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We previously demonstrated that spinal protein kinase C (PKC) is involved in the development of a neuropathic pain-like state induced by sciatic nerve ligation, and the morphine-induced rewarding effect is attenuated by sciatic nerve ligation in rodents. Here we first investigated whether sciatic nerve injury could change the activity of a conventional PKC (cPKC) and an atypical PKC isoform PKCzeta in the mouse spinal cord. The second experiment was to investigate whether direct inhibition of spinal PKC by intrathecal (i.t.) administration of a specific PKC inhibitor, 2-[8-[(dimethylamino)methyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-3-yl]-3-(1-methyl-1H-indole-3-yl)maleimide (RO-32-0432), could affect the rewarding effect induced by morphine following sciatic nerve ligation in mice. We found here that the activities of both cPKC and PKCzeta in the spinal cord were clearly increased following sciatic nerve ligation. Furthermore, i.t. administration of RO-32-0432 reversed a long-lasting pain-like syndrome as indicated by thermal hyperalgesia following sciatic nerve ligation in mice. These data provide direct evidence that activated cPKC and PKCzeta in the spinal cord may contribute to the development and maintenance of neuropathic pain. In the present study, we confirmed that the morphine-induced place preference was significantly suppressed by sciatic nerve ligation. It should be mentioned that i.t. pretreatment with RO-32-0432 significantly reversed the attenuation of morphine-induced rewarding effect following sciatic nerve ligation. These results suggest that activation of PKCs, including cPKC and PKCzeta, within the spinal cord is directly responsible for the attenuation of the morphine-induced rewarding effect under a neuropathic pain-like state following sciatic nerve ligation in mice.

This work presents the results of the determination of uranium concentration in the most commonly used phosphate fertilizers employed in Brazilian agricultural land. The technique employed was the nuclear fission track registration in plastic foils of Makrofol KG (dry method), together with a discharge chamber system for track counting. Phosphate fertilizer samples and uranium standards were irradiated together with thermal neutrons in the 2 MW IEA-R1 research reactor of IPEN/SP. The uranium concentration in Brazilian phosphate fertilizers ranging from 5.17 to 54.3 ppm is in good agreement with the results reported in the literature for similar fertilizers produced in other countries.

Since transmission lines pass through urban districts, national parks or along trunk roads and so on, we have often been asked to assess the impact which steel tower make on landscape by residents. Therefore, we have adopted special towers aiming at landscape impact reduction (environment harmony steel tower (EHST)), making several improvements on shape and color since around 1970. It varies with tower types however, the cost of EHST is 2 to 5 times higher than that of truss steel tower, which is normally used. It is the reduction of investment amount for reinforcement of facilities that all Japanese electric power companies think the most important problem, and each electric power company have made effort to accomplish low cost as well as consideration to environment simultaneously. Diverse preferences for EHSTs make it difficult to select appropriate tower for the sight. Therefore, TEPCO examines the possibility of introducing new EHST selecting method, that is, making local residents choose a tower among several candidate low cost EHSTs. In this paper, we introduce examination results of four kinds of low cost EHSTs for adoption to 500 kV overhead transmission line (simple truss type, rigid frame (H steel) type, triangular tie-rod type, octagonal truss type). The costs of these low costs EHSTs are all less than 1.2 times higher than those of normally used truss steel towers.

This paper proposes a new concept of real time image directory, for retrieving the designated live images from the index obtained by subtracting one image frame from the other in a stream of moving images. An example was demonstrated for a wild bird.

We have demonstrated noncritical phase matchable second harmonic generation of a Nd:YAG laser in Gd/sub 0.275/Y/sub 0.725/Ca/sub 4/O(BO/sub 3/)/sub 3/ (GdYCOB) at room temperature. The advantages, such as the high stability for angular and temperature variation, nonhygroscopicity, and ease in growing large crystals, suggest that the GdYCOB crystal is an attractive candidate for a high power green laser.

We present a method for mechanical stiffness control of the tendon-driven joints of a manipulator. First we propose a formula for controlling the joint stiffness and the joint angles independently. Next, we propose an elastic mechanism (nonlinear elastic module, NLEM) of which nonlinear elastic characteristics are easily designed. It is situated between the actuator and the tendon and it plays a key role for mechanically controlling the stiffness. Two types of the NLEM are designed and produced. A computer simulation of and experiments on the stiffness and joint displacement control, which show validity of the proposed formula are described.

