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Carthamin, a dimeric quinochalcone that is sparingly soluble in water, is obtained from the yellow-orange corolla of fully blooming safflower (Carthamus tinctorius L.) florets. Carthamin is a natural red colorant, which has been used worldwide for more than 4500 years and is the major component of Japanese ‘beni’ used for dyeing textiles, in cosmetics and as a food colorant. The biosynthetic pathway of carthamin has long remained uncertain. Previously, carthamin was proposed to be derived from precarthamin (PC), a water-soluble quinochalcone, via a single enzymatic process. In this study, we identified the genes coding for the enzyme responsible for the formation of carthamin from PC, termed ‘carthamin synthase’ (CarS), using enzyme purification and transcriptome analysis. The CarS proteins were purified from the cream-colored corolla of safflower and identified as peroxidase homologs (CtPOD1, CtPOD2 and CtPOD3). The purified enzyme catalyzed the oxidative decarboxylation of PC to produce carthamin using O2, instead of H2O2, as an electron acceptor. In addition, CarS catalyzed the decomposition of carthamin. However, this enzymatic decomposition of carthamin could be circumvented by adsorption of the pigment to cellulose. These CtPOD isozymes were not only expressed in the corolla of the carthamin-producing orange safflower cultivars but were also abundantly expressed in tissues and organs that did not produce carthamin and PC. One CtPOD isozyme, CtPOD2, was localized in the extracellular space. Based on the results obtained, a model for the stable red pigmentation of safflower florets during flower senescence and the traditional ‘beni’ manufacturing process is proposed.

To investigate the surgical results for consecutive exotropia with or without insertion abnormalities on the basis of the position of the lateral rectus muscle at surgery. Patients with consecutive exotropia who had undergone medial rectus recession as a primary procedure or advancement of previously recessed medial rectus muscles from 2002 to 2012 were included in the study. The characteristics, postoperative courses, and final results were compared among 3 patient groups. The patients’ characteristics including sex, refractive error, and age at the initial surgery were compared. The main outcome measures were the angles of deviation in the primary position and the average divergent drift per month after the exotropia surgery. Twenty-four eyes of 23 patients were investigated. The patients were divided into 3 groups according to insertion status: with normal muscle insertion (4 men, 4 women), slipped muscles (9 women), and stretched scars (2 men, 4 women). The preoperative angles of deviation at near differed significantly between the slipped muscle group and the normal muscle insertion group (P = 0.02). Only patients with normal insertions had significantly greater hyperopia in the nondominant eye (0.95 D) than in the dominant eye (0.53 D). The postoperative divergent shift per month was similar among the groups (0.3, 0.1, and 0.2 prism diopters per month in the slipped muscle, stretched scar, and normal muscle insertion groups, respectively; P = 0.70). Hyperopic anisometropia is an important factor in the natural course of outward drift. The postoperative course of advancement of the medial rectus muscle was equally stable in all 3 patient groups.

The blue petal color of the cornflower (Centaurea cyanus) is caused by protocyanin, a kind of metalloanthocyanin, which is a self-assembled supramolecular metal complex pigment. Protocyanin is composed of six molecules of anthocyanin, six molecules of flavone, one ferric ion, and one magnesium ion. The ferric ion is essential for blue color development. Here, we identify the vacuolar iron transporter gene (CcVIT) from the blue petals of C. cyanus and its function is identified and characterized. The CcVIT transcript was observed only in the petals. Its amino acid sequence is highly homologous to the Arabidopsis thaliana (AtVIT1) and Tulipa gesneriana (TgVit1) vacuolar iron transporters. Heterologous expression of the CcVIT gene in yeast indicated that the corresponding gene product transports ferrous ion into vacuoles. Analysis of purple mutant-line petals clarified that the anthocyanin and flavone components were the same as those found in plants with blue petals, but the amount of iron ions in the colored cells decreased, and consequently the amount of blue protocyanin was reduced. The CcVIT gene was expressed even in purple mutant petals, however, an amino acid substitution (A236E) occurred in that case. This change in the CcVIT gene sequence also resulted in loss of iron transport activity. The CcVIT protein thus plays a critical role in the blue coloration of cornflower petals.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet dysfunction and ceroid deposition. We report suspected ocular albinism in two Japanese sisters, caused by mutations in the HPS6 (Hermansky-Pudlak syndrome 6) gene. Trio-based whole-exome sequencing (WES) identified novel compound heterozygous mutations in HPS6 (c.1898delC: mother origin and c.2038C>T: father origin) in the two sisters. To date, 10 associated mutations have been detected in HPS6. Although we detected no general manifestations, including platelet dysfunction, in the sisters, even in long-term follow-up, we established a diagnosis of HPS type 6 based on the HPS6 mutations and absence of dense bodies in the platelets, indicating that WES can identify cases of HPS type 6. To the best of our knowledge, this is the first report of HPS6 mutations in Japanese patients.

