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A new cladding process has been developed by means of a surface activated bonding technique. The metal sheets to be bonded are cleaned by Ar plasma ion etching activated and rolled with low distortion at room temperature in vacuum. In many respects, the clad sheets manufactured by this process have advantages over conventional clad sheets. For instance, they have a clean and flat interface without intermetallic alloy layer. Thin metal foil (10 /spl mu/m/spl sim/thickness) can be bonded with the metal sheet. The multi layer clad sheet produced by this process can be formed easily by selective chemical etching method Therefore, the sheet makes it possible to design a fine and solid conductive circuit with bump only through the chemical etching process.

In this paper, we focus on the relationship between learners' activity/attitude in face-to-face communication (FTF) and that in computer-mediated communication (CMC) using distributed computer supported collaborative learning (dCSCL). In general, even if dCSCL is applied in class, university students learn together by FTF while on campus. This study aims to reveal correlative factors in FTF which promote learners' participation in dCSCL. We approach a university class where students are instructed to use mailing-lists for distributed group activities. We analyze their behavior by studying mailing-lists content and through questionnaires. Results show that personal attitudes in both FTF and dCSCL discussions are related. Furthermore, we reveal that learners' understanding of the content and process of FTF encourages their participation in dCSCL. In conclusion, when dCSCL is introduced in a traditional classroom, learners' active participation in dCSCL is prompted by creating a connection between FTF and dCSCL by supporting FTF discussions.

In this paper, the authors reveal how learners evaluate different learning environments including CSCL and classroom, and how learners describe relationship between different groups in some learning environments. In order to demonstrate these relationships, they try to use combinations of qualitative semi-structured interviews and a collage method, which facilitate learners externalization of relation among learning environments and groups. They especially focused how learners describe CSCL on collages. As a result, three types of collages were found showing different relations. It is suggested that a collage method is useful for learners to transform internal thought into outer representations. hi addition to these effects, this method has possibilities to reconstruct their thinking more clearly. As a whole, it is suggested relations making like collages is important for learners to reflect about learning environments.

The hybrid algorithm presented in the paper illustrates a coupling of the genetic algorithm method with the gradient method without constraints. The parallel implementation of a hybrid algorithm, which consists of the genetic algorithm and Gaussian elimination method is presented.

In this paper, we propose a new system for estimating face pose from a facial image. In this system, an input facial image is compared with a database of images of various face pose, then the matched image provides the face pose. The database of images includes not only various face poses but also various illumination conditions, so that the face pose estimation system can be used under various illumination conditions. For collecting such various facial images, they are generated by computer, rather than using real images. The eigenspace method is used for searching a matched image with an input facial image. Since various illumination images are collected in the database of facial images, the extracted principle eigenvectors mostly depend on the face pose. By performing the matching process in the eigenspace, a matched image with the input facial image can be found. The pose of the matched image is closest to the input face. The matching process is also fast because it is performed in small dimensional space spanned by selected eigenvectors only. The proposed pose estimation system can continuously track the face pose of different persons under different light conditions.

Intelligent transport systems (ITS) have been developed as next generation systems which unite multimedia technology and the roadway. One ITS technology, image processing, for example, the detection and tracking of moving objects (e.g. vehicles), is studied. On the other hand, the coding technique of MPEG (Motion Picture Experts Group) is used as the worldwide standard method of video data compression. Japan Highway Public Corporation (JH) adopted MPEG to transmit picture data from the surveillance system on the roadway to the control center. Therefore, we propose a method to analyze moving pictures by directly manipulating the MPEG stream. Our proposed method extracts plural moving objects from the MPEG stream without a decoding process, and tracks them even if they approach and cross. It is implemented to extract moving cars on the roadway, and its effectiveness is verified.

Summary form only given. Progressive display of images by using a image segmentation algorithm is proposed. The regions in a segmented image are represented by assigning to them the mean intensity of the original image within the region boundary. The segmentation algorithm that merges repeatedly two neighborhood regions that minimize the sum squared error and that makes regions grow bigger is used. At one stage of the merging process two kinds of information are lost: the mean intensity values of two merged regions and the region boundary. So they are coded at each stage till the region number is one. In the decoding process, while the region is being split the image is reconstructed progressively. >

The authors report on the development of a liquid epoxy resin for bare-chip IC encapsulation on organic substrate. This resin is characterized by low stress and high adhesion strength at elevated temperature. This resin can be applied to many types of bare-chip encapsulation on organic substrate going through the soldering process. >

The authors try to represent a image with triangular patches. The triangular patch is defined as a triangle with linearly varying gray-level within it. To represent an image with triangular patches effectively for the human visual system, and to describe these triangular patches with small amount of data, the authors have tried to get a new style image coding method at very low bit rate. At first, a modified Delaunay triangulation algorithm is applied to the feature points extracted on the boundary lines in the image. Then linear interpolation is done within every triangular region using the gray-value at these feature points. Thus the approximately represented image is described with triangular patches. Using this image description method, an image coding method with progressive build-up is proposed. By the simulation results and subjective tests, it is confirmed that this coding scheme using triangular patch structure is effective at super-low bit rate. >

Excited states in 12Be and 14Be were studied by measuring the 6He + 6He and 6He + 8He breakup channels in the two-neutron removal and the inelastic scattering of an exotic 14Be beam, respectively.

