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Graphical abstract, Highlights • “Multiblock metabolomics” elucidates the global metabolic network in a whole body. • “Multiblock metabolomics” combines LC/MS-based metabolomics with multiblock PCA. • “Multiblock metabolomics” highlights and elicits organ-specific metabolism. • TGs with less unsaturated fatty acids were highly accumulated in the diabetic liver., Principal component analysis (PCA) is a useful tool for omics analysis to identify underlying factors and visualize relationships between biomarkers. However, this approach is limited in addressing life complexity and further improvement is required. This study aimed to develop a new approach that combines mass spectrometry-based metabolomics with multiblock PCA to elucidate the whole-body global metabolic network, thereby generating comparable metabolite maps to clarify the metabolic relationships among several organs. To evaluate the newly developed method, Zucker diabetic fatty (ZDF) rats (n = 6) were used as type 2 diabetic models and Sprague Dawley (SD) rats (n = 6) as controls. Metabolites in the heart, kidney, and liver were analyzed by capillary electrophoresis and liquid chromatography mass spectrometry, respectively, and the detected metabolites were analyzed by multiblock PCA. More than 300 metabolites were detected in the heart, kidney, and liver. When the metabolites obtained from the three organs were analyzed with multiblock PCA, the score and loading maps obtained were highly synchronized and their metabolism patterns were visually comparable. A significant finding in this study was the different expression patterns in lipid metabolism among the three organs; notably triacylglycerols with polyunsaturated fatty acids or less unsaturated fatty acids showed specific accumulation patterns depending on the organs.

Aims Coronary arteritis is a life-threatening complication that may arise in the acute stage of Kawasaki disease (KD), the leading cause of systemic vasculitis in childhood. Various microorganisms and molecular pathogens have been reported to cause KD. However, little is known about the key molecules that contribute to the development of coronary arteritis in KD. Methods and results To identify causative molecules for coronary arteritis in KD, we prospectively recruited 105 patients with KD and 65 disease controls in four different parts of Japan from 2015 to 2018. During this period, we conducted lipidomics analyses of their sera using liquid chromatography–mass spectrometry (LC-MS). The comprehensive LC-MS system detected a total of 27 776 molecules harbouring the unique retention time and m/z values. In the first cohort of 57 KD patients, we found that a fraction of these molecules showed enrichment patterns that varied with the sampling region and season. Among them, 28 molecules were recurrently identified in KD patients but not in controls. The second and third cohorts of 48 more patients with KD revealed that these molecules were correlated with inflammatory markers (leucocyte counts and C-reactive proteins) in the acute stage. Notably, two of these molecules (m/z values: 822.55 and 834.59) were significantly associated with the development of coronary arteritis in the acute stage of KD. Their fragmentation patterns in the tandem MS/MS analysis were consistent with those of oxidized phosphatidylcholines (PCs). Further LC-MS/MS analysis supported the concept that reactive oxygen species caused the non-selective oxidization of PCs in KD patients. In addition, the concentrations of LOX-1 ligand containing apolipoprotein B in the plasma of KD patients were significantly higher than in controls. Conclusion These data suggest that inflammatory signals activated by oxidized phospholipids are involved in the pathogenesis of coronary arteritis in KD. Because the present study recruited only Japanese patients, further examinations are required to determine whether oxidized PCs might be useful biomarkers for the development of coronary arteritis in broad populations of KD.

Virus-induced syncytium formation, or cell fusion, has been investigated as a potential therapeutic approach for cancer. HVJ virus infection or transfection of membrane glycoproteins of virions have been known to cause syncytium formation in affected cells. Also, it was known that other enveloped viruses such as Herpes viruses, leukaemia viruses induce cell fusion. However, substances or molecules that directly cause syncytium formation have not been identified to date. Here, we identify a peptide that efficiently induces syncytia and report its structure, as an actionable therapeutic agent for cancer and viral infection. We purified and identified the fusion factor from the exosomes of the cells infected with murine leukaemia virus but not producing viruses by column chromatography, mass spectrometry, and amino acid analyses. We confirmed the peptide purified from the cell culture media and synthesized peptides induce syncytia as well as the murine leukaemia viruses, or the membranes or exosomes of MuLV infected cell lines in RFL cells and several cancer cell lines leading to apoptosis. And this peptide suppresses in vivo growth of cancer cells significantly. Furthermore, we found the synthesized peptide can cause fusion of enveloped virions as well as virus infected cells or cancer cell lines. These results nominate the use of this peptide as a potentially promising therapeutic approach for cancer and viral infection through efficient induction of syncytium formation followed apoptosis.

