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Electromigration (EM)-derived void nucleation and growth in 65-nm-node dual-damascene interconnects were investigated, and the effects of impurity doping as well as copper adhesion strength to a capping-dielectric layer (CAP) are clarified. It is found that surface-reductive treatment of the copper line improves its adhesion to the SiCN-CAP, elongating the incubation time of voiding at the via bottom. An aluminum doping is effective in suppressing both the void nucleation and growth. Consequently, an aluminum-doped copper alloy with the strong copper/CAP interface improves the EM lifetime by 50 times compared to that of a conventional pure copper. These results clearly indicate that blocking migration paths of vacancies through both grain boundaries and the copper/CAP interface is essential in improving the EM reliability.

A plasma-enhanced co-polymerization technique was developed for low-k/Cu damascene integration on 300 mm wafers. This technique enables us to control dielectric film properties by introducing organo-siloxane and hydrocarbon into a He-plasma. The growth rate of the low-k film derived from divinyl siloxane–benzocyclobutene (DVS–BCB) as a matrix monomer is increased by adding C2H2 as a deposition acceleration monomer and the Young's modulus was enhanced by adding diisopropenylbenzene (DIPB) or divinylbenzene (DVB) as a reinforcement monomer. Cu damascene interconnects with plasma polymerized low-k films were successfully fabricated on 300 mm wafers.

Highly reliable metal–insulator–metal (MIM) capacitor with ultra-thin SiN dielectrics is developed on the surface-controlled bottom electrode in nanometer-scales. Coverage of the TiN bottom electrode with a Ta thin layer achieves smooth surface. In addition, this electrode structure exhibits excellent etching controllability even for the MIM with the ultra-thin SiN dielectrics. The smooth surface of the Ta/TiN stacked electrode improves the dielectric characteristics such as leakage, breakdown and time-dependent dielectric breakdown (TDDB) reliability in the MIM capacitors, integrated into Cu dual-damascene interconnects (DDIs). As a result, the SiN-MIM with the Ta/TiN bottom electrode achieves high capacitance of 7 fF/µm2 as well as high reliabilities, which are 20% higher breakdown field and 6000 times longer TDDB lifetime than that without Ta-insertion. These values guarantee the high performance operation for more than 10 years under the environment at 85 °C.

A novel interconnect design concept named "ASIS (Appilication-specific Interconnect Structure)" is presented for 45 nm CMOS performance maximization. Basic scheme of ASIS is that corresponding to applications, such as high-performance, low-power, or high reliability, interconnect structure as well as metal thickness is individually optimized in order to maximize chip-level performance matched to the application. Our investigation shows that for low-power application, the increased resistivity of scaled-down Cu-wire is not a main issue, so that thinner wire is more advantageous. For high-performance application, partially double pitch structure for local and intermediate layers is advantageous. For high-reliability requirement, Cu-Al alloy or CoWP cap-metal is quite effective for boosting reliability.

A feasibility study was done for 45-nm-node Cu interconnects using a novel molecular-pore-stacking (MPS) SiOCH film (k = 2.45), taking electron scattering in the scaled-down Cu lines into consideration. The as-deposited MPS SiOCH film, formed by plasma polymerization of a robust six-member-ring (hexagonal) siloxane with large steric-hindered hydrocarbon side chains, has self-organized subnanometer pores. An oxidation-damage-free dual-hard-mask etching process, along with a benzocylobuten liner technique, preserved the low permittivity of the MPS film in the Cu lines, with excellent interline dielectric reliability. The line aspect ratio was also balanced to decrease not only the interconnect parasitic capacitance but also the Cu line resistivity, which is increased by the electron scattering in the narrow lines. By combining the above etching process and the line-aspect control, the feasibility of the MPS SiOCH film was confirmed with outstanding performance and excellent reliability for the 45-nm-node ultralarge scale integrations

Malignant müllerian mixed tumors (MMMTs) of the fallopian tube are very rare neoplasms, and we present such a case with unusual findings here. A 57-year-old Japanese woman, after she received a medical checkup, underwent salpingo-oophorectomy on the suspicion of ovarian cancer. At the time of operation, the main tumor was present predominantly in the fallopian tube. Microscopically, the tumor consisted of carcinoma and sarcoma components. The carcinoma showed moderately to poorly differentiated adenocarcinoma. The sarcoma consisted of predominantly undifferentiated sarcoma and focally rhabdomyosarcomatous cells with abundant eosinophilic cytoplasm. Immunohistochemically, the differentiation toward rhabdomyosarcoma was confirmed. Interestingly, the cytoplasm of undifferentiated sarcoma cells contained hyaline globule-like structures. These structures showed a positive reaction for PAS, and these structures were not digested by the diastase pretreatment. Ultrastructurally, hyaline globule-like structures corresponded to lysosomes. Finally, pathologists should keep in mind that undifferentiated sarcoma cells in MMMT of the fallopian tube may contain hyaline globule-like structures in the cytoplasm.

