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Background Carbon fibers are high aspect ratio structures with diameters on the submicron scale. Vapor grown carbon fibers are contained within multi-walled carbon tubes, with VGCF™-H commonly applied as a conductive additive in lithium-ion batteries. However, several multi-walled carbon fibers, including MWNT-7, have been reported to induce lung carcinogenicity in rats. This study investigated the carcinogenic potential of VGCF™-H fibers in F344 rats of both sexes with the vapor grown carbon fibers VGCF™-H and MWNT-7 over 2 years. The carbon fibers were administered to rats by intratracheal instillation at doses of 0, 0.016, 0.08, and 0.4 mg/kg (total doses of 0, 0.128, 0.64, and 3.2 mg/kg) once per week for eight weeks and the rats were observed for up to 2 years after the first instillation. Results Histopathological examination showed the induction of malignant mesothelioma on the pleural cavity with dose-dependent increases observed at 0, 0.128, 0.64, and 3.2 mg/kg in rats of both sexes that were exposed to MWNT-7. On the other hand, only two cases of pleural malignant mesothelioma were observed in the VGCF™-H groups; both in male rats that received 3.2 mg/kg. The animals in the MWNT-7 groups either died or became moribund earlier than those in the VGCF™-H groups, which is thought related to the development of malignant mesothelioma. The survival rates were higher in the VGCF™-H group, and more carbon fibers were observed in the pleural lavage fluid (PLF) of the MWNT-7 groups. These results suggest that malignant mesothelioma is related to the transfer of carbon fibers into the pleural cavity. Conclusions The intratracheal instillation of MWNT-7 clearly led to carcinogenicity in both male and female rats at all doses. The equivocal evidence for carcinogenic potential that was observed in male rats exposed to VGCF™-H was not seen in the females. The differences in the carcinogenicities of the two types of carbon fibers are thought due to differences in the number of carbon fibers reaching the pleural cavity. The results indicate that the carcinogenic activity of VGCF™-H is lower than that of MWNT-7.

Multi walled carbon nanotubes (MWCNTs) are one of the most intensively explored nanomaterials because of their unique physical and chemical properties. Due to the widespread use of MWCNTs, it is important to investigate their effects on human health. The precise mechanism of MWCNT toxicity has not been fully elucidated. The present study was designed to examine the mechanisms of MWCNT toxicity toward human promyelocytic leukemia HL-60 cells. First, we found that MWCNTs decreased the viability of neutrophil-like differentiated HL-60 cells but not undifferentiated HL-60 cells. Because neutrophil-like differentiated HL-60 cells exhibit enhanced phagocytic activity, the cytotoxicity of MWCNTs is dependent on the intracellularly localized MWCNTs. Next, we revealed that the cytotoxicity of MWCNTs is correlated with the intracellular accumulation of iron that is released from the engulfed MWCNTs in an acidic lysosomal environment. The intracellular accumulation of iron was repressed by treatment with cytochalasin D, a phagocytosis inhibitor. In addition, our results indicated that iron overload enhanced the release of interleukin-8 (IL-8), a chemokine that activates neutrophils, and subsequently elevated intracellular calcium concentration ([Ca2+]i). Finally, we found that the sustained [Ca2+]i elevation resulted in the loss of mitochondrial membrane potential and the increase of caspase-3 activity, thereby inducing apoptotic cell death. These findings suggest that the iron overload caused by engulfed MWCNTs results in the increase of IL-8 production and the elevation of [Ca2+]i, thereby activating the mitochondria-mediated apoptotic pathway.

