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Carrier dynamics through a heterointerface of a Dirac material and a semiconductor was studied by the measurement of the full-range time-resolved core-level photoemission spectroscopy using synchrotron radiation. The electron-hole recombination process during relaxation of the surface photovoltage effect was delayed in a graphene layer due to the bottleneck effect of Dirac cones. When an intermediate buffer layer exists, the recombination mainly takes place at the interfacial Si dangling-bond sites and the relaxation time shortens by one-order of magnitude. The present result demonstrates unusual carrier dynamics at a semiconductor surface, terminated by a layer of the Dirac material. [ABSTRACT FROM AUTHOR]

Passive proton beam therapy (PPBT) for hepatocellular carcinoma (HCC) has a higher local control rate than surgery or photon beam therapy. Moreover, it is attracting attention as one of the new treatment options. In the PPBT planning, the selection of the beam angle is determined according to the subjective judgment of the planner. Therefore, there are differences in the dose distribution depending on the planner. It has not yet been clarified which the irradiation angle can be selected to reduce unnecessary dose on the organ-at-risks and maintain the target coverage. The purpose of this study was to determining the optimal beam angle for liver S8 lesions. The subjects were fifty-four treatment plans for HCC located in S8 irradiated using PPBT during the period of 2012.6-2021.3 at the National Cancer Center Hospital East. Tumor sizes were aggregated from the subjects. Clinical Target Volume (CTV) of the subject's liver ranged from 4 cm3 to 1370 cm3. Tumor sizes ranged from 132 cm to 655 cm3. From these results, the average CTV were represented on a virtual phantom, the dose distribution using PPBT was optimized using two irradiation angles. For the calculation of the optimum irradiation angle, the combination of the two beams rotated every 10 degrees and the best dose distribution was considered to be the optimum angle. The Conformity Index (CI) and Homogeneity Index (HI) of the CTV and the V30 (%) of the liver were calculated using the Dose volume histogram (DVH). The combination of beam angles showing 1 in the Conformity Index was 360 ° and 250 °, 350 ° and 230 °, 260 ° and 190 ° for small tumor volumes. Homogeneity Index and V30 averaged 1.06 and 28.0%, respectively. At the time of large tumor volume, it was 350 ° and 270 °, 350 ° and 250 °, 250 ° and 170 °. Homogeneity Index and V30 averaged 1.07 and 47.6%, respectively. The treatment schemes beam-arranged with a 70 ° difference in angle between the two beams were the most homogeneous with respect to the target. A significant difference was found in Conformity Index when compared to the most heterogeneous 190 ° difference (p <0.05). Based on our findings, we recommend using a 2-beam configuration with a beam tilted by approximately 70 ° between the two beams for passive irradiation of hepatocellular carcinoma located in S8. This has the potential to achieve a uniform dose distribution within the target and at the same time reduce the hepatic dose. However, it should be noted that there is a difference in dose increase / decrease depending on the positional relationship of organs and tumors. Further treatment planning studies on aspects of respiration and organ movement need to be conducted. [ABSTRACT FROM AUTHOR]

Hot carrier dynamics in the Dirac band of n-type epitaxial graphene on a SiC substrate were traced in real time using femtosecond-time-resolved photoemission spectroscopy. The spectral evolution directly reflects the energetically linear density of states superimposed with a Fermi-Dirac distribution. The relaxation time is governed by the internal energy dissipation of electron-electron scattering, and the observed electronic temperature indicates cascade carrier multiplication. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) often recurs after surgical or medical treatment.Methods: Eighty consecutive patients with HBV-positive cirrhosis and HCC who underwent potentially curative ablation for HCC were analyzed. Eleven patients received long-term interferon (IFN) therapy. HBV DNA was quantified at the time of HCC treatment. A DNA value of <6.0 log copies/ml was considered low.Results: Initial DNA was low in 39 and high in 41 patients. HCC recurrence rates in the low DNA group and high DNA group were 46.9% and 82.6% at the fifth year, and 73.5% and 91.3% at the tenth year, respectively (P = 0.0103). Similarly, recurrence rates after treatment of HCC in the normal aspartate aminotransferase (AST) group (<38 IU/l, n = 42) and abnormal AST group (n = 38) were 50.6% and 84.0% at the fifth year, and 71.3% and 100% at the tenth year, respectively (P = 0.0003). Six of the 38 patients with abnormal AST, and 5 of 42 patients with normal AST, received IFN after confirmation of tumor ablation. In the subgroup of abnormal AST, tumor recurrence rates in the IFN and untreated groups were 16.7% and 37.9% at the end of the first year, 16.7% and 60.1% at the second year, and 16.7% and 83.4% at the third year, respectively (P = 0.0139). Multivariate analysis revealed that IFN significantly reduced the recurrence rate (hazard ratio = 0.21, P = 0.037) even after adjusting for background characteristics.Conclusions: IFN was inferred to decrease tumor recurrence after treatment of HCC in patients with HBV-related cirrhosis, especially in the subgroup with high AST. [ABSTRACT FROM AUTHOR]

