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BACKGROUND Mammary analogue secretory carcinoma (MASC) with an ETS variant gene 6 (ETV6)–neurotrophic tyrosine kinase receptor type 3 (NTRK3) translocation is a newly described type of salivary gland cancer. It is known that overexpression of signal transducer and activator of transcription 5a (STAT5a) occurs in secretory carcinoma of the breast and MASC, and STAT5a expression may be related to the ETV6-NTRK3 translocation. It was hypothesized that phosphorylated signal transducer and activator of transcription 5 (p-STAT5) might be specifically expressed in MASC of the salivary gland. METHODS The expression of p-STAT5 and mammaglobin (MMG) was examined with immunohistochemistry (IHC)/immunocytochemistry (ICC) in tissue sections from 58 salivary gland cancers (8 MASCs and 50 other salivary gland cancers) and in cytological smears from 17 salivary gland cancers (7 MASCs with paired histologic samples and 10 other salivary gland cancers). RESULTS p-STAT5 IHC was clearly increased in MASC versus normal salivary gland tissue and other salivary gland cancers. p-STAT5 expression was found in 7 of 8 MASCs (87.5%) and in none of the 50 other salivary gland cancers (0%) by IHC. On cytology, p-STAT5 expression was found in all cases of MASC (7 of 7 or 100%) but in none of the 10 other salivary gland cancers (0%) by ICC. The expression rate of MMG by histology and cytology was higher than that of p-STAT5 in the other salivary gland cancers. CONCLUSIONS p-STAT5 might be useful as a detection marker of MASC in the differential diagnosis of salivary gland cancers, and initial screening with p-STAT5 IHC/ICC, combined with auxiliary fluorescence in situ hybridization confirmation, is a reliable, economical approach to identifying MASC of the salivary gland. Cancer (Cancer Cytopathol) 2015;123:603–11. © 2015 American Cancer Society.

Mitochondria are important cellular organelles that function as control centers of the energy supply for highly proliferative cancer cells and regulate apoptosis after cancer chemotherapy. Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors. Cisplatin may directly interact with mitochondria, which can induce apoptosis. The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance. However, the basis for the roles of mitochondria under treatment with chemotherapy is poorly understood. In this review, we present novel aspects regarding the unique characteristics of the mitochondrial genome in relation to the use of platinum-based chemotherapy and describe our recent work demonstrating the importance of the mitochondrial transcription factor A (mtTFA) expression in cancer cells.

The purpose of this study was to investigate the instructional model used by Japanese science teachers for mentoring gifted students. A total of thirty teachers were interviewed about the characteristics of his/her students who achieved excellent results in a science contest and about his/her instructional strategies for the students. The subjects include 27 high school science teachers and 3 elementary teachers; 29 out of the 30 are male and 27 have more than 10 years teaching experience. The interviews were conducted between July 2008 and August 2009 in Ehime, Ibaraki, Tokyo, and Okayama, Japan. Each teacher was interviewed for an average of 30 minutes. Interview transcripts were used in the data analysis. The results of the text analysis extracted some phrases that commonly described science instruction, specifically: (1) at first, themes were not given to the students; (2) opportunities for appropriate advice and coaching were needed; (3) teachers should continue to study; (4) originality was appreciated; (5) the process and experiences were more important than the results themselves; (6) teachers helped students to acquire basic understanding and skills; (7) students found study/research similar to play; (8) students established good networks with experts in a specific area; (9) teachers enjoy teaching gifted students science very much; (10) students were asked to design their own research; (11) students were asked to make things; and (12) students developed the habit of recording what they thought and found in everyday life. Finally, an instructional model for Japanese science teachers who teach gifted students is proposed on the basis of these results.

Epithelial tubular structures are essential units in various organs. Here, we used rat intestinal epithelial IEC6 cells to investigate tubulogenesis and we found that tubular formation was induced by a combination of Wnt3a and EGF signaling during three-dimensional culture. Wnt3a and EGF induced the expression of the P2Y2 receptor (P2Y2R, also known as P2RY2), and knockdown of P2Y2R suppressed tubular formation. A P2Y2R mutant that lacks nucleotide responsiveness rescued the phenotypes resulting from P2Y2R knockdown, suggesting that nucleotide-dependent responses are not required for P2Y2R functions in tubular formation. The Arg-Gly-Asp (RGD) sequence of P2Y2R has been shown to interact with integrins, and a P2Y2R mutant lacking integrin-binding activity was unable to induce tubular formation. P2Y2R expression inhibited the interaction between integrins and fibronectin, and induced cell morphological changes and proliferation. Inhibition of integrin and fibronectin binding by treatment with the cyclic RGD peptide and fibronectin knockdown induced tubular formation in the presence of EGF alone, but a fibronectin coat suppressed Wnt3a- and EGF-induced tubular formation. These results suggest that Wnt3a- and EGF-induced P2Y2R expression causes tubular formation by preventing the binding of integrins and fibronectin rather than by mediating nucleotide responses.