The authors propose a predictive interpolation method which can predict the intensity of a center unknown pixel solely from intensities of its adjacent known pixels. They obtain a smooth and reasonable high-resolution image from a low-resolution image and consider the appropriateness of the application of vector quantization to prediction in this study. >

A method which extracts the speed and direction of several moving objects in a spatio-temporal image using the 3-D Hough transform is described. The estimation of target feature parameters, such as velocity, is based on the contour matching technique. In practice, the solution to this problem is reliable on the assumption of little noise and occlusion in the image. Hence, the 3-D Hough transform is an effective method for the extraction of the global pattern features from the noise and scattered points spread over the image space. Therefore, the method is used for extracting the velocity of the moving objects in the image sequence. >

Chinese character structure data can be generated automatically. The authors propose an algorithm for the automated generation of the Chinese character structure data based on extracting stokes. As the inputs of Chinese characters, the Gothic styles are used. Examples are given throughout the text, using real images of Gothic style Chinese characters. >

A system for extracting characteristic bone regions, i.e., feature parts, from X-ray CT (computed tomography)-images (slices) of the human head is proposed. Such feature parts form regions of complex shapes and locations. Thus, to realize the system, a state transition model of the skull is first proposed, taking account of the topology of sliced skull shapes. Next, a sliced skull shape is recognized in each slice on the basis of the model. Finally, using the recognition results, feature parts are extracted from slices. An important feature of the method is the use of those search areas to guide the extraction process which are determined in each slice by constraints derived from the model and the recognition results. The method has been successfully applied to feature extraction of the skull. >

Road scene analysis from a perspective image plays a very important role in road navigation and road following. It seems, however, a formidable task if the road segments show as curves. In this paper we propose a method to perform an analysis of road segments containing both straight lines and curvatures. The method used is to investigate the features of the corresponding points between the road boundaries with the road modeled as planer surface patches. A constraint existing among Euler angles of viewpoint and the vanishing point related to corresponding points on the road plane is shown. To search for the corresponding points from the perspective image we define a function which by means of the Lagrange multiplier leads to a minimum at the corresponding points. Simulations are conducted on both a straight road segment and a curvature road boundary.

A filter-type WDM on a silica-based PLC is discussed from the view point of filter alignment tolerance in relation to /spl Delta/ of the waveguide. The significance of the angular filter placement error is clarified - it appeared to be the dominant loss factor for the 1.55 /spl mu/m port.

A new method to perform three-dimensional road recognition from a single two-dimensional image is proposed. Based on road edges which are characterized by properties of matching points, Euler angles between camera-centered coordinates and edge-centered coordinates can be evaluated and thus the depth information of edge points can be obtained from resultant perspective projections of matching points in the image. In the paper the road segment is assumed as plane and the road width remains invariant, while matching points are defined as edge points with parallel tangent lines which are vertical to the line through the matching points based on the construction of the road. The analysis for the determination of matching points in the image is investigated in detail and a modified algorithm to locate matching points is shown. Experiments are executed on synthetic image data and the results are shown to confirm the validity of the proposed method.

There have been many researches and implementations using image sensors to get information for traffic and vehicle control. The image seen from camera located beside or upon the road can be used for vehicle detection, velocity of car or car group measurement, parking car detection, etc. Moreover the image seen from camera located in vehicle can be used for previous car detection, distance to following vehicle measuring, obstacle detection, lane detection, etc. In this paper, items to measure, algorithms to measure with image processing, problems to overcome in future are described. >

At the parking lot of the expressway, the information concerning the state of congestion is offered to drivers. We propose the method of counting cars by using the tracking of moving objects from the sequential images taken at the outdoor parking lot. In this paper, we describe a loci extraction method by linkage and separation of the moving regions detected from time differential images, and a counting method by recognition of a car from the features of the extracted locus. We develop the system by combining a personal computer with a high speed image processor. Both the robustness and practicality of real time processing, at 0.2 second per frame, are confirmed through experiments using VTR real parking lot images. >

We have developed new direct bonding technology using anisotropic conductive film (ACF) connections between two chips. We applied this bonding technology in ultra fine pitch interconnections at 40 /spl mu/m between an LED array and a driver IC, and realized a minimized LED print head. The key point of direct bonding technology is assurance of connection reliability which can be improved by two important factors. One is the elastic recovery quantity of conductive particles between the connection electrodes, and the other is the adhesive strength of the chip bonding area. As a result of analysis with particular attention paid to these factors, we found two further features: (1) an elastic recovery quantity usually obtained by using soft conductive particles which was included in ACF, in the case of electrodes with variable form and hardness; (2) adhesive strength increased when accompanied with a rise in the curing temperature. We tested this technology by interconnection of 192 connection pads lined in 40 /spl mu/m pitch, and achieved good bonding reliability in temperature and relative humidity cycling tests. This new bonding technology is effective in ultra-fine pitch direct bonding, so that this technology can be widely applied to various types of device chip. In this paper, the details of the technology and the connection reliability are reported.

