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Recent studies have revealed a surprising diversity of sex chromosomes in vertebrates. However, the detailed mechanism of their turnover is still elusive. To understand this process, it is necessary to compare closely related species in terms of sex-determining genes and the chromosomes harboring them. Here, we explored the genusTakifugu, in which one strong candidate sex-determining gene,Amhr2, has been identified. To trace the processes involved in transitions in the sex determination system in this genus, we studied 12 species and found that while theAmhr2locus likely determines sex in the majority ofTakifuguspecies, three species have acquired sex-determining loci at different chromosomal locations. Nevertheless, the generation of genome assemblies for the three species revealed that they share a portion of the male-specific supergene that contains a candidate sex-determining gene,GsdfY, along with genes that potentially play a role in male fitness. The shared supergene span approximately 100 kb and are flanked by two duplicated regions characterized by CACTA transposable elements. These results suggest that the shared supergene has taken over the role of sex-determining locus fromAmhr2in lineages leading to the three species, and repeated translocations of the supergene underlie the turnover of sex chromosomes in these lineages. These findings highlight the underestimated role of a mobile supergene in the turnover of sex chromosomes in vertebrates.SignificanceAlthough turnover of sex chromosomes is very common in many vertebrate lineages, the transition process is still elusive. We studied the sex-determining region (SDR) of 12 congeneric fish species. We found that while nine species retained their ancestral SDR, three species had acquired derived SDRs. Although the derived SDRs resided in three different chromosomes, they harbored a shared supergene flanked by two putative transposable elements. The results highlight the underestimated role of a mobile supergene in turnover of sex chromosomes in vertebrates.

Morphological analyses of 183 specimens of Japanese common carp Cyprinus carpio (171 from Lake Biwa and 12 from nursery ponds) using genetic hybrid indices demonstrated that the typical native Japanese strain of C. carpio has a more elongate body, more branched dorsal-fin rays, fewer and shorter gill rakers, more developed pneumatic bulb, more coiled pneumatic duct, longer posterior swimbladder and shorter intestine than the typical introduced C. carpio. These results provide a basis for a better understanding of the ecological characteristics and taxonomic status of the endangered Japanese strain of C. carpio.

Complementary and alternative medicine (CAM) therapies are classified into five major domains: alternative medical systems (which includes traditional Chinese medicine, ayurveda, homeopathy, and naturopathy); mind-body interventions (including meditation, hypnosis, dance music, and art therapy); biologically based treatments (such as vitamins, minerals, herbs, and vegetarianism); manipulative and body-based methods (including chiropractic and massage therapies); and energy therapies - with some overlap across categories. Biomedical engineering (BME) is essential for exploring the safety and efficacy of these CAM therapies in the context of rigorous science. Recently, integrative medicine (IM) has been considered the ideal medical system for integrating conventional medicine and CAM. For this purpose, the concept of how to integrate these methods first must be investigated, and independent verification of CAM methods will be necessary. Biomedical engineering will be expected to be the most important method for verifying CAM scientifically.

SUMMARY: In order to elucidate the regulation of gonadotropin (GTH) gene expression by gonadal sex steroids, the effects of ovariectomy and sex steroid administration on pituitary mRNA levels of GTH subunits were examined in goldfish. Ovariectomy caused a marked increase in GTH Iβ mRNA levels, and steroid hormone replacement (testosterone, T; estradiol-17β, E2; and 11-ketotestosterone, KT) suppressed the elevated levels in sexually early recrudescent and mature females. Pituitary mRNA levels of α and GTH IIβ were not affected by ovariectomy and steroid hormone treatment. When sex steroids (T, E2, and KT) were administered to sexually immature juvenile fish, GTH Iβ mRNA levels were suppressed as observed in adult fish. However, GTH IIβ mRNA levels were observed to increase by sex steroids (T and E2 but not KT) unlike that observed with adult fish. These results indicate that sex steroids exert an inhibitory effect on GTH Iβ mRNA levels from the time goldfish are immature to the time they are mature. However, sex steroids (T and E2) have a stimulatory effect on GTH IIβ mRNA levels in juvenile goldfish and the effect becomes less pronounced when they become adult.

