Formation of cytochrome C–apatite composite layer on NaOH- and heat-treated titanium

A cytochrome C (cyt C) and apatite composite layer was formed on a NaOH- and heat-treated titanium substrate (Ti substrate) by immersing the Ti substrate for one day at 25 °C in supersaturated calcium phosphate solutions obtained by mixing infusion fluids. When the initial supersaturation level of the calcium phosphate solution was increased, the total amount of cyt C and apatite deposited on the Ti substrate increased. On the other hand, the cyt C content in the composite layer decreased with an increase in initial supersaturation level. The morphology of the composite layer markedly changed depending on the initial supersaturation level. Therefore, the initial supersaturation level affected the formation of the cyt C and apatite composite layer. It is expected that fibroblast growth factor-2 can be immobilized on NaOH- and heat-treated titanium substrates using the same method.     

Synthesis of an Enantiocomplementary Catalyst of β‐Isocupreidine (β‐ICD) from Quinine

Compound 20 , a pseudoenantiomer of β‐isocupreidine (β‐ICD), was synthesized from quinine employing a Barton reaction of nitrosyl ester 13 and acid‐catalyzed cyclization of carbinol 18 as key steps. The Baylis–Hillman reaction of benzaldehyde, p‐nitrobenzaldehyde, and hydrocinnamaldehyde with 1,1,1,3,3,3‐hexafluoroisopropyl acrylate (HFIPA) using 20 as a chiral amine catalyst was found to give the corresponding S‐enriched adducts in high optical purity (>91% ee) in contrast to the β‐ICD‐catalyzed reaction which affords R‐enriched adducts. This result suggests that compound 20 can serve as an enantiocomplementary catalyst of β‐ICD in the asymmetric Baylis–Hillman reaction of aldehydes with HFIPA.     

Bacterially Secretable Single-Chain Tandem Macrocyclic Peptides for High Affinity and Inhibitory Activity

The inhibition of protein-protein interactions (PPIs) is an effective approach for therapy. Owing to their large binding surface areas to target proteins, macrocyclic peptides are suitable molecules for PPI inhibition. In this study, we developed single-chain tandem macrocyclic peptides (STaMPtides) that inhibits the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2). They were artificially designed to comprise two different VEGFR2-binding macrocyclic peptides linked in tandem by peptide linkers and secreted by Corynebacterium glutamicum. Most potent VEGFR2-inhibitory STaMPtides with length-optimized linkers exhibited >1000 times stronger inhibitory activity than their parental monomeric peptides, possibly due to the avidity effect of heterodimerization. Our approach of using STaMPtides for PPI inhibition may be used to inhibit other extracellular factors, such as growth factors and cytokines.     

Seven-year temporal variation of Caesium-137 discharge inventory from the port of Fukushima Daiichi Nuclear Power Plant: continuous monthly estimation of Caesium-137 discharge in the period from April 2011 to June 2018

ABSTRACT

After direct discharges of highly contaminated water of the Fukushima Daiichi Nuclear Power Plant (1 F) from April to May 2011, Kanda suggested that relatively small amounts of run-off of radionuclides from the 1 F port into the Fukushima coastal region subsequently continued by his estimation method. However, the estimation period was limited to up to September 2012. Therefore, this paper estimatesthe discharge inventory up to June 2018. In the missing period, the Japanese government and Tokyo Electric Power Company Holdings have continued efforts to stop the discharge, and consequently, the radionuclide concentration in seawater inside the 1 F port has gradually diminished. We show the monthly discharge inventory of ¹³⁷Cs up to June 2018 by two methods, i.e., Kanda method partially improved by the authors and a more sophisticated method using Voronoi tessellation reflecting the increase in the number of monitoring points inside the 1 F port. The results show that the former always yields overestimated results compared with the latter, but the ratio of the former to the latter is less than one order of magnitude. Using these results, we evaluate the impact of the discharge inventory from the 1 F port into the coastal area and radiation dose upon fish ingestion.     

Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain

We established four new mouse strains with defective T and B cells as well as defects in innate immunological reactions using an NK cell depletion antibody and showed that all mutant mouse strains efficiently received human peripheral blood leukocyte (PBL) engraftment (hu-PBL-scid mice). Higher levels of human immunodeficiency virus type 1 (HIV-1) replication were observed in these new hu-PBL-scid mice than in conventional hu-PBL-C.B-17-scid mice. In one particular strain, hu-PBL-NOD-scid mice, high levels of HIV-1 viremia (more than 10(6) 50% infectious doses per ml) were detected after infection with HIV-1. The plasma viral load was about 100 to 1,000 times higher than that observed in other hu-PBL-scid mice infected with HIV-1. Although high-level viremia did not correlate with the total amount of HIV-1 RNA in cells from infected mice, high levels of free virions were detected only in hu-PBL-NOD-scid mice. HIV-1 viremia induced systemic HIV-1 infection involving the liver, lungs, and brain. PCR in situ hybridization confirmed that HIV-1-infected cells invaded the brain tissue of the hu-PBL-NOD-scid mice. Our results suggest that the genetic background, including innate immunity, is critical in the development of primary HIV-1 viremia and subsequent central nervous system invasion with HIV-1. The hu-PBL-NOD-scid mouse represents a useful model for the study of the pathogenesis of HIV-1 in vivo, especially brain involvement, and therapy of primary HIV-1 viremia.     