OBJECTIVE We have recently established a novel method to evaluate the emulsion stability of pharmaceutical skin cream. The key technology of the method is magnetic resonance imaging (MRI). The purpose of this study was to verify the usefulness of the method in the cosmetic industry. METHODS Milky lotion-type emulsions were employed as test samples. We note that the test samples were prepared by taking account of commercial milky lotions. After the sample preparation, a centrifugation treatment (5000 g for up to 120 min) was implemented to accelerate their destabilization processes. The centrifuged samples were monitored by using T2 relaxation time (T2 ) maps. Furthermore, the histograms generated from the T2 maps were analysed to investigate the destabilization process in more detail. In addition, small fractions of the upper and lower phases were collected from the centrifuged samples, and microscopic observations were conducted. RESULTS T2 maps successfully visualized the destabilization process accompanying the centrifugation protocol. From the microscopic observations, it was clarified that the main mechanism of the destabilization process was creaming. The sensitivity of the T2 map to creaming was much superior to that of visible observation; the T2 map can detect a slight creaming that is not visible to the naked eye. In addition, the T2 map also enables the detection of slight reversible creaming-dispersion changes accompanied by a repeated centrifugation-vortexing treatment. By using the parameters derived from the histogram analysis, the creaming behaviour can be evaluated more precisely and more objectively. This study prepared emulsions containing different thickener contents and then compared their creaming behaviours. As a consequence of the analysis, we could fully evaluate the effect of thickener on the emulsion stability by the evaluation method. CONCLUSION MRI is a promising tool for evaluation of the stability of cosmetic emulsions.

Non-alcoholic steatohepatitis (NASH) is the major cause of chronic liver disease worldwide. Endoplasmic reticulum (ER) stress is considered to be an important pathological characteristic in NASH. A sequence variation (I148M) in the patatin-like phospholipase domain-containing protein 3/adiponutrin (PNPLA3) gene is known to be associated with the development of NASH. However, PNPLA3 deficiency has been considered to not be associated with fatty liver disease. To clarify, therefore, the role of PNPLA3 in liver, we established PNPLA3 knockout (KO) mice and investigated the phenotypes and involved factors under ER stress.ER stress was induced by i.p. injection with tunicamycin or with saline at 0 and 24 h in KO and C57BL/6 (wild-type [WT]) mice. At 48 h after the starting of treatment, blood and liver samples were studied.Hepatic steatosis and triglyceride content were remarkably increased in WT mice than in KO mice under ER stress. The hepatic palmitate/oleate ratio was significantly higher originally in KO mice than in WT mice. Moreover, the expression of stearoyl-coenzyme A desaturase-1 (SCD1) in KO mice under ER stress was decreased further than that in WT mice. Expression of ER stress markers X-box binding protein 1 (XBP1) and ERdj4 was increased in WT mice but not in KO mice under ER stress.We first demonstrated the hepatic phenotype of PNPLA3 deficiency under ER stress. Our observations would indicate that PNPLA3 has an important role in hepatic fatty acid metabolism and triglyceride accumulation through XBP1 under ER stress.

The relative energies of Al-containing ITQ-21 (Al–ITQ-21), which generates Bronsted acid sites, and the deprotonation energies of the acid sites were calculated by ONIOM (ωB97X-D/6-311G(d,p):PM6) method. Model clusters composed of four unit cells of Al–ITQ-21, which contained one Al atom and one acidic proton, were used for the calculations. In addition, n-butane cracking and ethanol conversion over Al–ITQ-21 with different Al concentrations were evaluated by varying the temperatures for measuring the activation energies for these reactions. From the theoretical calculations and NMR measurement, oxygen anions in the ITQ-21 lattice could be designated as the site where two types of acidic protons having different acid strengths are bonded. The presence of the two types of acidic protons was also confirmed by the activation energies corresponding to n-butane cracking and the conversion of ethanol into ethene and diethyl ether.

A low-power 2Mb ReRAM macro was developed in 90 nm CMOS platform, demonstrating lower power data-writing (x1/7) and faster data-reading (x2∼3) as compared to a conventional flash. The memory window at −6σ for 10 years was confirmed with a high-speed 1-bit ECC considering operating temperature ranging from −40 to 85 °C, where the worst conditions are high-temperature (85°C) “Off” writing and low-temperature (−40°C) “On” writing followed by high-temperature (85°C) retention. A pulse-modulated Off-state verify and an interface-control of Ru electrode are effective for suppressing random fluctuation of R off readout and for sustaining the On-state retention, respectively.

Background: Granule characteristics are some of the important intermediate qualities that determine tablet properties. However, the relationships between granule and tablet characteristics are poorly understood. The aim of this study was to elucidate relationships among formulation factors, granule characteristics, and tablet properties using a non-linear response surface method (RSM) incorporating a thin-plate spline interpolation (RSM-S) and a Bayesian network (BN).Method: Tablets containing lactose (Lac), cornstarch (CS), and microcrystalline cellulose (MCC) were prepared by wet granulation. Ten formulations were prepared by an extreme vertices design. The angle of repose (Y1), compressibility (Y2), cohesion force (Y3), internal friction angle (Y4), and mean particle size (Y5) were measured as granule characteristics. Tensile strength (TS) and disintegration time (DT) were measured as tablet properties.Results: RSM-S results showed that TS increased with increasing amounts of MCC and Lac. DT de...

