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Design, development, manufacturing, and test activities of the RF power system (RFPS) for Linear IFMIF Prototype Accelerator (LIPAc) were completed in Europe. Installation and commissioning activities were carried out at the International Fusion Materials Irradiation Facility-Engineering Validation and Engineering Design Activities (IFMIF/EVEDA) site in Rokkasho, Japan. Challenging IFMIF requirements led to a number of innovations during design and development. Commissioning required a major effort on calibration and fine setting and led to development of new functionalities. The RFPS was validated under full power and 125-mA deuteron beam loading conditions, in the radio frequency quadrupole (RFQ), demonstrating good performance. This article is an overview about how technical challenges impacted the prototype RFPS design and its functional evolution during commissioning, cavity conditioning, and beam operation of the RFQ.

BA協定の下での日欧協力としてQST六ヶ所融合研究所でIFMIF原型加速器（LIPAc）の実証試験が実施されている。 LIPAcでは、超伝導RF（SRF）加速器の試験も計画されており、SRFライナックを冷却するための液体ヘリウムを製造するための冷凍機システムが調達され、六ヶ所研に設置された。この記事では、LIPAc用の冷凍機システムの概要、六ヶ所研における設置作業および動作試験の詳細について述べる。

The eight-chain RF system and radio frequency quadrupole (RFQ) linac were successfully integrated at the facility of the Linear IFMIF Prototype Accelerator (LIPAc). We achieved an unprecedented high current deuteron beam up to 55 mA in pulse operation ( $300~\mu \text{s}$ , 1 Hz). The keys of the success were (1) understanding reflected power from RFQ to RF system, (2) tuning each RF chain individually, (3) intensive RF conditioning for holding the stable RF power in the RFQ, and (4) optimizing the beam loading compensation control. Interestingly, the reflection at the breakdown in RF conditioning was higher than an estimation and reached up to 600 kW so far. In order to avoid damage on tetrodes by the high reflection, the impedance of each circulator was accurately adjusted.

加速器駆動核融合中性子源の凹型自由表面液体LiターゲットのCFDモデルを開発した。CFDシミュレーションより、遠心力により凹型自由表面流れの厚さが増大することが分かった。この結果は、先行研究の近似解析解やターゲット厚さ計測結果と定性的に一致する。, 日本原子力学会 2022年春の年会

IFMIF加速器の超伝導加速器(SRF)のように大電流非軸対称ビームの場合、ソレノイド収束系におけるビームサイズの計算は、計算時間を要する多粒子シミュレーションに限られていた。今回、非軸対称ビームのソレノイド収束系におけるビームサイズを、エンベロープ方程式を使って短時間で計算できる計算モデルを考案したので、TraceWinの計算結果と比較し、エンベロープ方程式を用いた計算モデルの妥当性・有用性の検証を実施したので、それについて発表する。, 2021年度核融合科学研究所共同研究形式研究会プログラム 「パルスパワー技術およびプラズマ・量子ビーム技術の最新動向」

Delayed sleep–wake phase disorder (DSWPD) is a subtype of circadian rhythm sleep–wake disorders, and is characterized by an inability to fall asleep until late at night and wake up at a socially acceptable time in the morning. The study aim was to identify low-frequency nonsense and missense variants that are associated with DSWPD. Candidate variants in circadian rhythm-related genes were extracted by integration of genetic variation databases and in silico assessment. We narrowed down the candidates to six variants. To examine whether the six variants are associated with DSWPD, we performed an association study in 236 Japanese patients with DSWPD and 1436 controls. A low-frequency missense variant (p.Val1205Met) in PER2 showed a significant association with DSWPD (2.5% in cases and 1.1% in controls, P = 0.026, odds ratio (OR) = 2.32). The variant was also associated with idiopathic hypersomnia known to have a tendency toward phase delay (P = 0.038, OR = 2.07). PER2 forms a heterodimer with CRY, and the heterodimer plays an important role in the regulation of circadian rhythms. Val1205 is located in the CRY-binding domain of PER2 and was hypothesized to interact with CRY. The p.Val1205Met substitution could be a potential genetic marker for DSWPD.

