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Additional file 2: Table S1. Results of hematological examination.

First Draft:March 2019; This Version:January 2020

症例は69歳女性.下血を主訴に近医受診し,下部消化管内視鏡検査で下部直腸(Rb)にIIc+IIa様の腫瘍を認め,生検では当初扁平上皮癌あるいは低分化腺癌と診断された.治療としては,本人の強い希望で直腸局所切除術を施行.手術標本では組織学的に腺管構造はみられず,免疫組織学的検索で粘液分泌や内分泌顆粒を認めず,未分化癌と診断した.大腸未分化癌の予後は極めて不良とされており早期発見が望まれるが,その初期像については不明な点が多い.稀とされる大腸未分化癌の一例を経験したので,報告する., This is the case report of a 69-year-old female patient, who presented to a hospital due to melena as the chief complaint. A lower gastrointestinal endoscopy confirmed a 0IIc + IIa tumor found in the patient’s lower rectum (Rb). On a biopsy, this patient was diagnosed with a squamous-cell carcinoma or an undifferentiated adenocarcinoma first. Upon the patient’ s strong request, a local excision of the rectum was performed as the medical treatment for this case. No duct-like structure was observed histologically in the surgical specimen, and the immunohistological detection did not confirm any mucoid secretion or endocrine granules. For these reasons, this patient was diagnosed with an undifferentiated carcinoma. Generally, undifferentiated carcinoma of the colon has a poor prognosis, thus early detection is desirable. However, there exist a number of unclear points in the initial picture of this carcinoma. This is to report our experience of this rare case, which is an example of undifferentiated carcinoma of the colorectal region.

R&D consortia (collaborative R&D projects among private firms, universities, and public research institutes) have been attracting increasing attention as an effective means of promoting innovation. Especially for SMEs, such collaboration provides important opportunities to access and obtain advanced scientific knowledge generated by universities and public research institutes. It is expected that not only the participants in R&D consortia will enhance their performance, through direct knowledge spillovers, but also that the business partners of consortia members may enjoy indirect effects (rent spillovers), through their business transactions. This paper empirically examines the spillover effects through government-sponsored R&D consortia using firm-level data and the propensity score method. Focusing on a major support program for R&D consortia in Japan, the “Consortium R&D Project for Regional Revitalization” by METI, we confirm that there are both direct (knowledge) spillover effects from firms’ participation in this program and indirect (rent) spillover effects on the customer firms of the consortia members. Moreover, by comparing SMEs and large firms, we find that only SMEs obtain knowledge spillovers in R&D consortia, whereas, among their customers, only large firms enjoy rent spillovers., 近未来の課題解決を目指した実証的社会科学推進事業

R&D consortia (collaborative R&D projects among private firms, universities, and public research institutes) have been attracting increasing attention as an effective means of promoting innovation. Especially for SMEs, such collaboration provides important opportunities to access and obtain advanced scientific knowledge generated by universities and public research institutes. It is expected that not only the participants in R&D consortia will enhance their performance, through direct knowledge spillovers, but also that the business partners of consortia members may enjoy indirect effects (rent spillovers), through their business transactions. This paper empirically examines the spillover effects through government-sponsored R&D consortia using firm-level data and the propensity score method. Focusing on a major support program for R&D consortia in Japan, the “Consortium R&D Project for Regional Revitalization” by METI, we confirm that there are both direct (knowledge) spillover effects from firms’ participation in this program and indirect (rent) spillover effects on the customer firms of the consortia members. Moreover, by comparing SMEs and large firms, we find that only SMEs obtain knowledge spillovers in R&D consortia, whereas, among their customers, only large firms enjoy rent spillovers.

エイジング・クイズの構造と年齢的変動に関する一考察.西村純一, 平澤尚孝.Antitumor effect induced by the expression of granulocyte macrophage-colony stimulating factor gene Ⅰ.Horitsu, Keisuke.

各種ビタミンのストレスに及ぼす影響.苫米地孝之助.Specific Enzyme Activity and Cellular Characteristic in Tumer Host : The Special Properties Related to Nicotinamide Methyltransferase and Cell Death, Part 3.Horitsu, Keisuke.主観的幸福感と年齢.西村純一, 平沢尚孝.

This paper provides a detailed comparison of the following five cases of Japanese and European clusters in biotechnology: (1) Kobe Biomedical Innovation Cluster (KBIC) in Kobe (Japan), (2) Fuji Pharma Valley Cluster in Shizuoka Prefecture (Japan), (3) BioM Biotech Cluster in Munich (Germany), (4) BioRegion Rhine-Neckar in Heidelberg (Germany), and (5) Alsace BioValley Cluster in Strasbourg (France). We pay special attention to the cluster policy and its management by each region's core cluster management organization. Information on the focal clusters and the management of cluster policies has been obtained through interviews with the cluster directors and core staff in 2010 and 2011. We find several similarities and differences among the five cases of Japanese and European clusters. We also discuss how the management of cluster policies by the core management organizations may be related with the performance of regional clusters.

