Ultra-High-Resolution Seismic Surveys: 3D Sea Trial at Beppu Bay

A 3D high-resolution seismic (3D-HRS) survey was conducted to clearly reveal and map faults and fractures in a shallow-water region of Beppu Bay, Japan. The 3D-HRS was conducted using a dense array of six short streamer cables combined with a single GI gun, which generate the primary pulse and create the main bubble with generator and collapse the main bubble with injector. This high-frequency seismic source and high-density seismic source/receiver point distribution achieved a significant improvement in seismic imaging resolution. Because the 3D-HRS system is compact and lightweight and can be operated by small vessels, its effectiveness and necessity have been demonstrated, especially in shallow coastal waters, where conventional seismic survey using large ships and long streamer cables is difficult. For seismic data processing, pre-stack noise attenuation, de-ghosting, multiple removal, and acquisition footprint removal had essential roles in enhancing seismic imaging quality. Compared to existing 2D seismic survey technology, the 3D-HRS achieved much higher resolution and delineated highly detailed features of the seafloor and subsurface. Following the seismic processing sequence, similarity and thinned fault likelihood attribute workflows were applied to detect and visualize faults and fractures within the 3D-HRS volume. These seismic attributes revealed a network of broadly distributed faults and fractures along an active fault system in Beppu Bay

Efficient production of bispecific antibody by FAST-IgTM and its application to NXT007 for the treatment of hemophilia A

ABSTRACTEfficient production of bispecific antibodies (BsAbs) in single mammalian cells is essential for basic research and industrial manufacturing. However, preventing unwanted pairing of heavy chains (HCs) and light chains (LCs) is a challenging task. To address this, we created an engineering technology for preferential cognate HC/LC and HC/HC paring called FAST-Ig (Four-chain Assembly by electrostatic Steering Technology – Immunoglobulin), and applied it to NXT007, a BsAb for the treatment of hemophilia A. We introduced charged amino-acid substitutions at the HC/LC interface to facilitate the proper assembly for manufacturing a standard IgG-type BsAb. We generated CH1/CL interface-engineered antibody variants that achieved > 95% correct HC/LC pairing efficiency with favorable pharmacological properties and developability. Among these, we selected a design (C3) that allowed us to separate the mis-paired species with an unintended pharmacological profile using ion-exchange chromatography. Crystal structure analysis demonstrated that the C3 design did not affect the overall structure of both Fabs. To determine the final design for HCs-heterodimerization, we compared the stability of charge-based and knobs into hole-based Fc formats in acidic conditions and selected the more stable charge-based format. FAST-Ig was also applicable to stable CHO cell lines for industrial production and demonstrated robust chain pairing with different subclasses of parent BsAbs. Thus, it can be applied to a wide variety of BsAbs both preclinically and clinically