現在、核融合エネルギー分野における日本と欧州による共同事業の一つである、国際核融合材料照射施設(IFMIF)の工学実証・工学設計活動(EVEDA)の一環として、原型加速器(LIPAc)の建設が量研六ヶ所核融合研究所で進行中である。高周波四重極加速器(RFQ: Radio Frequency Quadrupole accelerator)の長パルスビーム試験のため、超伝導高周波加速器(SRF: Superconducting Radio Frequency accelerator)を将来設置する箇所に新たなビーム輸送系(MEL: MEBT Extension Line)をクリーンな環境下で構築し、準備を進めている。 SRFを使用する施設では、ゲートバルブの開閉操作で発生・混入する微粒子によって生じるフィールドエミッション(FE)による性能劣化が問題視されている。LIPAcでは微粒子のサイズ・個数とSRFの性能劣化との関係を定量的に評価するのため、真空下で微粒子の動きを可視化できるパーティクルモニタをMELに導入し、ゲートバルブの開閉操作で発生する微粒子の測定を行った。本発表では微粒子測定の方法と結果について報告する。, 第18回日本加速器学会年会

超純水高圧水洗は、超伝導加速空洞内面を清浄に仕上げるための重要な工程である。三菱重工機械システムでは、超純水高圧水洗装置を自社導入し、各種超伝導加速空洞の洗浄に適用してきた。本発表では、三菱重工機械システムの超純水高圧水洗技術及び適用実績について報告する。, 第18回日本加速器学会年会

International audience; Design, development, manufacturing, and test activities of the RF power system (RFPS) for Linear IFMIF Prototype Accelerator (LIPAc) were completed in Europe. Installation and commissioning activities were carried out at the International Fusion Materials Irradiation Facility-Engineering Validation and Engineering Design Activities (IFMIF/EVEDA) site in Rokkasho, Japan. Challenging IFMIF requirements led to a number of innovations during design and development. Commissioning required a major effort on calibration and fine setting and led to development of new functionalities. The RFPS was validated under full power and 125-mA deuteron beam loading conditions, in the radio frequency quadrupole (RFQ), demonstrating good performance. This article is an overview about how technical challenges impacted the prototype RFPS design and its functional evolution during commissioning, cavity conditioning, and beam operation of the RFQ.

The Linear IFMIF Prototype Accelerator (LIPAc) is under construction as a collaboration between Europe and Japan for challenging the technical validation of the low energy part up to 9MeV of IFMIF deuteron accelerator unit with 40MeV-125mA CW. The staged installation and commissioning activities are ongoing at the BA site in Rokkasho Fusion Institute of QST, and the commissioning of RFQ is underway. A deuteron beam acceleration at 5 MeV, 125mA was achieved at short pulse (~1 ms pulse duration) at ~1 Hz repetition. Here, ~90 % beam transport was obtained. Here, 8-chains of 175 MHz CW RF sources are connected to the RFQ in parallel. After that, MEBT, D-plate, HEBT and high power beam dump were connected to the RFQ in series, and high duty cycle beam commissioning will be implemented., 30th International Linear Accelerator Conference 2020

The eight-chain RF system and radio frequency quadrupole (RFQ) linac were successfully integrated at the facility of the Linear IFMIF Prototype Accelerator (LIPAc). We achieved an unprecedented high current deuteron beam up to 55 mA in pulse operation (300 μs, 1 Hz). The keys of the success were (1) understanding reflected power from RFQ to RF system, (2) tuning each RF chain individually, (3) intensive RF conditioning for holding the stable RF power in the RFQ, and (4) optimizing the beam loading compensation control. Interestingly, the reflection at the breakdown in RF conditioning was higher than an estimation and reached up to 600 kW so far. In order to avoid damage on tetrodes by the high reflection, the impedance of each circulator was accurately adjusted.

The construction of the Linear IFMIF Prototype Accelerator (LIPAc) is in progress in order to demonstrate the feasibility of the low energy section of an IFMIF deuteron accelerator up to 9 MeV with a beam current of 125 mA in CW. The next milestone of the project is the so-called Phase-B beam commissioning, and one of the missions is to demonstrate the acceleration of the proton beam up to 2.5 MeV or the deuteron beam up to 5.0 MeV in pulsed mode with a low duty cycle of 0.1% through RFQ. Most of the components and subsystems necessary for Phase-B were delivered by 2016 under the responsibility of Fusion for Energy (F4E) as in-kind contributions of several European institutes, namely CEA (France), CIEMAT (Spain), INFN (Italy), and SCK-CEN (Belgium), and QST is in charge of the installation of the delivered equipment. The installation and check-out of the RFQ subsystem and the RF power system was completed by July 2017, and the RF conditioning of the RFQ cavity started. Also, the installation and the check-out of the important sub-systems for Phase-B, namely MEBT and beam diagnostics, have been completed. Keywords: IFMIF, LIPAc, RFQ, Accelerator, Deuteron, Neutron source