This paper provides a detailed comparison of the following five cases of Japanese and European clusters in biotechnology: (1) Kobe Biomedical Innovation Cluster (KBIC) in Kobe (Japan), (2) Fuji Pharma Valley Cluster in Shizuoka Prefecture (Japan), (3) BioM Biotech Cluster in Munich (Germany), (4) BioRegion Rhine-Neckar in Heidelberg (Germany), and (5) Alsace BioValley Cluster in Strasbourg (France). We pay special attention to the cluster policy and its management by each region's core cluster management organization. Information on the focal clusters and the management of cluster policies has been obtained through interviews with the cluster directors and core staff in 2010 and 2011. We find several similarities and differences among the five cases of Japanese and European clusters. We also discuss how the management of cluster policies by the core management organizations may be related with the performance of regional clusters.

Despite various expected advantages, university-industry research collaboration (UIC), a relationship between two different worlds, often faces serious difficulties. Thus, the performance of UIC depends on the research partners' strategies to bridge the gaps between them according to the institutional environment. In Japan, UIC has developed rapidly since the late 1990s based on drastic institutional changes regarding universities. We pay special attention to the role of the university intellectual property (IP) policy introduced after 2003 and empirically examine its impact on the performance of UIC projects. A clear and equitable IP policy that can be applied flexibly to the needs of partners would be optimal for a UIC to be efficiently managed. Otherwise, the project might face serious conflicts of interests and low incentive for cooperation. Using a sample of Japanese firms from our original survey, we find that the IP policy of partner universities indeed has a positive and significant impact on various performances of UIC projects, controlling for firm and project characteristics and considering potential selection bias from UIC participation., グローバルCOEプログラム = Global COE Program

This paper is a part of the outcomes from the research project “The Determinants, Organization, and Outcomes of University-Industry Interaction in Innovation Systems” funded by the Volkswagen Foundation in Germany, Contractual and organizational characteristics of university-industry research collaboration (hereafter UIC) are keys to its success. In this respect, government can play essential roles in UIC: Public subsidy for research and development (hereafter R&D) is not only an important financial support for UIC, but may also be a useful channel to promote trust along with contractual agreements and information sharing among the members, which results in effective coordination and thus the success of UIC. However, few empirical studies investigate the latter role of public R&D subsidy in UIC. Thus, using original survey data, this paper empirically examines and find that public R&D subsidy improves coordination in UIC, including trust formation, contractual agreements, and communication quality between the partners as well as commitment by the partners., グローバルCOEプログラム = Global COE Program

Over the past two decades, utilizing markets for technology through licensing and other outsourcing arrangements has emerged as a key to organizing innovative activity. We examine how the rent dissipation effect affects patent and knowhow licensing, controlling organizational capabilities such as firm size, vertical integration, exports, and diversity. A licensor's profit varies and the incentives to license change depending on the rent dissipation effect, which erodes a licensor's profit due to intensifying competition that results from a licensee's entry into the licensor's market. Firms faced with severe competition are marginally exposed to a small rent dissipation effect when licensing their technologies out to rivals, and they can obtain large royalty revenues through such licensing because there are many potential licensees. Using panel data on about ten thousand Japanese firms for the period 1995-2007, we show that the rent dissipation effect facilitates licensing not only between Japanese firms but also between Japanese and foreign firms.

健康増進と運動.三田禮造, 苫米地孝之助.Part 1 Specific Properties of Nicotinamide Methyltransferase of the Tumor Host and the Expectation of Life.Horitsu, Keisuke.現代学生にみる老いへの知識と態度.西村純一, 平沢尚孝.

We examine how R&D portfolios of drug pipelines affect pharmaceutical licensing, controlling firm size, diversity, and competitors in R&D and product markets. The data collected comprises 329 license-outs and 434 license-ins closed by 54 Japanese pharmaceutical companies between 1997 and 2007. We pay special attention to stage-specific licensing by dividing the innovation process into an early stage and a late stage. Estimates from the fixed-effect GMM model reveal that drug pipelines significantly affect stage-specific licensing. Particularly, the state of drug pipelines is leveled off by license-outs at the early stage and license-ins at the late stage. Theoretical implications are also discussed., グローバルCOEプログラム = Global COE Program

Industrial clusters have attracted considerable attention worldwide for their expected contribution to regional innovation. Recently, policymakers in various countries have developed specific cluster policies. However, there exist few empirical studies on cluster policies. Focusing on the Industrial Cluster Project (ICP) in Japan initiated by the Ministry of Economy, Trade and Industry in 2001, we address two research questions on the support programs of the cluster policies: if the project participants who exploit various support programs are more successful in network formation within the cluster than others, and which kind of support program contributes to firm performance. We pay special attention to the differences between direct R&D support and indirect networking/coordination support. The estimation results, which are based on recent original survey data, suggest that cluster participants who exploit support programs (especially indirect support measures) expand the industry-university-government network after participating in the ICP. Moreover, we find that not every support program contributes to firm performance; firms should therefore select the program that is most aligned with their aims. Indirect support programs have an extensive and strong impact on output whereas direct R&D support has only a weak effect., 近未来の課題解決を目指した実証的社会科学推進事業