Three different types of porous hydroxyapatite with pore sizes of 100-200 micrometer in diameter-porous particles of hydroxyapatite (PPHAP), porous blocks of hydroxyapatite (PBHAP), and honeycomb-shaped hydroxyapatite (HCHAP)-were compared in terms of their abilities to induce osteogenesis when implanted subcutaneously with recombinant human BMP-2 into rats and extracted at 1, 2, 3, and 4 weeks. Histologically, direct bone formation occurred in PPHAP and PBHAP while only endochondral ossification took place in HCHAP. Interestingly, cartilage in the central zones and bone in the orifice zones of the tunnels of the HCHAP were observed at 2 weeks. After 3 weeks, the cartilage disappeared and bone formation occurred throughout the inner surface of the tunnels of the HCHAP, always leaving space for capillaries within the tunnels. Alkaline phosphatase activity and osteocalcin content were the highest in HCHAP among the three hydroxyapatite implants. These results clearly indicate that BMP-induced bone formation is highly dependent on the geometry of the carrier, which provides feasible structural factors for vascularization.

The authors carried out shunt capacitor switching tests on 24 kV model vacuum interrupters with contact materials CuW and CuCr. The restriking probability of the contact material CuW is lower than that of CuCr. The contact material CuW is also an excellent candidate for shunt capacitor switching except for its high current interruption ability. The restriking probability of a 24 kV, 25 kA vacuum interrupter with contact material CuW is calculated as 10/sup -5/, which is practically zero. >

We have tested the switching performance of a multichip flat packaged 4500-V injection enhanced gate transistor (IEGT) for the first time. The device contains 12 or 15 chips of 15 mm by 15 mm square IEGTs and 6 chips of the same sized free wheel diodes. To examine the short pulse and rectangular pulse switching performance, special test circuits were designed and constructed. As a result, 1) quite easy gate control, and 2) excellent performance for both short pulse and rectangular pulse switching were confirmed.

The authors have developed 4-in and 6.5-in diagonal a-Si thin-film-transistor, active-matrix, liquid-crystal-display (TFT-LCD) modules using tape automated bonding (TAB) technology. The small frame size, 12.5 mm for 4-in modules, has been realized by using U-shape bending tape carriers. In the inner-lead-bonding process, the Au bumps on a driver LSI are connected to the Cu/Sn inner leads on a tape carrier by a high-speed, fully automated gang bonding technique. The LSIs are encapsulated with halogen-ion-free epoxy resin. In the outer-lead-bonding (OLB) process, the Al electrodes on an LC panel are connected to the outer leads on a tape carrier through an anisotropic conductive film (ACF) by a thermocompression apparatus. The ACF, which consists of thermosetting resin and dispersed Ni particles, realizes highly reliable OLB. The TFT-LCD module reliability was confirmed by various environmental and mechanical tests. >

Circumstances in the manufacturing industry have been rapidly changing. The market, user needs and manufacturing infrastructures are already not what they once were. Globalization of production and fabless operation of Japanese domestic production are strongly required. To achieve these demands, it is necessary to speed up manufacturing processes and to extend global production in the Japanese manufacturing field.To achieve these objectives, "digital manufacturing" can be defined. Digital manufacturing is a methodology for manufacturing which uses tangible knowledge (i.e., digital values) and information technology (IT). In digital manufacturing, the ambiguity of tacit knowledge in manufacturing should be eliminated thoroughly, and the tacit knowledge should be transformed into tangible knowledge, such as numerical values and/or equations and finally into digital values.