A new color representation method is proposed. This method is introduced by a fact which is experimentally obtained through the study of expressing illustrations in rare book. So paint-strength model is newly developed in RGB space, and by using it, we suggest a method of expressing illustrations in a rare book.

Porous Y/sub 2/O/sub 3/ ceramic was found to show huge thermopower values up to -50 mV/K at 900-1000 K in vacuum, but not in air. Such huge thermopowers may be generated by the electron gas emitted from the internal surfaces of the pores and are associated with some unknown effects. The non-dimensional thermoelectric figure of merit, ZT, of this porous ceramic was as large as /spl sim/0.95 at /spl sim/950 K, and hence it can be used as a new thermoelectric material.

The authors discuss the effects of applying image processing technology to the digital archiving and study of rare books, introducing our research activity in the HUMI Project, which was established by Keio University as an inter-faculty project, envisioning a research oriented digital library. Then, some methods of image processing application developed in the HUMI Project are outlined: adjustment method for curved page image, connection method for partial images of page, image representation method for illustration.

In this paper, we focus on similar image retrieval based on color-content. A two-phase matching strategy is adopted for achieving speed and accuracy of the proposed retrieval: the first phase of matching is intended to produce a candidate image list which are similar to the sample image using the global color histogram; the second phase of matching acts as a filter on the list obtained by the first phase, deleting dissimilar images using the spatial distribution of colors in the image. It is common knowledge that most of the images are dominated by a small number of colors, called dominant colors. We propose dominant color matrices for representing the spatial distribution of dominant colors in an image, which can serve as a basis for measuring the spatial similarity between images. In order to calculate the spatial similarity on dominant color matrices, we use two-dimensional DP matching technology extended from conventional DP matching. In addition, we have also applied the proposed approach to a range of color images, and obtained positive results.

Postmenopausal osteoporosis is a contributing factor to alveolar bone atrophy associated with tooth loss in the elderly. The use of dental titanium implants has been increasingly adapted to treat these edentulous patients. This study examines whether female gonadal hormone deficiency interferes with the critical integration process between bone and implants. Two types of experimental titanium implants with acid-treated surfaces were placed in the femurs of ovariectomized (ovx) and sham-operated control rats: T-cell implants with a hollow chamber for histomorphometric and steady-state mRNA expression assays, and unthreaded cylindrical implants for biomechanical push-in tests. At week 2, less bone area was found in the ovx-implant group (p 0.0495) than in the sham-implant group. The implant push-in test showed that the ovx-implant group had approximately half of the withstanding value of the sham-implant group (p 0.009). However, these differences between the ovx and sham groups became diminished at week 4. Total RNA samples were examined by a reverse transcriptase-polymerase chain reaction assay for col1a1, col3a1, bone sialoprotein (bSP) II, osteonectin, osteopontin, osteocalcin, integrin 1 and integrin 3. In untreated bones and in created bone defects without implant placement, ovx did not affect the steady-state levels of the mRNAs tested. When implants were placed, significant upregulation of these genes was observed in the sham-implant group; however, only osteocalcin and integrins were upregulated in the ovx-implant group. The results suggest a biphasic effect of female gonadal hormone deficiency that may temporarily interfere with the early implant-tissue integration process, and which may be associated with a failure to upregulate a selected set of bone extracellular matrix genes. Once established, however, functional bone-implant integration can be achieved even in ovx rats. (Bone 30:137–143; 2002) © 2002 by Elsevier Science Inc. All rights reserved.

Circular dichroism (CD) cells, equipped with quartz window, are used for measurements of CD in the ultraviolet (UV) region under high pressure. We describe here an improvement in these cells, which are typically distorted by high pressure, thus diminishing the CD signal. A slit with a small 3 mm diameter hole was placed in the light source-side in contact with the window, thus adjusting the center of the light path. This method gave reasonable CD spectra of camphorsulfonic acid, poly-glutamic acid, and RNase A at 150 MPa or lower. For measurements at higher pressure, synthetic diamond was used as windows of the CD cell and reliable CD spectra were obtained in the near-UV and visible light region at pressure of 400 MPa or lower, since the diamond strongly absorbed UV light at 230 nm and shorter wavelengths. By monitoring the molar ellipticity at 235 nm, it was possible to estimate pressure-induced changes in the secondary structure of poly-amino acids, myoglobin, and RNase A. The CD spectra of carboxypeptidase Y, lysozyme, and RNase A were also measured at 245–320 nm under high pressure to estimate structural changes which occur at these conditions. CD spectra of RNase A at 0.1–400 MPa were changed by pressurization at 100 to 250 MPa, showing a reversible two-state transition. However, this negligible discrepancy may be corrected when diamond windows are used.