The Radio Frequency Quadrupole (RFQ) linac and 1.6 MW RF power system of the Linear IFMIF Prototype Accelerator (LIPAc) facility in the International Fusion Energy Research Center (IFERC) in Rokkasho (Japan) has been installed and conditioned. During the assembly and tuning process, the RFQ cavity was protected with a temporary tent from the potential deterioration of performance caused by dust. The vacuum in the cavity was improved through the 100 °C baking process of the cavity. The high power test of the 175 MHz RF systems up to 200 kW in CW for each of the eight RF chains was performed for checking its stable output reproducibility in Japan, before connecting 9–3/16 inch coaxial transmission lines from the RF chains to the RF input couplers of the cavity. It was confirmed that the eight RF chains provided the balanced RF power to the single RFQ cavity in-phase using a feedback loop and a synchronization system. The peak power in the cavity achieved 150 kW in the pulsed mode, which corresponds approximately to the required electric field to accelerate proton beam. Such RF conditioning process is ongoing to achieve 600 kW approximately required for deuteron beam commissioning planned in 2018.

For the development of the International Fusion Materials Irradiation Facility (IFMIF) aiming at material tests for fusion power plants, the construction of the Linear IFMIF Prototype Accelerator (LIPAc) has been conducted at Rokkasho, Japan under the Broader Approach Agreement. The commissioning of LIPAc has been progressing significantly. The world most powerful RFQ successfully accelerated proton beam of 58 mA, and an important project milestone of the acceleration of deuteron beam to 5 MeV with the beam current of 125 mA in pulse mode was successfully achieved. The result proves the validity of the present RFQ design. The adjustment and tuning of the RF power system and the injector for enabling an operation at maximum performances played an important role in achieving this result. For the next step, the preparation of the high duty cycle operation of RFQ is underway. The installation of the HEBT (High Energy Beam Transport line) and the beam dump accepting 1 MW, CW beam, has been completed and a new beam transport line is under manufacturing. Also the assembly of the Superconducting RF (SRF) linac to accelerate the beam up to 9 MeV started in a clean room in Rokkasho., The 14th International Symposium on Fusion Nuclear Technology

For the development of the International Fusion Materials Irradiation Facility (IFMIF) aiming at material tests for fusion power plants, the construction of the Linear IFMIF Prototype Accelerator (LIPAc) has been conducted at Rokkasho, Japan under the Broader Approach Agreement. The commissioning of LIPAc has been progressing significantly. The world most powerful RFQ successfully accelerated proton beam of 58 mA, and an important project milestone of the acceleration of deuteron beam to 5 MeV with the beam current of 125 mA in pulse mode was successfully achieved. The result proves the validity of the present RFQ design. The adjustment and tuning of the RF power system and the injector for enabling an operation at maximum performances played an important role in achieving this result. For the next step, the preparation of the high duty cycle operation of RFQ is underway. The installation of the HEBT (High Energy Beam Transport line) and the beam dump accepting 1 MW, CW beam, has been completed and a new beam transport line is under manufacturing. Also the assembly of the Superconducting RF (SRF) linac to accelerate the beam up to 9 MeV started in a clean room in Rokkasho.

For the development of the International Fusion Materials Irradiation Facility (IFMIF) aiming at material tests for fusion power plants, the construction of the Linear IFMIF Prototype Accelerator (LIPAc) has been conducted at Rokkasho, Japan under the Broader Approach Agreement. The commissioning of LIPAc has been progressing significantly. The world most powerful RFQ successfully accelerated proton beam of 58 mA, and an important project milestone of the acceleration of deuteron beam to 5 MeV with the beam current of 125 mA in pulse mode was successfully achieved. The result proves the validity of the present RFQ design. The adjustment and tuning of the RF power system and the injector for enabling an operation at maximum performances played an important role in achieving this result. For the next step, the preparation of the high duty cycle operation of RFQ is underway. The installation of the HEBT (High Energy Beam Transport line) and the beam dump accepting 1 MW, CW beam, has been completed and a new beam transport line is under manufacturing. Also the assembly of the Superconducting RF (SRF) linac to accelerate the beam up to 9 MeV started in a clean room in Rokkasho.

Circadian rhythm sleep–wake disorders (CRSWDs) are characterized by disturbed sleep–wake patterns. We genotyped a PER3 variable number tandem repeat (VNTR) in 248 CRSWD individuals and 925 controls and found no significant association between the VNTR and CRSWDs or morningness–eveningness (diurnal) preferences in the Japanese population. Although the VNTR has been associated with circadian and sleep phenotypes in some other populations, the polymorphism may not be a universal genetic marker.