We have developed highly reliable oxide TFT arrays by allprinted maskless process from gate to passivation layers with 100 ppi RGB resolution. The threshold voltage shifts under positive and negative bias-temperature-stress at 50 °C after 105 seconds were less than 0.8 and 0.3 V, respectively.

A 67-year-old male with a history of asbestos exposure presented with fever, cough, and dyspnea and was found to have diffuse granular shadowing in both lungs, right pleural effusion, and hilar and mediastinal lymphadenopathy upon chest computed tomography. For definitive diagnosis, a thoracoscopic lung biopsy was performed. Intraoperative findings showed no remarkable macroscopic changes in the visceral and parietal pleura, although a high level of hyaluronic acid in the pleural effusion was noted. Histological findings showed proliferation of atypical cells with round-to-oval nuclei, prominent nucleoli, and eosinophilic cytoplasms. These cells were arranged into sheets or tubules and were located predominantly in the lung parenchyma. Lymphovascular invasion was conspicuous. Immunohistochemically, tumor cells were positive for calretinin, D2-40, and CK5/6, focally positive for Ber-EP4, but negative for WT-1, TTF-1, CEA, and MOC31. Fluorescence in situ hybridization for the tumor suppressor p16 revealed homozygous deletion in the tumor cells. Therefore, we diagnosed the tumor as diffuse intrapulmonary malignant mesothelioma (DIMM). The patient had a poor response to chemotherapy and died 1 year after diagnosis. Although rare, DIMM should be considered when patients present with multiple, tiny intrapulmonary nodules, regardless of macroscopic pleural changes. Furthermore, this is the first report on p16 status in DIMM.

High-temperature superconductors (HTS) are the key technology to achieve super-high magnetic field nuclear magnetic resonance (NMR) spectrometers with an operating frequency far beyond 1 GHz (23.5 T). (RE)Ba 2 Cu 3 O 7− x (REBCO, RE: rare earth) conductors have an advantage over Bi 2 Sr 2 Ca 2 Cu 3 O 10− x (Bi-2223) and Bi 2 Sr 2 CaCu 2 O 8− x (Bi-2212) conductors in that they have very high tensile strengths and tolerate strong electromagnetic hoop stress, thereby having the potential to act as an ultra-compact super-high field NMR magnet. As a first step, we developed the world’s first NMR magnet comprising an inner REBCO coil and outer low-temperature superconducting (LTS) coils. The magnet was successfully charged without degradation and mainly operated at 400 MHz (9.39 T). Technical problems for the NMR magnet due to screening current in the REBCO coil were clarified and solved as follows: (i) A remarkable temporal drift of the central magnetic field was suppressed by a current sweep reversal method utilizing ∼10% of the peak current. (ii) A Z2 field error harmonic of the main coil cannot be compensated by an outer correction coil and therefore an additional ferromagnetic shim was used. (iii) Large tesseral harmonics emerged that could not be corrected by cryoshim coils. Due to those harmonics, the resolution and sensitivity of NMR spectra are ten-fold lower than those for a conventional LTS NMR magnet. As a result, a HSQC spectrum could be achieved for a protein sample, while a NOESY spectrum could not be obtained. An ultra-compact 1.2 GHz NMR magnet could be realized if we effectively take advantage of REBCO conductors, although this will require further research to suppress the effect of the screening current.

Rehabilitation of post-mine land in open-pit coal mines is necessary for sustainable development of coal. Although topsoil containing much nutrition should be secured for plant growth, there was the shortage and the erosion of topsoil by heavy rain in the tropical climate, especially in South East Asian countries. Therefore, in this study, the application of Fly Ash (FA) to topsoil was evaluated in terms of the growth of plants with Acacia mangium, aiming at securing topsoil in open-pit coal mines. As the result of the plant experiment, the inhibition of plant growth attributing to the dissolution of Aluminum (Al) from FA was observed. The growth rate of the plants was decreased at the mixing ratio of more than 40% of FA. Thus, topsoil can be secured by mixing FA in topsoil in consideration of the mixing ratio, contributing to the successful rehabilitation of post-mine land in open-pit coal mine.