From the studies of the history of economic thought, we can learn that many theorems of the modern general equilibrium theory were well anticipated in the classical economics and the economics of the marginal revolution. For example, first, what Johann Heinrich von Thunen (1783–1850) did, in his strange theory of natural wage, can be interpreted as an early, pioneering attempt to use the so-called Negishi method (1960), which is now intensively used for the proof of the existence theorem and the numerical calculation of a general equilibrium. Second, as is well known, no exchanged transactions are permitted out of equilibria in the famous Walrasian tatonnement adjustment process towards market equilibria. Against this, the importance of transactions carried out at disequilibria is emphasized in the studies of the so-called Hahn–Negishi non-tatonnement process (1962). As a matter of fact, in the classical economics, this is exactly what William Thomas Thornton (1813–1380) insisted against the authority of John Stuart Mill (1800–1873). Finally, subjectively perceived (often kinked) demand curves are considered in my proof of the existence of a general equilibrium in the case of monopolistic competition (1961). To my surprise, however, I found later that such demand curves were already hidden in Adam Smith's (1723–1790) consideration of markets and the division of labor, and that the increase of demand never fails to lower the price of goods.

We defended Marshall from modern economic theorists' false accusation that he forgot producers' surplus in his proposition of the tax-subsidy scheme. After due attention is paid to Brahmananda's pioneering contribution, we argued, firstly, that Marshall did not forget producers' surplus but merely considered the case of no producers' surplus, in view of his distinction between the supply curve and the particular expenses curve and the long-run nature of the equilibrium considered. In addition to this purely theoretical vindication (rational reconstruction), we argued further more, from the view point of the history of economic thought, that Marshall did not forget producers' surplus in The Pure Theory, which was aimed at specialist readers, but deliberately assumed it away in Principles, which was aimed at more general readers. Finally, in view of the recent rapid development of the theoretical and applied general equilibrmm theory, we emphasize the role of Marshallian particular equilibrium analysis as a heuristic method.

No one can deny the important contributions made by Johann Heinrich von Thunen (1783-1850), a pioneer of the marginal revolution in economics, as an independent discoverer of the marginal productivity theory and as the father of the economics of space. Commemorating the two hundredth anniversary of his birth, Samuelson (1983) analyzed these contributions beautifully and skillfully. Von Thunen is, however, also known by the formula of natural wage inscribed on his grave stone. Classical economists before the marginal revolution explained the wage as the subsistence wage, while modern economists after the revolution emphasized the importance of the labor productivity in their theory of wage. In between, Thunen demonstrated the natural wage as the geometric mean of the subsistence wage and the average product of a laborer. Samuelson, who evaluated Thunen's positivistic economics (the marginal productivity theory and the economics of space) very high, interpreted the natural wage of Thunen as the socially optimal wage from the point of view of the welfare economics, and criticized that it is a major felony and a crime against normative economics.In Negishi (1990), we defended Thunen against Samuelson. Following an interpretation suggested by Yamada (1934), a pioneering study of Thunen in Japan, the natural wage is derived as an equilibrium wage in a competitive stationary economy, which Thunen himself studied in his famous Der isolierte Staat. In other words, we defended the theory of natural wage as a positive theory against Samuelson's criticism which regarded it as a normative theory. To be more decisive, however, as a rejoinder to Samuelson's critical comment that Thunen maximized a strange, irrational social welfare function, we have to argue further that the so-called Thunen's social welfare function itself is a rational, reasonable function, given his own model of a competitive stationary economy. In other words, what Thunen did can be interpreted as an early, pioneering attempt to use the so-called Negishi method, Negishi approach, or Negishi theorem, which is now intensively used for the proof of the existence of a general equilibrium and the numerical calculation of a general equilibrium. See Negishi (1960), Kehoe (1991), Mas-Colell and Zame (1991) and Ginsburgh and Keyzer (1997).

