Discovery of a Novel Scaffold as an Indoleamine 2,3‐Dioxygenase 1 (IDO1) Inhibitor Based on the Pyrrolopiperazinone Alkaloid,Longamide B

Indoleamine 2,3‐dioxygenase 1 (IDO1) has emerged as a key target for cancer therapy, as IDO1 plays a critical role in the capacity of tumor cells to evade the immune system. The pyrrolopiperazinone alkaloid longamide B and its derivatives were identified as novel IDO1 inhibitors based on docking studies and small library synthesis. The thioamide derivative showed higher IDO1 inhibitory activity than longamide B, and displayed an activity similar to that of a representative IDO1 inhibitor, 1‐methyl‐tryptophan. These results suggest that the pyrrolopiperazinone scaffold of longamide B could be used in the development of IDO1 inhibitors.     

The Role of a Nonribosomal Peptide Synthetase in l‐Lysine Lactamization During Capuramycin Biosynthesis

Capuramycins are one of several known classes of natural products that contain an l ‐Lys‐derived l ‐α‐amino‐?‐caprolactam (l ‐ACL) unit. The α‐amino group of l ‐ACL in a capuramycin is linked to an unsaturated hexuronic acid component through an amide bond that was previously shown to originate by an ATP‐independent enzymatic route. With the aid of a combined in vivo and in vitro approach, a predicted tridomain nonribosomal peptide synthetase CapU is functionally characterized here as the ATP‐dependent amide‐bond‐forming catalyst responsible for the biosynthesis of the remaining amide bond present in l ‐ACL. The results are consistent with the adenylation domain of CapU as the essential catalytic component for l ‐Lys activation and thioesterification of the adjacent thiolation domain. However, in contrast to expectations, lactamization does not require any additional domains or proteins and is likely a nonenzymatic event. The results set the stage for examining whether a similar NRPS‐mediated mechanism is employed in the biosynthesis of other l ‐ACL‐containing natural products and, just as intriguingly, how spontaneous lactamization is avoided in the numerous NRPS‐derived peptides that contain an unmodified l ‐Lys residue.     

Fracture behaviour and numerical study of resistance spot welded joints in high-strength steel sheet

Cross tension tests of resistance spot welded joints with varying nugget diameter were carried out using 980 MPa high strength steel sheet of 1.6 mm thickness. In proportion, as nugget diameter increased from 3√t to 5√t (where t is thickness), cross tension strength (CTS) increased while fracture morphology simultaneously transferred from interface fracture to full plug fracture. In cases of interface fracture, circumferential crack initiation due to separation of the corona bond arose at an early stage of loading. The crack opening process without propagation was recognized until just before fracture and then the crack propagated to the nugget immediately in a brittle manner around CTS. In full plug fracture, main ductile crack initiation from the notch-like part at the end of sheet separation occurred with the sub-crack initiated at an early stage. The ductile crack propagated toward the HAZ and base material to form full plug fracture. The mode I stress intensity factor was considered as a suitable fracture parameter because the circumferential crack behaved pre-crack for brittle fracture in the nugget region at the final stage. Based on the FE analysis, the mode I stress intensity factor was calculated as 116 MPa √m at CTS as fracture toughness for the nugget. With respect to full plug fracture, ductile crack initiation behaviour from the notch-like part was expressed by concentration of equivalent plastic strain. On the assumption that the ductile crack arose in critical value of equivalent plastic strain, the value was calculated as 0.34 by FE analysis. Reasonable interpretation for interface fracture and full plug fracture in the resistance spot welded joint was proposed due to first crack initiation by stress concentration, brittle fracture by using mode I stress intensity factor, and ductile crack initiation by using equivalent plastic strain.     

Effects of various ester groups in γ-radiation degradation of syndiotactic poly(methacrylate)s

The γ irradiation of poly(methacrylate)s with various ester groups at room temperature was investigated by gel permeation chromatography and NMR techniques. The G values for scission and crosslinking for each of the polymers were estimated from the changes in the molecular weights and molecular weight distributions. The new structures formed during γ irradiation were examined by ¹H-NMR spectroscopy. All of the investigated poly(alkanemethacrylate)s were found to produce the alkane formates during γ irradiation, and for poly(2-methyl heptyl methacrylate) G(S) was less than 4G(X), indicating gel formation in this polymer. In the investigation of poly(benzyl methacrylate), no formate ester was found, but some small molecule compounds formed from the benzyl radical were detected. The benzyl group was also found to stabilize the polymer against radiation damage. © 1996 John Wiley & Sons, Inc.     

Size-dependent separation of graphene oxide by deformation of packed-gel in a chromatographic column

ABSTRACT

A deformable gel-packed chromatographic column was used to separate as-synthesized graphite oxide with different sizes. The synthesized gel (56 µm) was deformed by pressure of the fluid flow and the gaps in the gels showed a range of sizes. A suspension of graphene oxide (0.1 g/L, 10 mL) was injected, and graphene oxide in the elution had a size at 0.56 μm and 0.14 μm, whereas in half upper and bottom domain of the gel layer graphene oxide had a size at 33 µm and 2.9 µm, respectively, demonstrating that graphene oxide suspension was separated by size through gel layer.     