This paper describes the reduction of the waiting time for users in high performance image retrieval systems on multimedia networks. Both the processing times for the systems and waiting times for the users were measured in the image retrieval systems. The processing time was found to be reduced to one-half of that in the conventional system when the image directories were installed in the new system. A mathematical model to derive the waiting time W from the processing time P was obtained as /spl lambda/ P/sup 2//(1-/spl lambda/ P), where /spl lambda/ is the rate of occurrence of the requests for the image retrieval. The calculated values were confirmed to agree with experimental data. Based on the studies, a high-speed image retrieval system was constructed using an image directory. When the processing time for the image retrieval decreased to one-half of that in the conventional system, the waiting time became approximately one eighth of the original value.

Summary form only given. In previous work, we reported that yttrium calcium oxyborate YCa/sub 4/O(BO/sub 3/)/sub 3/ (YCOB), which was an isomorph of GdCOB, was phase matchable for third-harmonic generation (THG) of Nd:YAG laser by type I sum frequency mixing, and it possessed moderate optical nonlinearity, sufficient mechanical hardness, and nonhygroscopicity. Recently, we succeeded to grow a substitutional solid solution of Gd/sub x/Y/sub 1-x/Ca/sub 4/O(BO/sub 3/)/sub 3/ (GdYCOB) with uniform composition. We could achieve a noncritically phase-matching (NCPM) at room temperature for THG of Nd:YAG laser with this crystal at x=0.24.

We propose an automated vector compression of bird songs spectra in water-sites by linear prediction method and principal component analysis, and present the experimental validation of the special features and effectiveness of the proposed method through automatic Bayesian discrimination of compressed vectors of the 14 different songs gathered. The result shows that the whole information to classify the songs completely can be fundamentally compressed to a vector of at least 30 dimensions consisting of the variance of residue series and optimal prediction coefficients. Further compression is proposed by unification of covariance matrices of different characteristics among the classes, and principal component analysis has the special features that it makes Bayesian discrimination possible even for cases where the conventional can not conduct the discrimination, with enhanced rates of 1.58 to 1.73 times and within reduction of mean correct classification rate only of 0.8%.

It is necessary to introduce nitrogen and phosphorus removal processes in the existing wastewater treatment plants of Fukuoka City to improve the water quality of Hakata Bay. An A2/O (anaerobic-anoxic-oxic) process using immobilized media is proposed here, as a high-end technology to meet stricter discharge standards when faced with treatment space limitations. In order to investigate the applicability of the process, a pilot-scale study using municipal wastewater was conducted. Fluidized immobilization media were added to the aerobic reactor to maintain a high concentration of nitrifying bacteria and nitrification rate. Relationships between nutrient removal performance and varied operating conditions were examined. The results of the pilot plant test indicated that the process performs well for removal of nitrogen and phosphorus. Under the condition of HRT = 8 hr, it was possible to obtain an effluent water quality as follows: T-N8.0 mg/L; T-P1.0 mg/L. It was observed that reaction time needed for a complete nitrification was shortened by the addition of immobilized media to the aerobic reactor, and longer reaction time would be needed for a completed phosphorus uptake process other than complete nitrification in an aerobic tank. Therefore, the phosphorus uptake rate, as well as nitrification process, should be considered as one of the important factors affecting the design parameters of an aerobic reactor.

The authors describe some specific features of VLSI manufacturing and concepts for factory automated systems for large-volume mass production and for large-variety production. An automated system for a pilot line in a laboratory and future trends are also discussed. >

We studied some characteristics of a double-sided Metal-In-Gap (DMIG) nano composite slider that has a low inductance structure, Fe-Ta-N type of magnetic film and new geometrical configuration of the gap area. The inductance of this head is approximately 1.0 nH/T/sup 2/. The electrical performance of this head has been evaluated with 5.5 /spl mu/m Track Width and 0.25 /spl mu/m Gap Length for 1800 Oe media. O/W is less than -34 dB at 53 kFCI. Output voltage is more than 150 nVp-p/(um.m/s.turns) at 53 kFCI. This performance is seen to be promising for 250 Mb/in/sup 2/ recording. >

The authors summarize the algorithm, architecture, and implementation of an LSI that can perform discrete cosine transform (DCT), inverse DCT (IDCT), motion estimation (ME), and video data statistical processing for inter/intra decision (DECISION) at 2.59 GOPS (giga operations per second). This LSI can perform the DCT, IDCT, ME and DECISION in a single chip by switching mode signals. The LSI has a power consumption of 2 W at 40.5-MHz input clock. The chip, designed in a 0.8-/spl mu/m, double-metal CMOS technology, has 405,000 transistors and a die size of 13.86 /spl times/ 13.51 mm/sup 2/.

