Crosslinked Structure of Polyacrylic Acid Affects Pulmonary Fibrogenicity in Rats

We conducted intratracheal instillations of polyacrylic acid (PAA) with crosslinking and non-crosslinking into rats in order to examine what kinds of physicochemical characteristics of acrylic-acid-based polymers affect responses in the lung. F344 rats were intratracheally exposed to similar molecular weights of crosslinked PAA (CL-PAA) (degree of crosslinking: ~0.1%) and non-crosslinked PAA (Non-CL-PAA) at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months post-exposure. Both PAAs caused increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 6 months following instillation. The release of lactate dehydrogenase (LDH) activity in the BALF was higher in the CL-PAA-exposed groups. Histopathological findings of the lungs demonstrated that the extensive fibrotic changes caused by CL-PAA were also greater than those in exposure to the Non-CL- PAA during the observation period. CL-PAA has more fibrogenicity of the lung, suggesting that crosslinking may be one of the physicochemical characteristic factors of PAA-induced lung disorder.     

FTY720 Reduces Lipid Accumulation by Upregulating ABCA1 through Liver X Receptor and Sphingosine Kinase 2 Signaling in Macrophages

Formation of foam cells as a result of excess lipid accumulation by macrophages is a pathological hallmark of atherosclerosis. Fingolimod (FTY720) is an immunosuppressive agent used in clinical settings for the treatment of multiple sclerosis and has been reported to inhibit atherosclerotic plaque development. However, little is known about the effect of FTY720 on lipid accumulation leading to foam cell formation. In this study, we investigated the effects of FTY720 on lipid accumulation in murine macrophages. FTY720 treatment reduced lipid droplet formation and increased the expression of ATP-binding cassette transporter A1 (ABCA1) in J774 mouse macrophages. FTY720 also enhanced the expression of liver X receptor (LXR) target genes such as FASN, APOE, and ABCG1. In addition, FTY720-induced upregulation of ABCA1 was abolished by knockdown of sphingosine kinase 2 (SphK2) expression. Furthermore, we found that FTY720 treatment induced histone H3 lysine 9 (H3K9) acetylation, which was lost in SphK2-knockdown cells. Taken together, FTY720 induces ABCA1 expression through SphK2-mediated acetylation of H3K9 and suppresses lipid accumulation in macrophages, which provides novel insights into the mechanisms of action of FTY720 on atherosclerosis.     

Continuous measurements of bronchial exposure induced by radon decay products during inhalation

The deposition of radon decay products is not equal in each of the respiratory regions and as the presence of radon has been linked with an increase in lung cancer risk, it is important to calculate the deposition of radon decay products in each of the respiratory regions. Recently, many studies on the deposition of radon in respiratory regions have been simulated using wire screens. The systems and equipment used in those studies are not suitable for field measurements as their dimensions are relatively massive, nor can they measure continuously. We developed a continuous bronchial dosimeter (CBD) which is suitable for field measurements. It was designed with specifications that allow it to be remain compact. The CBD simulates the deposition of radon decay products in the different respiratory regions by the use of a combination of wire screens. Deposition in the simulated regions of the lung can be continuously estimated in various environments. The ratio of activities deposited in a simulated nasal cavity (N) and tracheobronchial (TB) regions was calculated from the results of simultaneous measurements using CBD-R (reference), CBD-N (nasal), and CBD-TB (tracheobronchial) measurement units. After aerosols were injected into the radon chamber, the ratio of N and TB depositions decreased. This results indicate that the CBD gave a good response to changes in the environment. It was found that the ratio of N and TB deposition also varied with time in each actual environment.     

Classification of fermentation performance by multivariate analysis based on mean hypothesis testing

Multivariate analysis, such as principal component analysis and artificial autoassociative neural networks, is currently extensively applied to feature capturing, physiological state recognition, fault detection and bioprocess control. However, it is not clear which process variable should be selected as an important input for multivariate analysis to analyze physiological conditions and/or bioprocess performance a priori. An efficacious method to select more informative process variables from the repository of historical data is highly desired. In this study, we focused on a premodeling step. Mean hypothesis testing (MHT) was used to select appropriate variables for multivariate analysis. Fermentation data sets were classified into two classes "good" and "bad" according to the MHT results. The results showed that selecting discriminating process variables from the historical database by MHT enhanced the overall effectiveness of multivariate analysis prior to principal component analysis and artificial autoassociative neural network model creation.     

Point mutation of alanine (31) to valine prohibits the folding of reduced lysozyme by sulfhydryl--disulfide interchange

In the preceding paper in this issue, we described the overproduction of one mutant chicken lysozyme in Escherichia coil.Since this lysozyme contained two amino acid substitutions (Ala³¹ValandAsn¹⁰⁶Ser)in addition to an extra methionine residue at theNH₂-terminus the substituted amino acid residues were convertedback to the original ones by means of oligonucleotide-directedsite-specific mutagenesis and in vitro recombination. Thus fourkinds of chicken lysozyme [Met^–1 Val³¹Ser¹⁰⁶-, Met^–1Ser¹⁰⁶-,Met^–1 Val³¹-and Met^–1 (wild type)] wereexpressed in E. coli. From the results of folding experimentsof the reduced lysozymes by sulfhydryl-disulfide interchangeat pH 8.0 and 38°C, follow ed by the specific activity measurementsof the folded en zymes, the following conclusions can be drawn:(i) an extra methionine residue at the NH₂-terminus reducesthe folding rate but does not affect the lysozyme activity ofthe folded enzyme; (ii) the substitution of Asn¹⁰⁶ by Ser decreasesthe activity to 58% of that of intact native lysozyme withoutchanging the folding rate; and (iii) the substitution of Ala³¹Val prohibits the correct folding of lysozyme. Since the wildtype enzyme (Met^–1-lysozyme) was activated in vitro withoutloss of specific activity, the systems described in this study(mutagenesis, overproduction, purification and folding of inactivemutant lysozymes) may be useful in the study of folding pathways,expression of biological activity and stability of lysozyme.     

A TEA‐CO2 laser oscillation by an inductive energy storage pulsed‐power generator using a wire‐fuse opening switch

We have carried out experiments on TEA‐CO₂ laser oscillation using the inductive energy storage pulsed‐power generator, which has a copper wire fuse as an opening switch. Maximum laser output energy of about 1 J/pulse was obtained in the case of a fuse length of 5 cm and energy storage inductance of 8 μH. The laser output energy depends on the energy storage inductance and the parameters of the fuse. In this paper, the dependencies of laser output energy on inductance and fuse length, and a comparison between the inductive and capacitive system were described. Furthermore the laser efficiency was discussed by calculating the electron energy distribution of laser main discharge region. © 2000 Scripta Technica, Electr Eng Jpn, 132(1): 15–21, 2000     

Optimal placement of SVRs considering multiple loads

This paper presents a new approach to the optimal placement of a step voltage regulator (SVR) taking into consideration the installation of distributed generators (DG) based on a genetic algorithm (GA). In this case, it is necessary to solve problems such as the upper and lower limits for the voltage at each node and line capacity. In addition, given that the load and output of a distributed generator change, it is important to solve more than one of these problems. In order to solve these problems, the conventional genetic algorithm was improved and the proposed method was applied to the complex operating conditions of a distribution power system. © 2012 Wiley Periodicals, Inc. Electr Eng Jpn, 182(1): 39–47, 2013; Published online in Wiley Online Library ( wileyonlinelibrary.com ). DOI 10.1002/eej.21297