Low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) was originally identified as a coreceptor of the Wnt signaling pathway and has been shown to be involved in LDL transport. In polarized hepatocytes, many apical proteins are sorted to the basolateral membrane and then internalized and transported to the apical bile canalicular membrane—a process known as transcytosis. Herein, we show that LRP6 is transcytosed to the apical membrane of polarized hepatic HepG2 cells via a flotillin-dependent manner in the absence of LDL. LRP6 formed a complex with Niemann–Pick type C1-like 1 (NPC1L1), which is localized to the bile canalicular membrane of the liver and is involved in cholesterol absorption from the bile. LRP6 was required for apical membrane localization of NPC1L1 in the absence of LDL. Clathrin-dependent LRP6 internalization occurred in the presence of LDL, which resulted in trafficking of LRP6 to the lysosome, thereby reducing apical sorting of LRP6 and NPC1L1. These results suggest that LRP6 endocytosis proceeds by 2 routes, depending on the presence of LDL, and that LRP6 controls the intracellular destination of NPC1L1 in hepatocytes.

The use of REBCO coils is a promising approach to achieve super-high field NMR magnets. As the first step in this direction, we have started to develop an LTS/REBCO NMR magnet operated at 400-600 MHz (9.4-14.1 T). In this paper, based on numerical simulations, we describe a study of the thermal runaway of the REBCO innermost coil, which is one of the major problems of this type of magnet. Based on the simulation results, if an LTS coils quench occurs, the current in the REBCO coil continues to increase due to the electromagnetic induction and leads to a natural thermal runaway with a very high current density. The thermal runaway is limited to only the top and bottom ends of the REBCO coil, as the radial magnetic field is highest there and the quench propagation velocity is quite low. The current density for this type of thermal runaway is much higher than that of the operating current, resulting in the catastrophic overheating of the coil. This is the worst case scenario which must be prevented for the LTS/REBCO NMR magnet. An optimal size dump resistor for the REBCO coil can prevent the natural thermal runaway by suppressing the current increase due to electromagnetic induction.

Growth factor-dependent epithelial morphological changes and proliferation are essential for the formation of tubular structures, but the underlying molecular mechanisms are poorly understood. Co-stimulation with Wnt3a and epidermal growth factor (Wnt3a/EGF) induced development of tubes consisting of intestinal epithelial cells by inducing expression of Arl4c, an Arf-like small GTP-binding protein, in three-dimensional culture, while stimulation with Wnt3a or EGF alone did not. Arl4c expression resulted in rearrangement of the cytoskeleton through activation of Rac and inactivation of Rho properly, which promoted cell growth by inducing nuclear translocation of Yes-associated protein and transcriptional co-activator with PDZ-binding motif (YAP/TAZ) in leading cells. Arl4c was expressed in ureteric bud tips and pretubular structures in the embryonic kidney. In an organoid culture assay, Wnt and fibroblast growth factor signaling simultaneously induced elongation and budding of kidney ureteric buds through Arl4c expression. YAP/TAZ was observed in the nucleus of extending ureteric bud tips. Thus, Arl4c expression induced by a combination of growth factor signaling mechanisms is involved in tube formation.

Solid-state NMR observations of low-gamma half-integer quadrupolar nuclei

Wnt signal plays important roles in polarization. Here intestinal epithelial cells are shown to form apicobasal polarization at a single-cell level in an extracellular matrix adhesion–dependent manner. Wnt5a signaling promotes single-cell polarization through balanced control between Rac1 and RhoA activities spatially., Single epithelial-derived tumor cells have been shown to induce apical and basolateral (AB) polarity by expression of polarization-related proteins. However, physiological cues and molecular mechanisms for AB polarization of single normal epithelial cells are unclear. When intestinal epithelial cells 6 (IEC6 cells) were seeded on basement membrane proteins (Matrigel), single cells formed an F-actin cap on the upper cell surface, where apical markers accumulated, and a basolateral marker was localized to the rest of the cell surface region, in a Wnt5a signaling–dependent manner. However, these phenotypes were not induced by type I collagen. Rac1 activity in the noncap region was higher than that in the cap region, whereas Rho activity increased toward the cap region. Wnt5a signaling activated and inhibited Rac1 and RhoA, respectively, independently through Tiam1 and p190RhoGAP-A, which formed a tertiary complex with Dishevelled. Furthermore, Wnt5a signaling through Rac1 and RhoA was required for cystogenesis of IEC6 cells. These results suggest that Wnt5a promotes the AB polarization of IEC6 cells through regulation of Rac and Rho activities in a manner dependent on adhesion to specific extracellular matrix proteins.