Vertebrate eyes are known to contain circadian clocks, however, the intracellular mechanisms regulating the retinal clockwork remain largely unknown. To address this, we generated a cell line (hRPE-YC) from human retinal pigmental epithelium, which stably co-expressed reporters for molecular clock oscillations (Bmal1-luciferase) and intracellular Ca2+ concentrations (YC3.6). The hRPE-YC cells demonstrated circadian rhythms in Bmal1 transcription. Also, these cells represented circadian rhythms in Ca2+-spiking frequencies, which were canceled by dominant-negative Bmal1 transfections. The muscarinic agonist carbachol, but not photic stimulation, phase-shifted Bmal1 transcriptional rhythms with a type-1 phase response curve. This is consistent with significant M3 muscarinic receptor expression and little photo-sensor (Cry2 and Opn4) expression in these cells. Moreover, forskolin phase-shifted Bmal1 transcriptional rhythm with a type-0 phase response curve, in accordance with long-lasting CREB phosphorylation levels after forskolin exposure. Interestingly, the hRPE-YC cells demonstrated apparent circadian rhythms in phagocytic activities, which were abolished by carbachol or dominant-negative Bmal1 transfection. Because phagocytosis in RPE cells determines photoreceptor disc shedding, molecular clock oscillations and cytosolic Ca2+ signaling may be the driving forces for disc-shedding rhythms known in various vertebrates. In conclusion, the present study provides a cellular model to understand molecular and intracellular signaling mechanisms underlying human retinal circadian clocks.

Objective—To determine whether mitral valve repair (MVR) under cardiopulmonary bypass would be an effective treatment for mitral regurgitation in small-breed dogs. Design—Retrospective case series. Animals—48 small-breed dogs (body weight, 1.88 to 4.65 kg [4.11 to 10.25 lb]; age, 5 to 15 years) with mitral regurgitation that underwent surgery between August 2006 and August 2009. Procedures—Cardiopulmonary bypass was performed with a cardiopulmonary bypass circuit. After induction of cardiac arrest, a mitral annuloplasty was performed, and the chordae tendineae were replaced with expanded polytetrafluoroethylene chordal prostheses. After closure of the left atrium and declamping to restart the heart, the thorax was closed. Results—Preoperatively, cardiac murmur was grade 3 of 6 to 6 of 6, thoracic radiography showed cardiac enlargement (median vertebral heart size, 12.0 vertebrae; range, 9.5 to 14.5 vertebrae), and echocardiography showed severe mitral regurgitation and left atrial enlargement (median left atrium-to-aortic root ratio, 2.6; range, 1.7 to 4.0). 45 of 48 dogs survived to discharge. Three months after surgery, cardiac murmur grade was reduced to 0/6 to 3/6, and the heart shadow was reduced (median vertebral heart size, 11.1 vertebrae, range, 9.2 to 13.0 vertebrae) on thoracic radiographs. Echocardiography confirmed a marked reduction in mitral regurgitation and left atrium-to-aortic root ratio (median, 1.7; range, 1.0 to 3.0). Conclusions and Clinical Relevance—We successfully performed MVR under cardiopulmonary bypass in small-breed dogs, suggesting this may be an effective surgical treatment for dogs with mitral regurgitation. Mitral valve repair with cardiopulmonary bypass can be beneficial for the treatment of mitral regurgitation in small-breed dogs.

Objective: To describe surgical repair of a large atrial septal defect (ASD) in a cat. Study Design: Clinical report. Animal: A 3-year-old, 3.3 kg, intact male Japanese domestic short-haired cat. Methods: A 10.2-mm-diameter ASD detected by echocardiography was surgically corrected because pulmonary vascular resistance-to-systemic vascular resistance ratio (Qp/Qs) was 3.2. Using cardiopulmonary bypass (CPB), open surgical repair was achieved with an expanded polytetrafluoroethylene (e-PTFE) graft. The priming volume of the CPB circuit was minimized by cutting the CPB tubing, and partially replacing the priming fluid with whole cat blood. To prevent hemodilution associated with use of cardioprotective agents, surgery was performed on the beating heart. Results: At 1-year echocardiographic evaluation, the repair was intact, and at 3 years, the cat was alive without need of medication. Conclusions: Large ASD in a cat can be repaired using e-PTFE under CPB.

Objective: To describe surgical repair of a complete endocardial cushion defect (ECD) in a dog. Study Design: Clinical report. Animal: A 5-month-old, 9.2 kg male Shetland sheepdog. Methods: Echocardiographic examination revealed an ostium primum atrial septal defect (ASD), an inlet ventricular septal defect (VSD), mitral regurgitation (MR) and tricuspid regurgitation (TR), and a complete ECD was diagnosed. Surgical correction was performed using cardiopulmonary bypass (CPB) via right atriotomy. A polytetrafluoroethylene (PTFE) patch was secured along the margin of the inlet VSD using simple continuous suture, then the cleft in the septal mitral leaflet was sutured. Similarly, the cleft in the septal tricuspid leaflets was sutured. To complete inlet VSD closure, the VSD patch was secured to these sutured leaflets by simple continuous suture. Another PTFE patch was used to close the ostium primum ASD. Result: After surgery, MR, TR, and interventricular shunting were decreased. The dog was alive 6 years and 5 months after the surgery with no evidence of an interventricular shunt, TR, or other clinical signs. Conclusions: Complete ECD in a dog was corrected using a 2-patch technique under CPB.