Cyanidium caldarium (Tilden) Geitler, a unicellular red alga, has extraordinarily high aluminum (Al) tolerance. Algal cells cultured in the presence or absence of Al were subjected to transmission electron microscopy and energy dispersive X-ray analysis. Substantial changes to the thylakoid lumens were observed for the algal cells cultured in medium containing 200 mM Al, while other organelles were largely unaffected. Several spherical electron-dense bodies were found in the cytoplasm near the nucleus of both of the control and Al-treated cells. Although high levels of Fe and P were found in the bodies of control cells, immunocytochemical and morphological analysis data did not match the criteria established for Fe-accumulating substances like ferritin and phytate. In addition to these elements, Al was found in the bodies of the Al-treated cells. These results suggest that the electron-dense bodies function as an Fe-storage site under normal culture conditions, and that sequestration of Al in these bodies contributes to the high Al tolerance exhibited by C. caldarium.

In Negishi (1986), I developed my view on the so-called Mill's recantation of the wages fund doctrine, the short-run theory of wages in the classical school of the economics. According to a survey article on the recent John Stuart Mill interpretations, “a further twist to the debate has been given by Negishi (1986). He reminds us that Mill, in the 1871 edition of the Principles, retracted some of his earlier enthusiasm for Thornton. There he in effect rejected the idea that disequilibrium trades in any way undermine the importance of the principle of the equality of supply and demand, and cautioned that it was too early to adduce any firm conclusions from the discussion engendered by Thornton's book”(De Marchi, 1988).I have three purposes in this present article. The first one is to offer a Japanese version of Negishi (1986), which I think it worthwhile, since there are still no Japanese translation available of the related literature referred and quoted there, i. e., Thornton (1869), Mill (1869) and Thornton (1870). Secondly, I wish to record the appearance of some related literature published in 1990's, like Ekelund (1997), Forget (1991), Fukagai (1995), Mawatari (1997), Mirowsky (1990), Negishi (1998), Vint (1994), and White (1994). Particularly, I wish to make some detailed rejoinders to comments given by Mawatari (1997).The final one is to consider, from the point of view of the modern economic theory (Arrow and Hahn (1971), pp. 324-346, and Negishi (1972), pp. 207-227), how Mill should have replied to Thornton, who asked the significance of a small amount of trade at equilibrium prices, which are arrived after a great bulk of goods were already sold at disequilibrium prices (Thornton, 1869, pp. 53-54; 1870, p. 65). As is easily seen at a glance at Figures 6, 7 and 8 in the text of the present article, i. e., those of box diagram and of utility frontier, the importance of the final small amount of trade at equilibrium prices is that the Pareto optimality is assured.

Peters Plus syndrome is a very rare autosomal recessive condition characterized by ocular defects (typically Peters anomaly) and other systemic major/minor anomalies. Mutations in the B3GALTL gene encoding beta 1,3-glucosyltransferase have been found in virtually all patients with typical Peters Plus syndrome. We report on a female patient with unusually severe manifestations of Peters Plus syndrome, including anterior eye staphyloma, cleft lip and palate, and hypoplastic left heart syndrome (HLHS). Analysis of the B3GALTL gene revealed no mutation in the patient. To our knowledge, HLHS has not previously been reported in Peters Plus syndrome so far, and anterior staphyloma, a most severe defect of the anterior eye chamber, is also apparently rare in the syndrome. Our patient might represent a new syndrome of severe Peters Plus syndrome-like phenotype with anterior eye staphyloma and HLHS.