We have demonstrated all-printed oxide TFT arrays for 100 ppi RGB active matrix fabricated by inkjet printing and spin coating without photolithography and mask process. The average mobility of TFTs was 7.49 ± 1.67 cm2/Vs on a thermally oxidized SiO2 /Si substrate. Moreover, in the case of using of a printed oxide high-k gate insulator and an n-type doped active layer on a glass substrate, the average mobility of all-printed oxide TFTs was 2.54 ± 0.32 cm2/Vs.

The distinction between sarcomatoid mesothelioma and fibrous pleuritis is difficult based on histology, especially when the amount of tumor tissue examined via biopsy is small and immunohistochemical examination is inconclusive. We studied the usefulness of deletion of p16 with fluorescence in situ hybridization (FISH) and p16 hypermethylation with polymerase chain reaction for the diagnosis and prognosis of malignant pleural mesothelioma (MPM). We analyzed 50 MPMs, including 22 sarcomatoid mesothelioma cases and 10 fibrous pleuritis cases. We set the cutoff value of homozygous deletion pattern as 14.4% based on FISH signaling patterns using samples of fibrous pleuritis. The percentage of homozygous deletion pattern was higher than 14.4% in 55.6% of the epithelioid mesotheliomas (10/18) and in all of the sarcomatoid mesotheliomas (22/22). Methylation of p16 was observed in 7 (20.6%) of 34 informative cases. p16 FISH analysis can be a reliable test for distinguishing between sarcomatoid mesothelioma and fibrous pleuritis and a prognostic factor for MPM.

Malignant mesothelioma is a highly aggressive neoplasm, and the histologic subtype is one of the most reliable prognostic factors. Some biphasic mesotheliomas are difficult to distinguish from epithelioid mesotheliomas with atypical fibrous stroma. The aim of this study was to analyze p16/CDKN2A deletions in mesotheliomas by fluorescence in situ hybridization (FISH) and BAP1 immunohistochemistry to evaluate their potential role in the diagnosis of biphasic mesothelioma. We collected 38 cases of pleural mesotheliomas. The results of this study clearly distinguished 29 cases of biphasic mesothelioma from 9 cases of epithelioid mesothelioma. The proportion of biphasic mesotheliomas with homozygous deletions of p16/CDKN2A in total was 96.6% (28/29). Homozygous deletion of p16/CDKN2A was observed in 18 (94.7%) of 19 biphasic mesotheliomas with 100% concordance of the p16/CDKN2A deletion status between the epithelioid and sarcomatoid components in each case. Homozygous deletion of the p16/CDKN2A was observed in 7 (77.8%) of 9 epithelioid mesotheliomas but not in fibrous stroma. BAP1 loss was observed in 5 (38.5%) of 13 biphasic mesotheliomas and in both epithelioid and sarcomatoid components. BAP1 loss was observed in 5 (62.5%) of 8 epithelioid mesotheliomas but not in fibrous stroma. Homozygous deletion of p16/CDKN2A is common in biphasic mesotheliomas, and the analysis of only one component of mesothelioma is sufficient to show that the tumor is malignant. However, compared with histology alone, FISH analysis of the p16/CDKN2A status and BAP1 immunohistochemistry in the spindled mesothelium provide a more objective means to differentiate between biphasic mesothelioma and epithelioid mesothelioma with atypical stromal cells.

The increase in the number of coal-fired power plants with the increase in coal production and its consumption has caused the problem of the treatment of a large amount of coal ash in Indonesia. In the past studies, coal ash was applied to postmine land with the aim of improving soil conditions for plant growth; however, heavy rain in the tropical climate may cause soil erosion with the change in soil conditions. This study presents the effects of application of coal ash to postmine land on soil erosion by performing the artificial rainfall test as well as physical testing. The results indicate that the risk of soil erosion can be reduced significantly by applying the coal ash which consists of more than 85% of sand to topsoil in the postmine land at the mixing ratio of over 30%. Additionally, they reveal that not only fine fractions but also microporous structures in coal ash enhance water retention capacity by retaining water in the structure, leading to the prevention of soil erosion. Thus, the risk of soil erosion can be reduced by applying coal ash to topsoil in consideration of soil composition and microporous structure of coal ash.