Several species of the genus Karenia (Dinophyceae) form blooms and often cause the mortality of cultured and wild fish. In Japan, blooms caused by two species - namely Karenia mikimotoi and Karenia brevis - have been reported so far. On the basis of morphological and molecular-phylogenic examinations, the present investigation found Karenia papilionacea and its novel sister phylotype for the first time in the coastal waters of the various regions of Japan. Of 34 strains isolated from the coastal waters, 27 strains displayed the typical morphological characteristics of K. papilionacea and further showed consensus DNA sequences corresponding to those of the originally described K. papilionacea. The other 7 strains displayed the same morphological characteristics of K. papilionacea, but showed divergent DNA sequences, at a genetic distance of over 0.04 (Internal Transcribed Spacer regions) from those of the original phylotype of K. papilionacea. These divergent strains were characterized as a novel sister phylotype (phylotype-I) of K. papilionacea. In the coastal waters of Japan, K. papilionacea-like (K. papilionacea and/or its phylotype-I) formed blooms at 20.3-30.4°C and salinity 30.1-33.9. No K. brevis was identified in Japanese coastal waters during this study. These findings demonstrated that K. papilionacea occurs along the coasts of western Japan and possibly shares several coastal regions with K. mikimotoi and K. papilionacea phylotype-I. In order to assess the risks of Karenia blooms to aquaculture, it is essential that the growth physiology and ichthyotoxicity of K. papilionacea and its novel phylotype should be characterized.

Administration of 17-βestradiol (E2) with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) can induce ovulation in estrogen-deficient (ArKO) mice; nevertheless, ovulatory efficiency and rate are low. In this study, effects of insulin on the ovulatory responses were investigated. In ArKO ovary, hCG signal was found to be transmitted in an uncoordinated manner when phosphorylation levels of signaling molecules are examined. Co-administration of insulin with hCG improved the transmission of hCG signal as well as the ovulatory efficiency in ArKO mice. It also improved the ovulatory rate but far below the wild-type rate. Gene expression analysis demonstrated that Cyp11a1 and Cyp17a1 mRNAs were significantly induced 4 h after PMSG administration in the wild-type ovary, but not in ArKO ovary. Collectively, these results suggest that insulin improves ovulatory responses of ArKO mice, but it fails to ameliorate follicular dysfunctions caused possibly by an inappropriate intraovarian milieu during follicular maturation.

We are approaching an age of IoT, in which sensors and controllers in all types of devices, including smart phones and PCs, are connected together. The strongest candidate fora wireless interface is the Bluetooth Low Energy® (BLE) standard because it is already widely used in smart phones. Many markets, especially for wearable devices like smart watches, demand BLE devices with a small module area and low current consumption. In previous research, solutions to the requirements for BLE have been widely discussed such as using the sliding IF (SIF) architecture in the RX [1,2] and a Class-D amplifier [2] with HD2 calibration [4] in the TX to achieve lower current consumption. The SIF architecture, however, involves RF image blocking violation without exception rule or the use of additional off-chip filters. In the TX, meanwhile, the calibration incurs a weakness in terms of the offset issue. Moreover, there is no approach to achieve "zero" external components for the RF port. In this paper, a BLE transceiver, with a reconfigurable filter, embedded into an on-chip matching network without any external components, is presented.

In this study, we examined the distribution and origin of myofibroblasts around the perforations of appendicitis. Stromal cells of 45 cases were studied by immunohistochemistry. In the normal appendix, myofibroblasts were restricted to the mucosa, and CD34-positive stromal cells were distributed in the submucosal and subserosal layers. Some mesothelial cells were positive for cytokeratin CAM5.2, cytokeratin 5, or mesothelial cells (HBME-1). In perforation of appendicitis with both abscess and granulation tissue, a small to moderate or a moderate to large number of myofibroblasts appeared in the subserosal area around the perforation, respectively, but CD34-positive stromal cells were completely absent there. In the subserosal area of the perforation of appendicitis with abscess, cytokeratin 5-positive stromal cells were absent. However, a small to moderate number of cytokeratin CAM5.2-positive stromal cells were observed there. Double immunostaining showed the coexpression of alpha-smooth muscle actin (ASMA) and cytokeratin CAM5.2 and the coexpression of cytokeratin 5 and cytokeratin CAM5.2 in many or some stellate-shaped or spindle-shaped stromal cells existing in the subserosal area with granulation tissue around the perforation of appendicitis, respectively. Finally, many myofibroblasts appearing in the subserosal area of the perforation of appendicitis may be derived from submesothelial cells or mesothelial cells.

Previously we reported that immunization with pseudorabies virus (PRV), harboring chimeric Fc on the surface of the virus particles (PRV/Fc), induced higher immune responses than normal PRV particles. The chimeric Fc was fused with mouse transferrin receptor of transmembrane domain (mTR) and the Fc region of immunoglobulin G1. Since it has been reported that some chimeric protein of Fc and self-antigen induce auto-reactive antibodies, in this present study, we examined whether PRV/Fc induces auto-reactive antibodies that react with mTR. PRV/Fc immunized mice produced higher levels of anti-PRV antibodies and antibodies that reacted with mouse-derived 3T3/A31 cells (A31 cell), compared to normal PRV immunized mice. However, antibodies that reacted with mTR in A31 cells were not detected in both Western blot analyses and indirect immunofluorescence assay. The antibodies reacted with an antigen of approximately 16 kDa in A31 cells, but this antigen has a different molecular mass from that of mTR. The antibody also reacted with the antigen of approximately 16 kDa in RK13 cells in which the virus had been propagated. In addition, antibodies induced by immunization with normal PRV also reacted with the same antigen in A31 and RK13 cells. Moreover, neither kidney disorders, in which high levels of mTR were expressed, nor clinical symptoms of autoimmune diseases were observed in mice immunized with either PRV or PRV/Fc. These results indicated that the antibodies were not induced by mTR-Fc, but were instead induced by trace amounts of RK13 derived antigens contained in PRV or PRV/Fc preparations, and cross-reacted with equivalent molecules in mouse derived A31 cells. Therefore, this study confirmed that immunization with PRV/Fc did not induce harmful auto-reactive antibodies.

