Synthesis and Bacterial Mutagenicity of Oxidized Derivatives of-Polycyclic Aromatic Hydrocarbons

A series of oxidized derivatives of nitrophenanthrene and nitrobenz[a]anthracene were synthesized and their mutagenicities in Salmonella typhimurium TA98, TA98NR, TA98/1,8-DNP₆, TA100, and TA100NR were determined. These compounds exhibited markedly different mutagenicities. Orientation of the nitro group is an important structural feature for correlation with mutagenic potency.     

1‐Arylsulfonyl‐5‐(N‐hydroxyacrylamide)indolines Histone Deacetylase Inhibitors Are Potent Cytokine Release Suppressors

A series of 1‐arylsulfonyl‐5‐(N‐hydroxyacrylamide)indolines ( 7 – 15 ) has been developed; the compounds exhibited potent histone deacetylase (HDAC) inhibitory activities. Notably, almost all of this series exhibited better HDAC‐inhibitory and antiproliferative activities than 3‐(1‐benzenesulfonyl‐1H‐indol‐5‐yl)‐N‐hydroxyacrylamide ( 6 ), as reported in a previous study. Among these compounds, 3‐[1‐(4‐methoxybenzenesulfonyl)‐2,3‐dihydro‐1H‐indol‐5‐yl]‐N‐hydroxyacrylamide ( 9 ) showed a two‐ to tenfold increase in activity compared to SAHA ( 1 ) in the suppression of lipopolysaccharide‐induced cytokine production. Compound 9 also caused a marked reduction in carrageenan‐induced acute inflammation in a rat model. Taken together, these data indicated that 1‐arylsulfonyl‐5‐(N‐hydroxyacrylamide)indolines HDAC inhibitors exhibit potent anti‐inflammatory activity.     

Determination of Uniformity of Filter Deposits

Certain measurement techniques (such as the asbestos method using phase contrast microscopy) require uniform deposits of the sample on a filter. The asbestos fiber analytical methods require such uniform deposition because the analysis only observes small, randomly chosen locations on the filter. In this study, a vibrating orifice monodisperse aerosol generator was used to generate methylene blue particles. The aerosols were dried by filtered compressed air and then neutralized by inducing a charge on the droplet stream that emerged from the vibrating orifice. An Aerodynamic Particle Sizer was used to measure the number concentration and size distribution of the generated aerosol particles. Meanwhile, the filter deposits were examined via image processing, combined with statistical methods for defining uniformity. In order to better define uniformity and make the indicator more universal, the uniformity was defined as the exponential of the negative CV (coefficient of variation) value which was a transformation for easily understanding the uniformity of the filter deposits. The experimental results demonstrated that, when aerosol counting was performed, the equal area approach was superior to the equivalent distance approach.     

Experimental Investigation of Exhaled Aerosol Transport Under Two Ventilation Systems

Although the importance and implications of studying expiratory droplet concentration distribution in indoor environments are obvious, experimental measurements are very scarce and incomplete. In the work described herein, spatial and temporal aerosol concentrations generated by a modeled expiratory process were studied experimentally. Two heated manikins were placed inside a chamber with either a displacement ventilation system or a ceiling supply and ceiling return ventilation system. One of the manikins emitted 0.05 micrometer monodisperse polystyrene microspheres mimicking the generation of expiratory droplets. Flow characteristics were measured by a hot-film anemometry system before and after the momentary emission of aerosols at three locations. The temporal concentration profiles at eight locations were also measured. The results show that a high-speed air jet easily penetrates the boundary layer of the manikin regardless of the ventilation system used. Transient ventilation effectiveness was also evaluated and compared for both ventilation systems. The results show that the ventilation effectiveness of displacement ventilation is always higher than that of ceiling-type ventilation. Experimental observation also suggests that the presumption of complete mixing must be applied cautiously.     

Highly Reliable High-Brightness GaN-Based Flip Chip LEDs

The properties of indium-tin-oxide (ITO)/Ni films as transparent ohmic contacts of nitride-based flip chip (FC) light emitting diodes (LEDs) were studied. It was found that 300degC rapid thermal annealed (RTA) ITO(15 nm)/Ni(1 nm) could provide good electrical and optical properties for FC LED applications. It was also found that 20-mA operation voltage and output power of the 465-nm FC LEDs with ITO/Ni/Ag reflective mirror were 3.16 V and 21 mW, respectively. Furthermore, it was found that output intensity of the proposed LED only decayed by 5% after 1200 h under 30-mA current injection at room temperature.     

Molecular Dynamics Simulation of the Crystallizable Fragment of IgG1—Insights for the Design of Fcabs

An interesting format in the development of therapeutic monoclonal antibodies uses the crystallizable fragment of IgG1 as starting scaffold. Engineering of its structural loops allows generation of an antigen binding site. However, this might impair the molecule’s conformational stability, which can be overcome by introducing stabilizing point mutations in the CH3 domains. These point mutations often affect the stability and unfolding behavior of both the CH2 and CH3 domains. In order to understand this cross-talk, molecular dynamics simulations of the domains of the Fc fragment of human IgG1 are reported. The structure of human IgG1-Fc obtained from X-ray crystallography is used as a starting point for simulations of the wild-type protein at two different pH values. The stabilizing effect of a single point mutation in the CH3 domain as well as the impact of the hinge region and the glycan tree structure connected to the CH2 domains is investigated. Regions of high local flexibility were identified as potential sites for engineering antigen binding sites. Obtained data are discussed with respect to the available X-ray structure of IgG1-Fc, directed evolution approaches that screen for stability and use of the scaffold IgG1-Fc in the design of antigen binding Fc proteins.     

Seizure activity and lesions of neuronal cells by intrahippocampal injection of guanidinosuccinic acid in rats]

Intrahippocampal injection(ihci) of guanidinosuccinic acid (GSA) to rats, induced typical generarized clonic seizures and epileptiform discharges in electrohippocampogram (EHG) and electrocorticogram (ECoG), degenerative changes of neuronal cells in the injected side hippocampus. The pyramidal cells in CA1 area were found to be more vulnerable to GSA than the granular cells. Phenobarbital and phenytoin are typical antiepiletics, but in no case did they successfully protect against GSA induced convulsions, epileptiform discharges in the EHG and ECoG and neurolysis. Ketamine, a selective noncompetitive NMDA receptor antagonist, was shown to protect against not only seizures, but also neuronal cell damage induced by GSA. All these results indicate that GSA very like the endogenous excitatory amino acid, glutamic acid, it also has such effects mentioned above. Therefore, the NMDA receptor may mediate both effects of GSA.     

烧结理论进展——2.烧结初期多种扩散机制耦合作用的烧结模型

在恒体积条件下给出了多种扩散机制耦合作用两球单元烧结模型的推导过程,编制了相应的计算软件,计算了铜在不同的粒度、温度、时间条件下的颈长方程和对心收缩方程。结果表明:在相同条件下,多机制综合作用颈长方程略高于表面扩散机制单独起作用的颈长方程;多机制综合作用的对心收缩小于只考虑晶界扩散和体积扩散的对心收缩。颈长方程的时间指数随时间的增加而变小。在不同烧结条件下各种机制对颈部物质的贡献存在很大差别。加热速率影响颗粒的对心收缩,在相同烧结时间内,加热速率越低,烧结收缩量越大。压密度越高,在烧结初期颗粒的颈长速率和收缩速率越低。