Purpose: IGRT based on the bone matching may produce a larger target positioning error in terms of the reproducibility of the expiration breath hold. Therefore, the feasibility of the 3D image matching between planning CT image and pretreatment CBCT image based on the diaphragm matching was investigated. Methods: In fifteen-nine liver SBRT cases, Lipiodol, uptake after TACE was outlined as the marker of the tumor. The relative coordinate of the isocenter obtained by the contrast matching was defined as the reference coordinate. The target positioning difference between diaphragm matching and bone matching were evaluated by the relative coordinate of the isocenter from the reference coordinate obtained by each matching technique. In addition, we evaluated PTV margins by van Herk setup margin formula. Results: The target positioning error by the diaphragm matching and the bone matching was 1.31±0.83 and 3.10±2.80 mm in the cranial-caudal(C-C) direction, 1.04±0.95 and 1.62±1.02 mm in the anterior-posterior(A-P) direction, 0.93±1.19 and 1.12±0.94 mm in the left-right(L-R) direction, respectively. The positioning error by the diaphragm matching was significantly smaller than the bone matching in the C-C direction (p

Purpose: To verify volumetric modulated arc therapy (VMAT) using flattening filter free (FFF) mode with jaw tracking (JT) feature for single breath hold as long as 15 s per arc in liver stereotactic body radiation therapy (SBRT) against intensity modulated radiation therapy (IMRT) FFF-JT. Methods: Ten hepatocellular carcinoma (HCC) cases were planned with 10 MV FFF using Pinnacle3 treatment planning system which delivered by TrueBeam to administer 48 Gy/ 4 fractions. Eight non-coplanar beams were assigned to IMRT using step-and-shoot technique. For VMAT, two or three non-coplanar partial arcs (up to 180 degrees) were further divided into subarcs with gantry rotation less than 80 degrees to limit delivery time within 15 s. Dose distributions were verified using OCTAVIUS II system and pass rates were evaluated using gamma analysis with criteria of 3%/3 mm at threshold of 5% to the maximum dose. The actual irradiation time was measured. Results: The VMAT-FFF-JT of partial-arcs with sub-divided arcs was able to produce a highly conformal plan as well as IMRT-FFF-JT. Isodose lines and DVH showed slight improvement in dosimetry when JT was employed for both IMRT and VMAT. Consequently, VMAT-FFF-JT was superior in reducing the dose to liver minus gross tumor volume. VMAT-FFF-JT has shorter total treatment time compared with 3D conformal radiation therapy (3D-CRT) FFF because the gantry was rotated simultaneously with the beam delivery in VMAT. Moreover, due to the small and regular shape of HCC, VMAT-FFF-JT offered less multileaf collimator motion, thus the interplay effect is expected to be reduced. The patient specific QA of IMRT and VMAT acquired the pass rates higher than 90%. Conclusion: VMAT-FFF-JT could be a promising technique for liver SBRT as the sub-divided arcs method was able to accommodate a single breath hold irradiation time of less than 15 s without deterioration of the dose distribution compared with IMRT-FFF-JT.

Although the sentinel node (SN) concept has been validated in malignant melanoma and breast cancer, the application of this concept for other solid tumors, including gastrointestinal (GI) cancer, is still controversial. We have demonstrated the feasibility of radioguided SN mapping during laparotomy in patients with esophageal, gastric, and colorectal cancers. In 188 patients, the SNs identified by this technique had an overall diagnostic accuracy of 96% for regional lymph node metastasis. Aberrant drainage sites that have been called skip metastasis from the primary lesion were detectable using this method. More recently, we have undertaken SN mapping during laparoscopic surgery. A combination of radiotracer and blue dye optimized the identification of SNs that drained GI cancers. Our preliminary data indicate that laparoscopic mapping of the SN is a sensitive intraoperative technique for identifying lymph node micrometastasis, and we believe that it will become an important component of a minimally invasive approach to early-stage GI cancers.

Because of the high frequency and widespread distribution of lymph node metastasis in esophageal cancer, three-field dissection was introduced in the early 1980s. Although improvement in the long-term survival rate of patients who undergo three-field dissection has been reported, the clinical significance of cervical lymphadenectomy is still controversial because the effect of improved upper-mediastinal lymphadenectomy in these patients cannot be excluded. Recently, the sentinel node (SN) concept has been validated in gastrointestinal cancers including esophageal cancer using the radio-guided method. Aberrant drainage routes from the primary lesion have frequently been observed in esophageal cancer and are detectable by radio-guided SN mapping. SN navigation is useful to identify SNs as the functional first basin to evaluate the regional lymph node status and to determine the indications for extensive lymphadenectomy in patients with esophageal cancer. Individualized surgical management of patients with esophageal cancer is essential to improve the quality of life of patients and long-term results.

alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit (GluR1-4) mRNAs expressed by single neurons in rat hippocampal cultures were quantified by single-cell RT-PCR using an internal standard RNA after whole-cell patch-clamp recording. The internal standard RNA, derived from GluR2 with a single nucleotide substitution, was reverse-transcribed and PCR-amplified with the same efficiency as GluR1-4 mRNAs. The mean mRNA numbers harvested in vitro from pyramidal-like neurons on day 9 were 1150 +/- 324 molecules of GluR1, 1080 +/- 273 molecules of GluR2, 100 +/- 20 molecules of GluR3, and 50 +/- 10 molecules of GluR4 (mean +/- SEM, n = 12). In a non-pyramidal neuronal population that expresses AMPA receptors characterized by high Ca(2+) permeability, the numbers of GluR1, GluR3 and GluR4 mRNA molecules harvested per cell were 354 +/- 64, 25 +/- 17 and 168 +/- 36, respectively (n = 8). The GluR2 mRNA was not detected in this cell type. The calculated ratio of AMPAR mRNA molecules per total mRNA molecules was 1/240 in pyramidal-like neurons (1/500 for GluR2), being in the range obtained with total RNA from rat forebrain and cerebellum (1/170 and 1/380, respectively). Finally, our results indicated that the proportion of GluR1-4 mRNA located in neurites reached approximately 60% in pyramidal-like neurons. However, we found no evidence of preferential subcellular distribution of a given subunit.

Gene manipulation in order to artificially express a particular gene in neurons in the central nervous system is a powerful tool for the analysis of brain function. Sindbis viral vectors have been developed to express high levels of foreign genes in postmitotic brain neurons with little transfection of glial cells. In this study, we expressed the gene encoding the unedited GluR2 (GluR-B) subunit of the AMPA-type glutamate receptor that forms inwardly rectifying and Ca2+-permeable channels, in rat CA1 hippocampal neurons in slice cultures using Sindbis viral vectors. The pyramidal cell layer of the CA1 region was injected with recombinant Sindbis viruses encoding both enhanced green fluorescent protein (GFP) and unedited GluR2. The GFP fluorescence from CA1 neurons could be detected as early as 6 h and reached a maximal level about 48 h postinfection. The inwardly rectifying and Ca2+-permeable AMPA receptors were expressed in most CA1 pyramidal cells expressing GFP. These AMPA receptors expressed by gene transfer were involved in fast excitatory neurotransmission elicited by electrical stimulation of the Schaffer collaterals in the stratum radiatum. Tetanic stimulation of Schaffer collaterals induced NMDA receptor-independent, long-term potentiation due to Ca2+ influx through the newly expressed AMPA receptors in the area densely stained with GFP. Thus, the combined use of Sindbis viral vectors with the GFP reporter allowed physiological examination of the roles of a specific gene product in synaptic function in well-characterized brain neurons.

Progress in the field of pharmacogenetics has revealed that the phenotypically different responses of patients to drugs are genetically determined by the polymorphisms in the genes involved in their pharmacokinetics and pharmacodynamics. Information on genetic polymorphisms, including single nucleotide polymorphisms, found in the genes encoding drug-metabolizing enzymes, drug transporters, drug receptors, and so on, are now applicable to tailor-made(individualized) drug therapy. This report presents the current status of pharmacogenetic approaches to the individualized therapy.

Biomechanical and biological factors can co-dependently influence the establishment of implant-tissue integration; thus, concurrent evaluation of these factors should provide a better understanding of osseointegration. This study aimed to establish and validate an in vivo rat model frequently used in molecular/cellular biology for implant biomechanical studies. We tested the hypotheses that the implant push-in test assesses the degree of osseointegration by the breakpoint load at the implant-tissue interface and that it sensitively differentiates between the effects of different implant surface topographies. The implant push-in test, which produces a consistent load-displacement measurement, was used to test miniature cylindrical titanium implants placed at the distal edge of the adult rat femur. The push-in test values obtained at each post-implantation healing point (weeks 0, 2, 4, and 8) significantly increased in a time-dependent manner. The implant surface after the push-in test was associated with remnant tissues containing host-derived elements, such as calcium, phosphate, and sulfate. In this model, acid-etched implants (average roughness, 0.159 μm) showed significantly greater push-in test values than did turned implants (average roughness, 0.063 μm) throughout the experimental period (p < 0.0001). These results support the validity of the push-in test in rats, which may be used as a rapid and sensitive biomechanical assay system for implant osseointegration research.

The Tibet air-shower array operating at Yangbajing (4300 m above sea level) is sensitive to gamma-ray air showers at energies as low as 3 TeV. The observation of the moon’s shadow has provided a direct check of the angular resolution, the energy estimation and the systematic pointing error of this air-shower array. Using these data, we have searched for multi-TeV gamma-ray emission from 21 SNRs located within 5 kpc distance in the declination band of 0° to +60°. The signal from the Crab Nebula was detected at 5.5 σ level as described another paper. No significant DC excess exceeding 5 σ level was found from any of these SNRs except from the Crab Nebula. The results of nearby eight SNRs piled up gave a flux upper limit slightly lower than the expected values for a simple model of shock acceleration.