Some factors for the space charge formation in polyethylene

Information on space-charge behavior in thick insulated samples aids in understanding the dc characteristics of polymer-insulated dc cables. The pulsed electroacoustic method is used to investigate several space charge formation factors in 2 mm-thick polyethylene (PE). The following results were obtained. For measurement factors: (1) A polymeric semiconducting electrode provides a more accurate measurement than does a metal electrode as a result of better matching of acoustic impedance with PE. (2) Within a dc electrical stress range of several tens kV/mm, the space charge distributions under and after dc voltage application are almost the same; this is due to a comparatively long time of space-charge decay. (3) The space-charge distribution of a plate sample agrees with that of a cable sample having the same insulation thickness. For insulating material factors: (1) The amount of space charge in crosslinked polyethylene (XLPE) is much larger than that in low-density PE (base of XLPE). The space charge of XLPE continues to increase even after dc voltage application (24 h); that of LDPE reaches equilibrium with a few hours. (2) The aforementioned space charge difference between XLPE and LDPE is assumed to be caused by ionic impurities in XLPE, not by the additives themselves (acetophenon and cumylalcohol as byproducts of cross linking and antioxidant).     

Early experience of minimally invasive valve surgery

Gene therapy has been proposed for a wide variety of human conditions including monogenic disorders, such as the haemoglobinopathies and immunodeficiency syndromes, cancer and many other diseases. Prerequisites for the success of this approach include the ability to deliver the therapeutic gene intact to the target cell, persistent levels of transgene expression sufficient to correct the disease phenotype, lack of unwanted side-effects associated with vector exposure or gene transfer and relative simplicity allowing the widespread use of this methodology. Although substantial progress has been made in animal models since the inception of genetic therapy in the early 1980s, significant obstacles remain for human therapy, most notably in the area of vector development. The first generation of gene therapy vectors has failed to overcome many of the biological hurdles cited above necessitating the development of alternate means of gene delivery and expression.     

Synthesis and Polymerization of Novel Quinone Methide Ketals

Summary Novel quinone methide ketals, 8-[ 1'-cyano-1'-(ethoxycarbonyl)methylene]-l,4-dioxaspiro[4.5]deca-6,9-diene (1a) and 8-(1',l'-dicyanomethy1ene)-1,4-dioxaspiro[4.5]deca-6,9-diene (1b), were synthesized, and their polymerization behavior was investigated. Polymerizations of 1a and 1b initiated with BPO and BF₃·Et₂O gave corresponding novel ring-opening polymers, but no polymerization with BuLi. Copolymerization of 1a with St in the presence of AIBN at 60 °C gave the monomer reactivity ratios r₁(1a) = 0.50 ± 0.1 and r₂(St) = 0.1 ± 0.02, and Q and e values of 1a were 2.46 and +0.93, indicating that 1a is a highly conjugative, electron-accepting monomer. Homopolymers of 1a and 1b had better thermal stability than that of 7-cyano-7-(ethoxycarbonyl)- 1,4-benzoquinone methide. Received 23 January 2003/Revised version 28 February 2003/ Accepted 1 March 2003 Correspondence to Takahito Itoh     

‘Living’ radical polymerization of styrene mediated by spiro ring-substituted piperidinyl-N-oxyl radicals. The effect of the spiro rings on the control of polymerization

The bulk radical polymerizations of styrene (St) at 80-120 °C in the presence of 6-aza-7,7-dimethyl-9-hydroxyspiro[4.5]decane-6-yloxyl (1) and 1-aza-2,2-dimethyl-4-hydroxy[5.5]undecane-1-yloxyl (2) were studied. At 100 and 120 °C, the polymerizations were well controlled by those nitroxides to give poly(St)s with narrow polydispersities. On the other hand, the polymerization mediated by 2 at 80 °C showed a good ‘livingness’ of polymerization, but 1 had a poor ability to control the polymerization to give poly(St) with a broad polydispersity of 1.52. The rate constants (k_act) for the homolysis of the NO-C bond of the alkoxyamines prepared from 1 and 2 were measured at 333-373 K, and the A_acts and E_acts values were determined to be 2.8×10¹³ s⁻¹ and 128 kJ mol⁻¹ (1) and 4.0×10¹³ s⁻¹ and 125 kJ mol⁻¹ (2), respectively, from the Arrhenius plots. These results are compared with those for the structurally related piperidinyl-N-yloxyl radicals including TEMPO.     

Image-based magnification calibration for electron microscope

Magnification calibration is a crucial task for the electron microscope to achieve accurate measurement of the target object. In general, magnification calibration is performed to obtain the correspondence between the scale of the electron microscope image and the actual size of the target object using the standard calibration samples. However, the current magnification calibration method mentioned above may include a maximum of 5 % scale error, since an alternative method has not yet been proposed. Addressing this problem, this paper proposes an image-based magnification calibration method for the electron microscope. The proposed method employs a multi-stage scale estimation approach using phase-based correspondence matching. Consider a sequence of microscope images of the same target object, where the image magnification is gradually increased so that the final image has a very large scale factor $S$ (e.g., $S=1\!,\!\!000$ ) with respect to the initial image. The problem considered in this paper is to estimate the overall scale factor $S$ of the given image sequence. The proposed scale estimation method provides a new methodology for high-accuracy magnification calibration of the electron microscope. This paper also proposes a quantitative performance evaluation method of scale estimation algorithms using Mandelbrot images which are precisely scale-controlled images. Experimental evaluation using Mandelbrot images shows that the proposed scale estimation algorithm can estimate the overall scale factor $S=1\!,\!\!000$ with approximately 0.1 % scale error. Also, a set of experiments using image sequences taken by an actual scanning transmission electron microscope (STEM) demonstrates that the proposed method is more effective for magnification calibration of a STEM compared with a conventional method.