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Abstract: This review covers recent progress in the construction of metal complex wires on various substrates via the stepwise coordination method, their functions, and the electrochemical evaluation of bis(terpyridine)metal complex oligomer wires on electrodes. In the layer-by-layer process of metal complex wire construction, various combinations of anchor ligands, metal sources, and bridging ligands have been used. The prepared structures show multiple functions, including photocurrent generation, catalytic activity, insulation properties, and long-range electron transport abilities. The electron transport behavior, and the long-range electron transport abilities from the terminal redox site to the electrode via bis(terpyridine)metal complex wires, were evaluated using potential step chronoamperometry. The remarkable long-range electron transport abilities were evidenced in the small values for the attenuation factor, β. The influence of the building blocks in the metal complex wires on the β value and the electron transfer rate constant was demonstrated. [Copyright &y& Elsevier]

Abstract: A wide erosion magnetron sputtering system for nickel targets has been developed using a large, tall and eccentrically rotating center magnet. In this system, a water cooling unit was attached behind the target except the moving center magnet area. Therefore, the rotating mechanism of yoke magnet could be separated from the cooling water without decreasing the magnetic flux on the target surface and ensure a high reliability of long life use. Utilization on the 5-inches Ni target was 40%, as compared with 12% utilization of the conventional system. The sputtering rate and erosion depth linearly changed while the target was in use, because the increase of magnetic flux was lower than that of a conventional system. Hence, the target life will be precisely managed by the total sputtering time. [Copyright &y& Elsevier]

Abstract: A wider eroded and higher target utilized magnetron sputtering system for ferromagnetic nickel (Ni) target was developed using a large, tall and eccentrically rotating tilted center magnet. In this system, a tilted center magnet optimized the magnetic field strength between the inner and outer erosion areas by adjusting the tilt angle, and target utilization is found to be higher up to 49% for 5-inch and 4-mm thick Ni target, which is 8% better than when a non-tilted center magnet was used. Moreover, the center non-eroded area was decreased. Furthermore, the rotating mechanism of a yoke magnet could be separated from the cooling water and the target could be cooled more effectively because the water cooling unit was attached not only to the outer area of target, but also to the tilted space of the center magnet. [Copyright &y& Elsevier]

Abstract: Objective: Selenoprotein-P is a selenium-rich serum protein that carries more than 50% of serum selenium. We evaluated changes in serum selenoprotein-P levels in patients with inflammatory bowel disease. Methods: Serum selenoprotein-P levels were measured by enzyme-linked immunosorbent assay. Twenty healthy individuals (controls), 34 patients with ulcerative colitis, and 37 patients with Crohn¿s disease (CD) were studied. Results: A highly significant correlation was found between the serum selenium and selenoprotein-P levels. There was no significant difference in serum selenoprotein-P levels between healthy controls (average 3.4 ± 0.8 µg/mL, n = 20) and patients with ulcerative colitis (3.0 ± 1.0 µg/mL, n = 34). Serum selenoprotein-P levels were significantly lower in patients with CD (average 1.8 ± 0.5 µg/mL, n = 37). Serum selenoprotein-P levels were significantly lower in the elemental diet group of patients who had CD (average 1.4 ± 0.4 µg/mL, n = 17) than in the non-elemental diet group of patients who had CD (average 2.1 ± 0.3 µg/mL, n = 20). Conclusion: We found that the serum selenoprotein-P level is decreased in patients with CD. It may be a useful marker to monitor the systemic selenium status in various disorders. [Copyright &y& Elsevier]

Zinc methyl pheophorbides a / a ', which possess oxo and methoxycarbonyl groups at the C131- and C132-positions, respectively, on the exo -five membered ring fusing the cyclic tetrapyrrole of their chlorin π-skeletons, were prepared via chemical modifications of chlorophyll a produced in phototrophs. The C131-hydroxylated and unsubstituted analogues were synthesized by reduction of the ketone moiety. The C131- and C132-stereochemistry of these semi-synthetic compounds was confirmed by 1H NMR and circular dichroism spectroscopies. A methoxycarbonyl group at the chiral C132-position in the ketone was stereo-inverted under basic conditions, whereas those in the corresponding alcoholic and dihydro-forms were not. The in vitro BciC enzymatic reaction of the (132 R)-ketone was found to stereoselectively hydrolyze the C132-methoxycarbonyl group, followed by spontaneous decarboxylation. Similarly, the (132 R)-COOCH 3 group in the (131 S)-alcohol was hydrolyzed, whereas the (132 R)-COOCH 3 group in the (131 R)-alcohol was not. After the enzymatic reaction of the C131-dihydro-compound, its (132 S)-demethoxycarbonylated and hydroxylated product was observed. [Display omitted] • Zinc 131-hydroxylated and unsubstituted chlorophyll- a derivatives were synthesized. • The 131- and 132-stereochemistry was confirmed by 1H NMR and CD spectroscopies. • The 131-oxo analog was 132-epimerized, but 131-hydroxy and dihydro forms could not. • A recombinant BciC enzyme stereospecifically hydrolyzed the 132-COOMe in vitro. [ABSTRACT FROM AUTHOR]