Physicochemical properties of monosodium glutamate-compounded tapioca starch exceeds those of simple heat-moisture treated starch

Monosodium glutamate (GluNa)-compounded starch was prepared by heat-moisture treating a mixture of tapioca starch and GluNa. GluNa-compounded starch exhibited a higher gelatinization temperature and reduced swelling and solubility, essentially lower hardness of the granule center, and paste viscosity than those of the heat-moisture treated tapioca starch and the untreated starch. However, its appearance, unit chain length distribution, and α-amylase digestibility were similar to those of the heat-moisture treated tapioca. It is thus concluded that GluNa compounding is useful for providing a unique type of starch that possesses a less swollen and viscous texture than that produced with simple heat-moisture treatment.     

Application of electron beam for the reduction of PCDD/F emission from municipal solid waste incinerators

The electron-beam technology was applied to reduce the emission of polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) in a flue gas of 1000 m(3)N/h from the municipal solid waste incinerator (MSWI) at a temperature of 200 degrees C. More than 90% decomposition of PCDD/Fs was obtained using an electron accelerator at a dose of 14 kGy. The decomposition was initiated through reactions with OH radicals produced by the irradiation of flue gases, followed by oxidation such as the ring cleavage of the aromatic ring, the dissociation of ether bond, and dechlorination. The cost analysis estimated that the electron-beam system can cut the annualized cost by approximately 50% for the treatment of PCDD/Fs in a pre-dusted MSWI flue gas as compared with a bag-filter system when operating on electricity generated from an incineration. Electron-beam technology is an economically and technologically useful method for reducing PCDD/Fs in an incineration flue gas.     

Antimicrobial susceptibilities of Salmonella isolates obtained from layer chicken houses on a commercial egg-producing farm in Japan, 1997 to 2002

Susceptibility to antimicrobial agents was examined for 325 isolates of Salmonella enterica serotypes Cerro, Infantis, Livingstone, and Montevideo isolated from layer houses on a commercial egg-production farm in the western region of Japan between 1997 and 2002. No antimicrobials were used for therapeutic purposes on the farm during this period. From 1.8 to 3.1% of the isolates were resistant to ampicillin, chloramphenicol, and tetracycline. Resistance to streptomycin and sulfisoxazole was found in 52.9 and 65.5%, respectively, of Salmonella Montevideo isolates and in 0 to 13.2% of the isolates of the other serotypes. All the streptomycin-resistant isolates of Salmonella Montevideo also exhibited resistance to sulfisoxazole. Salmonella Montevideo isolates were first isolated in 1998, and 80.0% of the isolates obtained in this year were resistant to streptomycin and sulfisoxazole. The results suggest that Salmonella Montevideo isolates that had already acquired resistance may have been introduced into the layer houses, although the route and vehicle of transmission were uncertain. The proportion of Salmonella Montevideo isolates resistant to streptomycin and sulfisoxazole significantly decreased (P < 0.01) from 79.5% for 1998 through 1999 to 37.3% for 2000 through 2002. This decrease probably was due to the fact that no antimicrobials were used on the farm. Among 10 isolates from different serotypes obtained from 1997 to 2002 that were resistant to ampicillin, two and five isolates harbored 42- and 63-kb R plasmids and identical DraI restriction enzyme digest patterns, respectively, and carried the blaTEM gene. The results suggest that the ampicillin resistance determinants were transferred among different serotypes of Salmonella in the layer houses.     

Fabrication, Sinterability, and Mechanical Properties of Lead Zirconate Titanate/Silver Composites

High-toughness and high-strength lead zirconate titanate (PZT) composites that contain fine silver particles were successfully fabricated at low sintering temperatures. Addition of silver to a PZT matrix did not result in unwanted reaction phases; however, some silver diffused toward the perovskite crystal structure. A small quantity of silver accelerated the sinterability of the PZT composites. The formation of oxygen vacancies due to the partial substitution of silver appeared to enhance the sinterability of the PZT. Fracture toughness depended on the size and degree of sphericity of the silver particles, and SEM observations on crack propagation suggested that the toughening mechanism in the PZT/Ag composites involves crack bridging resulting from the ductile behavior of silver particles. It is proposed that high fracture strength in PZT/1 to 5 vol% Ag composites results from the relaxation of transformation-induced internal stress by the silver particles.     

Reduction and Sintering of a Nickel–Dispersed-Alumina Composite and Its Properties

High-density nickel–dispersed-alumina (Al₂O₃/nickel) composites with superior mechanical properties were obtained by the hydrogen reduction and the hot pressing of alumina–nickel oxide (Al₂O₃/NiO) mixed powders. The mixtures were prepared by using NiO or nickel nitrate (Ni(NO₃)₂· n H₂O) as a dispersion source of nickel metal. Microstructural investigations of the composite fabricated using nitrate powder revealed that fine nickel particles, } 100 nm in diameter, dispersed homogeneously at the matrix grain boundaries, forming the intergranular nanocomposite. High strength (.1 GPa) and high-temperature hardness were registered for the composite that contained a small amount of nickel dispersion. The ferromagnetic properties of nickel, such as high coercive force, were observed, because of the fine magnetic dispersions, which indicates a functional value of structural composites.