Carbon fibers have excellent physicochemical and electrical properties. Vapor-grown carbon fibers are a type of carbon fibers that have a multi-walled carbon tube structure with a high aspect ratio. The representative vapor-grown carbon fiber, VGCFTM-H, is extremely strong and stable and has superior thermal and electrical conductivity. Because some high-aspect-ratio multi-walled carbon nanotubes (MWCNTs) have been reported to have toxic and carcinogenic effects in the lungs of rodents, we performed a 13-week lung toxicity study using VGCFTM-H in comparison with one of MWCNTs, MWNT-7, in rats. Male and female F344 rats were intratracheally administered VGCFTM-H at doses of 0.2, 0.4, and 0.8 mg/kg bw or MWNT-7 at doses of 0.4 and 0.8 mg/kg bw once a week for 8 weeks and then up to week 13 without treatment. The lung burden was equivalent in the VGCFTM-H and MWNT-7 groups; however, the lung weight had increased and the inflammatory and biochemical parameters in the broncho-alveolar lavage fluid and histopathological parameters, including inflammatory cell infiltration, alveolar type II cells proliferation, alveolar fibrosis, pleural fibrosis, lung mesothelium proliferation, and diaphragm fibrosis, were milder in the VGCFTM-H group than in the MWNT-7 group. In addition, the proliferating cell nuclear antigen (PCNA)-positive index in the visceral and pleural mesothelium was significantly higher in the MWNT-7 group than in the controls, but not in the VGCFTM-H group. Thus, the results of this study indicate that the lung and pleural toxicities of VGCFTM-H were less than those of MWNT-7.

Effects of two kinds of multiwall carbon nanotubes (MWCNTs) on cells were examined. The effects of MWNT-7, which has been reported to be carcinogenic, and MWCNT-B, whose toxicity is unclear, were examined in both epithelial cells and macrophages. Human lung carcinoma A549 cells were used as representative epithelial cells and differentiated human monocyte THP-1 cells, as well as rat pulmonary macrophages NR8383, were employed to examine possible harmful effects of the MWCNTs. The MWCNTs induced the production of chemokines such as interleukin-8 (IL-8). MWCNTs were found to more strongly affect macrophages than epithelial cells. In addition, the toxicity was more pronounced in the MWNT-7 exposed cells than in those exposed to MWCNT-B. Cytochalasin D and amiloride treatment of differentiated THP-1 cells reduced cell-associated MWCNTs and IL-8 induction. To confirm these cellular influences in vivo, intratracheal administration of each type of MWCNT was performed by pharyngeal aspiration in the mouse lung. Analysis of bronchoalveolar lavage fluid (BALF) showed increase of inflammatory monocyte in MWNT-7 exposed animals at 1week after. In addition, neutrophils in the BALF were also significantly increased MWNT-7 exposed animals at 1 week and 1 month after. Aspiration of MWNT-7 caused formation of granulomas in the lung. Formation of the granulomas was not observed in the case of MWCNT-B. These results suggest that cellular uptake of the MWCNTs by phagocytosis and chemokine induction is important aspects of their toxicity.

This paper reports the microscopic fracture behavior of natural fiber-reinforced green composites. The acoustic emission (AE) method of nondestructive and real-time testing was applied to detect small-scale energy release phenomena during tensile deformation of the green composites. The unidirectional abaca fiber was embedded in a starch-based biodegradable resin matrix. Two kinds of pre-damaged abaca fibers as well as as-received (i.e. undamaged) fiber were used to examine the effect of the pre-damaged abaca fiber on the overall fracture behavior of the unidirectional green composites. In the case of the green composites reinforced with as-received abaca fiber, both of the tensile strength and fracture strain were relatively high. In the case of the green composites reinforced with pre-damaged abaca fiber, however, showed relatively smaller tensile strength and fracture strain. In addition, a wide range of amplitude AE events were measured during the tensile deformation. This tendency was enhanced in the composites reinforced with heavily damaged abaca fiber. The experimental results showed that the AE activity in the early deformation stage was associated with such the microscopic fracture of pre-damaged abaca fibers.

A practical method for electrochemical iodination of aromatic compounds was developed. The method involves the generation of I+ by electrochemical oxidation of I2 in CH3CN using H2SO4 as supporting electrolyte followed by the reaction with aromatic compounds. The para/ortho selectivity for the reaction of monosubstituted benzenes was significantly improved using dimethoxyethane as cosolvent in the second step. The reaction with highly reactive aromatic compounds led to the formation of significant amounts of diiodo compounds in a macrobatch reactor. This problem was solved by fast 1:1 mixing of I+ with an aromatic compound using a microflow system consisting of a T-shaped micromixer and a microtube reactor.

