Separate measurements of the flexoelectric and surface polarization in a model nematic liquid crystal p-methoxybenzylidene-p´-butylaniline : Validity of the quadrupolar approach

The temperature dependences of the surface polarization have been measured at the interface of a conductive glass with both the homogeneously and homeotropically oriented nematic liquid crystal p-methoxybenzylidene-p´-butylaniline. The polarization was found in the field-off regime from the pyroelectric response of a cell to a short laser pulse, absorbed in the bulk of the liquid crystal. The temperature increment was calculated from the measurements of the birefringence induced by the same light pulse. It has been shown that the surface polarization at the homeotropic (mh) and planar (mp) interfaces is directed from an interface into the bulk and from the bulk to an interface, respectively (with a magnitude mh~— 0.3 pC/m and mp' ≈ 0.2 pC/m at 25℃). The experimental data may be explained in terms of the quadrupole model of the order-electric polarization with account of some additional contribution from molecular dipoles. The same technique also allows for the measurements of the z component of the flexoelectric polarization using a pyroelectric response of a hybrid (homeoplanar) aligned nematic cell and proper subtracting of the surface contributions. The flexoelectric polarization has been shown to be opposite to the sum of the surface terms mh + mp and directed from the planar to homeotropic interface. This means that the sum of the flexoelectric coefficients e=(e1 + e3) is positive (e ≅ 1.7 pC/m at 28℃). The temperature dependence of e has been shown to involve a combination of both the quadrupolar and dipolar contributions

The Cool Japan Strategy and Tokyo Olympics 2020

This thesis examines Japan’s recent political and cultural strategy focusing on the soft power enabled by the popularity of Japan’s cool image in its cultural product in the so-called Cool Japan Strategy and its impact on the 2020 Tokyo Olympic Games. While starting as a political and economic strategy in the early 2000s, Cool Japan strategy capitalized on the popularity of Japanese cultural productions, especially of pop-culture such as anime, manga and video games. Cool Japan Strategy mainly developed to counter the economic stagnation in the 90s and the need to rebrand the Japanese image in response to the anti-Japan sentiment in the emerging East Asian countries due to the war responsibilities in World War II and the colonial era. However, Cool Japan strategy increasingly gained more nationalisitc turn in the 2010s with the impact of the Great East Japan Earthquake and Fukushima Nuclear Incident and the return of Shinzo Abe as the role of prime minister in 2012. In such a context, the thesis examines the Next Host City Artistic Segment in the Rio Olympics’ closing ceremony. In this ceremony, Shinzo Abe appeared in the costume of super mario as a symbolic representation of Japan’s new “cool” image. At first glance, Abe’s performance as super mario only seems like a performance, yet this thesis understands it as the reciprocal relation of Cool Japan strategy and Tokyo Olympics to present Japan as new transformed “Cool Nation” for the international audiences as well as mobilization of nationalism and national pride for the domestic audiences

Targeting the Allosteric Site of Oncoprotein BCR-ABL as an Alternative Strategy for Effective Target Protein Degradation

Protein degradation technology based on hybrid small molecules is an emerging drug modality that has significant potential in drug discovery and as a unique method of post-translational protein knockdown in the field of chemical biology. Here, we report the first example of a novel and potent protein degradation inducer that binds to an allosteric site of the oncogenic BCR-ABL protein. BCR-ABL allosteric ligands were incorporated into the SNIPER (Specific and Nongenetic inhibitor of apoptosis protein [IAP]-dependent Protein Erasers) platform, and a series of <i>in vitro</i> biological assays of binding affinity, target protein modulation, signal transduction, and growth inhibition were carried out. One of the designed compounds, <b>6</b> (SNIPER­(ABL)-062), showed desirable binding affinities against ABL1, cIAP1/2, and XIAP and consequently caused potent BCR-ABL degradation

Development of Protein Degradation Inducers of Androgen Receptor by Conjugation of Androgen Receptor Ligands and Inhibitor of Apoptosis Protein Ligands

Targeted protein degradation using small molecules is a novel strategy for drug development. We have developed hybrid molecules named specific and nongenetic inhibitor of apoptosis protein [IAP]-dependent protein erasers (SNIPERs) that recruit IAP ubiquitin ligases to degrade target proteins. Here, we show novel SNIPERs capable of inducing proteasomal degradation of the androgen receptor (AR). Through derivatization of the SNIPER­(AR) molecule at the AR ligand and IAP ligand and linker, we developed <b>42a</b> (SNIPER­(AR)-51), which shows effective protein knockdown activity against AR. Consistent with the degradation of the AR protein, <b>42a</b> inhibits AR-mediated gene expression and proliferation of androgen-dependent prostate cancer cells. In addition, <b>42a</b> efficiently induces caspase activation and apoptosis in prostate cancer cells, which was not observed in the cells treated with AR antagonists. These results suggest that SNIPER­(AR)­s could be leads for an anticancer drug against prostate cancers that exhibit AR-dependent proliferation