Preparation of epitaxial YBa 2 Cu 3 O 7 (YBCO) films on cerium oxide-buffered sapphire (r-cut α-Al 2 O 3 ) substrates by an excimer-laser-assisted metalorganic deposition (ELAMOD) is reported. The ELAMOD process has been developed to bring about the advantage of shorter heating time than that in the conventional metalorganic deposition; the coated films are irradiated by an excimer laser beam before firing. We initiated the ELAMOD-YBCO process using a homogenized 8-mm-square laser beam which irradiates the coated surface in a fixed substrate mode. In order to extend the process applicable to large-area films, a scan irradiation mode was employed and a high critical-current density over 6 MA/cm 2 has been observed. In the process, an appropriate choice of laser energy is difficult but crucial to obtain YBCO films with high superconducting properties. Then, laser irradiation from backside of the substrate was examined and proved to be beneficial to extend the experimental window of the laser energy. Moreover, a newly developed ELAMOD process using a 90-mm-wide line-beam is also reported which has a potential ability for large-area applications.

Objective—To clarify regulation of the renin-angiotensin (RA) system in cardiac tissues by measuring angiotensin-converting enzyme (ACE) and chymase activities in cats with pressure-overload cardiac hypertrophy. Animals—13 adult cats. Procedures—Pressure-overload cardiac hypertrophy was induced by coarctation of the base of the ascending aorta in 6 cats, and 7 cats served as untreated control animals. Cats were examined before and 3 months and 2 years after surgery. Two years after surgery, cardiac hypertrophy was confirmed by echocardiography, and the blood pressure gradient was measured at the site of constriction. Cats were euthanized, and ACE and chymase activities were measured in cardiac tissues. Results—Mean ± SD pressure gradient across the aortic constriction was 63 ± 6 mm Hg. Chymase activity predominated (75% to 85%) in the RA system of the cardiac tissues of cats. Fibrosis in the wall of the left ventricle was detected in cats with hypertrophy, and fibrosis of the papillary muscle was particularly evident. Conclusions and Clinical Relevance—Chronic pressure overload on the heart of cats can activate the RA system in cardiac tissues. A local increase in angiotensin II was one of the factors that sustained myocardial remodeling.

Epitaxial YBa 2 Cu 3 O 7 (YBCO) films were prepared on cerium oxide-buffered sapphire ( r -cut α-Al 2 O 3 ) substrates by an excimer-laser-assisted metalorganic deposition (ELAMOD) using a scanning substrate mode. The substrate surface was scanned under homogenized KrF excimer laser beam irradiation after application of a fluorine-free ingredient solution. The ELAMOD process has brought about the advantages of shorter heating time as well as higher critical current density ( J c ) of the YBCO films. The J c values over 6 MA/cm 2 were measured by an inductive method at 77.3 K for the laser-irradiated areas. The scanning laser irradiation is considered to produce a desirable precursor for crack free films with high- J c and to shorten the total time of heat treatment, in which three metal components are well-dispersed in short time. Such a precursor has contributed to prevent the occurrence of impurity phases, resulting in the high- J c YBCO films. The X-ray diffraction measurement of the irradiated area clearly showed a complete c -axis-oriented YBCO and no impurity phases, whereas a -axis-oriented YBCO was dominant in the area without irradiation. The ELAMOD process using the scanning substrate mode has a potential ability to apply to continuous production of the large-area films or long tapes of YBCO.

Objective—To investigate the relationship between myocardial performance index (MPI; also known as the Tei index) and cardiac function in anesthetized cats administered dobutamine. Animals—6 adult cats. Procedures—Cats were anesthetized by administration of propofol (6 mg/kg, IV), and anesthesia was maintained by administration of isoflurane. Heart rate and systolic arterial pressure (SAP) were monitored. Stroke volume, cardiac output, and aortic blood flow (ABF) were measured by use of transesophageal ultrasonography. Left ventricular fractional shortening (LVFS), mitral E-wave velocity-to-A-wave velocity (E:A) ratio, and ejection time were measured by use of transthoracic echocardiography. Dobutamine was administrated via a cephalic vein at rates of 2.5, 5.0, and 10 μg/kg/min. Results—Heart rate, SAP, cardiac output, and ABF increased with dobutamine administration, whereas stroke volume significantly decreased. The LVFS significantly increased, and the E:A ratio significantly decreased. Total isovolumic time and the MPI significantly decreased. The MPI was negatively correlated (r = −0.63) with LVFS. Conversely, the MPI was positively correlated with the E:A ratio (r = 0.47), stroke volume (r = 0.66), and total isovolumic time (r = 0.95). However, the MPI was not significantly correlated with heart rate, SAP, cardiac output, or ABF. Conclusion and Clinical Relevance—Analysis suggested that the MPI provides a sensitive clinical assessment of cardiac response to medication in cats, which may be similar to the usefulness of the MPI reported in humans.