Ovarian cancer is a leading cause of deaths among gynecological cancers, and a method to detect early-stage epithelial ovarian cancer (EOC) is urgently needed. We aimed to develop an artificial intelligence (AI)-based comprehensive serum glycopeptide spectra analysis (CSGSA-AI) method in combination with convolutional neural network (CNN) to detect aberrant glycans in serum samples of patients with EOC. We converted serum glycopeptide expression patterns into two-dimensional (2D) barcodes to let CNN learn and distinguish between EOC and non-EOC. CNN was trained using 60% samples and validated using 40% samples. We observed that principal component analysis-based alignment of glycopeptides to generate 2D barcodes significantly increased the diagnostic accuracy (88%) of the method. When CNN was trained with 2D barcodes colored on the basis of serum levels of CA125 and HE4, a diagnostic accuracy of 95% was achieved. We believe that this simple and low-cost method will increase the detection of EOC.

Comprehensive serum glycopeptide spectra analysis (CSGSA) evaluates >10,000 serum glycopeptides and identifies unique glycopeptide peaks and patterns via supervised orthogonal partial least-squares discriminant modeling. CSGSA was more accurate than cancer antigen 125 (CA125) or human epididymis protein 4 (HE4) for detecting early stage epithelial ovarian cancer. Combined CSGSA, CA125, and HE4 had improved diagnostic performance. Thus, CSGSA may be a useful screening tool for detecting early stage epithelial ovarian cancer.

Background Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19–9 are used in clinical practice as tumor markers to diagnose or monitor colorectal cancer (CRC) patients, However, their specificities and sensitivities are not ideal, and novel alternatives are needed. In this study, mass spectrometry was used to search for screening markers, focusing on glycan alterations of glycoproteins in the sera of CRC patients. Methods Glycopeptides were prepared from serum glycoproteins separated from blood samples of 80 CRC patients and 50 healthy volunteers, and their levels were measured by liquid chromatography time-of flight mass spectrometry (LC–TOF–MS). Results Leucine-rich alpha-2-glycoprotein-1 with fucosylated triantennary N-glycan (LRG–FTG) was identified as CRC marker after evaluating 30,000 candidate glycopeptide peaks. The average LRG–FTG level in CRC patients (1.25 ± 0.973 U/mL) was much higher than that in healthy volunteers (0.496 ± 0.433 U/mL, P

PURPOSE: Fully sialylated alpha-chain of complement 4-binding protein (A2160) is a member of the glycoprotein family and has recently been identified as a diagnostic biomarker for epithelial ovarian cancer. This study examined the utility of A2160 as a prognostic biomarker for this disease. METHODS: This is a retrospective analysis of prospectively collected plasma samples from 93 women with stage I–IV epithelial ovarian cancer who underwent primary cytoreductive surgery between 2009 and 2014. Pretreatment A2160 levels were correlated to clinico-pathological factors and survival outcome. RESULTS: Women with advanced-stage disease had significantly higher 2160 levels compared to those with early stage disease (stage I–II versus III–IV, median 2.17–2.70 versus 5.31–8.70 U/mL, P < 0.01). Women with high-grade serous ovarian carcinoma had higher A2160 levels compared to other histologies (6.60 versus 3.01 U/mL, P = 0.05). Women who had suboptimal cytoreduction had significantly higher A2160 levels than those who achieved optimal/complete cytoreduction (7.02 versus 2.30–3.17 U/mL, P < 0.01). On univariable analysis, higher A2160 levels were significantly associated with decreased progression-free survival (64–100 versus 1–33%ile, 5-year rates 53.4 versus 78.9%, P = 0.029). After controlling for age, CA-125 level, cytoreductive status, histology, and stage, higher A2160 levels remained an independent prognostic factor for decreased progression-free survival (adjusted-hazard ratio (HR) 2.48, 95% confidence interval (CI) 1.01–6.11, P = 0.049). Similarly, higher A2160 levels were independently associated with decreased cause-specific survival on multivariable analysis (adjusted-HR 3.07, 95% CI 1.19–7.93, P = 0.021). CONCLUSION: Our study suggests that A2160 may be a useful prognostic biomarker for epithelial ovarian cancer, and higher pretreatment levels of A2160 predicts poor survival outcome.