Abstract: In a particle accelerator system for heavy ion inertial fusion, space-charge-dominated beam dynamics is investigated during a final beam bunching. While the space charge effect undertakes an important role for the beam dynamics in the regime, the beam instability induced by space charge oscillation may occur, depending on the particle distribution of the beam. Particle simulations present that the instability due to the strong space charge effect may not be serious for realistic particle distributions during the final beam bunching. [Copyright &y& Elsevier]

It is believed that skin sensitivity will be important for future robots working in our daily life for home-care and entertainment purposes. However, relatively little progress has been made in the field of pressure recognition compared to the areas of sight and voice recognition, mainly because good artificial “electronic skin” with a large area and mechanical flexibility is not yet available. The fabrication of a sensitive skin consisting of thousands of pressure sensors would require a flexible switching matrix that cannot be realized with present silicon-based electronics. Organic field-effect transistors can be used complimentary to such conventional electronics because organic circuits are inherently flexible and potentially ultra-low in cost even for large area. In this paper, we describe that integration of organic transistors and rubber pressure sensors provides an ideal solution to realize a practical artificial skin. [ABSTRACT FROM AUTHOR]

Abstract: Three-dimensional computer simulations are performed for a heavy ion beam (HIB) irradiation onto a direct-driven spherical fuel pellet in heavy ion fusion (HIF). In addition, the non-uniformity growth due to a little pellet displacement from a reactor chamber center is investigated. The calculation results demonstrate that we can realize a rather low non-uniform energy deposition: for example, less than 2.0% even for a 32-beam irradiation system. Moreover, we developed the above simulation code for more common purposes in the research fields of medical treatment, material processing, indirect-driven HIF and so on. [Copyright &y& Elsevier]

Abstract: Beam dynamics is investigated by multiparticle simulations during final beam bunching and final beam focusing in a driver system for heavy-ion inertial fusion. The particle simulations predict the emittance growth during the longitudinal bunch compression for various particle distributions at initial conditions. Particle distributions in the beam transverse cross-section approach uniform during the final beam bunching. It is found that the distribution has the Gaussian profile at the focal spot in the radial direction after the final focusing. [Copyright &y& Elsevier]

A non-uniformity of heavy ion beam irradiation onto a direct-driven fuel pellet in heavy ion fusion (HIF) is studied numerically. The energy deposition non-uniformity is investigated by several beam irradiation systems. The results demonstrate for the first time in HIF that the deposition non-uniformity can be reduced to low values, for example, less than 2% for a 32-beam irradiation system. [Copyright &y& Elsevier]

We have fabricated GaN quantum dots (QDs) embedded in an AlGaN matrix on a uniform array of hexagonal pyramids of GaN, using metalorganic chemical vapor deposition with selective growth. Hexagonal pyramids of very sharp apices were realized. The radius of curvature at the apices was no more than 10 nm as shown by cross-sectional scanning electron microscopy. Intense photoluminescence from GaN QDs was observed at the peak wavelength of 343.5 nm at room temperature. [Copyright &y& Elsevier]

We have investigated intersubband absorption of GaN/Al0.58Ga0.42N multiple quantum well structures of high quality, which were grown by low-pressure metal organic chemical vapor deposition (MOCVD). The crystalline quality and uniformity of the AlGaN barriers were improved by suppressing gas-phase parasitic reaction between NH3 and TMAl. This, in turn, produced a very sharp intersubband absorption spectrum with a spectral linewidth as narrow as 35 meV. [Copyright &y& Elsevier]

We demonstrate an enhancement of spontaneous emission coupling factor β in a nitride-based vertical-microcavity surface-emitting laser. The 2.5λ vertical microcavity, the quality factor of which reaches 740, is sandwiched between a nitride and an oxide distributed Bragg reflector. From input–output measurements and analyses of the rate equations, the β of the lasing mode at a wavelength of 396.1 nm is estimated to be 1.6×10[sup -2]. The estimated β can be well accounted for by a simple theoretical model. © 2002 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Reports on the successful growing of nanometer-scale indium gallium nitride (InGaN) self-assembled quantum dots (QD) on GaN surface without any surfactant, using atmospheric-pressure metalorganic chemical vapor deposition. Average diameter of the InGaN QD; Dependence of QD properties on growth conditions; Emission seen at 2.86 eV at room temperature.