The rehabilitation program has been conducted at our psychiatric clinic for depressive patients who are absent from work, with the aim of assisting them to return to work. We have noticed that a substantial number of the patients have traits of developmental disorders, which contribute to chronicity and/or recurrence of depression. Therefore, we have recently created a new rehabilitation program in addition to the specialty outpatient clinic and peer support group. All these programs specialize in treating adult patients with mild developmental disorders [mostly autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD)]. Since then, we have investigated a lot of depressive patients whose ASD symptoms have been identified for the first time in their life. Symptoms were first noted after they started work where they experienced impaired social functioning because the social demands were higher than those at schools. To assist patients with their goals of improving symptoms and stabilizing social functions, it is valid to evaluate whether the autistic traits cause mental stress and impairment during occupational functioning, even if the diagnosis of ASD is not definitive or the symptoms are below the diagnostic threshold for ASD. The profile of ASD symptoms is different for each patient, and therefore personalized support is essential.

Recent studies have shown that functional variations in clock genes, which generate circadian rhythms through interactive positive/negative feedback loops, contribute to the development of circadian rhythm sleep disorders in humans. Another potential candidate for rhythm disorder susceptibility is casein kinase I epsilon (CKIepsilon), which phosphorylates clock proteins and plays a pivotal role in the circadian clock. To determine whether variations in CKIepsilon induce vulnerability to human circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24), we analyzed all of the coding exons of the human CKIepsilon gene. One of the variants identified encoded an amino-acid substitution S408N, eliminating one of the putative autophosphorylation sites in the carboxyl-terminal extension of CKIepsilon. The N408 allele was less common in both DSPS (p = 0.028) and N-24 patients (p = 0.035) compared to controls. When DSPS and N-24 subjects were combined, based on an a priori prediction of a common mechanism underlying both DSPS and N-24, the inverse association between the N408 allele and rhythm disorders was highly significant (p = 0.0067, odds ratio = 0.42, 95% confidence interval: 0.22-0.79). In vitro kinase assay revealed that CKIepsilon with the S408N variation was approximately 1.8-fold more active than wild-type CKIepsilon. These results indicate that the N408 allele in CKIepsilon plays a protective role in the development of DSPS and N-24 through alteration of the enzyme activity.

High performance YBa 2 Cu 3 O 7− y (YBCO) films with large area (50 mm-square) and 300 nm-thick were prepared by a combination of excimer-laser-assisted metalorganic deposition (ELAMOD) and conventional MOD using a fluorine-free coating solution. A characteristic feature in the ELAMOD process is that KrF excimer laser is irradiated on the solution-coated surface of specimen in an ambient atmosphere. The YBCO films on CeO 2 -buffered r -cut sapphire substrates showed low surface resistance ( R s ), high superconducting current density ( J c ), and good reproducibility in both R s and J c . The R s and J c values of the films were 0.6 mΩ (12 GHz) and around 2.0 MA/cm 2 at 77.3 K, respectively.

Panic disorder (PD) is a severe and chronic psychiatric disorder, with genetic components underlying in its etiology. The PERIOD2 (Per2) gene has been reported to be associated with familial advanced sleep phase syndrome. Considering the high frequency of sleep disturbance in PD, Per2 may be a candidate gene for PD. Therefore, we conducted a two-stage case-control association study in the Japanese population. In the first screening sample of 203 patients and 409 controls, we investigated three single-nucleotide polymorphisms in Per2. We found a potential association in the screening sample (rs2304672, genotype P=0.046, uncorrected), whereas we could not replicate the association in the second sample of 460 patients and 460 controls. Our results suggest that Per2 may not have a major role in the pathogenesis of PD in the Japanese population.

