"Impact of Natural Disasters on Industrial Agglomeration: A Case of the 1923 Great Kanto Earthquake"

One of the main implications of the New Economic Geography, developed since the 1990s, is that a temporary shock can create a persistent impact on the geographic distribution of economic activities because of multiple equilibria. This paper investigates the long-run impact of a temporary shock on the geographic distribution of industries in Tokyo Prefecture, Japan, using the Great Kanto Earthquake in 1923 as a natural experiment. It is revealed that the temporary shock from the Great Kanto Earthquake was basically dissipated by 1936, just before the full-scale war with China broke out. On the other hand, through industry-level investigation, it is found that with respect to the machinery and metal industry, the impact was persistent and remained even in 1936. These findings suggest the importance of the industrial structure and transaction networks within industry in the mechanism determining geographic distribution of industries.

B細胞性リンパ腫患者におけるR-CHOP療法の免疫機能回復への影響

藤田医科大

Potential Antitumor Activity of 2-O-α-D-Glucopyranosyl-6-O-(2-Pentylheptanoyl)-L-Ascorbic Acid

Intravenous administration of high-dose ascorbic acid (AA) has been reported as a treatment for cancer patients. However, cancer patients with renal failure cannot receive this therapy because high-dose AA infusion can have side effects. To solve this problem, we evaluated the antitumor activity of a lipophilic stable AA derivative, 2-O-α-D-glucopyranosyl-6-O-(2-pentylheptanoyl)-L-ascorbic acid (6-bOcta-AA-2G). Intravenous administration of 6-bOcta-AA-2G suppressed tumor growth in colon-26 tumor-bearing mice more strongly than did AA, even at 1/10 of the molar amount of AA. Experiments on the biodistribution and clearance of 6-bOcta-AA-2G and its metabolites in tumor-bearing mice showed that 6-bOcta-AA-2G was hydrolyzed to 6-O-(2-propylpentanoyl)-L-ascorbic acid (6-bOcta-AA) slowly to yield AA, and the results suggested that this characteristic metabolic pattern is responsible for making the antitumor activity of 6-bOcta-AA-2G stronger than that of AA and that the active form of 6-bOcta-AA-2G showing antitumor activity is 6-bOcta-AA. In in vitro experiments, the oxidized form of 6-bOcta-AA as well as 6-bOcta-AA showed significant cytotoxicity, while the oxidized forms of ascorbic acid showed no cytotoxicity at all, suggesting that the antitumor activity mechanism of 6-bOcta-AA-2G is different from that of AA and that the antitumor activity is due to the reduced and oxidized form of 6-bOcta-AA. The findings suggest that 6-bOcta-AA-2G is a potent candidate as an alternative drug to intravenous high-dose AA

Antiallergic Activity of 6-Deoxy-2-O-methyl-6-(N-hexadecanoyl)amino-L-ascorbic Acid

Allergy is an excessive immune response to a specific antigen. Type I allergies, such as hay fever and food allergies, have increased significantly in recent years and have become a worldwide problem. We previously reported that an ascorbic acid derivative having palmitoyl and glucosyl groups, 2-O-α-D-glucopyranosyl-6-O-hexadecanoyl-L-ascorbic acid (6-sPalm-AA-2G), showed inhibitory effects on degranulation in vitro and on the passive cutaneous anaphylaxis (PCA) reaction in mice. In this study, several palmitoyl derivatives of ascorbic acid were synthesized and a structure–activity relationship study was performed to discover more potent ascorbic acid derivatives with degranulation inhibitory activity. 6-Deoxy-2-O-methyl-6-(N-hexadecanoyl)amino-L-ascorbic acid (2-Me-6-N-Palm-AA), in which a methyl group was introduced into the hydroxyl group at the C-2 position of ascorbic acid and in which the hydroxyl group at the C-6 position was substituted with an N-palmitoyl group, exhibited much higher inhibitory activity for degranulation in vitro than did 6-sPalm-AA-2G. 2-Me-6-N-Palm-AA strongly inhibit the PCA reaction in mice at lower doses than those of 6-sPalm-AA-2G. These findings suggest that 2-Me-6-N-Palm-AA may be a promising therapeutic candidate for allergic diseases

Anti-Allergic Activity of Monoacylated Ascorbic Acid 2-Glucosides

2-O-α-D-Glucopyranosyl-L-ascorbic acid (AA-2G) is one of the stable ascorbic acid (AA) derivatives known as provitamin C agents. We have previously synthesized two types of monoacylated derivatives of AA-2G, 6-O-acyl-2-O-α-D-glucopyranosyl-L-ascorbic acids having a straight-acyl chain of varying length from C4 to C18 (6-sAcyl-AA-2G) and a branched-acyl chain of varying length from C6 to C16 (6-bAcyl-AA-2G) in order to improve the bioavailability of AA-2G. In this study, 6-sAcyl-AA-2G and 6-bAcyl-AA-2G per se showed the inhibitory effects on hyaluronidase activity and degranulation. 6-sAcyl-AA-2G exhibited strong inhibitory effects on hyaluronidase activity and degranulation in a concentration-dependent manner, and the inhibitory effects tended to become stronger with increasing length of the acyl chain. 2-O-α-D-Glucopyranosyl-6-O-hexadecanoyl-L-ascorbic acid (6-sPalm-AA-2G), which has a straight C16 acyl chain, was the most potent effective for inhibition of hyaluronidase activity and for inhibition of degranulation among the 6-sAcyl-AA-2G derivatives and the two isomers of 6-sPalm-AA-2G. Furthermore, percutaneous administration of 6-sPalm-AA-2G significantly inhibited IgE-mediated passive cutaneous anaphylaxis reaction in mice. These findings suggest that 6-sPalm-AA-2G will be useful for treatment of allergies