In order to determine the age and menopause-related changes in spinal bone mineral density (BMD) in healthy Japanese women, the spinal BMD at L(2-4) was measured by dual X-ray absorptiometry (DXA) in 172 healthy Japanese women aged 31-69 years (mean age 53.1+/-6.7 years) in 1990 and 2000. This prospective study showed that there was no significant decrease of BMD in premenopausal women, but there was a significant decrease of BMD (-1.59%/year) in the early post menopausal women when compared with the premenopausal and late postmenopausal women (P

Three different types of porous hydroxyapatite with pore sizes of 100-200 micrometer in diameter-porous particles of hydroxyapatite (PPHAP), porous blocks of hydroxyapatite (PBHAP), and honeycomb-shaped hydroxyapatite (HCHAP)-were compared in terms of their abilities to induce osteogenesis when implanted subcutaneously with recombinant human BMP-2 into rats and extracted at 1, 2, 3, and 4 weeks. Histologically, direct bone formation occurred in PPHAP and PBHAP while only endochondral ossification took place in HCHAP. Interestingly, cartilage in the central zones and bone in the orifice zones of the tunnels of the HCHAP were observed at 2 weeks. After 3 weeks, the cartilage disappeared and bone formation occurred throughout the inner surface of the tunnels of the HCHAP, always leaving space for capillaries within the tunnels. Alkaline phosphatase activity and osteocalcin content were the highest in HCHAP among the three hydroxyapatite implants. These results clearly indicate that BMP-induced bone formation is highly dependent on the geometry of the carrier, which provides feasible structural factors for vascularization.

Facial nerve stimulation by an activated cochlear implant was noted in a 56-year-old patient who had undergone cochlear implant with a Nucleus 22 implant 2 years previously as treatment for total sensorineural hearing loss following meningitis at age 54. Past history was complicated by total renal failure for which hemodialysis had been required during the past 13 years. Facial spasm occurred 5 months postoperatively with activation of the basal electrodes (channels 13 and 15 of the implant). The facial stimulation was eliminated by deprogramming these electrodes. High-resolusion computed tomography (CT) scanning was unable to demonstrate lucency of the otic capsule and cochlear ossification, but basal electrodes of the implant could be identified near the labyrinthine segment of the facial nerve. To further evaluate bone changes in the patient, the total and regional bone mineral density (BMD) of the head and radius was measured by dual energy X-ray absorptiometry. All BMD values of the patient were markedly low when compared to those of 62 other hemodialysis patient. These findings demonstrate that facial nerve stimulation can occur in the presence of low impedance due to cortical bone changes induced by long-term hemodialysis.

We performed vitreous surgery for macular holes following membrane peeling. The cases were five eyes of five females aged 42 to 67 years at the time of membrane peeling, out of 441 eyes of 414 patients who underwent membrane peeling. One eye had secondary epiretinal membrane combined with ocular sarcoidosis, two eyes had idiopathic epiretinal membrane, and two eyes had idiopathic vitreoretinal traction syndrome. The presumed interval from membrane peeling to macular hole formation was 5 to 90 months (average 14 months). For treatment of the macular holes, membrane peeling and SF6 gas tamponade were performed. In four eyes of the five eyes, the macular hole was closed. In the remaining eye, removal of the retinal pigment epithelium from the base of macular hole and application of fibrin glue were used in addition to SF6 gas tamponade, but the macular hole was not closed. The follow-up term was 10-24 months (average 17.6 months). Geometrical mean visual acuity was 0.34 before membrane peeling, 0.94 at maximum after membrane peeling, 0.19 after macular hole formation, 0.51 at maximum after macular hole surgery, and 0.44 at the final visit.

To observe microcirculation chronically is an important key to the successful evaluation of the continuous flow blood pump. In this study, we succeeded in developing a new apparatus by which microcirculation could be observed chronically without a microscope in a conscious animal. The apparatus utilizes a charge coupled device (CCD). A thin living tissue, such as mesentery, is put directly on a highly integrated CCD and is lit up through the tissue with a light-emitting diode (LED). The vascular nets in the tissue are projected onto the CCD like a contact photograph, which is then sent to a television screen and which can be used to analyze their motion and function. A 0.5-inch CCD having 250,000 pixels was used in this study. The cover glass of the CCD was removed, and a fiber optic plate was fixed onto the surface of the CCD for the tissue to be able to contact with the apparatus surface without clearance. The CCD as well as the LED were molded with epoxy resin for electrical insulation. The apparatus was 35 mm wide and 12 mm high with a micro stand for an LED, which can be easily implanted into an animal. The apparatus was implanted into a rabbit for 12 h. The configuration of arterioles and venules, tens of micrometers in diameter, and their motions in subcutaneous tissue could be observed.