We show how we have successfully identified the bug of a real chip by using formal verification techniques. Since excessive number of simulation cycles are necessary to debug the chip design, formal verification techniques, specifically CTL symbolic model checking, were adopted to identify the bug. We demonstrate several approaches including abstraction, which make it possible to apply symbolic model checking methods. The methods and ideas reported here are general enough for diagnosing other real chips. >

We present two logic synthesis systems which have been tuned for different purposes and a new one which is now being developed. The first one, ZEPHCAD, has been tuned for synthesizing control parts in the chip design. ZEPHCAD was developed in 1988. The other, FLORA, has been tuned for synthesizing datapath dominated chip designs. FLORA was developed in 1986. We are developing a new logic synthesis system which unifies the above two. They have been working well so far. However, the size of the LSI chip has been increasing year by year, creating many problems such as in CPU processing time, required memories, timing adjustment, and so on. We are especially preoccupied by the timing adjustment factor. The timing adjustment factor in both the setup and hold constraints of the entire chip is becoming more and more difficult because of the line delay effect. It is in the new logic synthesis system that the timing adjustment problem will be alleviated. >

A new fabrication method for Si single-electron transistors (SETs) is proposed. The method enables us to fabricate, in a self-aligned way, a twin-island SET in which two Si islands are aligned in parallel. Experimental devices demonstrated, at 40 K, that the twin-island SET structure can be operated as two individual SETs. Since the two SETs are packed in a tiny area, this method is suitable for constructing logic circuits based on pass-transistor-type logic and CMOS-type logic, which promises to lead to single-electron logic LSIs.

This paper describes a new type of image directory for butterflies, called an image navigation directory, which retrieves a desired image referring to a series of typical sample images specified as keys in place of keywords. After the image coming from the imagination of the user is sketched on the display, the image navigation directory having three functions is used to retrieve the desired image. In order to facilitate these functions, parameters are defined. The desired images can be retrieved from the distributed image databases all over the world using the image navigation directory. As an application of this concept, an image retrieval system of butterflies was generated utilizing the functions of the image navigation directory.

This paper describes a new image database system which combines distributed image databases utilizing a directory. The directory was generated to decrease the processing time to retrieve the desired photographic image from the distributed image databases which store a number of photographic images. A prototype of image database system of butterflies was constructed utilizing the directory. When an image database system without utilizing the directory was used, the processing time to obtain the resembled sample images was approximately 35.37 seconds. When the prototype system utilizing the directory was used, the processing time to obtain the resembled sample images was reduced to be approximately 18.36 seconds. On the basis of the result of the experiment, an application of the directory was found to be effective in an image database system which combines large-scale distributed image databases. Utilizing the directory, one can efficiently retrieve the desired image from the distributed image databases with a reduced processing time within a short period time.

When optical fiber radiation measurements are applied for a high dose rate area, there has been a problem of radiation induced loss in the optical fibers. In this study, red and near infrared (IR) fluorescence from rare earth ions has been used to reduce the problem. From continuous measurements using Gd/sub 2/O/sub 2/S:Pr/sup 3+/, the superiority of using long wavelength emission has been shown from the view point of radiation hardness. Linear relation between dose rate and peak counts was confirmed and it shows the possibility of using the long wavelength emission for radiation measurements. For calibration of the radiation induced loss, the optical time domain reflectometry (OTDR) technique has been applied. It has been shown that this method can broaden the dose rate limit of the optical fiber based measurements. Also, glass samples doped with rare-earth ions have been made and irradiated by gamma rays. Emission at a longer wavelength than 700 nm has been observed for Eu/sup 3+/ ions doped into silica, fluorophosphate and ZBLAN glass samples. Considering that it is easy to make silica glass and to connect it to usual silica glass optical fiber, silica glass doped with Eu/sup 3+/ is thought to be the most promising material for new scintillating fibers with high radiation resistivity.

A new image-search method is proposed for the distributed database environment. An agent is introduced in a search method that offers the best search technology in distributed database utilizing the directory database as an index of the search. A system model has been constructed based on the categorization of data and on the cost evaluation of the communication lines. The total serviceability is of prime interest to the system. The objective of this research is to develop the technologies for an image-based virtual museum in Hamamatsu city. The brief description of a new plan is also presented.

We present an abstraction technique for formal hardware verification by which we can verify realistic site chips for communication systems. The abstraction method makes it possible to abstract away datapaths relating to the packets format of communicating data. We successfully applied it to verification of the buffer control operations in one of our communication chips in parallel to the design process.

Based on the visual information processing system in the brain, we developed an association cortex to entorhinal - hippocampal neural network model (AEH model) for learning and recollection of human faces. We evaluated the learning and recollection performance of the AEH model by computer simulation. We presented each human face to the AEH model twice. We regarded that the AEH model recognized each face correctly if the AEH model learned the face the first time and recalled it the second time, in accordance with human perception. In the experiment, ten human faces were successively presented to the AEH model. The recognition performance of the model was 100 percent correct, indicating the effectiveness of the representation and transformation algorithm of the AEH model.