A system of self-sustained biological clocks controls the 24-h rhythms of behavioral and physiological processes such as the sleep-wake cycle. The circadian clock system is regulated by transcriptional and translational negative feedback loops of multiple clock genes. Polymorphisms in circadian clock genes have been associated with morningness-eveningness (diurnal) preference, familial advanced sleep phase type (ASPT), and delayed sleep phase type (DSPT). We genotyped single-nucleotide polymorphisms in circadian clock genes in 182 DSPT individuals, 67 free-running type (FRT) individuals, and 925 controls. The clock gene polymorphisms were tested for associations with diurnal preference and circadian rhythm sleep disorder (CRSD) phenotypes. The PER3 polymorphism (rs228697) was significantly associated with diurnal preference and the FRT phenotype. The minor allele of rs228697 was more prevalent in evening types than in morning types (sex-adjusted odds ratio (OR), 2.483, Bonferroni-corrected P = 0.012) and in FRT individuals compared with the controls (age- and sex-adjusted OR, 2.021, permutated P = 0.017). Our findings support the notion that PER3 polymorphisms could be a potential genetic marker for an individual's circadian and sleep phenotypes.

Epitaxial YBa 2 Cu 3 O 7 (YBCO) films with high-critical-current density ( J c ) properties were successfully prepared on cerium oxide-buffered sapphire ( r- cut α-Al 2 O 3 ) substrates by an excimer-laser-assisted metalorganic deposition (ELAMOD) using a new irradiation manner. The previously reported ELAMOD process in which the laser beam is irradiated from the surface of the substrate has brought about the advantages of shorter heating time as well as high- J c of the YBCO films [M. Sohma, T. Tsuchiya, K. Tsukada, I. Yamaguchi, T. Manabe, T. Kumagai, K. Koyanagi, T. Ebisawa, H. Ohtsu, IEEE Trans. Appl. Supercond. 15 (2007) 3612; M. Sohma, T. Tsuchiya, K. Tsukada, I. Yamaguchi, T. Manabe, T. Kumagai, K. Koyanagi, T. Ebisawa, H. Ohtsu, Physica C 463–465 (2007) 891]. The J c values over 6 MA/cm 2 has been reported by an inductive method at 77.3 K only for the laser-irradiated areas. An awaiting solution has remained since the appropriate fluence range of the laser beam is much limited to obtain high- J c ELAMOD–YBCO films with good reproducibility. In this paper we report a new irradiation manner to resolve the difficulty. The backside of the substrate was irradiated by homogenized KrF excimer laser beam (scanning mode) after application of a fluorine-free ingredient solution. The indispensable laser fluence increased to obtain the high- J c YBCO films because of absorption from the substrate and the CeO 2 buffer. High- J c values of around 6 MA/cm 2 at 77.3 K using an inductive method were obtained in the area irradiated at a wider fluence range, while a part of unirradiated area also showed relatively high- J c of 2–5 MA/cm 2 . Attenuation and scattering effects are considered to bring the extended option of the laser fluence.

The ciliary neurotrophic factor (CNTF) is a neurotrophic cytokine that plays a critical role in neurodevelopment. On the basis of neurodevelopmental hypothesis, the CNTF gene has been a candidate locus for schizophrenia. Several studies have investigated the association between the null mutation of the gene and schizophrenia, however, with inconsistent results. In the present study, we investigated the association in 222 Japanese patients with schizophrenia and 237 controls. The association between the mutation and personality traits was also studied, to investigate the effect of the mutation in participants from the general population. As a result, no association was observed between the mutation and schizophrenia nor personality traits, evaluated by using the Revised NEO Personality Inventory scores. The present study did not provide evidence for the association between the CNTF gene and schizophrenia or personality traits in the Japanese population.

Serotonin 2C receptor (5-HT 2C ), serotonin 6 receptor (5-HT 6 ), and tryptophan hydroxylase-1 (TPH1) genes could be candidates for personality-related genes considering the role of serotonin in various mental functions and behavior. However, a limited number of studies have investigated the association between these genes and personality traits. In the present study, we investigated the three serotonin-related genes, 5 - HT 2C , 5 - HT 6 , and TPH1 genes, in relation to personality traits in the Japanese population. The Cys23Ser polymorphisms in the 5 - HT 2C gene, the 267T/C polymorphism of the 5 - HT 6 gene, and the 779A/C polymorphisms in the TPH1 gene were genotyped in 253 healthy Japanese subjects. Personality traits were evaluated by using the Revised NEO Personality Inventory (NEO PI-R) and the State-Trait Anxiety Inventory (STAI). As a result, no significant association was observed between the polymorphisms and the NEO PI-R or the STAI scores. The present results did not provide evidence for the association between the three serotonin-related genes and personality traits. The genes might not have major role in the development of personality traits, although further investigation with larger sample size may be recommended for conclusion.