Determines the concentration of oxygen incorporated in GaAs/AlAs (gallium arsenide) interfaces and AlAs layers by secondary ion mass spectrometry (SIMS). Importance of minimizing the impurity incorporation from residual gas species in molecular-beam epitaxy; Details on the number of oxygen atoms adsorbed on the AlAs surfaces during growth interruption; Advantages of SIMS.

The resonant magneto-optical Kerr effect of an Fe nanofilm at the L -edge was investigated by theoretically and experimentally using the polarization controlled undulator. Large values of the Kerr rotation angle ( θ K ) were measured at the L 2 and L 3 absorption edges for both of s - and p -polarized incident lights. Furthermore, the sign changes of θ K depending on the photon energy and the polarization of incident light were also observed. [ABSTRACT FROM AUTHOR]

Describes the preparation of T-shaped gallium arsenide quantum wire (T-QWR) structure with aluminum arsenide barriers using the cleaved edge growth method. Observation of three photoluminescence (PL) peaks; Determination of the T-QWR binding energy; Comparison between the effective binding energy and thermal energy.

High-quality GaN with smooth surface morphology has been grown on vicinal a-plane sapphire substrates by metalorganic chemical vapor deposition. The misorientation angles of vicinal a-plane sapphire substrates were changed systematically and the results were compared with the growth on exact a- and c-plane sapphire substrates. Surface morphology and crystalline qualities are found to be very sensitive to misorientation angles of a-plane sapphire substrates and the misorientation angle was optimized to be 0.25°. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Photoluminescence (PL) spectra were measured for sub-nanometer-thick GaN quantum wells (QWs) with Al[sub 0.8]Ga[sub 0.2]N barriers, which were grown by atmospheric-pressure metal-organic chemical-vapor deposition. The thickness of the GaN QW layers was systematically varied from 1 to 4 ML. We clearly observed a PL peak at room temperature at a wavelength as short as 247 nm (5.03 eV) from 1-ML-thick QWs. The effective confinement energy, or difference between this recombination energy and the band gap of bulk GaN, is as large as 1.63 eV. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Influences of the thickness of the Si-doped n-type Al[sub 0.22]Ga[sub 0.78]N barrier and the thickness of the Al[sub 0.22]Ga[sub 0.78]N spacer on mobility and density of the two dimensional electron gas (2DEG) in modulation-doped Al[sub 0.22]Ga[sub 0.78]N/GaN heterostructures were investigated. 2DEG mobilities of 1274 cm2/V s at 300 K and 4495 cm2/V s at 77 K were reached. Both 2DEG mobility and density decrease dramatically when the Al[sub 0.22]Ga[sub 0.78]N barrier becomes partially relaxed, indicating that transport properties of the 2DEG are influenced significantly by the piezoelectric polarization of the Al[sub 0.22]Ga[sub 0.78]N layer. From our results, the critical thickness of an Al[sub 0.22]Ga[sub 0.78]N layer on GaN is estimated to be between 65 and 75 nm, which is much higher than that predicted by theoretical calculation. This may be attributed to the interaction of misfit dislocations and the presence of a high density of extended defects in the Al[sub 0.22]Ga[sub 0.78]N layer. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Photoluminescence (PL) of modulation-doped Al[sub 0.22]Ga[sub 0.78]N/GaN heterostructures was investigated. The PL peak related to recombination between the two-dimensional electron gases (2DEG) and photoexcited holes is located at 3.448 eV at 40 K, which is 45 meV below the free excitons (FE) emission in GaN. The peak can be observed at temperatures as high as 80 K. The intensity of the 2DEG PL peak is enhanced significantly by incorporating a thin Al[sub 0.12]Ga[sub 0.88]N layer into the GaN layer near the heterointerface to suppress the diffusion of photoexcited holes. The energy separation of the 2DEG peak and the GaN FE emission decreases with increasing temperature. Meanwhile, the 2DEG peak energy increases with increasing excitation intensity. These results are attributed to the screening effect of electrons on the bending of the conduction band at the heterointerface, which becomes stronger when temperature or excitation intensity is increased. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Ultrafast magnetization reversal of a ferrimagnetic metallic alloy GdFeCo was investigated by time-resolved resonant magneto-optical Kerr effect measurements using a seeded free electron laser. The GdFeCo alloy was pumped by a linearly polarized optical laser pulse, and the following temporal evolution of the magnetization of Fe in GdFeCo was element-selectively traced by a probe free electron laser pulse with a photon energy tuned to the Fe M-edge. The results have been measured using rotating analyzer ellipsometry method and confirmed magnetization switching caused by ultrafast heating. [ABSTRACT FROM AUTHOR]