This paper considers two different cases of division of labor: (i) the subdivision of different operations in order to produce a particular product in a given firm or plant; (ii) the specialization of firms in the same industry. Division of labor of the former type is limited by demand for output of a particular firm or plant, while division of labor of the latter type is limited by demand for the industry as a whole. It is argued that, in the case of an industry producing a homogenous product, an increase in the scale of production of any particular firm is likely to be associated with changes in the internal division of labor. In the case of inter-firm division of labor, decreasing unit costs may result from lateral disintegration. Finally, in the case of an industry producing a composite commodity (that is, a commodity composed of many different sub-commodities), firms’, disequilibrium behavior may lead to concentration of each firm to fewer sub-commodities, in the anticipation of the entry of new firms, or as a result of it. © 2000 Elsevier Science B.V. All rights reserved.

Alfred Marshall has been wrongly accused by many modern economic theorists that he forgot to take producers' surplus into consideration in Figure 31 in his Principles (Marshall, 1890, 1961, p.468, Ellis and Fellner, 1943, Samuelson, 1967), where he proposed the tax and bounty plan. Elsewhere we defended Marshall that Figure 31 can be interpreted as the case of no producers' surplus, in view of his distinction between the supply curve and the particular expenses curve. In other words, Marshall did not forget to consider producers' surplus, but merely considered the case of no producers' surplus (Negishi, 1999).

Marx insists that the richer country exploits the poorer one through an unequal exchange of labour quantities. Elsewhere I have confirmed that the unequal exchange of labour quantities is possible, but I failed to consider carefully whether this implies an unequal exchange of values, i.e. international exploitation. This paper argues that Marx is wrong to insist on it, in that he does not consider properly the comparison of values differently dated, and points out that a similar failure can be found in the theory of Bauer and Grossmann. Finally, I state my own theory, which is free from the difficulties found in Marxian theories. JEL Classification Numbers: B1, F0.

After a brief survey of the Japanese literature on Sraffa, the author explains how his own theory of the microfoundations of Keynesian macro-economics was influenced by Sraff's view of competitive markets. This view can be interpreted that firms perceive kinked demand curves. It is emphasized that Azariadis's theory of implicit contracts can explain unemployment only if we take Sraffa's not Walras's, view of competitive market.

The Shibata–Okishio theorem, which denied Marx's law of falling rate of profit, was demonstrated by the use of the Lausanne School model based on the assumptions of constant returns to scale and perfect competition, which Marx did not assume. The competition among capitalists which Marx described is a world of economies of scale and imperfect competition. The model to be used should, therefore, be either Cournot's model of oligopoly or Chamberlin's model of monopolistic competition, both of which, unlike the Lausanne model, can deal with economies of scale.

The nature and significance of input–output analysis or interindustry analysis, which was initiated by W. Leontief, can be interpreted in many different ways. It can be seen as the generalization of Keynesian multiplier theory, or as the modern version of Quesnay’s Tableau economique or Marx’s reproduction scheme, or as a degenerated linear programming model. From our point of view, however, it can be considered as an empirically oriented simplified version of the general equilibrium theory. While the importance of the analysis of interindustry input–output relations is duly emphasized, consumer demands are assumed to be given by outside information. The optimization and substitutability in production are assumed away by the use of the no-joint-output constant-coefficient production functions which are, however, numerically estimated by the data available from input–output tables. The input–output analysis can, therefore, provide numerical answers for a number of interesting problems of the general equilibrium of an economy.

In a modern society, indispensable roles are played by many different firms. Firms offers a large part of the goods and services which are consumed in the society. The majority of the people live on incomes they receive from firms. Those who run firms and those who are employed by them spend most of their days in offices and factories of the firms and try hard to make their career in the firms. Consumerstaste and industrial technology are much influenced by firmsactivities in advertising, marketing, researches and developments. The study on firms should, therefore, be an inter-disciplinary task among economics, sociology, psychology, business administration, engineering and system analysis. Except for the case of a small private firm, a firm is and organization composed by many decision-makers, with partly common, but partly conflicting interests, controlling different means and basing their decisions on partly different information. Even the economic theory of firms, therefore, should be in general based, not on a simple optimization theory, but on the theory of games or the theory of teams.