Nasu-Hakola disease (NHD) is an autosomal recessive disorder characterized by presenile dementia and bone cysts. Finnish patients revealed a large deletion in DAP12 gene encoding a key element for transducing activation signal. The authors examined six Japanese cases for DAP12 alleles. Five of the six had loss-of-function mutation, either a single-base deletion or a novel point mutation. The single patient without mutation normally expressed DAP12 protein. Japanese NHD has at least three genetic forms regarding DAP12.

In mammalian somatic cells, the X chromosome is active in XY males, whereas one X chromosome is inactivated in XX females. On the active male X chromosome, the XIST and TSIX genes are transcribed in undifferentiated cells of pre-implantation embryos (undifferentiated state) and then down-regulated upon cell differentiation (differentiated state). To explore the epigenetic mechanism involved in the on-off switching of XIST and TSIX transcription in the active X chromosome, male somatic cells were hybridized with male embryonic stem (ES) cells. Fluorescence in situ hybridization analysis revealed that the XIST gene derived from somatic cells was derepressed, as shown by the advent of two pinpoint signals. This was confirmed by strand-specific RT-PCR of XIST and TSIX genes. To analyze changes in chromatin structure in the promoter regions of XIST and TSIX derived from somatic cells, histone tail modifications were studied by chromatin immunoprecipitation analysis. Histones H3 and H4, which were hypoacetylated in the somatic cells, were hyperacetylated in the hybrid cells, and histone H3 lysine 4, which was hypomethylated in the somatic cells, was hypermethylated in the hybrid cells, indicating that the reactivation of XIST and TSIX was linked with chromatin modifications. In the telomeric region of DXPAS34, acetylation of histones H3 and H4 was dependent on reactivation of XIST and TSIX, whereas histone H3 lysine 4 was constitutively methylated independent of the transcriptional activity of those genes. We propose that the chromatin reprogramming is linked with the resetting of the memory found in the process of choosing an active X chromosome.

A meta-analysis by the Cochrane Stroke Group (CSG) showed that thrombolytic therapy increased deaths as well as symptomatic and fatal intracranial hemorrhage within the first seven to 10 days and at final follow-up, although these risks are offset by a reduction in disability in survivors, so that there is overall a significant net reduction in the proportion of patients dead or dependent. Trials testing intravenous (i.v.) tPA suggest that it may be associated with less hazard and more benefit. A recent trial demonstrated that intra-arterial pro-urokinase improved long-term outcome in patients with M 1 or M 2 occlusion within 6 hours of onset. Trials of the third generation of thrombolytic agents are ongoing in patients with acute ischemic stroke. The latest CSG's meta-analysis showed that immediate anticoagulant therapy in patients with acute ischemic stroke was not associated with net short or long-term benefit because there was no evidence that anticoagulant therapy reduced deaths or non-fatal stroke during treatment or patients dead or dependent at the end of follow-up. However, an i.v. low-molecular-weight heparinoid showed a trend toward improving long-term outcome in subgroup of patients with atherothrombotic stroke. The thrombin inhibitor argatroban was proven to be comparable to the thromboxane A2 synthetase inhibitor ozagrel in the effect on the outcome at one month in patients with atherothrombotic stroke within 48 hours of onset in Japan, and a trial of the agent is ongoing in patients with ischemic stroke within 12 hours of onset in the United States. Two large trials of aspirin in patients with ischemic stroke within 48 hours of onset indicated that aspirin had a modest effect on reducing patients dead or dependent at the end of follow-up. An international trial of abciximab, a monoclonal antibody directed against platelet glycoprotein IIb/IIIa, is ongoing in patients with ischemic stroke within 6 hours of onset.

We describe a patient diagnosed with lethal perinatal hypophosphatasia with a unique clinical presentation of convulsions that responded to vitamin B6. Genomic DNA sequence analysis of the tissue-nonspecific alkaline phosphatase (TNSALP) gene revealed two missense mutations: a G-to-A transition resulting in a Glu to Lys at codon 274 (E274K), and a G-to-C transversion resulting in a Gly to Arg at codon 309 (G309R). The first mutation was maternally transmitted and was previously characterized as a moderate one, whereas the latter was paternally transmitted and has not been previously reported. Phenotype/genotype correlation indicates that G309R is a deleterious mutation that can lead to seizures and a lethal outcome, as was demonstrated in our patient.