Quarter-wave reflectors consisting of sets of GaN and Al[sub 0.34]Ga[sub 0.66]N layers have been grown on sapphire substrates by atmospheric-pressure metal organic chemical vapor deposition. A periodic structure with flat interfaces was observed by high-resolution scanning electron microscopy. X-ray diffraction measurements were performed to characterize the structures, from which the Al content x in the Al[sub x]Ga[sub 1-x]N layers was determined to be 0.34. No cracks could be seen on the surface of the reflectors by optical microscopy. The measured peak reflectivity at 390 nm increases with the number of pairs and reaches as high as 96±2% in the 35-pair reflector. © 1998 American Institute of Physics. [ABSTRACT FROM AUTHOR]

To continuously and noninvasively monitor the cerebral tissue oxygen saturation (StO2) and hemoglobin concentration (gasHb) in cardiac surgery patients, a method combining the use of a cerebral tissue oximeter using near infrared time-resolved spectroscopy (tNIRS-1) and the bispectral index (BIS) was developed in this study. Moreover, the correlation between the estimated hemoglobin concentration (estHb), measured via tNIRS-1, and the hemoglobin concentration (gasHb), analyzed using a blood gas analyzer, were compared. The relationship between the BIS and gasHb was also examined. Through the comparison of BIS and StO2 (r1), and estHb and gasHb (r2), the correlation between the two was clarified with maximum r1 and r2 values of 0.617 and 0.946, respectively. The relationship between BIS and gasHb (r3), showed that there was a favorable correlation with a maximum r3 value of 0.969. There was also a continuous correlation between BIS and StO2 in patients undergoing cardiac surgery. In addition, a strong correlation was found between estHb and gasHb, and between BIS and gasHb. It was therefore concluded that the combined use of BIS and tNIRS-1 is useful to evaluate cerebral hypoxia, allowing for quick response to cerebral hypoxia and reduction of hemoglobin concentration during the operation. [ABSTRACT FROM AUTHOR]

An impact of serum hepatitis B virus (HBV) DNA on hepatocarcinogenesis has not been investigated in a cohort of patients with non-B, non-C cirrhosis. Eighty-two consecutive Japanese patients with cirrhosis, who showed negative hepatitis B surface antigen and negative anti-hepatitis C virus, were observed for a median of 5.8 years. Hepatitis B virus core (HBc) region and HBx region were assayed with nested polymerase chain reaction. Both of HBc and HBx DNA were positive in 9 patients (11.0%) and both were negative in 73. Carcinogenesis rates in the whole patients were 13.5% at the end of the 5th year and 24.6% at the 10th year. The carcinogenesis rates in the patients with positive DNA group and negative DNA group were 27.0% and 11.8% at the end of the 5th year, and 100% and 17.6% at the 10th year, respectively ( P = 0.0078). Multivariate analysis showed that men ( P = 0.04), presence of HBc and HBx DNA (hazard ratio: 8.25, P = 0.003), less total alcohol intake ( P = 0.010), older age ( P = 0.010), and association of diabetes ( P = 0.005) were independently associated with hepatocellular carcinogenesis. Existence of serum HBV DNA predicted a high hepatocellular carcinogenesis rate in a cohort of patients with non-B, non-C cirrhosis. [ABSTRACT FROM AUTHOR]

Abstract: Heavy ion beams (HIBs) are transported through a reactor chamber gas to a fuel pellet in heavy ion fusion. Due to the HIB high current, the HIB space charge should be neutralized in a reactor, and promising final transport schemes have been proposed. In this paper, we discuss the final transport in a neutralized ballistic final beam transport scheme, and point out a new mechanism of the HIB divergence by an ambipolar (plasma sheath) field generated by neutralizing electrons. The paper also proposes possible solutions to suppress the HIB divergence by the ambipolar field and presents a transportable window. [Copyright &y& Elsevier]

We investigated the effects of a 5-hydroxytryptamine (5-HT) 1A receptor gene polymorphism on the clinical response to fluvoxamine (FLV) in 65 depressed outpatients who gave written consent to participate in the study. Patients visited every 2 weeks after the first examination until the week 12 end point and were evaluated by the 17-item Hamilton Rating Scale for Depression (HAM-D-17) at each visit. FLV dose was changed in response to their clinical symptoms. The Gly272Asp polymorphism of the 5-HT1A receptor gene was identified by a PCR method. The subjects with the Asp allele had a significantly higher % reduction in the HAM-D-17 score than those with the Gly/Gly genotype at week 2 (P=0.009), week 6 (P=0.036), and week 12 (P=0.031). There was a significant difference in the genotype distribution between the responders and nonresponders. These results suggest that the Gly272Asp polymorphism of the 5-HT1A receptor gene may predict the response to FLV.The Pharmacogenomics Journal (2004) 4, 283-286. doi:10.1038/sj.tpj.6500256 Published online 18 May 2004 [ABSTRACT FROM AUTHOR]

