Microwave oscillator using piezoelectric thin-film resonator aiming for ultraminiaturization of atomic clock.

We developed a microwave oscillator and a micro electromechanical systems-based rubidium cell for the miniaturization of atomic clocks. A thin-film bulk acoustic resonator (FBAR) having a resonant frequency of the fundamental mode in the 3.5 GHz band was employed instead of a crystal resonator. It delivers a clock transition frequency of Rb atoms of 3.417 GHz without the need for a complicated frequency multiplication using a phase-locked loop. This topology considerably reduces the system scale and power consumption. For downsizing the atomic clock system toward the chip level as well as mass production, a microfabricated gas cell containing Rb and N2 gases was also developed. These microcomponents were incorporated into an atomic clock test bench, resulting in a clock operation with a short-term frequency instability of 2.1 × 10-11 at 1 s. To the best of our knowledge, this is the first report of a coherent population trapping clock operation using an FBAR-based microwave oscillator as well as a microfabricated gas cell.

Electro-optic probe measurements of electric fields in plasmas.

The direct measurements of high-frequency electric fields in a plasma bring about significant advances in the physics and engineering of various waves. We have developed an electro-optic sensor system based on the Pockels effect. Since the signal is transmitted through an optical fiber, the system has high tolerance for electromagnetic noises. To demonstrate its applicability to plasma experiments, we report the first result of measurement of the ion-cyclotron wave excited in the RT-1 magnetosphere device. This study compares the results of experimental field measurements with simulation results of electric fields in plasmas.

Chaos of energetic positron orbits in a dipole magnetic field and its potential application to a new injection scheme.

We study the behavior of high-energy positrons emitted from a radioactive source in a magnetospheric dipole field configuration. Because the conservation of the first and second adiabatic invariants is easily destroyed in a strongly inhomogeneous dipole field for high-energy charged particles, the positron orbits are nonintegrable, resulting in chaotic motions. In the geometry of a typical magnetospheric levitated dipole experiment, it is shown that a considerable ratio of positrons from a ^{22}Na source, located at the edge of the confinement region, has chaotic long orbit lengths before annihilation. These particles make multiple toroidal circulations and form a hollow toroidal positron cloud. Experiments with a small ^{22}Na source in the Ring Trap 1 (RT-1) device demonstrated the existence of such long-lived positrons in a dipole field. Such a chaotic behavior of high-energy particles is potentially applicable to the formation of a dense toroidal positron cloud in the strong-field region of the dipole field in future studies.

Usefulness of immunocytochemistry using a Breast Marker antibody cocktail targeting P63/cytokeratin7/18/cytokeratin5/14 for fine needle aspiration of the breast: a retrospective cohort study of 139 cases.

OBJECTIVE: The Breast Marker Cocktail from Biocare Medical comprises five antibodies recognising p63, and cytokeratins (CKs) 7, 18, 5 and 14. Immunohistochemistry using this cocktail is useful for diagnosing proliferative intraductal breast lesions. However, cytology using the cocktail has not been reported. METHODS: We report 139 cases of mammary samples collected by fine needle aspiration (FNA) for which histological diagnoses were available. After cell transfer, immunocytochemistry was performed using the cocktail, and clusters of cells were classified. A cluster with no or limited CK5/14 expression (<20% of cells) was classified as a monotonous cluster. One with more than 20% of cells showing CK5/14 expression was defined as a mosaic cluster. When at least one p63-positive cell was present, we defined it as a cluster with p63. We also evaluated background p63-positive myoepithelial cell densities. RESULTS: The diagnostic sensitivity and specificity for carcinomas were 97.8% (89/91) and 91.7% (11/12), respectively, using the criterion of two or more monotonous clusters lacking p63. Two false-negative cases were triple-negative cancers; one false-positive was an apocrine papilloma. The numbers of monotonous clusters with p63 differed significantly between benign lesions, ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS) and invasive carcinomas (P < 0.001). The background myoepithelial cell density was significantly higher in fibroepithelial tumours than in other lesions (P < 0.001). CONCLUSIONS: Immunocytochemistry using this antibody cocktail showed good sensitivity and specificity for diagnosing breast cancers. Thus, this method is useful for mammary cytology using FNA.