Identification of Zebrafish Fxyd11a Protein that is Highly Expressed in Ion-Transporting Epithelium of the Gill and Skin and its Possible Role in Ion Homeostasis

FXYD proteins, small single-transmembrane proteins, have been proposed to be auxiliary regulatory subunits of Na+–K+-ATPase and have recently been implied in ion osmoregulation of teleost fish. In freshwater (FW) fish, numerous ions are actively taken up through mitochondrion-rich cells (MRCs) of the gill and skin epithelia, using the Na+ electrochemical gradient generated by Na+–K+-ATPase. In the present study, to understand the molecular mechanism for the regulation of Na+–K+-ATPase in MRCs of FW fish, we sought to identify FXYD proteins expressed in MRCs of zebrafish. Reverse-transcriptase PCR studies of adult zebrafish tissues revealed that, out of eight fxyd genes found in zebrafish database, only zebrafish fxyd11 (zfxyd11) mRNA exhibited a gill-specific expression. Double immunofluorescence staining showed that zFxyd11 is abundantly expressed in MRCs rich in Na+–K+-ATPase (NaK-MRCs) but not in those rich in vacuolar-type H+-transporting ATPase. An in situ proximity ligation assay demonstrated its close association with Na+–K+-ATPase in NaK-MRCs. The zfxyd11 mRNA expression was detectable at 1 day postfertilization, and its expression levels in the whole larvae and adult gills were regulated in response to changes in environmental ionic concentrations. Furthermore, knockdown of zFxyd11 resulted in a significant increase in the number of Na+–K+-ATPase–positive cells in the larval skin. These results suggest that zFxyd11 may regulate the transport ability of NaK-MRCs by modulating Na+–K+-ATPase activity, and may be involved in the regulation of body fluid and electrolyte homeostasis

Pourquoi les politiques publiques sont-elles si peu suivies d’effets ?:Quelques interrogations

L’insertion des femmes sur le marché du travail a connu à la fois des avancées et des reculs. Si davantage de femmes accèdent à l’éducation supérieure et aux emplois qualifiés, d’autres sont touchées par la précarité et connaissent une dégradation de leurs conditions de travail et de vie. Face à ce constat ambivalent, on peut questionner la mise en œuvre et l’efficacité des politiques qui visent à promouvoir l’égalité entre les femmes et les hommes. Cet article a pour objectif de soulever quelques débats. Le plus souvent, les politiques publiques au sens large (y compris la protection sociale) sont définies en termes de compensation et de correction des inégalités et des discriminations. Mais elles ne concernent pas les causes effectives de l’extension du sous-emploi des femmes, qui relèvent du fonctionnement même du marché du travail. C’est donc la définition des politiques publiques qu’il faut interroger, en dépassant une vision binaire qui oppose d’une part un champ économique extérieur, d’autre part un champ social, juridique et culturel qui, seul, pourrait être l’objet d’inflexions. En réalité, le champ économique est aussi le produit des politiques publiques : la libre-concurrence et la prééminence du marché sont le résultat d’une action volontaire des États. Il faut donc réintégrer les politiques économiques dans le champ de la réflexion sur les moyens de combattre les discriminations à l’encontre des femmes.The integration of women into the labour market has gone through both upswings and downturns. In view of this ambivalent result, we can question the efficiency of public policies set up to overcome gender inequality and fight gender discrimination. Does a real will exist, and if so why is it so inefficient or so poorly implemented? What forms do individual and collective resistance take? Most of the time, public policies are defined in terms of compensation and correction. But they don’t deal with the actual causes of women’s underemployment resulting from labour market adjustments. It is therefore the definition of the public policies that we need to examine, going beyond a binary view that opposes economic issues, on the one hand, to social, juridical and cultural concerns on the other

Fibroblasts Show More Potential as Target Cells than Keratinocytes in COL7A1 Gene Therapy of Dystrophic Epidermolysis Bullosa

Dystrophic epidermolysis bullosa (DEB) is an inherited blistering skin disorder caused by mutations in the type VII collagen gene (COL7A1). Therapeutic introduction of COL7A1 into skin cells holds significant promise for the treatment of DEB. The purpose of this study was to establish an efficient retroviral transfer method for COL7A1 into DEB epidermal keratinocytes and dermal fibroblasts, and to determine which gene-transferred cells can most efficiently express collagen VII in the skin. We demonstrated that gene transfer using a combination of G protein of vesicular stomatitis virus-pseudotyped retroviral vector and retronectin introduced COL7A1 into keratinocytes and fibroblasts from a DEB patient with the lack of COL7A1 expression. Real-time polymerase chain reaction analysis of the normal human skin demonstrated that the quantity of COL7A1 expression in the epidermis was significantly higher than that in the dermis. Subsequently, we have produced skin grafts with the gene-transferred or untreated DEB keratinocytes and fibroblasts, and have transplanted them into nude rats. Interestingly, the series of skin graft experiments showed that the gene-transferred fibroblasts supplied higher amount of collagen VII to the new dermal–epidermal junction than the gene-transferred keratinocytes. An ultrastructural study revealed that collagen VII from gene-transferred cells formed proper anchoring fibrils. These results suggest that fibroblasts may be a better gene therapy target of DEB treatment than keratinocytes