This chapter describes a study on a new optical fiber sensor for detecting chemiluminescence and its application to immunoassay. An optical fiber sensor system based on acridinum chemiluminescence is developed. This system consists of five components connected in tandem: (1) photoncounter, (2) optical fiber, (3) sampling device, (4) chemiluminescent tip, and (5) immuno reaction tip. Immuno reactions were carried out in the immuno reaction tip, based on the principle of an antigen–antibody displacement. A solid-phase-immobilized antibody was saturated with the acridinium labeled antigen, and then it was attached chemiluminescent tip. Introduction of the unlabeled antigen of a sample into the immuno reaction tip induced displacement of the labeled antigen within five seconds, and chemiluminescence was detected in the chemiluminescent tip subsequently. Detection levels of insulin as model antigen was at least 10 −5 M. Chemiluminescence of acridinium was detected in the chemiluminescent tip, which included chemiluminescent powder mixture of Na 2 CO 3 and NaBO 3 . Acridinium solution was introduced into the chemiluminescent tip using sampling device, and emitted light signal was transmitted to photoncounter through optical fiber and was analyzed. It was concluded that the combination of chemiluminescent powder and antigen–antibody displacement assay brought a simple and fast-detectable immunosensor without any additional reagents.

A new pulsatile total artificial heart (TAH) system, combining a single centrifugal pump (CFP) with two three-way valves, was developed. One port of each three-way valve was connected to the inlet and outlet of a CFP, respectively. The other two ports of each valve ware connected to the right and left atrium, pulmonary artery, and aorta. The CFP can perfuse the pulmonary and systemic circulation alternately with pulsatile flow. A prototype system composed of a Sarns' CFP and solenoid valves was connected to a mock circulatory system resulting in 1) a pulsatile TAH that could be produced with a single CFP, 2) 5 L/min of pulsatile output with a normal flow wave form that can be obtained alternately on the right and left side by switching the solenoid valves, and 3) flow balance between the left and the right that could be controlled easily by the length of switching duration. This new system could be miniaturized and is feasible for a totally implantable TAH.

An artificial heart (AH) driving system, in which a sac or diaphragm type blood pump is liquid gas driven, is designed. The working mechanism of this system is as follows: 1) liquid gas is used for the driving source; 2) a liquid gas is stored in its liquid state in the circuit; 3) a liquid gas is vaporized, and the vaporizing pressure squeezes the blood pump, causing ejection of blood; 4) vaporized gas is aspirated and compressed by a small compressor to liquefaction through the heat exchanger, then negative pressure is applied to the blood pump and blood is aspirated; and 5) the blood pump is driven in this closed cycle. To demonstrate the mechanism of this system, a prototype was developed using Freon 114 as the liquid gas. In this system, the maximum flow of the AH at a 100 pulse per minute rate, was about 6.9 L/min, using a 90 ml sac type blood pump. The advantages of this AH driving mechanism are as follows: 1) a small system is available because pressure chambers are not necessary; 2) a biventricular system is available, with a single compressor; 3) no compliance chamber is necessary if the system is small enough to be implanted.

A total of 61 VASs developed in Tokyo University were evaluated at 21 institutions in the period 1985-1989 for determination of its reliability and effectiveness. The system is comprised of a pneumatic sack-type pump (Nippon Zeon Co.), and its driving console (Aishin Seiki Co.). The stroke volume of the pump is 40 ml and blood contacting surfaces are coated with Cardiothane. Ages of the patients (pts) ranged from 12-82 yrs (mean 58 yrs). VASs were used in the assist mode of LVAD (54 pts), RVAD (5 pts) and BVAD (2 pts). Most of the cases (58 pts) included postocardiotomy cardiogenic shock after surgery for ischemic (28 pts), valvular (22 pts), both ischemic and valvular (7 pts) and congenital (1 pt) heart diseases. Average duration of the assist ranged from 1 hr-20 days (mean 5.6 dys). The VADs could be weaned in 34 cases (56%) and among these, 13 cases (21%) survived to discharge from the hospital. Causes of death in cases which could be weaned from the VAD included multiple organ failure/due to delayed institution of adequate circulatory support, renal failure and systemic infection. Small and minute thrombus formations were noted in 7 cases however, no pump originated thromboembolism were complicated. No troubles of the pump including leakage nor breakage, no mechanical failures of the driving consoles were experienced in any of the cases. Thus, it is concluded that the system was proved to be clinically effective and reliable.