We have successfully grown GaN self-assembled quantum dots (QDs) on an AlN layer by low-pressure metalorganic chemical vapor deposition. The average diameter and height of the QDs were 35 and 1.6 nm, respectively. The density of GaN QDs was around 6×108 cm-2 when the amount of GaN deposited was 2.5 mono-layer (ML). The dependence of the QD density on the GaN coverage was investigated. The coverage when GaN QDs are formed is estimated to be 1.0 ML. The formation of the QDs was much affected by the growth temperature, and its behavior was same as other QDs grown by the Stranski–Krastanow mode. [Copyright &y& Elsevier]

Frequency-dependent carrier dynamics in dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT)- based organic field-effect transistors and metal-insulator-semiconductor capacitors were studied by using admittance measurements. Both the real (conductance) and imaginary (capacitance) components of admittance, which have a mutually complementary relationship, were analyzed in the same way. On the basis of an experimental study of devices with different contact geometries, peaks observed in the conductance spectra corresponding to slopes in the capacitance spectra were classified into two groups. The high-frequency peak was attributed to the carrier injection from the top contact to the DNTT/insulator interface just underneath the contact while the low-frequency peaks were attributed to the drift current spreading all over the interface. The model calculation of carrier diffusion reproduces the low-frequency peaks very well. It is shown that the field-effect mobility from the accumulation region to the subthreshold region can be estimated by the fitting. [ABSTRACT FROM AUTHOR]

The article discusses a study on soft sensors for a sensing-actuation system with high bladder voiding efficiency. It mentions that the solution integrates sensing-actuation elements that are bladder compatible but do not interfere with one another, achieving real-time bladder management.. It also mentions that the system represents an efficient voiding solution that avoids overfilling and represents a technological solution to bladder impairment treatment.

Multisubband transport of the two-dimensional electron gas (2DEG) in modulation-doped Al[sub 0.22]Ga[sub 0.78]N/GaN heterostructures has been investigated by means of magnetotransport measurements at low temperatures and high magnetic fields. It is found that the mobility of the 2DEG in the first subband in a triangular quantum well at the heterointerface decreases significantly, while the mobility of the 2DEG in the second subband increases, when the Al[sub 0.22]Ga[sub 0.78]N barrier is partially relaxed. Such behavior of the 2DEG mobility is explained by the nonuniformity of the piezoelectric polarization field at the heterointerface induced by the Al[sub 0.22]Ga[sub 0.78]N relaxation and strong interface scattering. Meanwhile, it is concluded that the scattering from the remote ionized donors is the main mechanism contributing to the quantum scattering time and responsible for the intersubband scattering in the quantum well at the heterointerface. [ABSTRACT FROM AUTHOR]

We fabricate semi-insulating InGaAs/GaAs multiple quantum wells and observe the excitonic enhancement of the photorefractivity in the Franz-Keldysh geometry at wavelengths of 0.92-0.94 μm. A maximum two-wave mixing gain of 138 cm[sup -1] and a maximum diffraction efficiency of 1.5x10[sup -4] are obtained. The saturation intensity and the spatial resolution are also measured by four-wave mixing. The diffraction efficiency is saturated at a high external electric field. The dominant cause of this saturation is the deviation of the excitonic electroabsorption from its quadratic law. © 2001 American Institute of Physics. We fabricate semi-insulating InGaAs/GaAs multiple quantum wells and observe the excitonic enhancement of the photorefractivity in the Franz-Keldysh geometry at wavelengths of 0.92-0.94 μm. A maximum two-wave mixing gain of 138 cm[sup -1] and a maximum diffraction efficiency of 1.5x10[sup -4] are obtained. The saturation intensity and the spatial ! resolution are also measured by four-wave mixing. The diffraction efficiency is saturated at a high external electric field. The dominant cause of this saturation is the deviation of the excitonic electroabsorption from its quadratic law. © 2001 American Institute of Physics. We fabricate semi-insulating InGaAs/GaAs multiple quantum wells and observe the excitonic enhancement of the photorefractivity in the Franz-Keldysh geometry at wavelengths of 0.92-0.94 μm. A maximum two-wave mixing gain of 138 cm[sup -1] and a maximum diffraction efficiency of 1.5x10[sup -4] are obtained. The saturation intensity and the spatial resolution are also measured by four-wave mixing. The diffraction efficiency is saturated at a high external electric field. The dominant cause of this saturation is the deviation of the excitonic electroabsorption from its quadratic law. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