Low-dose CT screening using hybrid iterative reconstruction: confidence ratings of diagnoses of simulated lesions other than lung cancer.

OBJECTIVE: To evaluate the confidence ratings of diagnoses of simulated lesions other than lung cancer on low-dose screening CT with hybrid iterative reconstruction (IR). METHODS: Simulated lesions (emphysema, mediastinal masses and interstitial pneumonia) in a chest phantom were scanned by a 320-row area detector CT. The scans were performed by 64-row and 160-row helical scans at various dose levels and were reconstructed by filtered back projection (FBP) and IR. Emphysema, honeycombing and reticular opacity were visually scored on a four-point scale by six thoracic radiologists. The ground-glass opacity as a percentage of total lung volume (%GGO), CT value and contrast-to-noise ratio (CNR) of mediastinal masses were calculated. These scores and values were compared between FBP and IR. Wilcoxon's signed-rank test was used (p < 0.05). Interobserver agreements were evaluated by κ statistics. RESULTS: There were no significant differences in visual assessment. Interobserver agreement was almost perfect. CT values were almost equivalent between FBP and IR, whereas CNR with IR was significantly higher than that with FBP. %GGO significantly increased at low-dose levels with FBP; however, IR suppressed the elevation. CONCLUSION: The confidence ratings of diagnoses of simulated lesions other than lung cancer on low-dose CT screening were not degraded with hybrid IR compared with FBP. ADVANCES IN KNOWLEDGE: Hybrid IR did not degrade the confidence ratings of diagnoses on visual assessment and differential diagnoses based on CT value of mediastinal masses, and it showed the advantage of higher GGO conspicuity at low-dose level. Radiologists can analyse images of hybrid IR alone on low-dose CT screening for lung cancer.

Protein S exacerbates alcoholic hepatitis by stimulating liver natural killer T cells.

BACKGROUND: Alcohol consumption is a major cause of liver injury but the mechanisms are not completely understood. Protein S (PS) is an anticoagulant glycoprotein with multiple functions. The role of PS in liver injury is unknown. OBJECTIVES: This study investigated the role of PS in acute alcoholic hepatitis. METHODS: A mouse overexpressing human PS (hPS-TG) was generated in which acute hepatitis was induced by intraperitoneal injection of ethanol. RESULTS: The levels of serum liver enzymes and liver tissue inflammatory cytokines and the degree of hepatic steatosis were significantly increased in hPS-TG mice treated with ethanol compared with ethanol-treated wild type (WT) mice. Cell expansion, activation and inhibition of apoptosis were significantly augmented in natural killer T (NKT) cells from hPS-TG mice compared with WT mice. Liver mononuclear cells from hPS-TG mice express higher levels of inflammatory cytokines than those from WT mice after stimulation with a specific stimulant of NKT cells in vitro. In a co-culture system of hepatocytes and NKT cells, the effects of PS on ethanol-mediated cell injury were suppressed by a CD1d neutralizing antibody. Alcoholic liver injury was significantly improved in mice pre-treated with PS siRNA and anti-protein S antibody compared with control mice. Patients with alcoholic hepatitis showed significantly increased plasma PS levels and enhanced liver expression of PS and CD1d compared with controls. CONCLUSIONS: The results of this study suggest that PS exacerbates acute alcoholic hepatitis by inhibiting apoptosis of activated NKT cells.

Detectability of simulated interstitial pneumonia on chest radiographs: comparison between irradiation side sampling indirect flat-panel detector and computed radiography.