We have cloned an orphan G protein-coupled receptor from a human pituitary cDNA library using a probe generated by PCR. The cDNA, designated H9, encodes a protein of 613 amino acids that is 45% identical at the amino acid level to the recently cloned human Mel1a and Mel1b melatonin receptors. Structural analyses of the encoded protein and its gene, along with phylogenetic analysis, further show that H9 is closely related to the G protein-coupled melatonin receptor family. Unusual features of the protein encoded by H9 include a lack of N-linked glycosylation sites and a carboxyl tail >300 amino acids long. H9 transiently expressed in COS-1 cells did not bind [125I]melatonin or [3H]melatonin. H9 mRNA is expressed in hypothalamus and pituitary, suggesting that the encoded receptor and its natural ligand are involved in neuroendocrine function.

A cDNA library was constructed from the pineal gland of rats injected with isoproterenol and screened with 32P-labeled cDNAs encoding arylamine N-acetyltransferases from rabbit and human liver. Two types of cDNAs for arylamine N-acetyltransferases (A-type and B-type) were isolated. Expression of the cDNAs in Chinese hamster ovary cells indicated that A-type W-acetyltransferase acetylates both aryl-amines and arylalkylamines, while the B-type enzyme acetylates only arylamines. Therefore, neither the A-type nor the B-type of enzyme seems to be the arylalkylamine TV-acetyltransferase involved in melato-nin synthesis in the pineal gland. Nucleotide sequence analysis revealed that both A-type and B-type cDNAs code for 290 amino acids, and that they showed 82.8% similarity in the coding region. However, the nucleotide sequence in the 5′ non-coding region was identical in the A-type and B-type cDNAs. In addition, the 5′ non-coding region contained another possible open reading frame for 79 amino acids. Data base research revealed that the complementary sequence of the 5′ non-coding region has high similarity with the coding regions of cDNAs for high-mobility-group proteins (HMG) 1 and 2, which are thought to regulate mRNA transcription.

Genetic studies have revealed several clock gene variations/mutations involved in the manifestation of sleep disorders or interindividual differences in sleep-wake patterns, but only part of the genetic risk can be explained by the gene variations/mutations identified to date. Recent progress in research into circadian rhythm generation has provided efficient tools for eliciting the molecular basis of clock-relevant sleep disorders, complementing traditional genetic analysis. While the human master clock resides in the suprachiasmatic nucleus of the hypothalamus (central clock), peripheral tissue cells also generate self-sustained circadian oscillations of clock gene expression (peripheral clock), enabling estimation of individual human clock properties through a single collection of skin fibroblasts or venous blood cells. Some of the established cell lines exhibit autonomous circadian oscillations of clock gene expression, and introduction of clock gene variations into these cell lines by gene targeting makes it possible to investigate changes in the circadian phenotype induced by these variations/mutations without the need for generating transgenic animals. Estimation of human clock properties using peripheral tissue cells, in addition to genetic analysis, will facilitate comprehensive explication of the genetic risk of a variety of disorders relevant to biological clock disturbances, including sleep disorders, mood disorders, and metabolic diseases.

The pineal hormone melatonin regulates seasonal reproductive function and modulates circadian rhythms in mammals. We now report the cloning and characterization of a high affinity receptor for melatonin from the sheep and human. The receptor cDNAs encode proteins that are members of a newly discovered group within the G protein-coupled receptor family. Expression of the sheep and human receptors in COS-7 cells results in high affinity 2-[125I]iodomelatonin binding and pharmacological characteristics similar to endogenous high affinity receptors. Functional studies of NIH 3T3 cells stably expressing the sheep receptor show that the mammalian melatonin receptor is coupled to inhibition of adenylyl cyclase through a pertussis toxin-sensitive mechanism. In situ hybridization studies of melatonin receptor mRNA in several mammals reveal hybridization signals in the hypophyseal pars tuberalis and hypothalamic suprachiasmatic nucleus. The cloned high affinity receptor likely mediates the reproductive and circadian actions of melatonin in mammals.

Using an expression cloning strategy, a high-affinity melatonin receptor cDNA has been isolated from Xenopus laevis dermal melanophores. Transient expression of the cDNA in COS-7 cells resulted in high-affinity 2-[125I]-iodomelatonin binding (Kd = 6.3 +/- 0.3 x 10(-11) M). In addition, six ligands exhibited a rank order of inhibition of specific 2-[125I]iodomelatonin binding that was identical to that reported for endogenous high-affinity receptors. Functional studies of CHO cells stably expressing the receptor cDNA showed that melatonin acting through the cloned receptor inhibited forskolin-stimulated cAMP accumulation in a dose-dependent manner. Northern blot analysis showed that melatonin receptor transcripts are moderately expressed in Xenopus dermal melanophores. The cDNA encodes a protein of 420 amino acids, which contains seven hydrophobic segments. Structural analysis revealed that the receptor protein is a newly discovered member of the guanine nucleotide binding protein-coupled receptor family.