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.     

Detection of light-absorbing iron oxide particles using a modified single-particle soot photometer

Copyright © 2016 American Association for Aerosol Research     

Quantitative Visualization of the Interaction between Complement Component C1 and Immunoglobulin G: The Effect of CH1 Domain Deletion

Immunoglobulin G (IgG) adopts a modular multidomain structure that mediates antigen recognition and effector functions, such as complement-dependent cytotoxicity. IgG molecules are self-assembled into a hexameric ring on antigen-containing membranes, recruiting the complement component C1q. In order to provide deeper insights into the initial step of the complement pathway, we report a high-speed atomic force microscopy study for the quantitative visualization of the interaction between mouse IgG and the C1 complex composed of C1q, C1r, and C1s. The results showed that the C1q in the C1 complex is restricted regarding internal motion, and that it has a stronger binding affinity for on-membrane IgG2b assemblages than C1q alone, presumably because of the lower conformational entropy loss upon binding. Furthermore, we visualized a 1:1 stoichiometric interaction between C1/C1q and an IgG2a variant that lacks the entire C_H1 domain in the absence of an antigen. In addition to the canonical C1q-binding site on Fc, their interactions are mediated through a secondary site on the C_L domain that is cryptic in the presence of the C_H1 domain. Our findings offer clues for novel-modality therapeutic antibodies.     

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.     

Steam Reforming of Methanol on Copper Catalysts Supported on Large-Surface-Area ZnAl2O3

Steam reforming of methanol on various supported Cu catalysts was examined. Supports strongly affected catalyst activity and, among the catalysts tested, Cu catalyst supported on large-surface-area ZnAl₂O₄ showed the highest activity, which, to the best of our knowledge, was higher than those for the supported catalysts reported so far. For supported Cu catalysts, two species were observed. One was a dispersed Cu species having strong interaction between Cu and support, and the other was an isolated Cu species. The activity of the former species strongly depended on supports.     

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.     

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.     

水中隐孢子虫和贾第鞭毛虫的替代检测指标

美国国家环保局（USEPA）制定并发布的1623方法是目前国际上常用的水中隐孢子虫和贾第鞭毛虫标准检测方法，该方法存在成本高、回收率低等缺陷。各国研究者试图通过考察其他水质指标与两虫的相关关系来寻找两虫密度和活性的有效替代指标，以间接反映两虫在水体中的存在水平，其中包括浊度、颗粒计数等物理学指标以及细菌、细菌孢子、病毒、噬菌体等生物学指标。虽然还未得出具有普遍性的结论，但研究表明颗粒计数、好氧孢子等有可能成为有效的两虫替代指标。