Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.     

Ceramics based on mixed zirconium phosphate prepared by solar-furnace melting

A solar technology to synthesize an NZP structure using the example of Zr(PO₄) was developed. The method is based on high-temperature chemical reactions in the melt and subsequent crystallization of the hexagonal structure of the compounds of this class. Ceramic samples were prepared from the material obtained, and the processes of their sintering were studied.     

Physical modeling of urban air-pollutant transport

Air-pollutant transport within an urban setting is conditioned by local urban geometry, urban-modified meteorological variables, a wide variety of source characteristics and local topography. Extreme complexity and local specificity of the resulting dispersion process requires the use of physical modeling rather than numerical or analytical methods to predict concentration distributions. Serving as an analog computer the boundary-layer wind tunnel provides reliable concentration data which can be applied directly to design and/or decision making.A brief review is made of similarity criteria for simulating physical modeling of the atmospheric boundary-layer and source characteristics in a boundary-layer wind tunnel. Applications to several problems related to stack, vent and automobile emissions are described. Rudimentary portions of a data bank are presented which, with additional data acquisition, can provide a practical method for prediction of automobile exhaust concentrations that will result from proposed freeways or alternative traffic routings.     

A sub-2.0 V BiCMOS logic circuit with a BiCMOS charge pump

A BiCMOS logic circuit with very small input capacitance has been developed, which operates at low supply voltages. A High-beta BiCMOS (Hβ-BiCMOS) gate circuit which fully utilizes the bipolar transistor features achieves 10 times the speed of a CMOS gate circuit with the same input capacitance and operating at 3.3 V supply voltage. In order to lower the minimum supply voltage of Hβ-BiCMOS, a BiCMOS circuit configuration using a charge pump to pull up the output high level of the BiCMOS gate circuit is proposed. By introducing a BiCMOS charge pump, Hβ-BiCMOS achieves very high speed operation at sub-2.0 V supply voltage. It has also been demonstrated that only a very small number of charge pump circuits are required to drive a large number of Hβ-BiCMOS gate circuits     

Inhibition by dexamethasone of human neutrophil apoptosis in vitro

The efficacy of collagen-sponge to reduce postoperative scar formation was investigated in 65 Japanese white rabbits that received laminectomy in the 7th and 8th thoracic vertebra. The defect after laminectomy was filled by collagen-sponge in 25 rabbits, by free fat in 20 rabbits, and by nothing in 20 rabbits as controls. The animals were sacrificed 2, 4, 8 and 12 weeks and additional 5 rabbits of which defects were filled with collagen-sponge were sacrificed after 24 weeks. All the defects were examined histologically. At 4 weeks after laminectomy, the defects filled by collagen-sponge showed that fibrous tissue had invaded into the sponge, but there was no remarkable adhesion to the dura mater. At 8 weeks, the defect with collagen sponge showed foaming cells, and no thickening of the dura mater was observed. At 12 weeks, the grouping of foaming cells was partially replaced by fat cells. At 24 weeks, most of the foaming cells were replaced by fat cells, and the defect was then similar to that filled by free fat at 12 weeks. In contrast, the defect with no interposed membrane was already filled with fibrous tissue at 4 weeks, and adhesion to the dura mater was observed. Although the free-fat graft at 12 weeks postoperatively showed no remarkable adhesion around the dura mater, infiltration of fat tissue into the spinal canal was observed in 2 of 5 rabbits. These results indicated that collagen-sponge can be utilized as a new biomaterial to effectively prevent scar formation after laminectomy.     

基于Web GIS的移民信息管理系统设计

基于在线地图服务,ArcGIS js for API提供的接口,以征地移民信息数据为基础,开发了基于Web GIS的移民信息管理系统.系统基于B/S架构,提供全面的地图操作、数据录入、红线内查询检索、汇总统计、综合分析等功能,实现移民实物指标调查数据的集中存储,确保数据处理的准确性,满足征地移民智能化管理的需要.     

动态网络安全模型信息安全风险分析

通过动态网络模型信息安全风险分析实验,在LazyLBR和VFI的ROC曲线进行统计和F-度量,采用10倍交叉验证方法.针对网络的脆弱性、外界的威胁和资产价值几种数据,对比四种动态网络模型信息安全风险的数字学习曲线.     

Screening of Inhibitors Targeting Heat Shock Protein 47 Involved in the Development of Idiopathic Pulmonary Fibrosis

Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is causally related to fibrotic diseases, including idiopathic pulmonary fibrosis. The identification of Compounds that interfere with the HSP47-collagen interaction is essential for the development of relevant therapeutics. Herein, we prepared human HSP47 as a soluble fusion protein expressed in E. coli and established an assay system for HSP47 inhibitor screening. We screened a natural and synthetic Compound library established at Nagasaki University. Among 1023 Compounds, 13 exhibited inhibitory activity against human HSP47, of which three inhibited its function in a dose-dependent manner. Epigallocatechin-3-O-gallate, one of these three Compounds, is a typical polyphenol Compound derived from tea leaves. Structurally related Compounds were synthesized and examined for their activity, revealing a hydroxyl group at A-ring position 5 as important for its activity. The present findings provide valuable insight for the development of natural product-derived therapeutics for fibrotic diseases, including idiopathic pulmonary fibrosis.     

An Engineered Biliverdin-Compatible Cyanobacteriochrome Enables a Unique Ultrafast Reversible Photoswitching Pathway

Cyanobacteriochromes (CBCRs) are promising optogenetic tools for their diverse absorption properties with a single compact cofactor-binding domain. We previously uncovered the ultrafast reversible photoswitching dynamics of a red/green photoreceptor AnPixJg2, which binds phycocyanobilin (PCB) that is unavailable in mammalian cells. Biliverdin (BV) is a mammalian cofactor with a similar structure to PCB but exhibits redder absorption. To improve the AnPixJg2 feasibility in mammalian applications, AnPixJg2_BV4 with only four mutations has been engineered to incorporate BV. Herein, we implemented femtosecond transient absorption (fs-TA) and ground state femtosecond stimulated Raman spectroscopy (GS-FSRS) to uncover transient electronic dynamics on molecular time scales and key structural motions responsible for the photoconversion of AnPixJg2_BV4 with PCB (Bpcb) and BV (Bbv) cofactors in comparison with the parent AnPixJg2 (Apcb). Bpcb adopts the same photoconversion scheme as Apcb, while BV4 mutations create a less bulky environment around the cofactor D ring that promotes a faster twist. The engineered Bbv employs a reversible clockwise/counterclockwise photoswitching that requires a two-step twist on ~5 and 35 picosecond (ps) time scales. The primary forward P_fr → P_o transition displays equal amplitude weights between the two processes before reaching a conical intersection. In contrast, the primary reverse P_o → P_fr transition shows a 2:1 weight ratio of the ~35 ps over 5 ps component, implying notable changes to the D-ring-twisting pathway. Moreover, we performed pre-resonance GS-FSRS and quantum calculations to identify the Bbv vibrational marker bands at ~659,797, and 1225 cm⁻¹. These modes reveal a stronger H-bonding network around the BV cofactor A ring with BV4 mutations, corroborating the D-ring-dominant reversible photoswitching pathway in the excited state. Implementation of BV4 mutations in other PCB-binding GAF domains like AnPixJg4, AM1_1870g3, and NpF2164g5 could promote similar efficient reversible photoswitching for more directional bioimaging and optogenetic applications, and inspire other bioengineering advances.