Vapor phase reactions in plasma polymerization of divinylsiloxane-bis-benzocyclobutene (DVS-BCB) low-k film depositions on 300mm wafers were studied using mass spectrometry, in situ Fourier transform infrared, and a surface wave probe. Polymerization via Diels-Alder cycloaddition reaction was identified by the detection of the benzocyclohexene group. Hydrogen addition and methyl group desorption were also detected in DVS-BCB monomer and related large molecules. The dielectric constant k of plasma polymerized DVS-BCB with a plasma source power range up to 250W was close to ∼2.7 of thermally polymerized DVS-BCB, and increased gradually over 250W. The electron density at 250W was about 1.5×1010cm−3. The increase of the k value at higher power was explained by the decrease of both large molecular species via multistep dissociation and incorporation of silica components into the polymer. It was found that the reduction of electron density as well as precursor residence time is important for the plasma polymeri...

Low-damage hard-mask (HM) plasma-etching technology for porous SiOCH film (k=2.6) has been developed for robust 65-nm-node Cu dual damascene interconnects (DDIs). No damage is introduced by fluorocarbon plasma etching irrespective of whether rigid (k=2.9) or porous (k=2.6) SiOCH films are used, due to the protective CF-polymer layer deposited on the etched sidewall. The etching selectivity of the SiOCH films to the inorganic HMs is kept high by controlling the radical ratio of carbon relative to oxygen in the etching plasma gas. However, oxidation damage penetrates the films from the sidewalls due to the O2 plasma used for photoresist ashing. This damage is increased by the porous structure. As a result, we developed a via-first multi-hard-mask process for the DD structure in porous SiOCH film with no exposure to O 2-ashing plasma, and we controlled the via-taper angle by RF bias during etching. We fabricated robust Cu DDIs with tapered vias in porous SiOCH film that can be applied to 65-nm-node ULSIs and beyond

Cisplatin (CP), a commonly used antineoplastic drug, is nephrotoxic. CP-induced nephrotoxicity involves oxidative pathways. A deficiency of selenium (Se) reduces glutathione peroxidase (GPx) activity resulting in oxidative stress. We investigated how Se deficiency or oral Se administration influences CP-induced nephrotoxicity. Thirty male Wistar rats were fed a Se-deficient or control diet for 4 weeks. Then they were given intraperitoneal (i.p.) CP alone, i.p. saline alone, or Se by gavage 24 and 1 h prior to i.p. CP. Blood and urine samples were collected and the kidneys were removed 5 days after CP treatment. Urinalysis, renal function, GPx activity, and expression of cellular GPx mRNA were measured. Histology was evaluated by light microscopy with immunohistochemistry for 4-hydroxy-2-nonenal (HNE), vimentin, and heme oxygenase (HO)-1. CP induced renal tubular damage with increased expression of vimentin, HO-1 and HNE staining, which represents lipid peroxidation. Se deficiency exacerbated CP-induced nephrotoxicity as shown by deterioration of the above parameters and depressed GPx activity and expression of GPx mRNA. Se treatment ameliorated CP-induced nephrotoxicity, but did not significantly improve renal function. These findings suggest that Se deficiency increases oxidative stress and enhances CP-induced nephrotoxicity, whereas oral Se treatment partially protects against the nephrotoxicity in rats.

Robust porous low-k/Cu interconnects have been developed for 65-nm-node ultralarge-scale integrations (ULSIs) with 180-nm/200-nm pitched lines and 100-nm diameter vias in a single damascene architecture. A porous plasma-enhanced chemical vapor deposition (PECVD)-SiOCH film (k=2.6) with subnanometer pores is introduced into the intermetal dielectrics on the interlayer dielectrics of a rigid PECVD-SiOCH film (k=2.9). This porous-on-rigid hybrid SiOCH structure achieves a 35% reduction in interline capacitance per grid in the 65-nm-node interconnect compared to that in a 90-nm-node interconnect with a fully rigid SiOCH. A via resistance of 9.7 /spl Omega/ was obtained in 100-nm diameter vias. Interconnect reliability, such as electromigration, and stress-induced voiding were retained with interface modification technologies. One of the key breakthroughs was a special liner technique to maintain dielectric reliability between the narrow-pitched lines. The porous surface on the trench-etched sidewall was covered with an ultrathin plasma-polymerized benzocyclobuten liner (k=2.7), thus enhancing interline time-dependent dielectric breakdown reliability. The introduction of a porous material and the control of the sidewall are essential for 65-nm-node and beyond scaled-down ULSIs to ensure high levels of reliability.

We observed postnecrotic tissue remodeling to examine vascularization in adult rat livers. Livers, bone marrow, and peripheral blood from rats at 24 h to 14 days after an injection of dimethylnitrosamine (DMN) were examined by light microscopic, immunohistochemical, and ultrastructural methods. Numerous ED-1 (a marker for rat monocytes/macrophages)-positive round mononuclear cells infiltrated in the necrotic areas at 36 h after DMN treatment. On day 5, when necrotic tissues were removed, some of the cells were transformed from round to spindle in shape. On day 7, these cells were contacted with residual reticulin fibers and became positive for SE-1, a marker of hepatic sinusoidal endothelial cells and Tie-1, an endothelial cell-specific surface receptor, associated with frequent occurrence of ED-1/SE-1 and ED-1/Tie-1 double-positive spindle cells. Ultrastructurally, the spindle cells simultaneously showed phagocytosis and endothelial cell-like morphology. With time necrotic areas diminished, and on day 14, the necrotic tissues were almost replaced by regenerated liver tissues and thin bundles of central-to-central bridging fibrosis. Bone marrow from 12 h to day 2 showed an increase of BrdU-positive mononuclear cells. Some of them were positive for ED-1. The BrdU-labeled and ED-1-positive cells appeared as early as 12 h after DMN injection and reached a peak in number at 36 h. They were similar in structure to ED-1-positive cells in necrotic liver tissues. These findings suggest that round mononuclear ED-1-positive cells proliferate first in bone marrow after DMN treatment, reach necrotic areas of the liver through the circulation, and differentiate to sinusoidal endothelial cells. Namely, hepatic sinusoids in DMN-induced necrotic areas may partly be reorganized possibly by vasculogenesis.