We developed a resonant magneto-optical Kerr effect (RMOKE) measurement system that includes polarization analysis by using a high harmonic generation laser. Energy components around the Fe 3 p absorption edge were separated by using multilayer mirrors. By using rotating-analyzer ellipsometry, we demonstrated longitudinal RMOKE measurements from the Fe(001)- p (1 × 1) terminated with oxygen. [ABSTRACT FROM AUTHOR]

Magnetointersubband scattering (MIS) oscillations of two-dimensional electron gas (2DEG) in Al[sub 0.22]Ga[sub 0.78]N/GaN heterostructures have been investigated by means of magnetotransport measurements at low temperatures and high magnetic fields. Double periodic Shubnikov–de Haas oscillations modulated by MIS oscillations have been observed due to the intersubband scattering of the 2DEG at the two lowest subbands in the triangular quantum well at the heterointerface. By using the fast Fourier transform analysis, it is found that the MIS oscillations become slightly weaker with an increase in temperature. From the MIS frequency, the energy separation between the first and the second subbands is determined to be 80 meV. The observation of the MIS effect indicates that the effective masses of the electrons in the first and second subbands are the same in Al[sub 0.22]Ga[sub 0.78]N/GaN heterostructures. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Risperidone (RIS) is a frequently used efficacious psychotropic drug. However, it prolongs the QTc interval and may cause fatal arrhythmia. Little is known on the determinants of this RIS side effect. RIS is metabolized by CYP2D6, and is subject to drug efflux by P-glycoprotein (P-gp) encoded by the ATP-binding cassette subfamily B member 1 (ABCB1) gene. P-gp removes both RIS and its metabolite 9-OH-RIS from cardiac tissue. To investigate the effect of RIS metabolism and ABCB1 gene polymorphisms on QTc, steady-state plasma RIS and 9-OH-RIS levels, and QTc were measured. CYP2D6, ABCB1 C3435T and G2677T/A genotypes were determined in 66 schizophrenia patients on RIS. QTc was significantly longer in patients with ABCB1 3435CT+3435 TT than in those with 3435CC (P=0.006). ABCB1 G2677T/A genotype did not affect QTc. Multiple regression analysis showed that C/T or T/T genotypes at the ABCB1 C3435T locus, lower weight, and older age prolonged QTc. In summary, the T allele of the ABCB1 C3435T genotype should be considered in future diagnostic development efforts for RIS-associated QT. [ABSTRACT FROM AUTHOR]

We implemented a two-step approach to detect potential predictor gene variants for neuroleptic-induced tardive dyskinesia (TD) in schizophrenic subjects. First, we screened associations by using a genome-wide (Illumina HumanHapCNV370) SNP array in 61 Japanese schizophrenia patients with treatment-resistant TD and 61 Japanese schizophrenia patients without TD. Next, we performed a replication analysis in 36 treatment-resistant TD and 138 non-TD subjects. An association of an SNP in the DPP6 (dipeptidyl peptidase-like protein-6) gene, rs6977820, the most promising association identified by the screen, was significant in the replication sample (allelic P=0.008 in the replication sample, allelic P=4.6 × 10−6, odds ratio 2.32 in the combined sample). The SNP is located in intron-1 of the DPP6 gene and the risk allele was associated with decreased DPP6 gene expression in the human postmortem prefrontal cortex. Chronic administration of haloperidol increased Dpp6 expression in mouse brains. DPP6 is an auxiliary subunit of Kv4 and regulates the properties of Kv4, which regulates the activity of dopaminergic neurons. The findings of this study indicate that an altered response of Kv4/DPP6 to long-term neuroleptic administration is involved in neuroleptic-induced TD. [ABSTRACT FROM AUTHOR]

Several studies have shown increased rates of hyperglycemia and diabetes in schizophrenic patients treated with olanzapine. However, the underlying mechanism is poorly understood. Glucose-dependent insulinotropic polypeptide (GIP) is known to affect insulin secretion by pancreatic β cells. Recently, a meta-analysis study reported an association between a GIP receptor (GIPR) gene polymorphism (rs10423928) and insulin secretion measured by an oral glucose tolerance test (OGTT). We assessed the influence of this GIPR gene polymorphism on glucose metabolism in 60 schizophrenic patients treated with olanzapine and 103 healthy controls. The GIPR gene polymorphism was determined using TaqMan methods. We performed repeated-measures analysis of variance (ANOVA) and one-way ANOVA for the glucose and insulin levels during OGTTs in four groups divided by the GIPR gene polymorphism and cohort (schizophrenia or control). We found significant effects of the GIPR gene and cohort on the insulin levels at 30 min. Our findings suggest that schizophrenic patients with the A allele of GIPR rs10423928 are at risk of developing hyperinsulinemia when treated with antipsychotics. [ABSTRACT FROM AUTHOR]