Up to now we have been concerned with the description and the analysis of how a market economy, composed of consumers and firms, actually behaves to allocate resources to produce products and to distribute incomes to be spent on them. Our study aims, of course, to consider basic principles of an abstract economy under ideal conditions rather than to describe the details of actual economies. However abstract it is, nevertheless, what we have studied is to be called the positive economics, since it is ultimately to be judged by facts. Ideal or perfect conditions are assumed merely from the point of view of the simplification of the consideration, and not meant to be desirable from some ethical point of view. Theory of perfect competition is, therefore, similar to the law of motion in vacuum.

Consumption of goods in households is the main purpose and the final result of a large part of economic activity. To demand for the consumables, however, households have to supply the service of factors of production to earn their incomes in the modern market economy. The role of the theory of the household is, therefore, to explain not only its demand for goods (the consumables) but also its supply of goods (the service of factors of production). But, fortunately, the households’ supply of the factors of production can be easily explained by an extension of the theory of their demand for goods. This is the reason why we can start with the theory of the behavior of a consumer who spends the given income to demand for the consumers’ goods. While the theory of the firm is developed as the theory of the constrained maximization, i.e., the maximization of profit subject to the production function, the theory of the consumers’ behavior also considers the constrained maximization, i.e., the maximization of utility subject to the budget constraint.

Economic theory can be divided into microeconomics and macroeconomics. The neoclassical theory of microeconomics has been much influenced by the theory of classical mechanics in physics. In the latter theory, a system which consists of a number of particles can be fully described by specifying mass, position, and velocity of each single particle. Similarly, microeconomic theory tries, as we saw in preceding chapters, to describe the behavior of an economy by specifying the behavior of each single consumer and the input–output activity of each single firm. There is, however, an alternative approach in physics. Consider the behavior of the gas contained in a balloon. The gas consists of different molecules and the behavior of these molecules like the collisions among them obeys the laws of classical mechanics. If we know the position, velocity and mass of each of these molecules, therefore, we can describe, at least in principle, the behavior of the gas. From the more practical point of view, however, it is much more important to measure the balloon’s volume, its pressure, its temperature, etc., to describe the behavior of the gas. For example, it can be described by the universal gas equation, pV = NRT, where p denotes pressure, V volume, N the number of mols, R the universal gas constant, and T the absolute temperature.

In the previous chapter, it was shown that there are many cases in which competitive markets fail to allocate resources optimally. Even if we disregard the existence of such difficulties, however, what competitive markets can do is only to achieve a Pareto optimal allocation, which may not be the optimal organization of an economy, since Pareto optimality is, though necessary, by no means sufficient for it. To choose the optimal organization of the economy from many Pareto optimal allocations is the problem of the optimal distribution of incomes, in view of the second half of the fundamental theorem of welfare economics, which insists that any Pareto optimal allocation can be achieved through perfect competition if incomes are properly distributed among consumers (Sect. 7.8). Since different individuals have different opinions on how should incomes be distributed, and the market mechanism cannot be relied on to solve it, the problem of optimal income distribution is a social choice which has to be made politically through voting in a democratic society.

In Chap. 2, we considered how firms supply the consumables and intermediate goods and demand factors of production and intermediate goods, when prices in the market are given. Chapter 3 was devoted to show how consumers demand the consumables and supply factors of production, taking market prices as given. Aggregate demand for each good and aggregate supply of each good are, therefore, functions of market prices which are taken by competitive firms and consumers as given and unchanged. Thesemarket prices are, then, to be determined so as to equate the aggregate demand and aggregate supply of all goods. The general equilibrium of a competitive economy is defined as a set of prices which clears all the markets.