Magnetic hyperthermia using magnetic nanoparticles (MNPs) draws significant interest for application in heat therapy for cancerous tumors, wherein it is important to improve the heating efficiency, i.e., to increase the hysteresis loss. In this paper, we examined the hysteresis loss of magnetically fractionated MNPs for hyperthermia application. Original Resovist MNPs were magnetically fractionated into three types, and their hysteresis loops were measured with an excitation field of 2.5 mT (rms) at a frequency of 20 kHz. The hysteresis loss of fractionated MNPs with the larger magnetic moment was approximately two times that of the original Resovist MNPs. A numerical simulation based on the Langevin function was performed to support the experimental results. From the experimental and simulation results, we can conclude that the efficiency of hyperthermia is improved by magnetically separating MNPs.

We developed a narrowband magnetic particle imaging (MPI) system that uses third-harmonic signal detection and electrical scanning of the field free point (FFP). Comparing with mechanical scanning, we can decrease the measurement time significantly and increase the signal-to-noise ratio as well. For electrical scanning, we designed and constructed gradient and shift coils. The gradient coil consisting of four pieces of planar coils generated the gradient field with a field gradient of 0.4 T/m at a height of 25 mm from the coil surface. The FFP can be moved ±8 mm by supplying a current of ±6.6 A to the shift coil. Using the developed system, we detected two magnetic nanoparticle (MNP) samples located at a depth of 35 mm below the pickup coil with a spacing of 10 mm. By applying an excitation field of 1 mT at 22.75 kHz, we measured the third-harmonic signal from the MNP samples and obtained a contour map of the signal field in an area of 16 $\times$ 16 mm2. Then, we converted the field map into an MNP distribution using singular value decomposition method. It was shown that the spatial resolution of the reconstructed MNP distribution was improved compared with that of the measured contour map of the signal field. The spatial resolution for MNP detection in MNP distribution was 5 mm and two MNP samples were distinguished clearly. This result indicated that MPI using electrical scanning of the FFP was successfully performed.

Objective While a certain fraction of endometriomas can develop de novo epithelial ovarian cancer (EOC) such as clear cell carcinoma (OCCC), there is currently no useful biomarker available for early detection of OCCC from endometriomas. The aim of this study was to describe the diagnostic utility of a novel biomarker for EOC especially for OCCC to distinguish from endometrioma. Methods More than 100,000 glycan structures of serum glycoproteins obtained from 134 pretreatment all stage EOC patients (including 45 OCCCs) and 159 non-cancer control women (including 36 endometriomas) were explored for a mass spectrum approach. Diagnostic accuracy of identified biomarker was compared to the one of CA-125 by comparing area under curve (AUC) and positive/negative predictive values (PPV and NPV). Results A2160, a fully-sialylated alpha-chain of complement 4-binding protein, was identified as a candidate target marker. A2160 was significantly elevated in all stages of OCCC compared to with endometriomas. Diagnostic accuracy of A2160 (cutoff 1.6U/mL) to distinguish early stage OCCC from endometrioma is significantly higher than that of CA-125 (cutoff 35IU/L): AUC for A2160 versus CA-125, 0.92 versus 0.67; PPV 95% versus 64%; and NPV 85% versus 58%. In addition, fully-sialylated glycans had a higher accuracy for diagnosing EOC as compared to partially-sialylated glycans of alpha-chain of complement 4-binding protein. Conclusion Our study suggested that A2160 may be a useful biomarker to distinguish early-stage OCCC from endometrioma. This new biomarker can be potentially applied for the monitoring of endometrioma patients, making possible the early diagnosis of OCCC.