What is known and Objective: Aripiprazole has a low risk of extrapyramidal symptoms. Switching to aripiprazole has been reported to improve tardive dyskinesia caused by other medications. The authors report a case and review previous reports of dystonia and dyskinesia associated with aripiprazole. Case summary: We present a case of a 22-year-old man with schizophrenia who experienced dyskinesia and dystonia associated with aripiprazole. Switching from olanzapine to aripiprazole resulted in worsening dyskinesia and new onset of dystonia. The patient's dyskinesia and dystonia improved after switching from aripiprazole to quetiapine therapy. What is new and Conclusion: There were several previous case reports on dyskinesia and dystonia associated with aripiprazole medication. The risk factors for tardive dyskinesia include older age and female sex. However, our case was a male patient who was younger compared with the previous cases and so should have been less at risk for dyskinesia in comparison with the previous cases. The effects of aripiprazole can include tardive movement disorders. Dyskinesia, dystonia and psychotic symptoms were improved with relatively small dose of quetiapine in this case. Whether some second-generation antipsychotics are more effective than others in the treatment of tardive dyskinesia remains unclear. [ABSTRACT FROM AUTHOR]

Neuregulin- 1 ( NRG1) gene is implicated in the etiology or neuropathology of schizophrenia, although its biological contribution to this illness is not fully understood. We have established an enzyme-linked immunosorbent assay (ELISA), which recognizes the NRG1β1 immunoglobulin-like (Ig) domain, and measured soluble Ig-NRG1 immunoreactivity in the sera of chronic schizophrenia patients ( n = 40) and healthy volunteers ( n = 59). ELISA detected remarkably high concentrations of Ig-NRG1 immunoreactivity in human serum (mean 5.97 ± 0.40 ng/mL, ~213 ± 14 pM). Gender and diagnosis exhibited significant effects on serum Ig-NRG1 immunoreactivity. Mean Ig-NRG1 immunoreactivity in the schizophrenia group was 63.2% of that measured in the control group. Ig-NRG1 immunoreactivity in women was 147.1% of that seen in men. We also attempted to correlate six SNPs of NRG1 genome with serum Ig-NRG1 immunoreactivity. Analysis of covariance with compensation for gender identified a significant interaction between diagnosis and SNP8NRG243177 allele. The T allele of this SNP significantly contributed to the disease-associated decrease in Ig-NRG1 immunoreactivity. Although we hypothesized a chronic influence of antipsychotic medications, there was no significant effect of chronic haloperidol treatment on serum Ig-NRG1 immunoreactivity in monkeys. These findings suggest that serum NRG1 levels are decreased in patients with chronic schizophrenia and influenced by their SNP8NRG243177 alleles. [ABSTRACT FROM AUTHOR]

Several genome-wide linkage studies have suggested linkage between markers on the long arm of chromosome 22 and schizophrenia. It has also been reported that 22q11.2 deletions increase the risk of schizophrenia. Therefore, 22q is a candidate region for schizophrenia. To search for genetic susceptibility loci for schizophrenia on 22q, we conducted a three-stage case-control association study in Japanese individuals. In the first stage, we examined 13 microsatellite markers on 22q in 766 individuals (340 patients with schizophrenia and 426 control individuals) and found a potential association of AFM262VH5 (D22S283) with schizophrenia. In the second stage, we performed fine mapping of the myosin heavy chain 9, non-muscle (MYH9) gene, where AFM262VH5 is located, using 25 tagging single nucleotide polymorphisms (SNPs). We obtained potential associations between three SNPs in MYH9 and schizophrenia in 1193 individuals (595 patients and 598 controls), which included the individuals analyzed in the first stage. In the third stage, however, we could not replicate these associations in 4694 independent individuals (2288 patients and 2406 controls). Our results suggest that MYH9 does not confer increased susceptibility to schizophrenia in the Japanese population, although we could not exclude possible contributions of other genes on 22q to the pathogenesis of schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract: In order to elucidate the spatial distribution of brominated flame retardants (BFRs) in the Japanese coastal environment, hexabromocyclododecanes (HBCDs), polybrominated diphenyl ethers (PBDEs) and organochlorines (OCs: PCBs, DDTs, CHLs, HCHs, HCB) were determined in bivalves (oysters and mussels) collected from Japanese coastal waters. HBCDs and PBDEs were detected in all samples analyzed. Concentration ranges of HBCDs were 12–5200ngg−1 lipid wt., followed by PCBs (20–3100ngg−1)>PBDEs (3.1–86ngg−1 lipid wt.). The highest concentration of HBCDs was found in the Osaka region. This result indicates that HBCDs are ubiquitous and predominant compounds in bivalves from the Japanese coastal waters. Since no species differences between oysters and mussels were observed for the bioaccumulation properties of HBCDs and PBDEs, oysters could be utilized for BFR contamination monitoring worldwide as an alternative to mussels. Global comparisons between oysters and mussels showed that HBCD concentrations in Japan are among the highest levels reported from Asia and Europe. Estimated dietary exposures of HBCDs and PBDEs through seafood were 0.45–34ngkg body weight−1 d−1, and 0.054–6.8ngkg body weight−1 d−1, respectively. These exposure levels were more than 1000 times lower than the lowest observable effects or no observable adverse effects levels for HBCDs and PBDEs, respectively. [Copyright &y& Elsevier]