Recently we reported that a chimeric molecule containing mouse transferrin receptor and immunoglobulin G1 (IgG1) Fc, mTR-Fc, induced higher immune responses and can be used as a vaccine adjuvant. In this study, the immunological property of the molecule was investigated. Although, the mTR-Fc did not activate complement classical pathway, it was recognized by activated macrophage as like intact IgG Fc, which is recognized by macrophage via Fcgamma receptor. In addition, we found that splenocyte simultaneously exposed to lipopolysaccaride (LPS) and mTR-Fc produced higher amount of interleukin-10, comparing to that exposed to only LPS. These results suggest that the mTR-Fc molecules conserved the IgG Fc property to biasing immune responses via modulation of cytokine production by antigen presenting cell.

This paper reports the results of an experiment for testing the applicability of a Wireless Fidelity (WiFi) positioning system to tracking free-range chickens. In this system, the location of a chicken on a continuous plane (an experiment field) at any time was represented by a point (referred to as a location point) on a one meter square grid lattice, and the trajectory of a chicken by the sequence of its location points. The system recorded the location point of a chicken at every second. The experiment used eight Domestic Fowl (Gallus gallus domesticus) and two Helmeted Guineafowl (Numida meleagris galeata), which were kept freely in a park (170 by 90 m), where their spatial behavior was observed for five days. The complete data were collected for three days. Because the observed location points contained random noise, they were treated as probabilistic variables. Data analysis showed that location accuracy was 2.6 m with a probability of 0.95. The living space of a chicken was represented by a two-dimensional probability density function of location points. The function was estimated by the kernel method with the bi-weight kernel function whose bandwidth was 2.6 m. The trajectory of a chicken was estimated by the moving average method. This experiment showed that the WiFi positioning system was practically applicable to tracking free-range chickens.

The plasma-etching technology presented in this paper is for fabricating highly reliable Cu dual damascene interconnects (DDI) with organic low-k film through modification of the in situ etched surface during low-k etching. Nitrogen-based plasma with oxygen and high-molecular-weight fluorocarbon gas (C>2) chemically modifies the sidewall surface of the etched low-k film, changing it into the carbon nitride with fluorocarbon-polymer passivation from the etching gas. After wet cleaning, the fluorocarbon-polymer is removed selectively, leaving a carbon nitride modified layer (CNL) on the sidewall. The CNL has been found to suppress Cu diffusion into the low-k film. A stacked barrier structure of conventional barrier metal and CNL is expected to have high tolerance to Cu diffusion. Combining a dual-hard-mask etching sequence with the CNL modification, Cu DDIs with organic low-k film were fabricated with high yield.

An add-on-type, Pb(Zr,Ti)O/sub 3/ (PZT) metal-insulator- (MIM) capacitor on Al multilevel interconnects is developed for embedded FeRAM devices, concluding that the oxygen-doping into the ruthenium (Ru) electrodes is crucial for obtaining large remnant polarization under a limited process temperature below 450/spl deg/C. The oxygen-doped, Ru bottom-electrode with a granular structure reduces the PZT sputtering temperature below 450/spl deg/C to obtain the ferroelectric perovskite-phase. On the other hand, oxygen doping into the Ru top-electrode suppresses the reductive damage at the interface between the top-electrode and the PZT, keeping the leakage current low. The PZT MIM capacitor with these oxygen-doped, Ru electrodes exhibits the remnant polarization of 21 /spl mu/C/cm/sup 2/ on the Al multilevel interconnects with no degradation of the interconnect reliability, thus applicable to the embedded FeRAM in 0.25 /spl mu/m-CMOS logic LSIs.

Aim The purpose of our study was to elucidate factors in socioeconomic and family backgrounds of 3-year-old children in Tokyo, Japan that were associated with problematic behaviours among the children. Study design 670 eligible 3-year-old children underwent an evaluation of problematic behaviour by the Japanese Child Behaviour Checklist (CBCL/2–3) and of socioeconomic and family backgrounds. Results Stepwise multi-logistic regression analyses using all 28 variables showed that longer hours watching TV, smoking during pregnancy, coffee drinking during and after pregnancy increased, whereas higher family income, a larger number of older brothers/sisters, higher educational level of father decreased problematic behaviours. Maternal anxiety measured by trait anxiety using the STAI was associated with behaviour problems measured by CBCL, particularly with externalizing domains composed by aggressiveness, oppositional and attention domains. Conclusion These results suggest that problematic behaviours among children may be increased by adverse socioeconomic and family backgrounds that may be associated with maternal anxiety.