OBJECTIVE: To compare the detectability of simulated interstitial pneumonia on chest radiographs between an irradiation side sampling indirect flat-panel detector (ISS-FPD) and computed radiography (CR). METHODS: Simulated interstitial pneumonia findings (ground-glass opacity, reticular opacity and honeycomb lung) were superimposed on an anthropomorphic chest phantom. Chest radiographs were acquired under three exposure levels (4.0, 3.2 and 2.0 mAs) with an ISS-FPD and with CR. 5 thoracic radiologists evaluated 72 images for the presence or absence of a lesion over each of 6 areas. A total of 1296 observations were analysed in a receiver-operating characteristic analysis. A jackknife method was used for the statistical analysis. RESULTS: The areas under the curves (AUCs) for the detection of simulated honeycomb lung obtained with the ISS-FPD were significantly larger than those obtained with CR at all exposure conditions. For the detection of simulated ground-glass opacity and reticular opacity, there were no significant differences between the two systems. In addition, the AUCs for the detectability of simulated honeycomb lung obtained with the ISS-FPD at all exposure levels were significantly larger than those obtained with CR at 4 mAs. CONCLUSION: The ISS-FPD was superior to CR for the detection of simulated honeycomb lung. Provided that the chosen model is representative of interstitial pneumonia, the use of an ISS-FPD might reduce a patient's exposure dose during the detection of interstitial pneumonia. ADVANCES IN KNOWLEDGE: The ISS-FPD has shown its advantage compared with CR in the detection of honeycombing, one sign of interstitial pneumonia.

Occlusal trauma accelerates attachment loss at the onset of experimental periodontitis in rats.

BACKGROUND AND OBJECTIVE: Occlusal trauma is an important factor that influences the progression of periodontitis, but it is unclear whether occlusal trauma influences periodontal destruction at the onset of periodontitis. We established an experimental periodontitis model with both site-specific loss of attachment and alveolar bone resorption. The purpose of the present study was to investigate the effects of occlusal trauma on periodontal destruction, particularly loss of attachment, at the onset of experimental periodontitis. MATERIAL AND METHODS: Sixty rats were used in the present study. Forty-eight rats immunized with lipopolysaccharide (LPS) intraperitoneally were divided into four groups. In the trauma (T) group, occlusal trauma was induced by placing an excessively high metal wire in the occlusal surface of the mandibular right first molar. In the inflammation (I) group, periodontal inflammation was induced by topical application of LPS into the palatal gingival sulcus of maxillary right first molars. In the trauma + inflammation (T+I) group, both trauma and periodontal inflammation were simultaneously induced. The PBS group was administered phosphate-buffered saline only. Another 12 nonimmunized rats (the n-(T+I) group) were treated as described for the T+I group. All rats were killed after 5 or 10 d, and their maxillary first molars with surrounding tissues were observed histopathologically. Loss of attachment and osteoclasts on the alveolar bone crest were investigated histopathologically. To detect immune complexes, immunohistological staining for C1qB was performed. Collagen fibers were also observed using the picrosirius red-polarization method. RESULTS: There were significant increases in loss of attachment and in the number of osteoclasts in the T+I group compared with the other groups. Moreover, widespread distribution of immune complexes was observed in the T + I group, and collagen fibers oriented from the root surface to the alveolar bone crest had partially disappeared in the T, T+I and n-(T+I) groups. CONCLUSION: When inflammation was combined with occlusal trauma, immune complexes were confirmed in more expanding areas than in the area of the I group without occlusal trauma, and loss of attachment at the onset of experimental periodontitis was increased. Damage of collagen fibers by occlusal trauma may elevate the permeability of the antigen through the tissue and result in expansion of the area of immune-complex formation and accelerating inflammatory reaction. The periodontal tissue destruction was thus greater in the T+I group than in the I group.

A retrospective analysis of 335 Japanese lung cancer patients who responded to initial gefitinib treatment.