The dopamine D3 receptor (DRD3) has been suggested to be involved in the pathophysiology of schizophrenia. DRD3 has been tested for an association with schizophrenia, but with conflicting results. A recent meta-analysis suggested that the haplotype T-T-T-G for the SNPs rs7631540-rs1486012-rs2134655-rs963468 may confer protection against schizophrenia. However, almost all previous studies of the association between DRD3 and schizophrenia have been performed using a relatively small sample size and a limited number of markers. To assess whether DRD3 is implicated in vulnerability to schizophrenia, we conducted case-control association studies and performed an updated meta-analysis. In the first population (595 patients and 598 controls), we examined 16 genotyped single nucleotide polymorphisms (SNPs), including tagging SNPs selected from the HapMap database and SNPs detected through resequencing, as well as 58 imputed SNPs that are not directly genotyped. To confirm the results obtained, we genotyped the SNPs rs7631540-rs1486012-rs2134655-rs963468 in a second, independent population (2126 patients and 2228 controls). We also performed an updated meta-analysis of the haplotype, combining the results obtained in five populations, with a total sample size of 7551. No supportive evidence was obtained for an association between DRD3 and schizophrenia in our Japanese subjects. Our updated meta-analysis also failed to confirm the existence of a protective haplotype. To draw a definitive conclusion, further studies using larger samples and sufficient markers should be carried out in various ethnic populations. [ABSTRACT FROM AUTHOR]

Abstract: Chromosome 1p13 is linked with schizophrenia in Japanese families, and one of the candidate genes in this region is the netrin G1 (NTNG1) gene at 1p13.3. Associations of 56 tag single-nucleotide polymorphisms (SNPs) with schizophrenia were explored by transmission disequilibrium analysis in 160 Japanese trios and by case–control analysis in 2174 Japanese cases and 2054 Japanese controls. An association between SNP rs628117 and schizophrenia was identified by case–control comparison (nominal allelic p =0.0009; corrected p =0.006). The associated polymorphism is located in intron 9 and in the haplotype block encompassing the alternatively spliced exons of the gene. Allelic association of a different SNP in the same haplotype block in Japanese families was previously reported. These findings support that the NTNG1 gene is associated with schizophrenia in the Japanese. [Copyright &y& Elsevier]

Background Evidence suggests that, as a group, patients with schizophrenia have intellectual deficits that may precede the manifestation of psychotic symptoms; however, how successfully intelligence tests are able to discriminate schizophrenia from other psychotic disorders has yet to be investigated in detail. Methods Using Wechsler Adult Intelligence Scale – Revised (WAIS-R) data for 55 inpatients with schizophrenia and 28 inpatients with non-schizophrenic psychotic disorders (NSPD) (schizophreniform disorder, brief psychotic disorder, delusional disorder, psychotic disorder due to a general medical condition, and psychotic disorders not otherwise specified), intelligence performance was compared between schizophrenia and NSPD and among different subtypes of schizophrenia. Results There were no significant differences in intelligence quotient (IQ), verbal IQ (VIQ) and performance IQ (PIQ) discrepancy, and subtest scores of WAIS-R between the patients with schizophrenia and those with NSPD. These diagnostic groups were not discriminated well by any WAIS-R variables. Schizophrenia patients with prominent negative symptoms, on the other hand, had a significantly larger IQ discrepancy (VIQ > PIQ) than those without prominent negative symptoms and NSPD patients. Intelligence performance in schizophrenia did not differ with respect to diagnostic subtypes and longitudinal courses. Conclusions The current study failed to show diagnostic usefulness of WAIS-R in discriminating schizophrenia and other psychoses. A diagnosis of schizophrenia does not significantly impact intellectual deficits in psychotic disorders. [ABSTRACT FROM AUTHOR]