We explored the effect of viscosity on harmonic signals from a magnetic fluid. Using a numerical simulation that accounts for both the Brownian and Neel processes, we clarified how the magnetization mechanism is affected by viscosity. When the excitation field varies much slower than the Brownian relaxation time, magnetization can be described by the Langevin function. On the other hand, for the case when the excitation field varies much faster than the Brownian relaxation time, but much slower than the Neel relaxation time, the easy axes of the magnetic nanoparticles (MNPs) turn to some extent toward the direction of the excitation field in an equilibrium state. This alignment of the easy axes of MNPs caused by the AC field becomes more significant with the increase of the AC field strength. Consequently, the magnetization is different from the Langevin function even though Neel relaxation time is faster than time period of the external frequency. It is necessary to consider these results when we use harmonic signals from a magnetic fluid in a high-viscosity medium.

We have developed a 2-D magnetic nanoparticle (MNP) imaging system using an orthogonal gradient held and third-harmonic signal detection. An ac excitation held was applied to generate third-harmonic signals from MNP on the basis of their nonlinear magnetization curves, and a dc gradient held was applied perpendicular to the excitation held. The dependence of the third-harmonic signal on the dc held was very different from that in the conventional parallel case. We obtained a contour map of the signal held from the MNP located at z = 35 mm below the pickup coil using an excitation held of 1 mT and gradient held of 0.4 T/m. We could obtain spatial resolution of 10 mm even in this small gradient held. Then, we analyzed the contour map using singular value decomposition (SVD) to improve the spatial resolution of the position estimation of MNP. Using SVD, we converted the held map to the MNP distribution. The spatial resolution was improved from 10 to 6.7 mm. We could clearly distinguish three MNP samples separated with 10 mm spacing located at z = 35 mm.

Serum levels of fully sialylated C4-binding protein (FS-C4BP) are remarkably elevated in patients with epithelial ovarian cancer (EOC) and can be used as a marker to distinguish ovarian clear cell carcinoma from endometrioma. This study aimed to develop a stable, robust and reliable liquid chromatography-hybrid mass spectrometry (UPLC-MS/MS) based diagnostic method that would generalize FS-C4BP as a clinical EOC biomarker. Glycopeptides derived from 20 μL of trypsin-digested serum glycoprotein were analyzed via UPLC equipped with an electrospray ionization time-of-flight mass spectrometer. This UPLC-MS/MS-based diagnostic method was optimized for FS-C4BP and validated using sera from 119 patients with EOC and 127 women without cancer. A1958 (C4BP peptide with two fully sialylated biantennary glycans) was selected as a marker of FS-C4BP because its level in serum was highest among FS-C4BP family members. Preparation and UPLC-MS/MS were optimized for A1958, and performance and robustness were significantly improved relative to our previous method. An area under the curve analysis of the FS-C4BP index receiver operating characteristic curve revealed that the ratio between A1958 and A1813 (C4BP peptide with two partially sialylated biantennary glycans) reached 85%. A combination of the FS-C4BP index and carbohydrate antigen-125 levels further enhanced the sensitivity and specificity.

Background: One of the current problems in the field of metabolomics is the difficulty in integrating data collected using different equipment at different facilities, because many metabolomic methods have been developed independently and are unique to each laboratory. Methods: In this study, we examined whether different analytical methods among 12 different laboratories provided comparable relative quantification data for certain metabolites. Identical samples extracted from two cell lines (HT-29 and AsPc-1) were distributed to each facility, and hydrophilic and hydrophobic metabolite analyses were performed using the daily routine protocols of each laboratory. Results: The results indicate that there was no difference in the relative quantitative data (HT-29/AsPc-1) for about half of the measured metabolites among the laboratories and assay methods. Data review also revealed that errors in relative quantification were derived from issues such as erroneous peak identification, insufficient peak separation, a difference in detection sensitivity, derivatization reactions, and extraction solvent interference. Conclusion: The results indicated that relative quantification data obtained at different facilities and at different times would be integrated and compared by using a reference materials shared for data normalization.