BACKGROUND: Gefitinib treatment results in considerably better progression-free survival compared with that of platinum doublets in the first line treatment of nonsmall-cell lung cancer (NSCLC) carrying an activating epidermal growth factor receptor (EGFR) mutation. Some patients who respond to gefitinib have an overall survival (OS) of more than 5 years, whereas other initial responders do less well. Although there has been considerable effort made to elucidate the mechanisms of acquired resistance, there have only been a few studies that addressed the effect of clinical backgrounds and treatment histories on the survival of the patients who had responded to an EGFR-tyrosine kinase inhibitor (TKI). In this study, we especially focused on the clinical benefit of EGFR-TKI administration after progression. PATIENTS AND METHODS: We retrospectively analyzed consecutive patients with advanced NSCLC who were diagnosed before October 2010, treated with gefitinib after July 2002, and responded to it. The primary objective of this study was to evaluate how clinical backgrounds and treatment histories influence survival of the patients who respond to gefitinib. The secondary objectives were to evaluate the safety of long-term gefitinib use and to establish the optimal treatment sequence using a dynamic treatment regimen analysis (DTRA). RESULTS: A total of 335 patients were recruited. Twenty-eight (8.4%) patients survived more than 5 years. Sixty-five and 93 patients received gefitinib as rechallenge and beyond progressive disease (BPD), respectively. A statistically significant difference in OS was observed between the patients who underwent gefitinib rechallenge and those who did not rechallenge (median: 1272 days vs. 774 days; p < 0.001), a result supported by a DTRA. Patients treated with gefitinib BPD also showed a tendency of longer survival. CONCLUSIONS: Gefitinib rechallenge and BPD played a central role in long term survival of the patients who initially responded to gefitinib.

Dose-dependent differential effects of thrombin in allergic bronchial asthma.

BACKGROUND: Apart from its role in the coagulation system, thrombin plays an important role in the inflammatory response through its protease-activated receptors (PARs). However, the role of thrombin in the immune response is not clear. OBJECTIVE: To evaluate whether thrombin has a modulatory role in allergic bronchial asthma. METHODS: Bronchial asthma was induced in mice by intraperitoneal sensitization and inhalation challenge with ovalbumin. Thrombin or its inhibitors were administered by inhalation before each allergen challenge. RESULTS: Mice with low but sustained coagulation activation had reduced allergic inflammation, and allergic asthma was inhibited by low doses of thrombin but worsened by high doses. Allergic asthma was worsened by antithrombin, argatroban, hirudin, and anti-thrombomodulin antibody. Mice with a higher level of an inhibitor of both thrombin and activated protein C had worse disease. Heterozygous PAR-1 mice had less allergic inflammation, but PAR-1 agonist worsened it. Allergic bronchial inflammation was worsened in mice that received adoptive transfer of PAR-1 agonist-treated Th2 cells as compared with controls. Low levels of thrombin suppressed the maturation and secretion of cytokines in dendritic cells, but high levels enhanced this. CONCLUSIONS: The effects of thrombin on allergic asthma are dose-dependent, with detrimental effects at high doses and protective effects at low doses. These data demonstrate that thrombin modulates the outcome in allergic bronchial asthma.

Associations of intrauterine growth restriction with placental pathological factors, maternal factors and fetal factors; clinicopathological findings of 257 Japanese cases.

Intrauterine growth restriction (IUGR) is the leading cause of fetal mortality and morbidity. As an etiology, each of placental findings, maternal factors and fetal factors has been reported to be associated with IUGR, although a comprehensive approach to examine all of these parameters as a cause of IUGR has not been reported. In the present study, therefore, we comprehensively examined the placental findings and maternal and fetal factors in the cases of IUGR (n=257, mean maternal age, 30 years; gestational weeks, 34 weeks) and normal growth pregnancies (n=258, mean maternal age, 30 years; gestational weeks, 33 weeks), and determined risk factors for IUGR. The prevalence of pregnancy hypertension (PHT) (19% vs. 8%, P<0.01), smoking habit (3% vs. 0.7%, P<0.05) and fetal anomaly (3.5% vs. 0.8%, P<0.05) were higher in IUGR cases than normal growth pregnancies. Pathologically, the prevalence of infarction (33% vs. 14%, P<0.05), fetal vessel thrombosis (22% vs. 6%, P<0.001) and chronic villitis (11% vs. 3%, P<0.001) were higher in IUGR cases than those in normal growth pregnancies. A multivariable regression analysis revealed that maternal factors (PHT), fetal factors (anomaly), and placental findings (infarction, fetal vessel thrombosis, and chronic villitis) are independently associated with increased risk of IUGR (all P<0.01).