We searched for multi-TeV counterparts to the gamma–ray bursts (GRBs) at keV energies detected by BATSE during the period from October 2, 1995 to March 18, 1999 using the data of the Tibet Air Shower Array. In the field of view of the array there were 70 GRBs detected by BATSE in this period. The search was done based on the sky survey within error circles of BATSE bursts and with time scales during 10 to several hundred seconds. No significant signals of counterparts were detected.

The halo structure of the neutron-dripline nucleus 14Be has been investigated by various approaches, such as the interaction cross section measurement, dissociation reaction and 14Be fragmentation. In the recent plausible view, the mixing of s and d-wave components in the halo wave function has been suggested. In the present study, the halo structure of 14Be was investigated by measuring its Isobaric Analog State (IAS). Since the wave function of the IAS is essentially the same as that of its isobaric partner, possible exotic natures of 14Be may be traced in properties of the IAS such as the Coulomb displacement energy (ΔE C) and the width of the IAS. The IAS of the 14Be was excited by the charge-exchange reaction which was successfully applied to the neutron-dripline nucleus 11Li and obtained the halo properties [1, 2]. In the present study, applying this reaction to 14Be, we have measured the 14Be(p,n)14B* reaction in inverse kinematics at E in = 74 A MeV [3].

We determined the role that vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), plays in the progression of human renal cell cancer in nude mice. Low metastatic and low VEGF/VPF-expressing human renal cancer cells SN12C were transfected with the VEGF165 cDNA or plasmid alone as control. VEGF165-transfected SN12C cells produced large amounts of biologically active VEGF in culture that did not affect cell doubling time or confluence. Subsequent to implantation into the renal subcapsule of nude mice, the VEGF165-transfected SN12C cells produced fast-growing (PCNA labeling), large tumors that expressed high levels of VEGF/VPF and were well vascularized (CD3-positive vessels). The tumors produced hyperpermeability of peritoneal blood vessels (Evans blue dye-leak assay), bloody ascites, and short survival time. Parental or control transfected SN12C cells produced less vascularized, slower growing tumors with no ascites. Regardless of in vivo expression level of VEGF, the incidence of spontaneous lung metastasis was low, suggesting that in itself, the expression of VEGF/VPF by renal cancer cells is not sufficient to produce metastasis.

A thermostable phenol sulfotransferase, SULT1A1, has been implicated in numerous detoxification and bioactivation pathways; however, little is known regarding its endogenous function or its putative role in mediating risk for human environmental disease. A simple endpoint colorimetric assay is described that can be used for rapid phenotyping of SULT1A1 activity in human populations. The assay utilizes a microtiter-plate format and relatively small amounts of platelet cytosol-derived enzyme. The enzyme catalyzes the synthesis of 2-naphthylsulfate from 2-naphthol and 5'-phosphoadenosine 3'-phosphosulfate (PAPS), whereas addition of p-nitrophenyl sulfate to the assay contributes to an effective PAPS-regenerating system. In contrast to other sulfotransferase assay methods, 3'-phosphoadenosine 5'-phosphate (PAP) does not accumulate during the incubation to interfere with enzyme activity, but instead serves as a cofactor to cause the removal of sulfate from p-nitrophenyl sulfate to regenerate PAPS. This reaction concomitantly results in generation of p-nitrophenol that can be quantified colorimetrically at 405 nm (epsilon = 18,200 M(-1)) to give an indirect measure of sulfotransferase activity. Using platelet enzyme preparations from adult human subjects, sulfation rates of two prototypical thermostable phenol sulfotransferase substrates (2-naphthol and p-nitrophenol) and one thermolabile phenol sulfotransferase substrate (dopamine) were determined using standard radiochemical protocols. These data were then compared with results from the colorimetric assay using 2-naphthol as substrate. There was a good correlation between the phenotyping assay and radiochemical assays for both 2-naphthol sulfotransferase and p-nitrophenol sulfotransferase activity (r = 0.85 and 0.69, respectively). However, SULT1A1 activity was approximately 10 to 20 times higher with the colorimetric determination. As anticipated, there was no correlation between SULT1A1 activity and dopamine sulfotransferase activity (r = 0.07) in these human platelet preparations. This inexpensive and rapid method for phenotyping SULT1A1 activity may help investigators assess a role for this enzyme in disease susceptibility.

