Synthesis of alkyl or aryl pyridazinyl ethers

This paper presents the synthesis of some alkyl or aryl pyridazinyl ethers from 2‐alkyl‐4‐halo‐5‐hydroxy‐and 2‐alkyl‐4,5‐dichloropyridazin‐3(2H)‐ones or 3,6‐dichloropyridazine. Reaction of 2‐alkyl‐4‐halo‐5‐hydroxypyridazin‐3(2H)‐ones 1 with 1,2‐dibromoethane or 1,3‐dibromopropane gave the corresponding monopyridazin‐5‐yl ethers 2 and α,ω‐[di(pyridazin‐5‐oxy)]alkanes 3 . Treatment of 4 with 4‐substituted‐phenol afforded 5‐(4‐substituted‐phenoxy)‐2‐(4‐substituted‐phenoxymethyl) derivatives 5 . Reaction of 2‐alkyl‐4,5‐dichloro derivatives 7 with 1 gave the corresponding di(pyridazin‐5‐yl) ethers 8 in good yields. Compound 10 was reacted with catechol to give monopyridazin‐3‐yl ether 11 and/or di(pyridazin‐3‐yl) ether 12 . Also we described the results for the reaction of 2‐alkyl‐4‐chloro‐5‐(4‐substituted‐phenoxy)pyridazin‐3(2H)‐ones with nucleophiles.     

Dehalogenation of 1-methyl-5-halo-4-substituted-pyridazin-6-ones

In order to confirm the regiochemistry for the functionalization of 1-(1,1-dibromo-2-oxopropyl)-4,5-dihalopyridazin-6-ones, the dehalogenation of 1-methyl-5-halo-4-substituted-pyridazin-6-ones using Pd/C and hydrogen was carried out. The results of the title reaction are reported.     

Genome-wide scan of granular corneal dystrophy, type II: confirmation of chromosome 5q31 and identification of new co-segregated loci on chromosome 3q26.3

Granular corneal dystrophy, type II (CGD2; Avellino corneal dystrophy) is the most common corneal dystrophy among Koreans, but its pathophysiology is still poorly understood. Many reports showed that even though the causative mutation is the same TGFBI R124H mutation, there are severe and mild phenotypes of the corneal dystrophy. We also observed the phenotype differences in our samples. For this reason, we focused our effort on the identification of unknown genetic factor related to phenotype variation. A total 551 individuals from 59 families were genotyped with SNP chip and used in genome-wide linkage analysis. From single-point linkage analyses, we confirmed the known 5q31 region for TGFBI gene, and selected novel nine candidate loci for CGD2. In simulation analysis, the only 3q26.3 region including neuroligin 1 gene (NLGN1) was supported by empirical statistic significance. To investigate the effect of genetic heterogeneity in linkage analysis, we classified CGD2 families into two subgroups. Although we could not find a significant evidence for correlation between the 3q26.3 region and CGD2 phenotypes, this first genome-wide analysis with CGD2 families in Korea has a very important value for offering insights in genetics of CGD2. In addition, the co-segregating loci with CGD2 including 3q26.3 would be a good target for further study to understand the pathophysiology of CGD2.     

Numerical and theoretical study on the mechanism of biopolymer translocation process through a nano-pore

We conducted a numerical study on the translocation of a biopolymer from the cis side to the trans side of a membrane through a synthetic nano-pore driven by an external electric field in the presence of hydrodynamic interactions (HIs). The motion of the polymer is simulated by 3D Langevin dynamics technique using a worm-like chain model of N identical beads, while HI between the polymer and fluid are incorporated by the lattice Boltzmann equation. The translocation process is induced by electrophoretic force, which sequentially straightens out the folds of the initial random configuration of the polymer chain on the cis side. Our simulation results on translocation time and velocity are in good quantitative agreement with the corresponding experimental ones when the surface charge on the nano-pore and the HI effect are considered explicitly. We found that the translocation velocity of each bead inside the nano-pore mainly depends upon the length of the straightened portion of the polymer in forced motion near the pore. We confirmed this by a theoretical formula. After performing simulations with different pore lengths, we observed that translocation velocity mainly depends upon the applied potential difference rather than upon the electric field inside the nano-pore.     

A Comparison of the Prospective Acquisition Correction Technique with Respiratory Triggering Technique in a 3-D MR Pancreaticobiliary System Angiography: A Focus on Normal Healthy Subjects

This study aimed at comparing the quality of images produced using the prospective acquisition correction (PACE) technique based on a navigator with that produced by the respiratory triggering (RT) technique based on a wireless respiratory triggering cushion. Twenty normal healthy people underwent magnetic resonance (MR) cholangiopancreatography based on a three-dimensional (3-D) respiratory triggering technique using either the PACE or RT techniques. For quantitative analysis, the signal-to-noise and contrast-to-noise ratios were calculated. For qualitative analysis, the morphology of the anatomical structures, artifacts due to respiration and the definition of cholangiopancreatography were evaluated based on the following five-point scale. The excellence of the images was also evaluated independently by two specialists in abdominal imaging and two radiological technicians, whose results were analyzed statistically using a Wilcoxon signed-rank test. With regard to the morphology of the anatomical structures and sharpness of the pancreaticobiliary tract, the PACE technique had higher scores than the RT one (P?=?0.07). However, there were no significant differences in artifacts due to respiration between the two techniques (P?=?0.774). The signal-to-noise and contrast-to-noise ratios were significantly higher in the PACE technique (P?<?0.05), with the exception of the common hepatic duct (P?=?0.085). A comparison was made between the PACE and RT techniques in respiratory triggering 3-D MR cholangiopancreatography, which showed that the PACE technique produces a higher image quality.     