Objectives: To conduct a comprehensive glycopeptide spectra analysis of serum between cancer and non-cancer patients to identify early biomarkers of epithelial ovarian cancer (EOC). Methods: Approximately 30,000 glycopeptide peaks were detected from the digested serum glycoproteins of 39 EOC patients (23 early-stage, 16 advanced-stage) and 45 non-cancer patients (27 leiomyoma and ovarian cyst cases, 18 endometrioma cases) by liquid chromatography mass spectrometry (LC&ndash, MS). The differential glycopeptide peak spectra were analyzed to distinguish between cancer and non-cancer groups by employing multivariate analysis including principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and heat maps. Results: Examined spectral peaks were filtered down to 2281 serum quantitative glycopeptide signatures for differentiation between ovarian cancer and controls using multivariate analysis. The OPLS-DA model using cross-validation parameters R2 and Q2 and score plots of the serum samples significantly differentiated the EOC group from the non-cancer control group. In addition, women with early-stage clear cell carcinoma and endometriomas were clearly distinguished from each other by OPLS-DA as well as by PCA and heat maps. Conclusions: Our study demonstrates the potential of comprehensive serum glycoprotein analysis as a useful tool for ovarian cancer detection.

Magnetic particle imaging (MPI) is a new imaging technique that uses the nonlinear magnetic response of magnetic nanoparticles (MNPs). We have been developing a single-sided MPI system, where excitation and detection of MNPs are performed from one side of the human body. For this purpose, we developed a planar gradient coil made up of four pieces of a square coil, as schematically shown in Fig. 1(a). The field free point (FFP) of the gradient field occurred at the center of the coil: By using the FFP, we can improve the spatial resolution in MNPs detection. In the previous study, we demonstrated the MPI using this system, where MNPs sample was mechanically scanned to obtain a contour map of the signal field [1].

High-sensitivity and -specificity diagnostic techniques to detect early-stage hepatocellular carcinoma (HCC) are in high demand. Screening with serum HCC markers, such as alpha-fetoprotein, is not practical because they possess poor sensitivity and specificity. As such, we focused on glycan alterations of glycoproteins found in patient sera in an attempt to discover novel HCC markers that are more specific and sensitive than current HCC markers. Sera from 42 HCC patients and 80 controls, composed of 27 chronic hepatitis B patients, 26 chronic hepatitis C patients, and 27 healthy volunteers, were analyzed in this study. Glycopeptides obtained from serum proteins by trypsin digestion were enriched by ultrafiltration and Aleuria aurantia lectin-based affinity chromatography, followed by analysis using liquid chromatography time-of-flight mass spectrometry. The data were analyzed by our newly developed software, which calculates peak intensities and positions (m/z and elution time), aligns all sample peaks, and integrates all data into a single table. HCC markers were extracted from more than 30 000 detected glycopeptide peaks by t test, mean-fold change, and ROC analyses. As a result, we revealed that alpha-1-acid glycoprotein with multifucosylated tetraantennary N-glycans was significantly elevated in HCC patients, whereas the single fucosylated derivative was not.

The design criteria that achieve the excess loss of less than 1.0 dB in entire C-band has been clarified for MMI mode converter. As a result, we have confirmed that MMI width in addition to access waveguide width ratio over MMI width are the important design criteria.

Propagation loss of core-top etched Si/SiO2 waveguide was preliminarily evaluated for the first time. As a result, approximately 8 dB/cm increase has been confirmed after core-top etching.

We evaluated the complex harmonic signals from magnetic nanoparticles (MNPs) for magnetic particle imaging (MPI). We measured the complex harmonic signals from Resovist MNPs, one of the candidates for an MPI tracer, when only an ac excitation field and both the ac and the dc excitation fields were applied. To evaluate the complex harmonic magnetization spectra, we performed a numerical simulation accounting for the distributions of magnetic moments, anisotropy energy barriers, and hydrodynamic sizes of MNPs in the sample. The simulation results agreed well with experimentally obtained amplitude of the harmonic signals. The simulation results of the phase lag, which was caused by the finite relaxation time, agreed with the experiments for low harmonic numbers. The phase lag deviation between them became significant for higher harmonic numbers. For quantitative evaluation of the phase lag for higher harmonic numbers, a more accurate estimation of the Neel relaxation time is required.