Drug metabolizing enzymes (DMEs) play an important role in the biotransformation of various xenobiotics, generally by detoxifying and eliminating substrates by converting them to more hydrophilic derivatives, or in some cases, activating substrates by conversion to intermediates that are highly reactive with biological macromolecules. It is widely accepted that the enzymatic activities of hepatic DMEs are one of the most important determinants of the concentration of drugs at their site of action or in the blood. Wide inter-individual variability in drug concentrations in the blood has been demonstrated even after the administration of the same doses on the basis of body weight, and in many cases the wide differences in plasma drug concentrations have been attributed to the individual differences in the enzymatic activities of DMEs. Attempts have therefore been made to estimate the hepatic DME activities of each individual before administration of drugs clinically. Three different approaches were taken to estimate patients' hepatic DME activities: 1) the use of probe drugs (phenotyping); 2) molecular diagnosis of genetic DME deficiency (genotyping); 3) examination of DME levels/activities in peripheral blood leukocytes/lymphocytes on the assumption that their activities in leukocytes/lymphocytes are well correlated with hepatic enzyme activities. A great number of data have been accumulated concerning the specificity of certain DME for candidate probe drugs, and searches have been made for mutated alleles of DME genes that indicate whether an individual is deficient in DMEs. Gene expression is measured by sensitive methods such as the reverse-transcriptase polymerase chain reaction and/or immunochemical methods in peripheral blood leukocytes/lymphocytes, which are less invasive tissues. Knowledge is being accumulated that will allow the development of useful methods of predicting the activities of hepatic DMEs that affect individual pharmacokinetics/pharmacodynamics. In this article, various reported methods of assessing hepatic DME activities are reviewed for the purpose of maximizing the efficacy and safety of pharmacotherapy.

We determined whether down-regulation of the epidermal growth factor-receptor (EGF-R) signaling pathway by oral administration of a novel EGF-R tyrosine kinase inhibitor (PKI166) alone or in combination with gemcitabine (administered i.p.) can inhibit growth and metastasis of human pancreatic carcinoma cells implanted into the pancreas of nude mice. Therapy beginning 7 days after orthotopic injection of L3.6pl human pancreatic cancer cells reduced the volume of pancreatic tumors by 59% in mice treated with gemcitabine only, by 45% in those treated with PKI166 only, and by 85% in those given both drugs. The combination therapy also significantly inhibited lymph node and liver metastasis, which led to a significant increase in overall survival. EGF-R activation was significantly blocked by therapy with PKI166 and was associated with significant reduction in tumor cell production of VEGF and IL-8, which in turn correlated with a significant decrease in microvessel density and an increase in apoptotic endothelial cells. Collectively, our results demonstrate that oral administration of an EGF-R tyrosine kinase inhibitor decreased growth and metastasis of human pancreatic cancer growing orthotopically in nude mice and increased survival. The therapeutic effects were mediated in part by inhibition of tumor-induced angiogenesis attributable to a decrease in production of proangiogenic molecules by tumor cells and increased apoptosis of tumor-associated endothelial cells.

Laparoscopic surgery for esophageal achalasia was first reported by Shimi et al. in 1991. Subsequently the procedure has been performed all over the world and laparoscopic Heller myotomy and Dor fundoplication (Heller and Dor operation) is now thought to be the operation of first choice. It is indicated for patients who are resistant to medical therapy (calcium blocker etc.) or have pneumatic dilatation and those with frequent aspiration at night. As Csendes et al. reported that surgical treatment was better than pneumatic dilatation and as laparoscopic surgery is less invasive, the indications for the laparoscopic Heller and Dor operation can include all achalasia patients except those who respond to medical therapy, do not accept surgery, or cannot tolerate surgery. We successfully performed the laparoscopic Heller and Dor operation on 22 patients, all of whom had an uneventful postoperative course. Manometric evaluation, endoscopic examination, and 24-hour pH monitoring showed good results. There are six important technical points: 1) flexible laparoscopy; 2) pneumoperitoneum; 3) gauze in the abdominal cavity to absorb blood; 4) laparosonic coagulating shears; 5) extracorporeal knot-tying technique; and 6) intracorporeal knot-tying technique. If an experienced surgeon is in charge, the laparoscopic Heller and Dor operation is an ideal, minimally invasive treatment for esophageal achalasia.

Master-slave manipulators enhance surgeons' dexterity and improve the precision of surgical techniques by filtering out surgeons' tremors and scaling the movements of surgical instruments. Among clinically available master-slave manipulators, the epoch-making system called "da Vinci" developed by Intuitive Surgical Inc. (Mountain View, CA, USA), equipped with 2 articulated joints at the tip of the surgical instruments allowing 7 degrees of freedom, mimics the movements of surgeons' wrists and fingers in the abdominal or thoracic cavity. Today advanced telecommunications technology provides us excellent motion images using only 3-ISDN telephone lines. Experienced surgeons at primary surgical sites have been able to perform complex procedures successfully by consulting specialists at remote sites. Because telecommunications costs have become lower each year, telementoring will be come a routine surgical practice in the near future. The usefulness of surgical telementoring has been greatly enhanced by the development of a technique to illustrate on video images from two directions. Moreover, remote advisory surgeons will be able to provide the optimal operative field to operating surgeons using robotic camera holders with voice-recognition systems. In the near future, when master-slave manipulators will also be coupled with telementoring systems, remote experts could actually perform complex surgical procedures.