Prickle is known to be involved in planar cell polarity, including convergent extension and cell migration; however, the detailed mechanism by which Prickle regulates cellular functions is not well understood. Here, we show that Prickle1 regulates front-rear polarization and migration of gastric cancer MKN1 cells. Prickle1 preferentially accumulated at the cell retraction site in close proximity to paxillin at focal adhesions. Prickle1 dynamics correlated with those of paxillin during focal adhesion disassembly. Furthermore, Prickle1 was required for focal adhesion disassembly. CLASPs (of which there are two isoforms, CLASP1 and CLASP2, in mammals) and LL5β (also known as PHLDB2) have been reported to form a complex at cell edges and to control microtubule-dependent focal adhesion disassembly. Prickle1 was associated with CLASPs and LL5β, and was required for the LL5β-dependent accumulation of CLASPs at the cell edge. Knockdown of CLASPs and LL5β suppressed Prickle1-dependent cell polarization and migration. Prickle1 localized to the membrane through its farnesyl moiety, and the membrane localization was necessary for Prickle1 to regulate migration, to bind to CLASPs and LL5β, and to promote microtubule targeting of focal adhesions. Taken together, these results suggest that Prickle1 promotes focal adhesion disassembly during the retraction processes of cell polarization and migration.

Growth factor signaling is involved in the development of various organs, but how signaling regulates organ morphogenesis and differentiation in a coordinated manner remains to be clarified. Here, we show how Wnt signaling controls epithelial morphogenetic changes and differentiation using the salivary gland as a model. Experiments using genetically manipulated mice and organ cultures revealed that Wnt signaling at an early stage (E12-E15) of submandibular salivary gland (SMG) development inhibits end bud morphogenesis and differentiation into proacini by suppressing KIT expression through the up-regulation of Myb transcription factor, and concomitantly increased the expression of distal progenitor markers. In addition, Wnt signaling at the SMG development early stage promoted end bud cell proliferation, leading to duct formation. In contrast, Wnt signaling reduction at a late stage (E16-E18) of SMG development promoted end bud maturation and suppressed duct formation. Thus, Wnt signaling controls the timing of SMG organogenesis by keeping end bud cells in an undifferentiated bipotent state.

Glypicans are members of the heparan sulfate proteoglycans (HSPGs) and are involved in various growth factor signaling mechanisms. Although HSPGs affect the β-catenin-dependent and -independent pathways of Wnt signaling, how they regulate distinct Wnt pathways is not clear. It has been suggested that the β-catenin-dependent pathway is initiated through receptor endocytosis in lipid raft microdomains and the independent pathway is activated through receptor endocytosis in non-lipid raft microdomains. Here, evidence is presented that glypican-4 (GPC4) is localized to both membrane microdomains and that the localization affects its ability to regulate distinct Wnt pathways. GPC4 bound to Wnt3a and Wnt5a, which activate the β-catenin-dependent and -independent pathways, respectively, and colocalized with Wnts on the cell surface. LRP6, one of Wnt3a coreceptors, was present in lipid raft microdomains, whereas Ror2, one of Wnt5a coreceptors, was localized to non-lipid raft microdomains. Expression of GPC4 enhanced the Wnt3a-dependent β-catenin pathway and the Wnt5a-dependent β-catenin-independent pathway, and knockdown of GPC4 suppressed both pathways. A GPC4 mutant that was localized to only non-lipid raft microdomains inhibited the β-catenin-dependent pathway but enhanced the β-catenin-independent pathway. These results suggest that GPC4 concentrates Wnt3a and Wnt5a to the vicinity of their specific receptors in different membrane microdomains, thereby regulating distinct Wnt signaling.

A quasi-microgravity environment appears in a high-field superconducting magnet bore where a large magnetic force counterbalances gravity acting on a diamagnetic substance. This suppresses convection of the diamagnetic solution in the crystallization cell placed in the bore from which protein crystals precipitate. A 16 T class superconducting magnet has been developed with a special coil configuration; one of the component coils produces a magnetic field the direction of which is opposite to that of the other coils. Thus, a large magnetic field gradient occurs, creating a magnetic force large enough to levitate water and hinder convection. This magnet system is operated in persistent mode, which is adequate for a rather time-requesting crystallization process of proteins. Preliminary experiments have shown that the protein crystallization process is substantially retarded in the magnetic force field.

High-temperature bulk superconductors have significant potential for superconductivity applications. For this paper, the magnetic shielding properties of GdBCO bulk with different crystal orientations were investigated at different temperatures for the purpose of determining its application as field concentrators. Four discs with a diameter of 20 mm and thickness of 5 mm were cut from the GdBCO single domain. In two discs, the c -axis of crystal was parallel to the disc radius, and, in the others, the c -axis was perpendicular to it. The magnetic shielding effects in a couple of bulks with a gap of 2 mm were measured in background fields up to 11 T. The magnetic fields were measured at the center and edge points between the two bulks at LN2, LHe, and temperatures controlled with a cryocooler. In LHe, the discs whose c -axes were parallel to the external magnetic fields maintained a zero field up to 11 T. Even in LN2, the field was shielded to 1 T. The results confirmed the strong magnetic shield effects of GdBCO bulk and can be used for the design of a field concentrator.