Chromosomal structure within the nucleus influences various biological processes such as transcription and replication. Telomeres are located at the end of eukaryotic chromosomes and they can be a decisive factor for correct chromosomal positioning. To gain new insight into telomere dynamics, we examined telomere length and positional changes during spermatogenesis using improved fluorescence in situ hybridization (FISH) and in situ telomeric repeat amplification protocols (TRAP) on histological sections. FISH revealed telomere length and chromosome position within nuclei change dynamically. Telomere extension occurred during spermiogenesis. In situ TRAP analysis verified elevated telomerase activity in elongating spermatids. Together, these data show that elongated spermatids have longer telomeres than precursor spermatogenic cells. This observation indicates that telomere elongation in haploid cells occurs after meiosis and in the absence of genomic replication. Analyses of testes from telomerase null mice further support the significance of telomere dynamics during spermatogenesis and the existence of an alternative telomere extension pathway.

The hindlimbs of the Malayan sun bear (Helarctos malayanus), the polar bear (Ursus maritimus), the brown bear (Ursus arctos) and the giant panda (Ailuropoda melanoleuca) have been anatomically and osteometrically studied. The Musculus tibialis cranialis of the Malayan sun bear and the giant panda possessed a well-developed rich fleshy portion until the distal end of the tibia. In the polar bear and the brown bear, however, the fleshy portion of the M. tibialis cranialis was not developed until the distal end of the tibia. The tendon of the M. tibialis cranialis inserting on the proximal end of the Ossa metatarsalia was shorter in the Malayan sun bear and the giant panda than in the polar bear and the brown bear. In the Malayan sun bear and the giant panda, moreover, the M. popliteus was attached more distally to the tibia than in the polar bear and the brown bear. The stable dorsiflexion and supination of the foot and the efficient pronation of the crus are important for skillful tree climbing. The present study suggests that the Malayan sun bear and the giant panda have hindlimbs especially adapted to tree climbing by the well-developed fleshy portion of the M. tibialis cranialis reaching the distal end of the tibia, its short tendon, and the M. popliteus inserting near the distal end of the tibia.

Sry is transiently activated in pre-Sertoli cells of the gonadal ridge to initiate testis differentiation in mice. In pre-Sertoli cells, however, the cellular events induced immediately after the onset of Sry expression remain largely unknown. Here we show that testis-specific glycogen accumulation in pre-Sertoli cells is one of the earliest cellular events downstream of Sry action. In developing XY gonads, glycogen accumulation starts to occur in pre-Sertoli cells from around 11.15 dpc (tail somite 14 stage) in a center-to-pole pattern similar to the initial Sry expression profile. Glycogen accumulation was also found in XX male gonads of Sry-transgenic embryos, but not in XX female gonads of wildtype embryos at any developmental stage. In vitro analyses using various culture conditions suggest that testis-specific glycogen deposition is a tissue-autonomous event that can be induced even in serum-free conditions and in a culture of gonadal explants without adjacent mesonephros. Moreover, glycogen accumulation in pre-Sertoli cells was significantly inhibited in vitro by the PI3K inhibitor LY294002, but not by the MEK inhibitor PD98059. Active phospho-AKT (PI3K effector) showed a high degree of accumulation in gonadal somatic cells of genital ridges in a testis-specific manner, both in vitro and in vivo. Therefore, these findings suggest that immediately after the onset of Sry expression, activation of the PI3K-AKT pathway promotes testis-specific glycogen storage in pre-Sertoli cells. To the best of our knowledge, this is a novel Sry-downstream cellular event which preserves this readily available energy source in Sertoli cells for testis-specific morphogenesis and hormone production.

Aromatase is an enzyme responsible for the conversion of androgen to estrogen. We genetically engineered an aromatase-deficient mouse (Ar - / - mouse) to express an enhanced green fluorescent protein (EGFP) gene in the uterus, ovary, adrenal and pituitary glands in a 17β-estradiol (E2)-inducible manner. In this study, we analyzed estrogenic activities of diethylstilbestrol, genistein, daidzein and E2 in the Ar - / - tissues by using the EGFP expression as an indicator. These analyses manifest differential responses of the tissues to the compounds and also allow to determine the relative estrogenic potency of the compounds to that of E2 in vivo. Furthermore, analyses of the EGFP expression in ERa-deficient mice suggested that the expression is ERa-dependent in the uterus and pituitary gland. In conclusion, the Ar - / - mouse carrying the E2-inducible EGFP gene is a valuable tool for quantitative analyses of natural and synthetic estrogenic compounds in vivo.

The performance and reliability of Cu/Low-/spl kappa/ damascene interconnects are investigated from the view point of the material interface structure. We are focusing especially on the heterointerfaces between the Cu and the barrier metal (BM), as well as between the hard mask (HM) and the capping barrier dielectrics (CAP) covered on the Cu interconnects. It is found that the highest via reliabilities of electromigration (EM) and thermal cycle are established by the barrier-metal-free (BMF) structure without the heterointerface between the Cu and the BM due to the strong Cu-to-Cu connection at the via bottom. The interline time-dependant dielectric breakdown lifetime is improved mostly by using a HM with the same materials as the CAP layer, referred to as an unified structure, which diminishes the heterointerface between the HM and the CAP. These ideal structures without the material heterointerfaces derive the highest reliability and performance. Structural control of the material heterointerfaces in the actual Cu/low-/spl kappa/ damascene interconnect is crucial for the high reliability and performance.