An anionic boron-substituted phosphorane, a phosphoranyl-triarylborate, was synthesised by stabilising the P–B bond with a pair of the N , O -bidentate ligands. The new P–B bonded compound was characterised crystallographically and by NMR spectroscopy. It was found that withdrawing electrons from both sides around the P–B bond, which shows large s-character, contributes to its stability. Its low oxidation potential was attributed to the oxidation of the bidentate ligands. • Synthesis of a phosphoranyl-triarylborate using a N , O -bidentate ligand. • Withdrawing electrons from both sides of the P–B bond stabilised the structure. • Low oxidation potential corresponding to relatively high HOMO energy level. An anionic boron-substituted phosphorane, a phosphoranyl-triarylborate, was synthesised by stabilising the pentacoordinated phosphorus atom with a pair of N , O -bidentate ligands. Its structure was characterised by NMR spectroscopy and X-ray crystallographic analysis. The 11B and 31P NMR spectral data showed large s-character of the phosphorus–boron bond. DFT calculations revealed the charge distributions and molecular orbitals. The first oxidation potential of the phosphoranyl-borate was corresponded to the oxidation of the N , O -bidentate ligands from the distribution of the HOMO of the anion moiety. [ABSTRACT FROM AUTHOR]

Abstract: Antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism by which antibodies exert anti-tumor effects. Here, we show that Fc multimerization augments the binding avidities for all of the low-affinity Fcγ receptors, increasing ADCC activity very much. A chimeric antibody, designated M-Ab, was constructed with the V regions from mouse anti-CD20 mAb 1F5 and the C regions from human IgG1 and κ chain. Two or three Fc domains were tandemly repeated downstream of the C-terminus of the M-Ab to give D0-Ab (Fc dimer Ab without a linker), T0-Ab (Fc trimer Ab without a linker), and T3-Ab (Fc trimer Ab with a (GGGGS)3 linker in front of the second and third hinge regions). HPLC and SDS-PAGE analyses of the purified antibodies indicated that the H and L chains were appropriately linked with interchain disulfide bonds and that the Ab preparations did not contain aggregated molecules. Although flow cytometry indicated that Fc multimerization decreased the binding activity for CD20-bearing cells to 1/3∼1/4, the binding avidities for the extracellular domains of low-affinity Fcγ receptors were greatly augmented. The avidities were in the order of T3-Ab, T0-Ab, D0-Ab and M-Ab, with T3-Ab showing about 100 times greater avidity than M-Ab not only for FcγRIIIA, but also for FcγRIIA and FcγRIIB. The rank order of ADCC activity with human PBMC was the same, and T3-Ab induced ADCC at a 50–100 times less concentration, compared to M-Ab. These Fc tandem repeat antibodies are promising candidates for anti-tumor therapeutics, and should also be useful as tools to elucidate the biological roles of FcγRIIA, FcγRIIB, and FcγRIIIA. [Copyright &y& Elsevier]

The article reports on a study conducted on atopic dermatitis (AD) which is a chronic skin disease with severe inflammation and irritation and the elevated concentration of plasma immunoglobulin E (IgE) against the allergens. The study informs that IgE is involved in the type I hypersensitivity through mast cells. It further informs that the affects of IgE against chronic allergic diseases is not fully known.

Pharmacological reactivation of the γ-globin gene for the production of fetal hemoglobin (HbF) is a promising approach for the management of β-thalassemia and sickle cell disease (SCD). We conducted a phenotypic screen in human erythroid progenitor cells to identify molecules that could induce HbF, which resulted in identification of the hit compound 1. Exploration of structure–activity relationships and optimization of ADME properties led to 2-azaspiro[3.3]heptane derivative 18 , which is more rigid and has a unique structure. In vivo using cynomolgus monkeys, compound 18 induced a significant dose-dependent increase in globin switching, with developable properties. Moreover, compound 18 showed no genotoxic effects and was much safer than hydroxyurea. These findings could facilitate the development of effective new therapies for the treatment of β-hemoglobinopathies, including SCD. [ABSTRACT FROM AUTHOR]

Heritable disorders associated with hemoglobin production are the most common monogenic disorders. These are mainly represented by disorders such as β-thalassemia and sickle cell disease. Induction of fetal hemoglobin (HbF) has been known to ameliorate the clinical severity of these β hemoglobinopathies. A high throughput phenotypic screening was used in this study to isolate novel compounds that may enhance the expression of γ-globin, the component of HbF, in human erythroid cell lines and primary erythroid progenitors derived from human CD34+ cells. The effect of lead compounds on epigenetic enzymes and key transcriptional factors was evaluated to identify their mode of action. One hit compound was further evaluated in vivo using monkey models. Among the ~18,000 compounds screened, 18 compounds were selected and tested to determine their ability to induce HbF in human erythroid cell lines and primary erythroid cells. One of these compounds, a 3-phenyl-isoxazole derivative, could potentially induce HbF in monkey bone marrow cells when administered orally. The compound downregulated negative transcriptional regulators of HbF, Bcl11a and LRF without inhibiting the known epigenetic enzymes. These studies demonstrated the advantages associated with phenotype-screening and identified novel fetal globin inducers that may be useful for treating hemoglobinopathies. [ABSTRACT FROM AUTHOR]