Incomplete Appropriability of R&D and the Role of Strategies and Cultural Factors in International Trade: A Japanese Case

One of the proudest achievements of classical and neoclassical economics is the derivation of the superiority of free trade. This result is obtained by assuming constant returns to scale, perfect competition and absence of externalities. The recent realization that the incomplete appropriability of R&D is a main source of externalities and hence the effect of R&D on national welfare is potentially subject to strategic manipulations necessitates a careful examination of these assumptions. This paper discusses R&D and diffusion of technology in international trade from two different perspectives. In Section II, we consider the role of cultural, social and historical factors in the appropriation of technology by reviewing how Japan has appropriated foreign technology. In Section III, we survey three strategic trade models to obtain some insights into the role of R&D and diffusion of technology in the context of imperfect competition. The issues we discuss include the effectiveness of R&D polices by a national government and the impact of R&D policies and diffusion of technology on the incentive to do R&D and on the outcome of trade.

The Posterior Condylar Cartilage Affects Rotational Alignment of the Femoral Component in Varus Knee Osteoarthritis

Rotational alignment of the femoral component in total knee arthroplasty (TKA) is important for patellar tracking and ligament balance. Preoperative planning based on radiography might have a potential risk for over-rotation because these X-ray based measurements can not detect asymmetric cartilage wear on posterior condyle. The purpose of this study is to evaluate the effect of the posterior condylar cartilage of varus osteoarthritic knee on rotational alignment of the femoral component in TKA. We established two different condylar twist angles (CTA) from intraoperative multiplanar reconstruction (MPR) images and intraoperative information of navigation system. The CTA measured by a navigation system that includes the cartilage (4.8±2.0°) was smaller than those measured by MPR images, which does not include the cartilage (6.6±2.1°) (p<0.05). The difference between these two angles that corresponds to the remaining posterior condylar cartilage was 1.7±1.2°. This result demonstrated that the posterior condylar cartilage might lead to over-rotational of the femoral component in varus osteoarthritic knee. Therefore, when determining rotational alignment of the femoral component, surgeons should consider the effect of the remaining posterior condylar cartilage to avoid the over-rotation of the femoral component, especially in severe varus knees

ATM suppresses c-Myc overexpression in the mammary epithelium in response to estrogen

ATM遺伝子変異による乳癌発症機構を解明 --HBOC症候群の乳腺特異的発癌機構の解明に貢献--. 京都大学プレスリリース. 2023-02-09.ATM gene mutation carriers are predisposed to estrogen-receptor-positive breast cancer (BC). ATM prevents BC oncogenesis by activating p53 in every cell; however, much remains unknown about tissue-specific oncogenesis after ATM loss. Here, we report that ATM controls the early transcriptional response to estrogens. This response depends on topoisomerase II (TOP2), which generates TOP2-DNA double-strand break (DSB) complexes and rejoins the breaks. When TOP2-mediated ligation fails, ATM facilitates DSB repair. After estrogen exposure, TOP2-dependent DSBs arise at the c-MYC enhancer in human BC cells, and their defective repair changes the activation profile of enhancers and induces the overexpression of many genes, including the c-MYC oncogene. CRISPR/Cas9 cleavage at the enhancer also causes c-MYC overexpression, indicating that this DSB causes c-MYC overexpression. Estrogen treatment induced c-Myc protein overexpression in mammary epithelial cells of ATM-deficient mice. In conclusion, ATM suppresses the c-Myc-driven proliferative effects of estrogens, possibly explaining such tissue-specific oncogenesis

Collaborative Action of Brca1 and CtIP in Elimination of Covalent Modifications from Double-Strand Breaks to Facilitate Subsequent Break Repair

Topoisomerase inhibitors such as camptothecin and etoposide are used as anti-cancer drugs and induce double-strand breaks (DSBs) in genomic DNA in cycling cells. These DSBs are often covalently bound with polypeptides at the 3′ and 5′ ends. Such modifications must be eliminated before DSB repair can take place, but it remains elusive which nucleases are involved in this process. Previous studies show that CtIP plays a critical role in the generation of 3′ single-strand overhang at “clean” DSBs, thus initiating homologous recombination (HR)–dependent DSB repair. To analyze the function of CtIP in detail, we conditionally disrupted the CtIP gene in the chicken DT40 cell line. We found that CtIP is essential for cellular proliferation as well as for the formation of 3′ single-strand overhang, similar to what is observed in DT40 cells deficient in the Mre11/Rad50/Nbs1 complex. We also generated DT40 cell line harboring CtIP with an alanine substitution at residue Ser332, which is required for interaction with BRCA1. Although the resulting CtIPS332A/−/− cells exhibited accumulation of RPA and Rad51 upon DNA damage, and were proficient in HR, they showed a marked hypersensitivity to camptothecin and etoposide in comparison with CtIP+/−/− cells. Finally, CtIPS332A/−/−BRCA1−/− and CtIP+/−/−BRCA1−/− showed similar sensitivities to these reagents. Taken together, our data indicate that, in addition to its function in HR, CtIP plays a role in cellular tolerance to topoisomerase inhibitors. We propose that the BRCA1-CtIP complex plays a role in the nuclease-mediated elimination of oligonucleotides covalently bound to polypeptides from DSBs, thereby facilitating subsequent DSB repair

Practical Synthesis of Dirhodium (II) Tetrakis[N-phthaloyl-(S)-tert-leucinate]

An efficient and reliable procedure for the preparation of dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leuci-nate], Rh_2(S-PTTL)_4, a universally effective catalyst for a range of enantioselective carbene transformations, is described. The N-phthaloylation of (S)-tert-leucine by the method of Bose with essentially no racemization is a key to this process