Development of a field test for evaluating aerobic fitness.

The purpose of this study was to investigate the reproducibility and utility of a standardised and externally paced field test (15-m Incremental Shuttle Walk and Run Test [15 mISWRT]) to assess aerobic fitness in middle-aged adults. 14 middle-aged participants performed the 15-m ISWRT 3 times within one week (Test 1, Test 2, Test 3). Reproducibility of the 15-m ISWRT was tested by comparing 15-m ISWRT performance (distance completed), HRmax, and VO 2max for each test. The utility of the 15-m ISWRT for evaluating VO 2max over a wide range in middle-aged adults was tested by comparing the range of VO 2max obtained from the portable expired gas analyzer with the VO 2max reference values and ranges for health promotion published by Japan's Ministry of Health, Labour and Welfare. A multiple comparison of distance completed in the 15-m ISWRT Test 1, Test 2, and Test 3 found no significant difference between Test 2 and Test 3. The ICC was 0.99 for Test 2 vs. Test 3. VO 2max measured from the 15-m ISWRT in Test 3 had a minimum value of 22.8 ml/kg/min and a maximum value of 38.7 ml/kg/min. In conclusion, the 15-m ISWRT is reliable and useful for evaluating VO 2max in middle-aged adults.

Exogenous activated protein C inhibits the progression of diabetic nephropathy.

BACKGROUND: Activated protein C (APC) can regulate immune and inflammatory responses and apoptosis. Protein C transgenic mice develop less diabetic nephropathy but whether exogenous administration of APC suppresses established diabetic nephropathy is unknown. OBJECTIVES: We investigated the therapeutic potential of APC in mice with streptozotocin-induced diabetic nephropathy. METHODS: Diabetes was induced in unilaterally nephrectomized C57/Bl6 mice using intraperitoneal (i.p.) injection of streptozotocin. Four weeks later, the mice were treated with i.p. exogenous APC every other day for 1 month. RESULTS: APC-treated mice had a significantly improved blood nitrogen urea-to-creatinine ratio, urine total protein to creatinine ratio and proteinuria, and had significantly less renal fibrosis as measured by the levels of collagen and hydroxyproline. The renal tissue concentration of monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF) and the RNA expression of platelet-derived growth factor (PDGF), transforming growth factor-ß1 and connective tissue growth factor (CTGF) were significantly lower in APC-treated mice than in untreated animals. The percentage of apoptotic cells was reduced and the expression of podocin, nephrin and WT-1 in the glomeruli was significantly improved in mice treated with APC compared with untreated mice. The levels of coagulation markers were not affected by APC treatment. CONCLUSION: Exogenous APC improves renal function and mitigates pathological changes in mice with diabetic nephropathy by suppressing the expression of fibrogenic cytokines, growth factors and apoptosis, suggesting its potential usefulness for the therapy of this disease.

Correlation of circulating dehydroepiandrosterone with activated protein C generation and carotid intima-media thickness in male patients with type 2 diabetes.