N-Glycan structures on the surface of cancer cells have diverse structures and play significant roles in metastatic process. However, little is known about their roles in organ-selective metastasis. Our study revealed that an alpha1,6-fucosylated biantennary N-glycan structure designated A2G2F is characteristic of lungs, with far more abundant expression in normal human and murine lungs than in other organs. In this study, we further examined the role of A2G2F in pulmonary metastasis. We stained metastatic cancers by alpha1,6-fucose-specific Lens culinaris agglutinin lectin and revealed that pulmonary metastatic nodules more abundantly expressed alpha1,6-fucosylated N-glycans than hepatic metastatic nodules from common primary cancers. The most specific alpha1,6-fucosylated N-glycan structure in pulmonary metastatic cancer was identified to be A2G2F. Using a B16 melanoma cell metastasis model, we showed that A2G2F-rich B16 cells formed more pulmonary metastatic nodules than A2G2F-poor cells. Our results suggest that A2G2F plays a critical role in pulmonary metastasis.

We established a Thermus thermophilus strain in which the pyrE gene (coding for orotate phosphoribosyltransferase of the pyrimidine biosynthetic pathway) was totally deleted. We also constructed an integration vector, which consisted of the Escherichia coli plasmid vector pBluescript and a 2.1-kb segment of the T. thermophilus leu operon sequence, for the integration of a foreign gene into a chromosome of the thermophile. pyrE and leuB genes were used as probes to test the integration vector. The integration vector pINV, bearing the pyrE gene, transformed the delta pyrE strain at a frequency of 6 x 10(-5) through a single crossover event. The leuB gene could also be used as another marker of the integration vector system. The vector could be integrated at the expected site. By digesting the chromosomal DNA of the T. thermophilus transformants with a unique restriction enzyme, the vector could be recovered into E. coli after the recircularization in vitro. The kanamycin nucleotidyltransferase gene could be successfully expressed in the thermophile by using pINV.

595 Background: CEA and CA19-9 are measured widely in daily practice for colorectal cancer to monitor the condition of treatment, though its specificity and sensitivity is not satisfied enough. While, the innovation of mass spectrometry in this decade is dramatically. The revolutionized approach for the screening of glycomarkers provides a chance to discover more desirable tumor markers. We focused on glycan alterations of serum glycoproteins and tried to find new markers which are more specific and sensitive than the current markers. Methods: Sera of 80 CRC patients and 50 healthy volunteers were analyzed in this study. Glycopeptides were prepared from serum proteins by trypsin digestion, enriched by filtration and aleuria aurantia lectin(AAL), and then applied to liquid chromatography time-of flight mass spectrometry* (*LC-TOF-MS). Data was analyzed with our newly developed software, which calculates all of peak intensities and positions (m/z and elution time), aligns all peaks for all samples, and finally screens markers from a million of candidates. Results: Leucine-rich alpha-2-glycoprotein-1 with fucosylated triantennary N-glycan (LRG-FTG) was discovered as a new CRC marker from over 100,000 candidate glycopeptide peaks. The level of LRG-FTG in CRC patients (1.25 ± 0.973 U/ml) was much higher than that of healthy parsons (0.496 ± 0.433 U/ml, p < 10-10). Its sensitivity and specificity exceeded those of CA19-9. CEA and LRG-FTG levels were moderately correlated (r = 0.61), however their relation was independent and complementary. Combination marker of LRG-FTG and CEA showed 84% of sensitivity, 90% of specificity and 0.91 of AUC (ROC analysis), and responded well to the efficacy of chemotherapy. Conclusions: Serum LRG-FTG was significantly elevated in CRC patients compared to healthy volunteers. The combination with CEA is expected to be an alternative diagnostic marker which distinguishes CRC from healthy persons and a sensitive monitoring marker for evaluation of efficacy during chemotherapy. Further validation study is warranted to evaluate serum LRG-FTG combination test compared with conventional tumor markers.