We reported a 64-years-old woman with pachymeningitis associated with a ruptured mycotic cerebral aneurysm due to Aspergillus infection. She had suffered from diabetes mellitus and been treated since she was 49 years old. She complained of headache at the age of 62 and loss of her left visual acuity three months later. She was treated by the pulse therapy of methylprednisolone as neuritis retrobulbaris and her visual acuity recovered. But her headache continued. Three months later, her right visual acuity was lost, and the pulse therapy was not effective this time. Six months later, she died of subarachnoid hemorrhage following acute meningitis. The autopsy was granted, but limited to the cranial cavity. Macroscopically, it disclosed brownish thickened dura around sella turucica involving trigeminal ganglion and optic nerve, and fresh subarachnoid hemorrhage in the basal cisterns and a ruptured aneurysm (3 mm in diameter) between internal carotid and posterior cerebral artery on the left side. Histologically, the brownish thickened dura was infiltrated by lymphocytes, plasma cells, and multinucleated giant cells. The wall around the aneurysm was infiltrated by lymphocytes and plasma cells as well as many fungi. Immunohistochemistry demonstrated the presence of Aspergillus in the thickened dura and the arterial wall around the aneurysm. There were lymphocytes and plasma cell infiltration in the basal subarachnoid space and scattered microabcesses in the brain. Although the first entry of Aspergillus to the dura was unclear, we assume that the final intravascular dissemination of Aspergillus from the dura caused meningitis and mycotic aneurysm.

Ghrelin, a novel growth hormone (GH)-releasing peptide, was recently isolated from the rat stomach as an endogenous ligand to growth hormone secretagogue receptor (GHS-R). Ghrelin specifically stimulates the release of GH from the rat anterior pituitary gland, but the regulational effect of ghrelin on GH secretion has not yet been clarified. We used a perifusion system to examine the single effect and combined effects of ghrelin with growth hormone-releasing hormone (GHRH) and somatostatin on GH secretion from rat anterior pituitary cells. The increase in GH concentration due to ghrelin stimulation showed a transitory peak that was almost the same as that previously reported for GHS, but apparently distinct from that of GHRH. Ghrelin (10(-10) M to 10(-8) M) stimulated GH secretion from the rat anterior pituitary cells in a dose-dependent manner. Serial ghrelin stimulation of the dispersed cells at 1-h intervals decreased the GH response, but the response recovered with stimulation at 3-h intervals, indicating that ghrelin strongly desensitized cells. Costimulation with ghrelin and GHRH elicited neither a synergistic nor an additive GH response from the rat pituitary cells. Furthermore, pretreatment to anterior pituitary cells with somatostatin strongly abolished ghrelin- and/or GHRH-stimulated GH secretion. In this study, we demonstrated that ghrelin caused weaker GH secretion than that caused by GHRH, and we also showed that costimulation with GHRH had no additive or synergistic effect on GH secretion, suggesting that ghrelin indirectly affects coordinated GH release from pituitary gland, as found in vivo.

Antioxidant activity of green tea extract or tea-derived polyphenols has been extensively studied. However, antioxidant activity in the non-polyphenolic fraction of green tea has been poorly analyzed. In the present study, we analyzed the antioxidant activity of the non-polyphenolic fraction of the residual green tea (Camellia sinensis) after hot water extraction using the aluminum chloride method. The non-polyphenolic fraction of residual green tea caused a significant suppression against hydroperoxide generation from oxidized linoleic acid in a dose-dependent manner. When the concentrate of the non-polyphenolic fraction was applied to a silica gel TLC plate and developed, six color spots were observed, which were considered to be chlorophylls a and b, pheophytins a and b, carotenoids, such as beta-carotene and lutein according to their specific colors, Rf values of silica gel TLC and spectrophotometric properties. Among these pigments, pheophytins a and b showed relatively abundant amounts, and the second major group of the pigment was chlorophylls a and b, and carotenoids such as beta-carotene and lutein indicated lower concentrations. Although all these pigments exhibited significant antioxidant activities, the ranks of suppressive activity against hydroperoxide generation were chlorophyll aluteinpheophytin achlorophyll bbeta-carotenepheophytin b. These results suggest that the non-polyphenolic fraction of residual green tea has a potent suppressive activity against hydroperoxide generation from oxidized linoleic acid, which is derived from the antioxidant activities of chlorophylls a and b, pheophytins a and b, beta-carotene and lutein. This finding also implies that the combined intake of polyphenols in water-soluble fraction and antioxidative pigments in the non-polyphenolic fraction of green tea will be more efficient to prevent life style-related chronic diseases.