So far we have been assuming that markets are perfectly competitive and consumers and firms are taking market prices as given. The assumption is justified by the supposition that there are very large number of consumers and firms so that market prices are not much affected by the actions of any single consumer or firm. As a result of perfect competition, equilibrium prices are equalized to marginal costs. Perfect competition is, however, an exceptional polar case, which should be regarded as an idealistic or limiting situation, since many firms are not taking prices as given and prices are, in general, different from marginal costs in the real world. While perfectly competitive markets are homogeneous and resemble one another as happy families, imperfectly competitive markets are heterogeneous and imperfect, like unhappy families, in many different ways.

Starting with Adam Smith’s criticism against mercantilism, economists of the classical school generally advocated the free trade and were critical to the protection of domestic industries. J. S. Mill admitted, however, the protection of the so-called infant industry, though he imposes a condition which an industry must satisfy to be protected. Then, it was Bastable who followed Mill to add another necessary condition for protection. This Mill–Bastable infant industry dogma was discussed critically by some modern economists from the point of view of the dynamic theory of the gains from trade.

Adam Smith, who criticized mercantilists fot their wrong concept of the wealth of nations, considered that the real wealth is the annual produce of the land and labour of the society (Smith [1976], p. 12). According to Smith, furthermore, the high productivity of labour in civilized and thriving nations seems to have been the effects of the division of labour. International trade certainly pre-supposes the division of labour among different countries. As for the nature and causes of international trade, therefore, we can expect to learn very much from Smith’s theory of the divisions of labour. For this purpose, let us have a glance of the content of his Wealth of Nations (1776), which consists of five Books, i.e., Book 1: Of the Causes of Improvement in the productive Powers of Labour, and of the Order according to which its Produce is naturally distributed among the different Ranks of the People. Book 2: Of the Nature, Accumulation, and Employment of Stock. Book 3: Of the different Progress of Opulence in different Nations. Book 4: Of Systems of political Oeconomy. Book 5: Of the Revenue of the Sovereign or Commonwealth. An outline of each Book now follows.

J. S. Mill (1806–1873)s Principles of Political Economy (1848) was written as “a work similar in its object and general conception to that of Adam Smith, but adapted to the more extended knowledge and improved ideas of the present age” (Mill 1909, p. xxviii). It was highly successful as the last of the great books of the classical economics founded by A. Smith. From the point of view of the history of international trade theory, it is, in general, to be remembered by its extension of Ricardo’s theory of comparative costs to take account of the effects of reciprocal demand on the terms of trade. We must emphasize, however, that Mill seems to start the so-called modern interpretation of Ricardo, which we criticized in Chap. 4.

The basic economic model of the so-called Heckscher–Ohlin Theory is the two- country two-commodity two-factor model where production functions are linear-homogeneous and the endowment of two factors of production is exogenously given for each country. Besides the factor price equalization theorem and Heckscher–Ohlin theorem discussed in Chap. 10, we can have also two additional well-known theorems derived from this Heckscher–Ohlin model. The first one is the so-called Stolper–Samuelson Theorem (Stolper and Samuelson (1941)) which considers the effects of an import tariff on the factor prices. In other words, it concerns with the changes in factor prices caused by a change in the relative price of two commodities. The second one is called Rybczynski Theorem (Rybczynski 1955) which deals with the changes in the scale of production of two industries caused by a change in the factor endowment in the case of a small country. This is the problem of the effects of the economic growth on the relative scale of the two domestic industries, when the relative price of two commodities is assumed to be constant.

In the classical theory of international trade, the comparative advantage in the sense of the comparative costs is simply given exogenously. In other words, it is presupposed that different countries have different technology of production, which includes the difference in natural conditions for the production like the climate. In the modern theory of international trade, however, it is assumed that different countries have the identical technology which is given in the form of the identical production function. The comparative advantage of the different countries is explained, then, not by the difference in technology, but by the difference in the factor endowments. Such a modern theory is generally known as Heckscher–Ohlin theory, because the groundwork for substantial developments in the theory is laid by Eli Heckscher (1919) and Bertil Ohlin (1933).