopy. The patterning could be conducted in air while, in vacuum at the order of 10(-6) Torr, no detectable patterns were fabricated. The presence of adsorbed water at the probe/sample junction was confirmed to be crucial for the patterning of the SAM/Si. Its mechanism was, thus, ascribed to electrochemical reactions of both the SAM and Si with adsorbed water.