Sertoli cell tumor of the testis (not otherwise specified) in a 43-year-old man is reported. Macroscopically, the testicular mass measured 3.0 x 2.3 x 1.5 cm and was well circumscribed. The cut surface was white to tan-gray in color. Neoplastic cells with eosinophilic cytoplasm proliferated with solid and tubular structures. Neoplastic cells focally contained vacuoles of various sizes in the cytoplasm. Cystic formation and cord formation in the hyalinized stroma was also observed. Immunohistochemically, neoplastic cells were positive for cytokeratin 8, chromogranin A and synaptophysin, but neoplastic cells were negative for placental alkaline phosphatase, inhibin-alpha and pancytokeratin. The stroma in the tumor center and capsule contained a significant number of myofibroblasts that were positive for alpha-smooth muscle actin and negative for h-caldesmon, but no CD34-positive stromal cells were detected in the stroma of the tumor center. Ultrastructurally, neoplastic cells had cytoplasmic processes and abundant rough endoplasmic reticulum and lipid droplets in the cytoplasm. However, dense core granules were absent. It is important to differentiate between Sertoli cell tumor and carcinoid tumor because of the positive reaction for neuroendocrine markers in both tumors. Myofibroblasts are a major stromal component of Sertoli cell tumor of the testis.

Background: Obesity, hypertriglyceridemia, and diabetes have been reported as frequent complications observed in patients with nonalcoholic steatohepatitis (NASH) in Western countries. The aim of this study was to investigate the genetic predisposition on NASH pathogenesis in the Japanese population. Methods: Genotypes of two previously described functional polymorphisms—β3-adrenergic receptor 190 T/A polymorphism, which results in Trp64Arg (W64R) amino acid replacement, and interleukin-1β-511 T/C polymorphism in the promoter sequence—were determined in 63 Japanese NASH patients and 100 healthy volunteers using polymerase chain reaction and restriction fragment length polymorphism. Results: β3-adrenergic receptor R allele frequency and the R/− (W/R and R/R) genotype frequency were significantly higher in NASH patients than those in control subjects. Interleukin-1β-511 T allele frequency and the T/T genotype frequency were significantly higher in NASH patients than those in control subjects. Obesity, hypertriglyceridemia, and hyperinsulinemia were associated with NASH patients with the R/− genotype, whereas an increase in fasting plasma glucose level and a decrease in insulinogenic index were associated with NASH patients with the W/W genotype. Conclusion: This study confirmed the contribution of obesity, glucose intolerance, and hypertriglyceridemia to NASH development in the Japanese population. In addition to these factors, genetic predispositions to obesity and inflammation in the Japanese population were shown to contribute much to the development of NASH.

Low-grade tubular-mucinous renal neoplasm (LGTMRN) was recently established as a distinct carcinoma classification. A 70-year-old, female traffic accident victim underwent a detailed examination that disclosed a huge mass in the lower pole of the left kidney. The patient underwent a nephrectomy based on a diagnosis of renal tumor. Macroscopically, the tumor was well demarcated and a whitish color with focal hemorrhage. Histological examination showed that tumor cells proliferated through tubular, trabecular, and solid growth patterns in the mucinous background. Focally, foci of clear cells or the proliferation of spindle cells was also observed. Nuclei were generally round and uniform in size. No abnormal mitotic figures were identified. Immunohistochemically, tumor cells were diffusely positive for AE1/AE3, vimentin and chromogranin A, and focally positive for cytokeratin (CK) 18, CK19, Ulex europaeus agglutinin-1, epithelial membrane antigen, neuron-specific enolase (NSE), CD9 and CD57. Ultrastructurally, tumor cells contained a moderate number of mitochondria, rough endoplasmic reticulum and dense-core granules. No renin granules or glycogen were observed. Microvilli were focally seen. Our results render further evidence that LGTMRN is a distinct entity from the hitherto established renal neoplasms. Foci of clear cells and neuroendocrine differentiation should be added to the histological spectrum of LGTMRN.

We examined the phylogeographic structure of the Lesser Mouse deer (Tragulus javanicus) and the Greater Mouse deer (Tragulus napu) from sequence data of mitochondrial cytochrome b gene. Three major clusters were observed on phylogenetic trees, as follows: 1) T. javanicus from the Asian mainland (Malayan Peninsula and Laos), 2) T. javanicus from Borneo Island (Sabah, Malaysia), 3) T. napu from Borneo and Pulau Tioman. Tragulus napu forms the sister lineage to all populations of T. javanicus, thereby supporting the current separation of these taxa at species level and traditional taxonomical identification of the two species by throat color. Within T. javanicus, the primary genetic separation is between the Borneo Island population and those from the Southeast Asian mainland. We suggest that subspecies should be recognised within this widespread taxon. A secondary separation within T. javanicus is observed between populations to the north and south of the Isthmus of Kra.

Meckel-Gruber syndrome (MGS) is a rare disorder characterized by occipital encephalocele, polydactyly and polycystic kidney. Early diagnosis is very important because MGS has a high risk of recurrence and infants with MGS are frequently stillborn or die soon after birth. An autopsy case of MGS is presented and the focus is specifically on the myofibroblastic cells of the liver and polycystic kidney. Although routine histological examination did not reveal hepatic fibrosis, a specific distribution of alpha smooth muscle actin (alpha-SMA)-positive and h-caldesmon (h-CD)-negative stromal cells (myofibroblastic cells) was observed along the limiting plate of the portal area. Furthermore, myofibroblastic cells were focally distributed along the sinusoidal wall and around the bile ducts in the portal area. In the polycystic kidney, the presence of myofibroblastic cells in the stroma between the cystic lesions was also confirmed by electron microscopy. In conclusion, myofibroblastic cells were distributed in the liver and kidney of a patient with MGS and their specific distribution in the liver may be indicative of prestage hepatic fibrosis.