Although the sentinel node concept has been validated and clinically applied to breast cancer and malignant melanoma, its clinical significance in other solid tumors has not been thoroughly investigated. With regard to gastrointestinal (GI) cancers in particular, our surgeons have been cautious because of the high frequency of skip metastasis and the complicated lymphatic system in the GI tract. We would like to emphasize that so-called skip metastasis has been defined according to anatomic classification of regional lymph nodes and that the lymphatic drainage route must be patient or lesion specific. To test the validity and feasibility of this concept in GI cancers, we have established a radio-guided intraoperative sentinel node navigation system using preoperative endoscopic submucosal injection of radioactive tracer followed by intra-operative gamma-probing. In 131 patients with GI cancers (esophagus: 22, stomach: 71, colorectum: 38), the detection rate of sentinel nades was 91% and overall diagnostic accuracy of lymph node metastasis by sentinel node status was 97%. Initial results suggest further investigation of this procedure as an accurate staging and a minimally invasive approach to early GI cancers.

Vascular endothelial growth factor (VEGF) expression and tumor microvessel density (MVD) were examined by immunohistochemical staining in 117 cases of thoracic esophageal squamous cell carcinoma. Thirty-six (31%) of the 117 cases were evaluated as VEGF-positive. The average number of metastatic lymph nodes at surgery was 5.6 in the VEGF-positive cases and 3.0 in the VEGF-negative cases and was significantly higher in those with VEGF-positive cases (P = 0.04). The incidence of pathological tumor (PT)2-4 cases among the high-MVD cases was significantly higher than among the low-MVD cases (P = 0.01). MVD was 59.4 +/- 4.7 (mean +/- SE)/mm2 in the VEGF-positive cases and 47.9 +/- 3.8/mm2 in the VEGF-negative cases. The MVD of the VEGF-positive tumors was higher than that of VEGF-negative tumors, but the difference was not significant (P = 0.08). The survival rate of the patients with high-MVD tumors was significantly poorer than those with low-MVD tumors, and the survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors (P = 0.009 and P = 0.04, respectively). The cumulative survival rates in the VEGF-positive groups were found to be significantly poorer in the pT3 and pathological node (pN)1 groups when stratified according to pT factor (pathological T category) and pN factor (pathological N category) in the tumor-node-metastasis (TNM) classification. VEGF expression had the second highest hazard ratio in the multivariate analysis, after pN factor. These results indicate that VEGF is a useful marker for predicting the outcome in patients with more advanced esophageal squamous cell carcinoma. It seems that TNM factors and VEGF expression are important factors in the selection of appropriate treatments.

The defective bone resorption in the osteopetrotic (op/op) mouse brings about failure of tooth eruption. Furthermore, the op/op mouse has been studied as a "toothless" mouse in recent morphological and physiological investigations of the relationship between mastication and masseter muscle development. The present study was conducted to examine in detail the nasal bone and the premaxillary bone in this mutant mouse and to assess the roles of incisor growth and the mechanical stress of mastication in nasal bone and premaxillary bone growth. The forms of the nasal bone and the premaxillary bone were observed using roentgenography in both toothless op/op and normal (control) mice. In the op/op mouse, the nasal bone and the premaxillary bone show remarkable deformity. In contrast, the normal mouse appears well developed. This suggests that growth of the incisor root is important to normal upper jaw growth in the mouse. Furthermore, it is proposed that the upper facial phenotype seen in the op/op mice results from not only decreased bone resorption, but also from absence of the mechanical stress provided by normal mastication.

An endoluminal surface coil: Esophageal cancer was studied by high resolution magnetic resonance imaging (MRI) to determine the histopathologic basis for signal intensity in these lesions and to determine the potential of this modality for evaluating the depth of cancer invasion. In a basic study, 14 tumors were examined with a 1.5-T superconductive MR system using a surface coil. The esophageal wall could be differentiated into four layers on the T1-weighted images and seven layers on the T2-weighted images. The signal intensity of the tumor varied from low to intermediate on the T1- and T2-weighted images. The submucosal layer is important in evaluating cancer invasion on the T2-weighted images. In a clinical study, 30 patients with esophageal cancer were examined with a 1.5-T superconductive MR system using an endoluminal surface coil. In terms of depth of cancer invasion, the accuracy rate of MRI using the endoluminal surface coil was 83%. In conclusion, MRI with an endoluminal surface coil will be a useful examination for esophageal cancer in the future. Antibody-coated magnetite particles: A highly specific and effective MRI contrast agent was prepared by coating superparamagnetite particles with monoclonal antibodies (MAbs) directed against epidermal growth factor receptors (EGFRs), which are overexpressed in esophageal squamous cell carcinoma. The agent was shown to have EGFR-specific MRI contrast capacity in vivo in athymic rats bearing TE8 or H69 tumors. Immunospecific MRI using magnetite particles coated with MAbs against EGFR seems to be useful in the diagnosis of squamous cell carcinoma of the esophagus.