本報文は耐熱, 耐老化性に秀れているブチルゴムについて, 共振法により動特性を求あ, 防振ゴムとして使用に耐えるかどうかを調べてみた. ところが動試験によれば一応予想される通りの結果を得たが, 欠点として永久歪が大きいことを認めた. また他に防振ゴムとして必要な特性も併せて調べてみた.

Much ultrasonic diagnosis has the advantage that it requires no surgery, but if this advantage is forgone, scope for diagnosis can be extended. The authors describe examination of the liver by a p.p.i. display with a probe placed in the inferior vena cava via the femoral vein and a method of detecting and measuring an atrial septal defect (a.s.d.) with a probe inserted in the right atrium through the external jugular vein or the femoral vein. In detecting a.s.d. a C-scan technique is usually used. No harmful effects have been observed in either examination. This article is based on a paper which was presented at the 5th Conference on Medical Electronics at Liege in July, 1963

Current circulatory assist methods, such as intra-aortic balloon pumping (IABP), are not always adequate to save acute circulatory failure patients. Therefore, a stronger, percutaneously accessible method is required. We found that the combination of IABP and CP generated a profound circulatory assist effect, and we have consequently developed a new assist system in this study. A sac type blood pump with a volume of 20 ml and a single port without a valve, was developed for CP. In the mock circulatory test, a 20 ml stroke volume was obtained using a cannula with a 5 mm diameter under the following driving conditions: air pressure = 200/-100 mmHg; S/D = 50%; pulse rate = 100 bpm. In vivo experiments were performed using four mongrel dogs with body weights of 12-20 kg. A cannula for CP was inserted via the brachial artery or subclavian artery into the aortic root. The pump flow (PF), coronary artery flow (CF), renal arterial flow (RF), and aortic pressure (AP) were measured, and the combined effects of IABP and CP were compared with their individual effects. In the most effective case, a marked increase in diastolic AP (60%), cardiac output (40%), and CF (100%) was obtained by the combination of IABP and CP, which produced a remarkable effect compared with the single use of IABP and CP. There was no negative effect on RF by this assist method. As this new circulatory support system has many circulatory assist effects, and is percutaneously accessible, it will be available for clinical use.

High output AH pumping causes a marked decrease in hematocrit, as well as peripheral circulatory insufficiency. By the application of a new control method, based on our hypothesis of regulating the output of the pump, maintenance of normal outputs, long term survival, after total heart replacement, has improved from 10 days to 37 days, with the average survival of 18 days. In addition, the experimentsl animals' general condition has been markeldy improved.

We developed control system of total artificial heart (TAH) during exercise simulating the circulatory response of natural heart. The following procedures were taken to develop this system. 1) Measurement of hemodynamics and physical activity rate (PAR) of natural heart goats during treadmill exercise. 2) Estimation of cardiac output from PAR using a non-linear model. 3) Development of a pneumatic artificial heart (AH) driver with high speed controllability and a control unit to deliver CO calculated from PAR beat by beat. 4) Evaluation of the physiological condition of the TAH goat during exercise controlled by this system. Using this control method, CO of TAH goats was similar to that of natural heart goats during treadmill exercise. Hypertension was observed during exercise. This hypertension was considered to be derived from two causes. One was high inflow and outflow resistance of cannulae between AH pump and living body. The other was the disorder of peripheral circulatory control mechanism in TAH animal. Such as increased sympathetic activity, insufficient secretion of atrial natriuretic polypeptide (ANP) and decreased sensitivity of peripheral circulatory system with ANP.

A TAH goat survived 344 days postoperatively. The cause of death was hypoxia due to lung embolism and anemia.