Because most of malignant pleural mesothelioma (MPM) patients first present with pleural effusion, detection of mesothelioma cells on effusion smears is critical for early diagnosis. Recently, accumulating evidence indicating that the cytological diagnosis of MPM supported by ancillary techniques is as reliable as that based on histopathology has led to new guidelines for the cytopathologic diagnosis of MPM. Based on the guidelines, a combination of cytomorphological criteria and verification by ancillary techniques is required for the cytologic diagnosis of MPM. Detection of p16 homozygous deletion by fluorescence in situ hybridization (FISH) is the most reliable ancillary technique for differentiating MPM from reactive mesothelial cells (RMC) because of its relatively high sensitivity and extremely high specificity. We showed that the p16 deletion status of MPM cells in pleural effusions reflected that of the underlying invasive MPM tissues, indicating the usefulness of p16 FISH in effusion smear cytology for MPM diagnosis. Thus, for differentiating MPM from RMC, we propose to perform p16 FISH as often as possible. A positive p16 homozygous deletion supports the diagnosis of MPM. However, a negative result does not rule out the possibility of MPM. In such cases, a morphological assessment is critical. Therefore, we analyzed the morphological characteristics of p16 deletion-positive mesothelioma cells using a combination of virtual microscopy and p16 FISH, and identified three morphological characteristics useful for the differentiation, including cell-in-cell engulfment with or without hump formation, multinucleate cells, and larger berry-like cell aggregates. Diagn. Cytopathol. 2016;44:774-780. © 2016 Wiley Periodicals, Inc.

Use of high-temperature superconducting (HTS) inner coils in combination with conventional low-temperature superconducting (LTS) outer coils for an NMR magnet, i.e. a LTS/HTS NMR magnet, is a suitable option to realize a high-resolution NMR spectrometer with operating frequency >1GHz. From the standpoint of creating a compact magnet, (RE: Rare earth) Ba2Cu3O7-x (REBCO) HTS inner coils which can tolerate a strong hoop stress caused by a Lorentz force are preferred. However, in our previous work on a first-generation 400MHz LTS/REBCO NMR magnet, the NMR resolution and sensitivity were about ten times worse than that of a conventional LTS NMR magnet. The result was caused by a large field inhomogeneity in the REBCO coil itself and the shielding effect of a screening current induced in that coil. In the present paper, we describe the operation of a modified 400MHz LTS/REBCO NMR magnet with an advanced field compensation technology using a combination of novel ferromagnetic shimming and an appropriate procedure for NMR spectrum line shape optimization. We succeeded in obtaining a good NMR line shape and 2D NOESY spectrum for a lysozyme aqueous sample. We believe that this technology is indispensable for the realization of a compact super-high-field high-resolution NMR.

Because of their high critical fields, high-Tc superconductors (HTS) are considered to be the only solution to dramatically increase the highest fields of NMR magnets. We have successfully demonstrated that a 500 MHz HTS/LTS NMR system with a Bi-2223 innermost coil could be used for solution NMR in a driven-mode operation. As the next step, the upgrade of the 920 MHz NMR system installed at the Tsukuba Magnet Laboratory is underway. The innermost Nb3Sn coil has been replaced by a Bi-2223 coil. The coil was fabricated as a layer-wound coil using five Bi-2223 conductors reinforced with bronze tapes. It was connected in series with the outer Nb3Sn and NbTi coils. The magnet is expected to generate a field of 24.2 T (1.03 GHz of 1H resonance frequency) at an operating current of 244.4 A. The test using the Bi-2223 coil and the outer Nb3Sn coils in combination was successfully carried out. The coil has been installed in the 1.03 GHz NMR magnet. Its cooling and operation are scheduled to take place within Fiscal Year 2010.