Serum glycans are promising markers for early-stage cancer detection, but the research remains challenging because low concentrations of serum glycoproteins are secreted from early-stage tumors. We have established an N-glycan profiling method using liquid chromatography electrospray ionization-mass spectrometry with high sensitive derivative, trimethyl(4-aminophenyl)ammonium chloride (TMAPA). The mass sensitivity of TMAPA-labeled oligosaccharides was enhanced more than 50 times compared with 2-aminopyridine (PA) labeled oligosaccharides, and the analytical period was significantly shortened compared with traditional HPLC 2D-mapping. Using this method, we found about 28 major N-linked oligosaccharides in human sera, and we investigated their alterations in patients who developed hepatocellular carcinoma (HCC). We found that outer arm fucosylation (attached GlcNAc via an alpha 1-3/4 linkage) in highly branched oligosaccharides increased significantly in sera of HCC patients. Normalizing the level of outer arm fucosylation by taking into account platelet concentration allowed us to distinguish more clearly between HCC and LC patients.

The Beckmann rearrangement is one of the most important industrial reactions for e-caprolactam production. A theoretical study focusing on the mechanism of the reaction is presented. The initial attack by a proton on oxygen and on nitrogen of the oxime molecule is monitored. Then, using an acetone oxyme as a model molecule, the central part of the rearrangement is studied by molecular orbital method. Transition state (TS) of the rearrangement from oxime to the intermediate of caprolactam is determined as a concerted transition state. Various attacking species such as proton, SO3, HSO3+, ReO3+, ReO3+ with pyridine, cyclohexanoneoxime with H+, and cyclohexanone-oxime with ReO3+ are examined to clarify the determining factors of the transition state energy. Finally, the mechanism of the most promising catalyst of Re20? is studied taking into account adduct-byproduct formation.

We study the third harmonic signal of magnetic nanoparticles (MNPs) for use in narrow-band magnetic nanoparticle imaging. We measured the properties of the third harmonic signal, such as frequency and magnetic field dependencies, when the behavior of MNPs was dominated by Neel relaxation. It was shown that the third harmonic signal had both real and imaginary parts, although only the real part is expected from the conventional Langevin function. The real and imaginary parts exhibited different dependences on the frequency and magnetic field. The dynamic behavior of MNPs was analyzed by taking into account the Neel relaxation of MNPs. It was shown that the imaginary part was generated due to Neel relaxation. We obtain an analytical expression for the third harmonic signal, in which distributions of magnetic moment and anisotropic energy of MNPs in the sample were also considered. We show that the analytical results quantitatively explain the experimental results. Our results indicate that the properties of the third harmonic signal of immobilized MNPs are significantly affected by Neel relaxation.

還元型ニコチンアミドアデニンジヌクレオチド(NADH)及びそのリン酸型(NADPH)の定量にイソルミノール(IL)と1-メトキシフェナジンメチルサルフェートーマイクロペルオキシダーゼを用い,高感度に測定できる化学発光分析法を確立した.更にNADHの化学発光測定法は血清中の総胆汁酸の測定に,又,NADPHの化学発光測定法はグルコース-6-リン酸脱水素酵素活性の測定及びヘキソナーゼ/グルコース-6-リン酸脱水素酵素,アデノシン5'-三リン酸,塩化マグネシウムの共存下,血中グルコースの定量に応用し,それぞれ高感度に定量でき,日常分析法とも良い相関を示した.

The local structure of amorphous states in PbTiO3 has been determined by the Fourier transform of EXAFS function. The effect of annealing the amorphous specimen has also been studied.

Many compounds with calcium fluorite type structure show anomalies in the specific heat at elevated temperatures, a few hundred degrees below their melting temperature. The anomalies are associated with an order-disorder phase transition which is accompanied by a rising in ionic conductivity.

From an EXAFS study of amorphous PbTiO 3 its local structure is determined. The Pb-O and Pb-Ti distances in the amorphous specimen are shorter than those of the ferroelectric PbTiO 3 crystal. The annealing effect of the locally distorted structure is discussed comparing the Raman spectra of the annealed amorphous specimen with those of crystalline PbTiO 3 under high pressure.