Regio-, diastereo-, and enantioselective intermolecular [4 + 2] carbocyclizations of vinylarylaldehydes with alkenes and alkynes leading to substituted tetralones and 1-naphthols have been developed by using a cationic rhodium(I)/dppb or dppp complex as a catalyst.

We established that a cationic rhodium(I)/dppf or dppb complex catalyzes a regio- and diastereoselective intermolecular [4+2] carbocyclization of 5-trimethylsilyl-4-pentynals with electron-deficient alkenes leading to cyclohexanones. We also established that a cationic rhodium(I)/(R,R)-Walphos complex catalyzes a regio- and enantioselective intermolecular [4+2] carbocyclization of 5-substituted 4-pentynals and 2-alkynylbenzaldehydes with N,N-dialkylacrylamides leading to enantio-enriched cyclohexanones and tetralones, respectively. A single olefin isomer was produced in every carbocyclization. Regioselectivities of the alkene insertion depend on the alkenes used. Mechanistic study suggested that a key intermediate in this intermolecular [4+2] carbocyclization is a five-membered acylrhodium intermediate, formed by cis addition of the rhodium hydride to the metal-bound alkyne. This method serves as an attractive new route to highly functionalized cyclohexanones in view of the one-step access to 5-substituted 4-pentynals and 2-alkynylbenzaldehydes starting from readily available terminal alkynes.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

This research was carried out as part of the research in order to construct design support system for the industrial product. The research purpose are consideration on inference model applied to the design support system and construction of design support system for the printing machine. In the first half of the research, the study on the inference model for applying to design support system was carried out. The following were taken up as inference models: multivariate regression model, fuzzy inference model and neural network. To begin with, experimental systems using these models were constructed. Then, the simulation, which acquired the design plan was carried out using the simple form. This result was examined from the viewpoint of the relation between design plan and inference model. As a result of the consideration, the fuzzy inference model was chosen for design support system constructed here as an appropriate inference model. In the latter half of the research, the design support system using fuzzy inference was constructed. As a case of supported product, the printing machine was chosen. The reason is because the design of this machine is researched as a development of the fundamental shape. In addition, it is because the application of the system constructed here can be expected in such product. Using the constructed system, simulation was performed in order to acquire the design plan. As the result, it was shown that the design plan in proportion to a demand could be acquired.

Recently, in the field of the accommodation design of passenger ship, it is increasingly been demanded alternativesh ave to be examined in three dimensions even in initial stage of the development. As a helping tool for such demands system which output three-dimensional prototype from designer's sketches has been constructed here. In this paper that system is presented through the description of its usage in a specific case. It has been found that the system completes it's task appropriately after simple appraisal is carried out for the figure which the system outputs. Considering the non-linearity concerning design and the vague knowledge, fuzzy inference was applied to calculate the value of the parameters which was used to define the figure.

The synthesis of a two-stage photobase generator (PBG) based on photoinduced aromatization is described. This material was designed for use in resolution-enhanced photolithography. Computer modeling predicts that a delay in the onset of base generation can lead to improved image quality. This delay can be realized by a PBG that must undergo two sequential photoreactions for each molecule of base generated. Toward that end, latent PBGs were designed that are oxime esters of aliphatic acids, which undergo Norrish type II reactions to yield oxime esters of aromatic acids that are efficient PBGs.

The investigation of the photochemistry of a two-stage photobase generator (PBG) is described. Absorption of a photon by a latent PBG (1) (first step) produces a PBG (2). Irradiation of 2 in the presence of water produces a base (second step). This two-photon sequence (1 + hν → 2 + hν → base) is an important component in the design of photoresists for pitch division technology, a method that doubles the resolution of projection photolithography for the production of microelectronic chips. In the present system, the excitation of 1 results in a Norrish type II intramolecular hydrogen abstraction to generate a 1,4-biradiacal that undergoes cleavage to form 2 and acetophenone (Φ ∼ 0.04). In the second step, excitation of 2 causes cleavage of the oxime ester (Φ = 0.56) followed by base generation after reaction with water.