Shielding of magnetic fields (magnetic shielding) by rare earth-based REBCO coated conductors with a highly oriented superconducting layer was measured. The shielding of magnetic fields was measured using a Hall effect sensor installed between bundles consisting of commercial REBCO conductors 12 mm in width. Measurements of the shielding of magnetic fields by other commercial high-Tc superconductors were performed for comparison. The shielding of magnetic fields was found to depend on the number of conductors in the bundle and the route of the applied magnetic fields and was observed even for fields over 10 T. In steady magnetic fields, a temporal change in the shielding of magnetic fields, that is, a decay of shielding currents induced in conductors against applied magnetic fields, was measured. The temporal change of the shielding of magnetic fields exhibited the behavior typical of high-Tc superconductors, as explained by the flux creep model. Remanent magnetic fields measured in the experiments of the shielding of magnetic fields suggest that the bundle can be used as a magnet. A quasi-bulk magnet consisting of 100 Zr-doped Zr:REBCO conductors could hold over 3 T at 4.2 K.

Wnt5a is a representative ligand that activates the β-catenin-independent pathways. Because the β-catenin-independent pathway includes multiple signalling cascades in addition to the planar cell polarity and Ca(2+) pathway, Wnt5a regulates a variety of cellular functions, such as proliferation, differentiation, migration, adhesion and polarity. Consistent with the multiple functions of Wnt5a signalling, Wnt5a knockout mice show various phenotypes, including an inability to extend the embryonic anterior-posterior and proximal-distal axes in outgrowth tissues. Thus, many important roles of Wnt5a in developmental processes have been demonstrated. Moreover, recent reports suggest that the postnatal abnormalities in the Wnt5a signalling are involved in various diseases, such as cancer, inflammatory diseases and metabolic disorders. Therefore, Wnt5a and its signalling pathways could be important targets for the diagnosis and therapy for human diseases.

Consistency in endometrial cytology is relatively poor. This can be partly attributed to generally accepted criteria based on cellular features. The cytological distinction between grade-1 adenocarcinoma and endometrial hyperplasia is more reliant on architectural features than cellular features. We examined statistical criteria based on cytoarchitecture for detecting grade-1 adenocarcinoma in endometrial cytology. Histologically, the study population consisted of 11 cases of grade-1 adenocarcinoma, 6 of atypical endometrial hyperplasia, 16 of endometrial hyperplasia without atypia, and 74 of a normal proliferative endometrium. In each case, all cellclumps were divided into five patterns (tubular; sheet; dilated and/or branched tubular; regular overlapping; atypical). The frequencies of each pattern were submitted to five-variate cluster analysis. The validity and reproducibility of cluster analysis were tested by canonical discriminant analysis and multigroup linear discriminant analysis, respectively. All 107 cases were classified into three groups, A (11), B (36), and C (60), by five-variate cluster analysis. In comparison with this classification and histopathologic diagnosis, group A corresponded to adenocarcinoma, and groups B and C correlated with non-carcinoma. Most cases of atypical endometrial hyperplasia were included in group B. These data suggest that statistical groupings based on cytoarchitecture are useful in the discrimination of grade-1 adenocarcinoma from endometrial hyperplasia and normal tissue.

A high temperature superconducting wire (HTS wire) is promising for various superconducting magnet applications because it operates at a higher temperature than a low temperature superconducting wire (LTS wire) is. Particularly, a MRI magnet using the HTS wires (HTS-MRI magnet) is expected to obtain light-weight, compact and low operating cost compared to a LTS-MRI magnet. The MRI magnets are generally operated by a persistent current mode. A magnet of the persistent current mode consists of multiple superconducting magnets and persistent current switch (PCS) that connects with superconducting joints. However, the superconducting joint of the HTS wires has not been realized stably at this time. We have developed a superconducting joint by using a commercial REBCO wire. The HTS-MRI magnet requires that resistivity of less than 10−12 ohm and current capacity of more than 100 A is achieved by a direct-joint between superconducting layers of the two REBCO wires. Moreover, measurement equipment for low joint resistivity was prepared as measuring the decay of the magnetic field in the one-turn loop. In our R&D, the joint resistance and the critical current were achieved with 155 A and 5.3×10−13Ω.

Using high-Tc superconductors (HTS) is considered to be the only solution to dramatically increase the highest fields of NMR magnets because of their high critical fields. However, it is not easy to apply HTS to an NMR spectrometer (HTS-NMR) because a persistent-mode operation with HTS cannot satisfy the field stability of 0.01 ppm/h at present. To overcome this problem, we are now developing an HTS-NMR spectrometer in a driven-mode operation. As the first step, a layer-wound coil was fabricated with bronze-reinforced Bi-2223 conductors. Instead of the Nb3Sn coil, the Bi-2223 coil was installed as the innermost part of an existing NMR magnet. The magnet operated at a field of 11.7 T with a highly stabilized power supply. NMR measurements were carried out, and it was demonstrated that the quality of the multi-dimensional NMR spectra on the protein was equivalent to that obtained with a persistent-mode system. The next step will be to demonstrate its usefulness as a high-field NMR system. The upgrade of the 920 MHz NMR system installed at the Tsukuba Magnet Laboratory is underway. Its innermost coil is scheduled to be replaced by a Bi-2223 layer-wound coil for 2010. Its target field is 24.2 T (1.03 GHz).

