Suchergebnisse

Abstract
We introduce a behavioral contract theory idea, "shading" (Hart and Moore (2008). "Contracts as Reference Points." Quarterly Journal of Economics 123 (1): 1–48)) as a component of ex-post haggling (addressed by Coase (1937. "The Nature of the Firm." Economica 4 (16): 386–405) and Williamson (1975. Markets and Hierarchies: Analysis and Antitrust Implications. New York: Free Press)) into the collusion model à la Tirole (1986. "Hierarchies and Bureaucracies: On the Role of Collusion in Organizations." Journal of Law, Economics, and Organization 2: 181–214, 1992. "Collusion and the Theory of Organizations." In Advances in Economic Theory: The Sixth World Congress, edited by J. J. Laffont. Cambridge: Cambridge University Press), thereby constructing a new model of hierarchical organization. By integrating the two ideas, i.e. collusion and shading, we enrich the existing collusion model, thereby obtaining a new result for Collusion-proof versus Equilibrium Collusion. The basic idea is that the increase in shading pressure strengthens the incentive for collusion, thereby making it difficult to implement collusion-proof incentive schemes, which leads to the Equilibrium Collusion. In addition, we also provide a micro-foundation for ex-post haggling costs, where we view rent-seeking associated with collusive behavior and ex-post haggling generated from aggrievement and shading as the two sources of the costs. This model is used to examine the optimal organizational design problem as an optimal response to the trade-off between gross total surplus and ex-post haggling costs, and to take a step further the idea of efficient organization design (Milgrom (1988. "Employment Contracts, Influence Activities and Efficient Organization Design." Journal of Political Economy 96: 42–60)). We believe that our model could help provide a deep understanding of resource allocation and decision processes in hierarchical organizations.

Abstract
Although the treatment armamentarium for patients with metastatic prostate cancer has improved recently, treatment options after progression on cabazitaxel (CBZ) are limited. To identify the mechanisms underlying CBZ resistance and therapeutic targets, we performed single-cell RNA sequencing of circulating tumor cells (CTCs) from patients with CBZ-resistant prostate cancer. Cells were clustered based on gene expression profiles. In silico screening was used to nominate candidate drugs for overcoming CBZ resistance in castration-resistant prostate cancer. CTCs were divided into three to four clusters, reflecting intrapatient tumor heterogeneity in refractory prostate cancer. Pathway analysis revealed that clusters in two cases showed up-regulation of the oxytocin (OXT) receptor–signaling pathway. Spatial gene expression analysis of CBZ-resistant prostate cancer tissues confirmed the heterogeneous expression of OXT-signaling molecules. Cloperastine (CLO) had significant antitumor activity against CBZ-resistant prostate cancer cells. Mass spectrometric phosphoproteome analysis revealed the suppression of OXT signaling specific to CBZ-resistant models. These results support the potential of CLO as a candidate drug for overcoming CBZ-resistant prostate cancer via the inhibition of OXT signaling.

Ziel der sechsten GATT-Runde ist es, die Schranken im Welthandel weiter abzubauen. Anders als bei den fünf früheren GATT-Runden herrscht dieses Mal in vielen Ländern Skepsis gegenüber einer weiteren Liberalisierung, weil man die Risiken, die mit zunehmendem Importwettbewerb verbunden sein können, höher bewertet als die möglichen Vorteile der Liberalisierung. Das Aufrechterhalten von Handelsschranken kostet Ressourcen. Die Protektion wenig effizienter Industrien in den wohlhabenden Ländern hält deren Einkommen unter dem Niveau, das sie sonst erreichen könnten und verzögert das Tempo der Industrialisierung in den Entwicklungsländern. Die ökonomischen Argumente zugunsten eines freieren Handels sind stark und weitgehend unanfechtbar. Handelsbeschränkungen sind zudem politisch belastend. Es gibt eine Reihe staatlicher Maßnahmen, die geeignet sind, die Schocks einer Anpassung an wirtschaftliche Veränderungen zu mindern. Interne Anpassungmaßnahmen spielen daher eine bedeutende Rolle in der künftigen Handelspolitik. Sehr zweifelhaft ist, ob alle Möglichkeiten für wirksame Anpassungsmaßnahmen bereits ausgeschöpft sind. In der Textilindustrie, der Stahlindustrie und im Kohlenbergbau existieren nach allgemeiner Meinung hartnäckige Anpassungsprobleme, die besondere und permanente Schutzmaßnahmen gegen den Importwettbewerb verlangen. Obwohl es viele Anstrengungen gegeben hat, den Status quo aufrechtzuerhalten, hat in allen drei Fällen die Dynamik des Strukturwandels die Lage grundlegend verändert. Diese Entwicklungstendenzen erlauben den Schluß, daß weitere Schritte zur Liberalisierung auch in den schwierigsten Fällen nicht nur wünschenswert wären, sondern wahrscheinlich durch den immanenten Strukturwandel in der Wirtschaft erleichtert werden. Eine Veränderung ist selten bequem, selbst dann nicht, wenn sie zu Verbesserungen führt. Für die Politik darf die relevante Frage nicht sein, wie man eine Anpassung an veränderte Umstände verlangsamen oder verhindern könnte. Sie lautet vielmehr, wie man die Chancen, die ein freierer Handel bietet, dadurch nutzen kann, daß man die Anpassung erleichtert und ihre Kosten minimiert.

Abstract
Pollinosis, also known as pollen allergy or hay fever, is a global problem caused by pollen produced by various plant species. The wind-pollinated Japanese cedar (Cryptomeria japonica) is the largest contributor to severe pollinosis in Japan, where increasing proportions of people have been affected in recent decades. The MALE STERILITY 4 (MS4) locus of Japanese cedar controls pollen production, and its homozygous mutants (ms4/ms4) show abnormal pollen development after the tetrad stage and produce no mature pollen. In this study, we narrowed down the MS4 locus by fine mapping in Japanese cedar and found TETRAKETIDE α-PYRONE REDUCTASE 1 (TKPR1) gene in this region. Transformation experiments using Arabidopsis thaliana showed that single-nucleotide substitution ("T" to "C" at 244-nt position) of CjTKPR1 determines pollen production. Broad conservation of TKPR1 beyond plant division could lead to the creation of pollen-free plants not only for Japanese cedar but also for broader plant species.

The Helix Research Institute (HRI) in Japan is releasing 4356 HUman Novel Transcripts and related information in the newly established HUNT database. The institute is a joint research project principally funded by the Japanese Ministry of International Trade and Industry, and the clones were sequenced in the governmental New Energy and Industrial Technology Development Organization (NEDO) Human cDNA Sequencing Project. The HUNT database contains an extensive amount of annotation from advanced analysis and represents an essential bioinformatics contribution towards understanding of the gene function. The HRI human cDNA clones were obtained from full-length enriched cDNA libraries constructed with the oligo-capping method and have resulted in novel full-length cDNA sequences. A large fraction has little similarity to any proteins of known function and to obtain clues about possible function we have developed original analysis procedures. Any putative function deduced here can be validated or refuted by complementary analysis results. The user can also extract information from specific categories like PROSITE patterns, PFAM domains, PSORT localization, transmembrane helices and clones with GENIUS structure assignments. The HUNT database can be accessed at http://www.hri.co.jp/HUNT.