Pitch division lithography (PDL) with a photobase generator (PBG) allows printing of grating images with twice the pitch of a mask. The proof-of-concept has been published in the previous paper and demonstrated by others. Forty five nm half-pitch (HP) patterns were produced using a 90nm HP mask, but the image had line edge roughness (LER) that does not meet requirements. Efforts have been made to understand and improve the LER in this process. Challenges were summarized toward low LER and good performing pitch division. Simulations and analysis showed the necessity for an optical image that is uniform in the z direction in order for pitch division to be successful. Two-stage PBGs were designed for enhancement of resist chemical contrast. New pitch division resists with polymer-bound PAGs and PBGs, and various PBGs were tested. This paper focuses on analysis of the LER problems and efforts to improve patterning performance in pitch division lithography.

The semiconductor industry is pursuing several process options that provide pathways to printing images smaller than the theoretical resolution limit of 193 nm projection scanners. These processes include double patterning, side wall deposition and pitch division. Pitch doubling lithography (PDL), the achievement of pitch division by addition of a photobase generator (PBG) to typical 193 nm resist formulations was recently presented.1 Controlling the net acid concentration as a function of dose by incorporating both a photoacid generator (PAG) and a PBG in the resist formulation imparts a resist dissolution rate response modulation at twice the frequency of the aerial image. Simulation and patterning of 45 nm half pitch L/S patterns produced using a 90 nm half pitch mask were reported.2 Pitch division was achieved, but the line edge roughness of the resulting images did not meet the current standard. To reduce line edge roughness, polymer bound PBGs and polymer bound PAGs were investigated in the PDL resist formulations. The synthesis, purification, analysis, and functional performance of various polymers containing PBG or PAG monomers are described herein. Both polymer bound PBG with monomeric PAG and polymer bound PAG with monomeric PBG showed a PDL response. The performance of the polymer bound formulations is compared to the same formulations with small molecule analogs of PAG and PBG.

Acetyltransferase and nitroreductase are enzymes involved in the intracellular metabolic activation of nitroarenes and/or aromatic amines in Salmonella typhimurium. The plasmid carrying both the acetyltransferase and nitroreductase genes was introduced into S. typhimurium TA98 and TA100. The resulting strains, YG1041 and YG1042, respectively, showed high levels of both enzyme activities and were more sensitive to the mutagenic action of some nitro-aromatic compounds such as 2-nitrofluorene, 1-nitropyrene and p-nitrophenetole than did the sensitive strains previously established in this laboratory or the conventional strains. These results indicate that the new strains permit the very efficient detection of the mutagenicity of nitroarenes in the environment.

The Non-genotoxic Carcinogen Study Group in the Environmental Mutagen Society of Japan organised the second step of the inter-laboratory collaborative study on one-stage and two-stage cell transformation assays employing BALB/c 3T3 cells, with the objective of confirming whether the respective laboratories could independently produce results relevant to initiation or promotion. The method was modified to use a medium consisting of DMEM/F12 supplemented with 2% fetal bovine serum and a mixture of insulin, transferrin, ethanolamine and sodium selenite, at the stationary phase of cell growth. Seventeen laboratories collaborated in this study, and each chemical was tested by three to five laboratories. Comparison between the one-stage and two-stage assays revealed that the latter method would be beneficial in the screening of chemicals. In the test for initiating activity with the two-stage assay (post-treated with 0.1μg/ml 12- O-tetradecanoylphorbol-13-acetate), the relevant test laboratories all obtained positive results for benzo[ a]pyrene and methylmethane sulphonate, and negative results for phenanthrene. Of those laboratories assigned phenacetin for the initiation phase, two returned positive results and two returned negative results, where the latter laboratories tested up to one dose lower than the maximum dose used by the former laboratories. In the exploration of promoting activity with the two-stage assay (pretreated with 0.2μg/ml 3-methylcholanthrene), the relevant test laboratories obtained positive results for mezerein, sodium orthovanadate and TGF-β1, and negative results for anthralin, phenacetin and phorbol. Two results returned for phorbol 12,13-didecanoate were positive, but one result was negative — again, the maximum dose to achieve the latter result was lower than that which produced the former results. These results suggest that this modified assay method is relevant, reproducible and transferable, provided that dosing issues, such as the determination of the maximum dose, are adequately considered. The application of this two-stage assay for screening the initiating and promoting potential of chemicals is recommended for consideration by other research groups and regulatory authorities.