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in Japan since July 1982. This paper describes the results obtained in fiscal 1998 (from April 1998 to March 1999). The number of cases investigated as objectives was 225 for one year. A total of 429 strains (121 strains from primary infections and 308 strains from postoperative infections) were isolated from 183 cases (81.3% of total cases). In primary infections, the isolation rates of anaerobes and Escherichia coli were higher than in postoperative infections, while in postoperative infections, those of Gram-positive aerobes and Pseudomonas aeruginosa were higher than in primary infections. On the whole, among Gram-positive aerobes, the isolation rate of Enterococcus faecalis was the highest, followed by Staphylococcus aureus with high frequency in isolation from postoperative infections. Among Gram-positive anaerobes, Peptostreptococcus spp. and Streptococcus spp. were predominantly isolated. Among Gram-negative aerobes, E. coli, P. aeruginosa, Klebsiella pneumoniae and Enterobacter cloacae were frequently isolated. Among Gram-negative anaerobes, Bacteroides fragilis group was the majority of isolates. In primary infections, the percentage of Gram-negative aerobes has gradually increased since fiscal 1995 or 1996 with these years as the turning point, while those of Gram-positive and Gram-negative anaerobes have gradually declined. In postoperative infections, the percentage of Gram-negative anaerobes has increased continuously since the mid-1980s. The percentage of MRSA among S. aureus rose to 89.7%, which was the highest level since the beginning of this study. The susceptibilities of B. fragilis, which did not show apparent changes, were recognized to have decreased against cephems in fiscal 1998. Among other bacteria in B. fragilis group, development of resistance to cephems has continued on a long-term basis since the mid-1980s. E. coli and K. pneuminiae have obviously not changed in susceptibilities, however, the susceptibilities of isolated strains in fiscal 1998 against high-generation cephems, oxacephems and monobactams have declined. We found neither vancomycin-resistant nor teicoplanin-resistant strains of S. aureus and Enterococcus spp.

We apply the Distinct Element Method (DEM) to analyze the dynamic behavior of soil. However, the conventional DEM model for calculation of contact forces between elements has some problems; for example, the movement of elements is too discrete to simulate real soil particle movement. Therefore, we modify the model to solve the difficulties. To investigate the validity of the modified model, we conduct an experiment in which soil is cut with a pendulum-typeblade, and simulate the soil loosening process with the modified DEM model. This paper presents details of the experimental apparatus and the comparison of soil behavior and energy absorption between the simulation and the experiment. Some characteristic phenomena of the experiment are reproduced in the simulation giving us confidence that the modified model is better than the conventional model for the simulation of soil behavior. (C) 2003 ISTVS. Published by Elsevier Ltd. All rights reserved.

This paper contains a description of a method and apparatus used for the comparison of a vehicle system control model with the automatically generated code which represents that model. The apparatus, referred to as hardware in the loop, consists of electronic control units, hybrid electric vehicle driveline components, dynamometers, and a Nighthawk super-computer. In the method presented, the model and generated code are executed concurrently in real-time. Output from the model can then be compared with the generated code in order to ensure that the code accurately represents the model.

Murine peritoneal macrophages were preincubated with amphotericin B (AMPH) and were then stimulated with bacterial lipopolysaccharide or streptococcal preparation (OK432). These macrophages produced a large amount of tumor necrosis factor. When administered to mice, the priming activity of amphotericin B for tumor necrosis factor production in vivo was also observed.

A (K,Na)NbO3-based lead-free piezoelectric ceramic was successfully densified. It exhibited an enhanced electromechanical coupling factor of kp = 0.52, a piezoelectric constant d33 = 252 pC/N, and a frequency constant Np = 3170 Hz m because of the incorporation of an elaborate secondary phase composed primarily of KTiNbO5. The ceramic's nominal composition was 0.92K0.42Na0.44Ca0.04Li0.02Nb0.85O3–0.047K0.85Ti0.85Nb1.15O5–0.023BaZrO3–0.0017Co3O4–0.002Fe2O3–0.005ZnO, abbreviated herein as KNN–NTK composite. The KNN–NTK ceramic exhibited a dense microstructure with few microvoids which significantly degraded its piezoelectric properties. Elemental maps recorded using transmission electron microscopy with energy-dispersive X-ray spectroscopy (TEM–EDS) revealed regions of high concentrations of Co and Zn inside the NTK phase. In addition, X-ray diffraction patterns confirmed that a small portion of the NTK phase was converted into K2(Ti,Nb,Co,Zn)6O13 or CoZnTiO4 by a possible reaction between Co and Zn solutes ...

The purpose of this study was to evaluate the association between loss of ovarian function and bone mineral density changes in the mandibles of ovariectomized rabbits using peripheral quantitative computed tomography. Twenty-four adult female Japanese white rabbits were used in this experiment. The mandibular incisors were initially extracted to create implant bone. Twelve animals were bilaterally ovariectomized and the other twelve sham-ovariectomized 12 weeks after tooth extraction. All rabbits were sacrificed at 4 and 12 weeks after ovariectomy and sham-ovariectomy, with 6 rabbits in each of the four resultant groups. The edentulous parts of distal mandibular bodies were measured by peripheral quantitative computed tomography. There were significant decreases in total bone mineral density and trabecular bone mineral density in the mandibles of rabbits at 12 weeks post-ovariectomy. The results demonstrate the mineralized bone loss in the mandibles of ovariectomized rabbits.