The aim of this study was to investigate the phenotypes of antigen (Ag) presenting cells (APCs) in the conjunctiva during the development of experimental immune-mediated blepharoconjunctivitis (EC), which serves as a model for investigation of severe types of human allergic conjunctivitis.Brown Norway rats treated by ovalbumin (OVA) were used in this study. To confirm the restriction of MHC class II by OVA-specific T cells, monoclonal Abs against MHC class II were added to the conventional proliferation assay. To evaluate the MHC class II expression in the conjunctiva during the development of EC, an immunohistochemical analysis, either as the single or double staining, was performed. Conjunctival fibroblast cell lines were established from naive rats and the MHC class II expression was evaluated by flow cytometric analysis. To examine the roles of costimulatory molecules, OVA-specific T cells were stimulated with anti-TcR Ab and anti-CD28 Ab and then subjected for Western blotting to evaluate the ERK phosphorylation. Finally, in vivo expression of B7 molecules was examined immunohistochemically.OVA-specific T cells recognized OVA in the context of MHC class II. MHC class II was expressed in conjunctival macrophages but not in fibroblasts. EC induction was accompanied by abundant infiltration of macrophages positive for MHC class II. MHC class II was also expressed in conjunctival epithelial cells by EC induction. Stimulation from CD28 was necessary for ERK phosphorylation. B7-2, but not B7-1, was expressed in the conjunctiva.Conjunctival macrophages may represent a major source of APCs for the induction of EC in the conjunctiva.

We osteometrically examined the skulls of the black giant squirrel (Ratufa bicolor) from three mainland populations (M. Malayan Peninsula, V. South Vietnam, and B. Burma, India and North Thailand) and from two island populations (T. Tioman, and S. Sumatra Islands). The skull in the Malayan peninsula population was significantly smaller than that of the two other mainland populations. It is consistent with Bergmann's rule as shown in the gray-bellied squirrel. The two island populations did not show obvious differences in comparison with the Malayan population in many measurements. In the proportion analysis eliminating the size factor, the differences among populations were not easily confirmed and we concluded that the osteological characters peculiar to each population could not be shown in this species. The first and second principal component scores of M, S, and T populations were intermingled, whereas the V and B populations of V and B were not separated in the chart. We pointed out that the morphological differences were demonstrated between northern and southern groups of the Isthmus of Kra in the mainland populations, and that the two island populations did not show the island-isolation effect in comparison with the M population. The adaptational variation related to feeding and locomotion could not be confirmed among populations of the black giant squirrel as shown in the proportion analysis.

The geographical variations of the skulls were osteometrically examined in the gray-bellied squirrel (Callosciurus caniceps) from the populations of Korat, Ranong, southernmost Thailand, and Terutau Island. The skull size was larger in northern population than in the southern population in the continental mainland. The zoogeographical influences of the Isthmus of Kra remained unclear, since the plots from Korat population were intermingled with those from southernmost Thailand population in the principal component charts. Although Korat population has been thought to belong to north group, we suggest that Ranong and southernmost Thailand populations may contain individuals from both north and south groups separated by the ancient Kra barrier. Terutau Island population was similar to southernmost Thailand population in skull size, although Terutau population has been isolated in the island and separated from the south group of the Isthmus of Kra. In the proportional analysis the interorbital space was narrower and the binocular sense has been well-developed in Terutau population. It suggests that this population has been highly adapted to arboreal behavior. In contrast, the skull with larger interorbital space was more adaptive for terrestrial life in Korat population. The canonical discriminant analysis could clearly separate the four populations in the scattergrams of discriminant scores.

セキショクヤケイ(G.gallus)の亜種認識に関する統一の見解は現在も得られていない。一般にセキショクヤケイの亜種は生息地,羽装,耳朶色などによって分類される。また,その広大な生息地にはさまざまな気候や植生が存在する。このような環境条件は草むらに身を隠す習性をもつセキショクヤケイの羽装に影響を与えている可能性が考えられる。さらに羽装は繁殖季節によって影響を受けやすい形質であり,また観察条件や観察者の主観によっても異なる。耳朶色に関しても,赤色と白色の2形質が亜種分類の基準にされてきたが,白耳朶は単一遺伝子により発現する形質ではないことが報告されている。従来の分類ではG.g.murghi,G.g.jabouilleiおよびG.g.bankivaの3亜種は大きさや羽装によって明確に分類されている。G.g.gallusとG.g.spadiceusの分類に関しては,G.g.gallusに完全白耳朶と不完全白耳朶の2型の存在が認められているが,現在ではそれらを一括してG.g.gallusとし,赤耳朶のG.g.spadiceusとは耳朶色のみによって区別している。タイとマレーシアのG.g.gallusにおいて,タイのG.g.gallusは完全白耳朶,マレーシアのG.g.gallusは不完全白耳朶を呈し,両者の生息地はG.g.spadiceusの生息地によって分断されている。もし白耳朶形質の完全,不完全を亜種分類の根拠とするならば,G.g.gallusはさらに2つのグループに分類することもできる。さらにmtDNA情報を用いたいくつかの研究においても,この分類を示唆する結果が報告されている。したがってセキショクヤケイの亜種分類は,これまでの形態学的手法を新たな視点で見直すとともに,最新の空間分析や分子遺伝学などの手法などを用いることが望ましいと考えられる。