Our objectives were to compare the effects of subcortical ischemic vascular dementia (SIVD) and Alzheimer's disease (AD) on cerebral blood flow (CBF), and then to analyze the relationship between CBF and subcortical vascular disease, measured as volume of white-matter lesions (WMLs).Eight mildly demented patients with SIVD (mean +/- SD; aged 77 +/- 8 years; Mini-Mental State Examination score 26 +/- 3 years) and 14 patients with AD were compared with 18 cognitively normal elderly subjects. All subjects had CBF measured using arterial spin-labeling magnetic resonance imaging, and brain volumes were assessed using structural magnetic resonance imaging.AD and SIVD showed marked CBF reductions in the frontal (P = 0.001) and parietal (P = 0.001) cortices. In SIVD, increased subcortical WMLs were associated with reduced CBF in the frontal cortex (P = 0.04), in addition to cortical atrophy (frontal, P = 0.05; parietal, P = 0.03).Subcortical vascular disease is associated with reduced CBF in the cortex, irrespective of brain atrophy.

Electrical and mechanical characteristics of Type HT tape, which is standard 4.2 mm wide DI-BSCCO tape reinforced with metallic tapes, have been evaluated. Longitudinal distributions of critical current and n-index in kilometer long Type HT tape has proved uniform from end to end just like the original insert tape, which is Type H tape. Type HT-CA reinforced with 50 mum thick heat-resistant copper alloy is highly balanced tape with high mechanical properties and low splice resistance. Type HT-SS reinforced with 20 mum thick stainless steel has the best mechanical properties, which has been demonstrated under the actual environment in high field magnet, namely the hoop stress load test energizing a one-turn coil in external high magnetic field and liquid helium.

Magnetic flux concentration is a very important technique for the effective generation of high magnetic fields. We propose the use of the diamagnetism of a high T c bulk superconductor (HTS bulk) instead of ferromagnetic materials such as Ho and Dy. We fabricated a magnetic field concentrator using Gd-Ba-Cu-O bulk. The essential point was slits to suppress the current along the circumference. The concentrator was cooled at the center of a superconducting magnet with liquid helium. By increasing the external field to 1.00 T, a magnetic flux density of 3.20 T was obtained at the center of the concentrator. At an external field of 2.00 T, a field of 5.65 T was also obtained. A magnetic lens using HTS bulk was successfully demonstrated. The experimental results were well explained by numerical analyses assuming HTS bulk as a perfect conductor.

In this study, we investigated in field properties of high-Tc superconductor (HTS) tapes electrically as well as mechanically. Metallic reinforced Bi-2223/Ag superconductor tapes were used in this work. The critical current (Ic), which is highly dependent on the magnetic field, was measured using fields applied parallel and perpendicular to the tape surface. The conductor was exposed to fields of up to 28 T at 4.2 K. In order to confirm the performance of tapes in practical NMR operation, Ic was also measured around 2 K. The conductor was wound on a large diameter bobbin and mechanical properties were then measured as the coil current was increased. Finally, we verified the conductor properties from coil Ic and maximum stress/strain of it.

Logic-gate operations displaying macroscopic outputs are promising systems for the development of intelligent soft materials that can perform effective functions in response to various input patterns. A supramolecular hydrogel comprising the phosphate-type hydrogelator 1 exhibits macroscopic gel-sol behavior in response to four distinct input stimuli: temperature, pH, Ca(2+), and light. We characterized this performance through microscopic, spectroscopic, and rheological measurements. On the basis of its multiple-stimulus responsiveness, we constructed gel-based supramolecular logic gates from hydrogelator 1 that demonstrated AND, OR, NAND, and NOR types of stimulus-responsive gel-sol behavior in the presence of various combinations of the four stimuli. Implementation of such logic-gate functions into semiwet soft materials (e.g., supramolecular hydrogels) is an important step toward the design of controlled drug delivery and release systems. Indeed, we demonstrate herein that one of our gel-based supramolecular logic gates is capable of holding and releasing bioactive substances in response to logic triggers. Furthermore, combining our supramolecular gel-based AND logic gate with a photoresponsive supramolecular gel could temporarily modulate the release rate of the bioactive substance.