Proceedings of the Japan Academy, Series B
Online ISSN : 1349-2896
Print ISSN : 0386-2208
ISSN-L : 0386-2208
Volume 92, Issue 5
Displaying 1-2 of 2 articles from this issue
    2016 Volume 92 Issue 5 Pages 135-155
    Published: May 11, 2016
    Released on J-STAGE: May 11, 2016
    Utilizing results obtained over the past quarter century mainly with Japanese X-ray astronomy satellites, a review is given to some aspects of neutron stars (NSs), with a particular emphasis on the magnetic fields (MFs) of mass-accreting NSs and magnetars. Measurements of electron cyclotron resonance features in binary X-ray pulsars, using the Ginga and Suzaku observatories, clarified that their surface MFs are concentrated in a narrow range of (1–7) × 108 T. Extensive studies of magnetars with Suzaku reinforced their nature as neutron stars with truly strong MFs, and revealed several important clues to their formation, evolution, and physical states. Taking all these results into account, a discussion is made on the origin and evolution of these strong MFs. One possible scenario is that the MF of NSs is a manifestation of some fundamental physics, e.g., neutron spin alignment or chirality violation, and the MF makes transitions from strong to weak states.
  • Kazuya NAGANO, Yasuo TSUTSUMI
    2016 Volume 92 Issue 5 Pages 156-166
    Published: May 11, 2016
    Released on J-STAGE: May 11, 2016
    Attempts are being made to develop therapeutic proteins for cancer, hepatitis, and autoimmune conditions, but their clinical applications are limited, except in the cases of drugs based on erythropoietin, granulocyte colony–stimulating factor, interferon-alpha, and antibodies, owing to problems with fundamental technologies for protein drug discovery. It is difficult to identify proteins useful as therapeutic seeds or targets. Another problem in using bioactive proteins is pleiotropic actions through receptors, making it hard to elicit desired effects without side effects. Additionally, bioactive proteins have poor therapeutic effects owing to degradation by proteases and rapid excretion from the circulatory system. Therefore, it is essential to establish a series of novel drug delivery systems (DDS) to overcome these problems. Here, we review original technologies in DDS. First, we introduce antibody proteomics technology for effective selection of proteins useful as therapeutic seeds or targets and identification of various kinds of proteins, such as cancer-specific proteins, cancer metastasis–related proteins, and a cisplatin resistance–related protein. Especially Ephrin receptor A10 is expressed in breast tumor tissues but not in normal tissues and is a promising drug target potentially useful for breast cancer treatment. Moreover, we have developed a system for rapidly creating functional mutant proteins to optimize the seeds for therapeutic applications and used this system to generate various kinds of functional cytokine muteins. Among them, R1antTNF is a TNFR1-selective antagonistic mutant of TNF and is the first mutein converted from agonist to antagonist. We also review a novel polymer-conjugation system to improve the in vivo stability of bioactive proteins. Site-specific PEGylated R1antTNF is uniform at the molecular level, and its bioactivity is similar to that of unmodified R1antTNF. In the future, we hope that many innovative protein drugs will be developed by combining these technologies.