The RIETI inventor survey, which was conducted in 2007, invited inventors to contribute their views and opinions on the constraints on the R&D performance of their organizations, and the policies and managerial agenda for improving it. A total of 1,300 inventors (around one quarter of those who received the survey) contributed their comments. This paper categorizes their responses into the following eight broad classes and evaluates their incidence. In relation to management, respondents' comments were divided into four categories: (1) the remuneration, evaluation, and constraints on research of inventors, (2) R&D strategy of the firm, (3) the commercialization capability and exploitation of intellectual property rights, and (4) other issues (such as lack of mobility in human resources and shortage of available funds for R&D). Policy issue questions were divided into (1) fiscal and financial support for R&D and regulatory barriers, (2) patent system (examination, protection, globalization and disclosure), (3) the role of a university and a national laboratory, and (4) others (including support for small and medium sized enterprises and individual inventors). This paper also highlights comments representative of the field, which may serve as important suggestions for improving the R&D system in Japan. There are some differences in the distribution of responses across organizational types and the units to which an inventor is affiliated; however there is significant commonality in frequently identified issues.

Industrial clusters have attracted increasing attention as important locations of innovation. Therefore, several countries have started promotion policies for industrial clusters. However, there are few empirical studies on cluster policies. This paper examines the effects of the "Industrial Cluster Project" (ICP) in Japan on the R&D productivity of participants, using a unique dataset of 229 small firms, and discusses the conditions necessary for the effective organization of cluster policies. Different from former policy approaches, the ICP aims at building a collaborative network between universities and industries and supports the autonomous development of existing regional industries without direct intervention in the clustering process. Thus far, the ICP is similar to indirect support systems adopted by successful European clusters. Our estimation results suggest that participation in the cluster project alone does not affect R&D productivity. Moreover, research collaboration with a partner in the same cluster region decreases R&D productivity both in terms of the quantity and quality of patents. However, cluster participants apply for more patents than others without reducing patent quality when they collaborate with national universities in the same cluster region. These results imply the effectiveness of indirect support systems that remove obstacles and relax constraints in the clusters. In order to improve the R&D efficiency of local firms, it is also important to construct a wide-range collaborative network within and beyond the clusters, although most clusters focus on the network at a narrowly defined local level. These characteristics may be important factors for the effective organization of cluster policies.

Revised Version : September 2009

This paper examines the effect of participation in government-sponsored R&D consortia on the R&D productivity of firms in the case of robot technology in Japan. We attempt to provide a new empirical analysis and discussions on the issue of government project evaluation by using indicators of the quality of patents, by investigating the impact of the evolution of government programs, and comparing government-sponsored R&D consortia with collaborative R&D among firms. Using indicators of the quality of patents which enables us to provide an estimation of quality-adjusted research productivity, we find that participation in government programs has a positive impact on the research productivity of participating firms, but the impact of participation became much higher after the design of government programs in this field changed in the late 1990s. Also, we find that participation in government-sponsored consortia has a greater impact on research productivity than participation in collaborative R&D among firms. This may support government involvement in R&D as a coordinator of R&D collaboration.

The growing trend of collaborative R&D has been well documented recently, both at a global level and through national and industry case studies. However, there is not yet any consensus regarding the following decisive questions: what are the exact level and evolution of R&D collaboration? What are the benefits of collaboration? What are the motives and determinants of firms engaging in R&D collaboration? In our opinion, these questions have not yet been answered due to the limitations of the data used in most empirical studies (large questionnaire surveys or very specific case studies). The main novelty of this paper is the use of patent data with a focus on information concerning inventors. These data are less biased than questionnaire surveys in terms of the size of the institutions; they are objective and are particularly appropriate for analyzing the benefits of collaboration. As the identification of the institutions to which individual inventors are affiliated is a particularly time consuming task, we focus on robot technology in Japan since the beginning of the 1990s. Our results are as follows. First, although the level of R&D collaboration in RT in Japan increased between 1991 and 2004, especially in the case of collaboration between firms and universities, it still remains low and is dominated by inter-firm collaborations. Second, we cannot definitively reject the conclusion that only the scale of the research has an impact on the quality of patents, when the unit of analysis is the patent; however, we show that there are significant spillover effects of collaboration, which imply an indirect effect on quality. Third, the determinants and motives which encourage firms to decide to engage in collaborative research differ depending on the partner they are collaborating with. In the case of collaboration with other firms, IO theories hold, as the existence of spillovers acts as an incentive. Regarding the collaboration with universities and public research institutes, the validity of capability theory, which emphasizes the quest for complementary knowledge and capability, is confirmed by our empirical investigation.

21世紀COEプログラム = 21st-Century COE Program