Effect of burn-up on the radioactivation behavior of cladding hull materials studied using the ORIGEN-S code

The effect of fuel burn-up on the radioactivation behavior of cladding hull materials was investigated using the ORIGEN-S code for various materials of Zircaloy-4, Zirlo, HANA-4, and HANA-6 and for various fuel burn-ups of 30, 45, 60, and 75 GWD/MTU. The Zircaloy-4 material is the only one that does not contain Nb as an alloy constituent, and it was revealed that ¹²⁵Sb, ^125mTe, and ⁵⁵Fe are the major sources of radioactivity. On the other hand, ^93mNb was identified as the most radioactive nuclide for the other materials although minor radioactive nuclides varied owing to their different initial constituents. The radioactivity of ⁹⁴Nb was of particular focus owing to its acceptance limit against a Korean intermediate-/low-level waste repository. The radioactivation calculation results revealed that only Zircaloy-4 is acceptable for the Korean repository, while the other materials required at least 4,900 of Nb decontamination factor owing to the high radioactivity of ⁹⁴Nb regardless of the fuel burn-up. A discussion was also made on the feasibility of Zr recovery methods (chlorination and electrorefining) for selective recovery of Zr so that it can be disposed of in the Korean repository.     

Flip Angle for the Optimal <Emphasis Type="Italic">T</Emphasis><Subscript>1</Subscript>-weighted Image in the 3-D Volumetric Interpolated Breath-hold Examination Abdominal Magnetic Resonance Imaging Technique

The purpose of this study was to determine an optimal flip angle for T ₁-weighted images on abdominal examination by comparing the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) depending on the change in flip angle based on the volumetric interpolated breath-hold examination (VIBE) technique. The subjects in this study included 50 patients (20 men and 10 women; average age, 60 years) who visited the hospital between October 2009 and March 2010 to receive an abdominal magnetic resonance imaging (MRI) examination. Among the 50 patients, there were 27 patients with hypervascular hepatocellular carcinomas (HCCs) and 23 patients with hemorrhagic HCCs. A 3 T MR scanner (Magnetom Tim Trio; Siemens, Germany) with a 12-channel body coil was used. For the pulse sequence, the VIBE (time of repetition TR, 3.18 ms; time of echo TE, 1.16 ms; matrix, 384 × 307; slice thickness, 3 mm; field of view FOV, 380 mm; bandwidth BW, 720 Hz) and breath-hold examination with an examination time of 19 s were used. Images of the axial and coronal planes at three flip angles (10°, 25°, and 35°) were obtained. Based on the images obtained, the signal intensities of the liver, lesions, and background noise were measured and the SNR and CNR were calculated. For evaluation of the optimal flip angle, SPSS for Windows (version 17.0) was used to conduct the non-parametric Kruskal–Wallis test. The SNRs for hypervascular and hemorrhagic HCCs, depending on changes in flip angle of the VIBE, were 11.12 ± 0.98, 10.83 ± 1.44, and 9.61 ± 1.66, and 76.00 ± 6.43, 43.32 ± 5.89, and 30.45 ± 4.27 at angles of 10°, 25°, and 35°, respectively. The CNRs were 14.83 ± 0.12, 7.38 ± 0.41, and 5.70 ± 0.66, and 3.95 ± 0.21, 2.42 ± 0.58, and 1.69 ± 0.93, respectively (p < 0.05). At a flip angle of 10°, the SNR and CNR were the highest. When the flip angles were 25° and 35°, the contrast of the image, as well as the SNR, were shown to have a downward trend (p < 0.05). A flip angle of 10° is considered to be useful for the optimal T ₁-weighted image to detect HCC in the three-dimensional VIBE abdominal MRI technique.     

Nanoparticulate-induced toxicity and related mechanism in vitro and in vivo

In urban areas, the quantity of exhaust particles from vehicle emissions is tremendous and has been regarded as the main contributor to particulate matter (PM) pollution. Recently, the nano-sized PM on public health has begun to raise the attention. The increased toxicity of nanoparticulate can be largely explained by their small size, high airborne concentration, extensive surface area and high content of organic carbon and transition metals. We have attempted to address the toxicity of nano sized-particlulate matter by comparing various particulates including micro-SiO₂ (mSiO₂), nano-SiO₂ (nSiO₂), micro-TiO₂ (mTiO₂), and nano-TiO₂ (nTiO₂) in RAW264.7 cells and in vivo. The cell viability of all particulates decreased dose dependently. 24-h incubation with nSiO2 demonstrated apoptosis in RAW264.7 using Annexin-V binding immunofluorescent microscopy, but not in any other particulates. In vivo, cytotoxicity of nanosized was higher than micro-sized particulates. As higher the concentration of particulates, the more pulmonary injury and neutrophilic infiltration were observed in nano-sized than micro-sized particulates, respectively. Particularly, 5.0 mg/kg of mTiO₂ never shows any increase of neutrophile even with high cellularity of total cells and macrophages. From these results, we suggested that particulate-induced respiratory toxicity be influenced by component, size, and dose of particulates including the characteristic nature of the target cells in vitro and in vivo.