AIMS: Dehydroepiandrosterone exerts a protective effect against cardiovascular diseases. However, the relationship of dehydroepiandrosterone with the anticoagulant factor activated protein C, generated by the thrombin-thrombomodulin complex on vascular endothelial cells, remains unknown. This study aimed at studying the relationship between dehydroepiandrosterone and activated protein C generation in patients with Type 2 diabetes. METHODS: Sixty-two male patients with Type 2 diabetes were enrolled in this study. Data obtained from 40 healthy male subjects were used as controls. The plasma levels of dehydroepiandrosterone, the activated protein C-protein C inhibitor complex, high-sensitivity C-reactive protein and monocyte chemoattractant protein-1 were measured by enzyme immunoassays. Carotid intima-media thickness was measured by ultrasonography. RESULTS: The plasma levels of dehydroepiandrosterone (5.15 ± 2.81 vs. 3.76 ± 2.16 ng/ml; P < 0.005) and the activated protein C-protein C inhibitor complex (1.90 ± 1.07 vs. 1.02 ± 0.51 ng/ml; P < 0.001) were significantly lower in patients with diabetes than in normal subjects. Univariate analysis showed a significant correlation of the plasma level of dehydroepiandrosterone with that of the activated protein C-protein C inhibitor complex (r = 0.48, P < 0.001), high-sensitivity C-reactive protein (r = -0.30, P < 0.05) and with the mean intima-media thickness (r = -0.28, P < 0.05) in patients with diabetes. Stepwise multiple regression analysis showed that the plasma level of dehydroepiandrosterone is significantly correlated with the plasma levels of the activated protein C-protein C inhibitor complex (F = 18.06) and high-sensitivity C-reactive protein (F = 4.94). There was no correlation between the plasma levels of dehydroepiandrosterone and monocyte chemoattractant protein-1. CONCLUSIONS: These results suggest that lower circulating levels of dehydroepiandrosterone are associated with decreased activated protein C generation and higher intima-media thickness in patients with Type 2 diabetes.

SU-E-I-21: Effect of Different Fluorescent Lights with Various Colors of a Reading Room on Chromaticity of LCD.

PURPOSE: To examine variation of chromaticity of LCD in different types of fluorescent lights in a reading room. METHODS: A color LCD (RX320, antiglare type, 450 cd/m2 , three-megapixel, Eizo Nanao), and a monochrome LCD (G31-S, anti glare type, 450 cd/m2 , three-megapixel, Eizo Nanao) were used in this study. The chromaticity in grayscale images with eighteen luminance levels were measured under five types of fluorescent lights with different color spectrums (Daylight: 6,700 K, Natural white: 5,000 K, White: 4,200 K, Warm white: 3,500 K, Light bulb: 3,000 K) by using a colorimeter (CS-200: KONICA MINOLTA). The chromaticity of LCDs was measured at various ambient lighting conditions (a dark room, 36, and 300 lux) and different types of fluorescent lights. RESULTS: The chromaticity of LCDs measured under ambient lights was changed from that measured in a dark room. The chromaticity of LCDs varied with different types of fluorescent lights. As illuminance of the room increased, variations in chromaticity at relatively lower luminance levels increased. The direction of changes in chromaticity shifted to the color for each fluorescent light. CONCLUSIONS: Fluorescent lights having different color spectra affect the chromaticity of LCDs.

Numerical and Experimental Study to Fabricate the New Type Compact NMR Device Using Stacked HTS Bulks.

In fabrication of a compact NMR (Nuclear Magnetic Resonance) magnet which consists of a stacked HTS (High Temperature Superconducting) bulk annuli, generally there are three key issues: spatial homogeneity, temporal stability, strength of trapped magnetic fields. This paper presents a study on the effects of axial gap length between stacked HTS bulks on the three key issues of a bulk HTS magnet for compact HTS NMR applications. The HTS bulk magnet of which the ID and OD are 20 and 60 mm respectively has a 50 and 80 mm heights depending on the axial gap lengths between HTS bulks. The gap length between each HTS bulk varied from 0 mm to 10 mm and were used as parameters to optimize, analytically as well as experimentally, the overall field homogeneity of the HTS bulk magnet. The optimized axial gap length was obtained by analytical results, and the better magnetic field homogeneity and temporal stability of trapped magnetic field were achieved by lower magnetization field. The improved spatial homogeneity and strength of generated magnetic field by a new compact NMR magnet will be presented.