Since it was recently reported that an antibody for proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces the risk of cardiovascular events in a clinical context, PCSK9 inhibition is thought to be an attractive therapy for dyslipidemia. In the present study, we created a novel small biologic alternative to PCSK9 antibodies called DS-9001a, comprising an albumin binding domain fused to an artificial lipocalin mutein (ABD-fused Anticalin protein), which can be produced by a microbial production system. DS-9001a strongly interfered with PCSK9 binding to low-density-lipoprotein receptor (LDL-R) and PCSK9-mediated degradation of LDL-R. In cynomolgus monkeys, single DS-9001a administration significantly reduced the serum LDL-C level up to 21 days (62.4% reduction at the maximum). Moreover, DS-9001a reduced plasma non-high-density-lipoprotein cholesterol and oxidized LDL levels, and their further reductions were observed when atorvastatin and DS-9001a were administered in combination in human cholesteryl ester transfer protein/ApoB double transgenic mice. Additionally, their reductions on the combination of atorvastatin and DS-9001a were more pronounced than those on the combination of atorvastatin and anacetrapib. Besides its favorable pharmacologic profile, DS-9001a has a lower molecular weight (about 22 kDa), yielding a high stoichiometric drug concentration that might result in a smaller administration volume than that in existing antibody therapy. Since bacterial production systems are viewed as more suited to mass production at low cost, DS-9001a may provide a new therapeutic option to treat patients with dyslipidemia. In addition, considering the growing demand for antibody-like drugs, ABD-fused Anticalin proteins could represent a promising new class of small biologic molecules.
The state-selective dissociation dynamics for anionic and excited neutral fragments of gaseous SiCl 4 following Cl 2p and Si 2p core-level excitations were characterized by combining measurements of the photoninduced anionic dissociation, x-ray absorption and UV/visible dispersed fluorescence. The transitions of core electrons to high Rydberg states/doubly excited states in the vicinity of both Si 2p and Cl 2p ionization thresholds of gaseous SiCl 4 lead to a remarkably enhanced production of anionic, Si − and Cl − , fragments and excited neutral atomic, Si * , fragments. This enhancement via core-level excitation near the ionization threshold of gaseous SiCl 4 is explained in terms of the contributions from the Auger decay of doubly excited states, shake-modified resonant Auger decay, or/and post-collision interaction. These complementary results provide insight into the state-selective anionic and excited neutral fragmentation of gaseous molecules via core-level excitation.
The plastic films are modified by various plasmas (CF4, 02, Ar, N2) in order to know the difference of effects by kinds of their plasmas and the condition of the change of the surface characteristics with time after each plasma treatment is investigated in detail. Moreover, we developed the reduction method of its change with time. The condition of the surface modification by Ar plasma is similar to that of N2 plasma. But, that by 02 plasma was different from them. This reason is that the modification source is mainly ions on Ar plasma or N 2 plasma, and radicals on 02 plasma. The contact angle modified by Ar plasma (N2 plasma) became smaller than that by 02 plasma; 0° (Ar plasma), 35° (02 plasma).The contact angle after the plasma treatment was seldom reduced even if time passed when plastic film was treated by Ar plasma treatment with heating. The bounding property of oxygen atoms was controlled by heating in the plasma treatment. On the other hand, the change with time was not reduced by CF 4 plasma with heating. But, treatment effect had been slightly increased. It is considered that the fluorine atoms which are causes of hydrophobic property are introduced much, however, are removed much.
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