We investigated whether depressed plasma antithrombin and protein C activity, considered as a specific finding of disseminated intravascular coagulation (DIC), is due to consumption coagulopathy in septic patients with DIC. An analysis of hemostatic parameters was performed in 139 septic patients (68 with DIC and 71 without DIC). Plasma activity of antithrombin and protein C tended to be significantly decreased in septic patients with DIC but not in those without DIC (p0.001). However, when the septic patients were classified into three groups according to the albumin (or choline esterase) level, no significant differences in antithrombin activity or protein C activity were observed between the patients with and without DIC in any of the subgroups. Notably, neither the plasma activity of antithrombin nor protein C was decreased even in septic patients with DIC who had normal plasma levels of albumin (or choline esterase). No significant correlation was observed between plasma levels of thrombin-antithrombin complex (TAT) and antithrombin activity, or between plasma levels of TAT and protein C activity either in septic patients with DIC or without DIC. It is reasonable to conclude that the markedly reduced plasma activity of antithrombin and protein C is not due to consumption coagulopathy in septic patients with DIC.

Fifty-eight patients with hepatic tumor which consisted of 22 hepatocellular carcinomas and 36 metastatic liver tumors were treated by microwave coagulation therapy with MRI navigation. The tumors were located in all segments of liver except S1. In 24 cases among them, the abdominal approach was difficult, because the tumors were located just below the diaphragm. These cases were selected for thoracoscope-assisted microwave ablation under MR-guidance across the diaphragm. All MR data were collected on a vertically oriented open MRI system (0.5 T SIGNA SP/i system: GE Medical Systems). The microwave electrode was introduced into the liver through a 14G needle via a percutaneous puncture with real-time MR image navigation. Microwave ablations at 60 W for 60 seconds were repeated several times depending on the tumor size. MR imaging may be employed as a reliable guide for percutaneous puncture. Moreover, sufficient safety margin could be obtained for hepatic tumor ablation. MR-guided microwave thermoablation therapy is a feasible method of treatment for hepatic tumors.

Prominent neurite outgrowth induced by genipin, a plant-derived iridoid, was substantially inhibited by addition of NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase (NOS) inhibitor, and carboxy-PTIO, an NO scavenger, in PC12h cells. Increases of the NADPH-diaphorase activity and neuronal and inducible NOS proteins in cells preceded the neurite outgrowth after addition of genipin to medium. NO donors could induce the neurite outgrowth dose-dependently in the cells. On the other hand, an inhibitor of soluble guanylate cyclase (SGC), which is known to be a stimulatory target of NO, abolished greatly the genipin-induced neurite outgrowth. Addition of extracellular signal-regulated kinase (ERK) kinase inhibitors could almost completely abolish the neurite induction. L-NAME remarkably depressed genipin-stimulated phosphorylation of ERK-1 and -2. A neuritogenic effect of nerve growth factor (NGF) in PC12h cells was also remarkably inhibited by the NOS inhibitor, NO scavenger and SGC inhibitor. These findings suggest that induced NO production followed by cyclic GMP-mediated stimulation of the mitogen-activated protein kinase (MAPK) cascade is implicated in the neuritogenesis by genipin and NGF in PC12h cells.

We report NMDA receptor-dependent expression of synaptopodin mRNA in the dentate granule cells of the hippocampus following induction of long-term potentiation (LTP) in vivo. Synaptopodin did not belong to immediate-early genes, as de novo protein synthesis was required for the induction of synaptopodin gene transcription. An increased level of synaptopodin mRNA was observed at 75 min and 3.5 h after the onset of LTP. Importantly, there was correlation between the induction of mRNA expression and the persistence of LTP. Synaptopodin immunoreactivity was elevated specifically in synaptic layers, middle and outer molecular layers of dentate gyrus where LTP was induced. As synaptopodin is an actin-associated protein present in spine neck and implicated in the modulation of cell morphology, our results suggest that synaptopodin, by regulating the dynamics of the actin cytoskeleton, contributes to the morphological change in spine shape considered to be important for the maintenance of synaptic plasticity.