[structure: see text]. A cationic rhodium(I)/dppb complex catalyzed direct intermolecular hydroacylation of N,N-dialkylacrylamides with both aliphatic and aromatic aldehydes has been achieved through the stabilization of acylrhodium intermediates by alkene chelation to rhodium. This method represents a versatile new route to gamma-ketoamides in view of the high atom economy and commercial availability of substrates.

Reverse-tone step and flash imprint lithography (S-FIL/R) requires materials that can be spin-coated onto patterned substrates with significant topography and that are highly planarizing. Ideally, these planarizing materials must contain silicon for etch selectivity, be UV or thermally curable, and have low viscosity and low volatility. One such unique material, in particular, a branched and functionalized siloxane (Si-12), is able to adequately satisfy the above requirements. This paper describes a study of the properties of epoxy functionalized Si-12 (epoxy-Si-12) as a planarizing layer. An efficient synthetic route to epoxy-Si-12 was successfully developed, which is suitable and scalable for an industrial process. Epoxy-Si-12 has a high silicon content (30.0%), low viscosity (29 cP at 25°C), and low vapor pressure (0.65 Torr at 25°C). A planarizing study was carried out using epoxy-Si-12 on trench patterned test substrates. The material showed excellent planarizing properties and met the calculated critical degree of planarization (critical DOP), which is a requirement for a successful etch process. An S-FIL/R process using epoxy-Si-12 was demonstrated using an Imprio® 100 (Molecular Imprints Inc., Austin, Texas) imprint tool. The results indicate that epoxy-Si-12 works very well as a planarizing layer for S-FIL/R.

Consumption of certain product lots of L-tryptophan (LT) has been reported to be epidemiologically associated with an outbreak of eosinophilia-myalgia syndrome (EMS) in the United States. Since the production lots were found to contain 3-phenylamino alanine (PAA) as an impurity, its effects were studied by administering the substance orally by gavage to 5-week-old Sprague-Dawley rats. Groups of animals were given PAA for 13 consecutive weeks at dose levels of 1, 10 and 100 mg/kg per day. The animals were killed at 4 or 8 weeks. Hematological and blood biochemical tests were performed and detailed histopathological observations were made. No significant abnormalities were observed in the test animals and in particular no EMS-like conditions. A brief summary of other animal studies using several species of rats and mice performed in our laboratory since 1989 on various LT related substances is also presented. No EMS-like effects were observed in these studies.

not Available.

A robot design contest, called the “Embedded Technology (ET) Software Design Robot Contest,” which involves designing software to automatically control a line-trace robot, was held in Tokyo, in 2005. The contest was intended to provide a practical opportunity to educate young Japanese developers in the field of embedded software development. In this paper, we give the results of the contest from the viewpoint of software quality evaluation. We created a framework for evaluating software quality, which integrated the design model quality and the final system performance, and we conducted an analysis using this framework. As a result of the analysis, the quantitative measurement of the structural complexity of the design model was found to have a strong relationship to the qualitative evaluation of the design by the contest judges. On the other hand, no strong correlation between the design model quality evaluated by the judges and the final system performance was found. For embedded software development, it is particularly important to estimate and verify reliability and performance in the early stages, according to the design and analysis models. Based on the results, we consider possible remedies with respect to the models submitted, the evaluation methods used, and the contest specifications. To adequately measure several quality characteristics, including performance, in terms of a model, it is necessary to improve the approach to developing robot software (for example, by applying model-driven development) and to reexamine the