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For the development of effective drug carriers, nanocapsules that respond to micro-environmental changes including a decrease in pH and a reductive environment were prepared by the stabilization of polymer vesicles formed from head-tail type polycations, composed of a polyamidoamine dendron head and a poly(L-lysine) tail (PAMAM dendron-PLL), through the introduction of disulfide bonds between the PLL tails. Disulfide bonds were successfully introduced through the reaction of Lys residues in the PAMAM dendron-PLL polymer vesicles with 2-iminothiolane. The stabilization of PAMAM dendron-PLL polymer vesicles was confirmed by dynamic light scattering measurements. In acid-base titration experiments, nanocapsules cross-linked by disulfide bonds had a buffering effect during the cellular uptake process. The PAMAM dendron-PLL nanocapsules were used to incorporate the fluorescent dyes rhodamine 6G and fluorescein as a drug model. Cationic rhodamine 6G was generally not released from the nanocapsules because of the electrostatic barrier of the PLL membrane. However, the nanocapsules were destabilized at high glutathione concentrations corresponding to intracellular concentrations. Rhodamine 6G was immediately released from the nanocapsules because of destabilization upon the cleavage of disulfide bonds. This release of rhodamine 6G from the nanocapsules was also observed in HeLa cells by laser confocal microscopy.

This book presents pioneering work on an interregional input-output table of the Chinese economy and its applications to the analysis of interregional and interindustrial relations in China. It is the fruit of the authors' joint efforts of more than five years to establish a solid basis for the analysis of interregional relations in China, in the hope of laying the foundation for further studies of regional development in that country. The book endeavors to make a contribution to the regional typology of the Chinese economy. The Chinese provinces are classified into seven large regions. The interregional input-output table is constructed accordingly. Chapter I describes the methodology for producing this interregional input-output (IRIO) table. Chapter II presents the (IRIO) table after a brief explanation of the Chinese statistical data needed for the compilation of the table. Chapter III explains the basis of seven large regions adopted for the IRIO table. Chapter IV deals with the interdependence of regions and the effects of the changes in some parameters of one region on the activities in other regions. Chapter V, the last chapter, applies the IRIO table to policy analysis.

This book offers the representative macroeconometric models and their applications for the Japanese economy in different development stages throughout the postwar years up to the present. It presents a summary of three types of macroeconometric models and analyses: -Social accounting analyses of national income and related indices — following the tradition of C Clark, S Kuznets, R Stone and World Bank Development Reports; -Inter-industrial and inter-regional analyses of the Japanese economy a la W Leontief and the CGE (computable general equilibrium) type of applications to Comprehensive Development Plans; -Macroeconometric model building for the Japanese economy and its applications with a survey of various models in Japan, including the historic Osaka University ISER (Institute of Social and Economic Research) model and present day Government models.

This book explores the important topic of fiscal decentralization in Asian countries, and focuses on how government finance and administration are being reformed to bring budgetary decisions closer to voters.

Mutations in SLC26A4 cause a broad phenotypic spectrum, from typical Pendred syndrome to nonsyndromic hearing loss associated with enlarged vestibular aqueduct. Identification of these mutations is important for accurate diagnosis, proper medical management and appropriate genetic counseling and requires updated information regarding spectrum, clinical characteristics and genotype-phenotype correlations, based on a large cohort. In 100 patients with bilateral enlarged vestibular aqueduct among 1511 Japanese hearing loss probands registered in our gene bank, goiter data were available for 79, of whom 15 had Pendred syndrome and 64 had nonsyndromic hearing loss. We clarified the mutation spectrum for the SLC26A4 mutations and also summarized hearing levels, progression, fluctuation and existence of genotype-phenotype correlation. SLC26A4 mutations were identified in 82 of the 100 patients (82.0%). Of the Pendred syndrome patients, 93% (14/15) were carriers, as were 77% (49/64) of the nonsyndromic hearing loss patients. Clinical characteristics of patients with SLC26A4 mutations were congenital, fluctuating and progressive hearing loss usually associated with vertigo and/or goiter. We found no genotype-phenotype correlations, indicating that, unlike in the case of GJB2 mutations, the phenotype cannot be predicted from the genotype. Our mutation analysis confirmed the importance of mutations in the SLC26A4 gene among hearing loss patients with enlarged vestibular aqueduct and revealed the mutation spectrum, essential information when performing genetic testing.

Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α) is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase domain-containing protein have been developed. In addition, suppression of factor inhibiting HIF-1 (FIH-1) has also been shown to have the potential to activate HIF-α. However, few small-molecule inhibitors of FIH-1 have been developed. In this study, we synthesized a series of furan- and thiophene-2-carbonyl amino acid derivatives having the potential to inhibit FIH-1. The inhibitory activities of these compounds were evaluated in SK-N-BE(2)c cells by measuring HIF response element (HRE) promoter activity. Several furan- and thiophene-2-carbonyl amino acid derivatives inhibited FIH-1 based on correlations among the docking score of the FIH-1 active site, the chemical structure of the compounds, and biological HIF-α/HRE transcriptional activity.