Primitive blood cells differentiate from the ventral mesoderm blood islands in Xenopus embryos. In order to determine the tissue interactions that propagate blood formation in early embryogenesis, we used embryos that had the ventral cytoplasm removed. These embryos gastrulated normally, formed a mesodermal layer and lacked axial structures, but displayed a marked enhancement of alpha-globin expression. Early ventral markers, such as msx-1, vent-1 and vent-2 were highly expressed at the gastrula stage, while a dorsal marker, goosecoid, was diminished. Several lines of experimental evidence demonstrate the critical role of animal pole-derived ectoderm in blood cell formation: 1) Mesoderm derived from dorsal blastomeres injected with beta-galactosidase mRNA (as a lineage tracer) expressed alpha-globin when interfaced with an animal pole-derived ectodermal layer; 2) Embryos in which the animal pole tissue had been removed by dissection at the blastula stage failed to express alpha-globin; 3) Exogastrulated embryos that lacked an interaction between the mesodermal and ectodermal layers failed to form blood cells, while muscle cells were observed in these embryos. Using dominant-negative forms of the BMP-4 and ALK-4 receptors, we showed that activin and BMP-4 signaling is necessary for blood cell differentiation in ventral marginal zone explants, while FGF signaling is not essential. In ventralized embryos, inactivation of the BMP-4 signal within a localized area of the ectoderm led to suppression of globin expression in the adjacent mesoderm layer, but inactivation of the activin signal did not have this effect. These observations suggest that mesodermal cells, derived from a default pathway that is induced by the activin signal, need an additional BMP-4-dependent factor from the overlying ectoderm for further differentiation into a blood cell lineage.

We investigated a 56-year-old Japanese man with protein C deficiency, who was referred to our hospital because of venous sinus thrombosis and pulmonary thromboembolism. Protein C (PC) activity and the corresponding antigen level in plasma were 66% and 106% of the normal values, respectively. Both the activity and antigen levels of protein C were reduced by approximately 50% in plasma from the patient's mother. All exons and their flanking intron regions were amplified by PCR from genomic DNA. Sequencing analysis of the PCR fragments revealed that the patient was heterozygous for a C to T substitution at nucleotide position 6218, resulting in a single amino acid substitution of arginine (CGG) by tryptophan (TGG) at codon 169 of the heavy chain. We analyzed the patient, his mother, and normal controls by a Sac II digestion study of exon 7 and found that the patient and his mother had the same C to T point mutation at base 6218. This mutation could have been responsible for the defective activation of the molecule and the resulting thrombotic disorder. The patient is now being treated with warfarin, and so far no further clinical thrombotic episode has occurred.

Neuroblastoma originates from neural crest cells and is the most common extracranial solid tumor in childhood. Bone metastasis in neuroblastoma is an unfavorable prognostic factor even with intensive therapy. In the present study, we screened four cell lines of human neuroblastoma (NB-1, NB-16, NB-19, and NH-6) for tumorigenicity and metastatic capacity in nude mice and found that NB-19 cells caused osteolytic lesions after s.c. injection into mice. To detect micrometastases in the host tissue, we performed two kinds of PCR-based metastasis assays: (a) genomic PCR assay using the primers for human genome-specific Alu sequence; and (b) reverse transcription-nested PCR assay that detects the expression of tyrosine hydroxylase, a marker specific for neuroblastoma. The results of these PCR assays revealed the colonization of human neuroblastoma cells in the bone marrow of the mice that had received the s.c. injection of NB-19 cells. Because osteoclastic bone resorption has been reported to play important roles in osteolysis in some cancers such as breast cancer, we next examined the osteoclast (OC)-inducing activity of NB-19 cells using a coculture system in which NB-19 cells were cultured with murine bone marrow cells containing OC precursors and stromal cells. NB-19 cells induced tartrate-resistant acid phosphatase-positive multinucleated OC-like cells without requirement of 1,25-dihydroxyvitamin D3 or other osteoclastogenic stimulators. To investigate the factors involved in the osteoclastogenesis in the coculture of mouse marrow cells and NB-19 cells, we performed reverse transcription-PCR analysis and revealed the increased expression of receptor activator of nuclear factor kappaB ligand (RANKL) in the coculture compared with the culture of bone marrow cells alone. Interleukin-1alpha and cyclooxygenase-2 expression in the murine marrow cells was also increased in the presence of NB-19 cells. To further study the role of RANKL in the OC-like cell formation in the coculture of NB-19 cells and murine marrow cells, an expression vector encoding the active portion of the murine osteoprotegerin, which is the native inhibitor of RANKL action, was constructed and introduced into COS-7 cells. The conditioned media of the COS-7 cells transfected with the osteoprotegerin expression vector effectively blocked OC-like cell formation in the coculture of the bone marrow cells and NB-19 cells. These results suggested that in the bone microenvironment of NB-19-bearing mice, the stimulated expression of RANKL plays an important role in OC formation, leading to osteolytic bone metastasis.