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Monopolar spindle 1 (Mps1) is an attractive cancer drug target due to the important role that it plays in centrosome duplication, the spindle assembly checkpoint, and the maintenance of chromosomal stability. A design based on JNK inhibitors with an aminopyridine scaffold and subsequent modifications identified diaminopyridine 9 with an IC50 of 37 nM. The X-ray structure of 9 revealed that the Cys604 carbonyl group of the hinge region flips to form a hydrogen bond with the aniline NH group in 9. Further optimization of 9 led to 12 with improved cellular activity, suitable pharmacokinetic profiles, and good in vivo efficacy in the mouse A549 xenograft model. Moreover, 12 displayed excellent selectivity over 95 kinases, indicating the contribution of its unusual flipped-peptide conformation to its selectivity.

This paper offers a brief summary of nontraditional monetary policy measures adopted by the Bank of Japan (BOJ) during the last two decades, especially the period 1998–2006, when the so-called zero interest rate policy (ZIRP) and quantitative easing (QE) were put in place. The paper begins with a typology of policies usable at low interest and inflation rates. They are: strategy (i), management of expectations about future policy rates; strategy (ii), targeted asset purchases; and strategy (iii), QE. Alternatively, QE may be decomposed into a pure attempt to inflate the central bank balance sheet, QE0, purchases of assets in dysfunctional markets, QE1, and purchases of assets to generate portfolio rebalancing, QE2. Strategy (ii), when nonsterilized, is either QE1 or QE2. Using this typology, I review the measures adopted by the BOJ and discuss evidence on the effectiveness of the measures. The broad conclusion is that strategies (i) and (ii) have affected interest rates, while no clear evidence exists so far of the effectiveness of the pure form of strategy (iii), or QE0. Strategy (ii) has been effective especially in containing risk/liquidity premiums in dysfunctional money markets; that is, QE1 has been effective. The effectiveness of QE2, however, is less clear-cut. The strategies, however, have failed to bring the Japanese economy out of the deflation trap so far. I discuss some possible reasons for this and also implications for the current U.S. situation.

This paper summarizes non-traditional monetary policy measures adopted by the Bank of Japan (BOJ) during the last 2 decades and by other G7 central banks since the start of the current global financial turmoil and analyses the effectiveness of such measures. The paper begins with a typology of policies usable near the zero lower bound on interest rates. They are: (i) forward guidance of future policy rates; (ii) targeted asset purchases; and (iii) quantitative easing. Using this typology, I review the measures adopted by the BOJ and other central banks. I then offer a news analysis of the effects of the measures adopted by the BOJ on asset prices, comparing them with those adopted by the Fed. Many of the measures, with the exception of strategy (iii), are shown to have moved asset prices in the expected directions. Another exception is that most of the monetary easing measures failed to weaken the yen. Despite some effects on asset prices, however, the measures have failed to stop the deflationary trend of the Japanese economy clearly. I discuss some possible reasons for this and more general implications for monetary policy.

This paper compares the three recent episodes of boom and bust cycles in asset prices: Japan in the late 1980s to the 1990s; the USA since the mid-1990s; and China during the past decade. Although we have not yet seen a collapse of Chinese property prices, their increases so far are comparable to those in the other two episodes and seem to warrant a careful comparative study. The present paper first examines the behavior of asset prices, of property prices in particular, in the three cases, and highlights some similarities. The paper emphasizes the role played by extremely easy monetary policy in generating bubble-like asset price behavior in the three cases. The reason for easy monetary policies is investigated. In the US case, the monetary authority was concerned about the risk of deflation in the early to mid-2000s. The experiences of Japan and China are quite similar in that the monetary authorities of both countries were seriously concerned about the possible deflationary effects of exchange rate appreciation on the economy. Implications of such a finding for the future of appropriate Chinese macroeconomic policy are also discussed.

The second of two consecutively presented sounds may be perceived as being longer than if that sound had been presented in isolation. We performed five experiments using heterophonic patterns in which a sine tone was preceded by a frequency-band noise. We observed significant overestimations of sine-tone duration, the size of which depended on intensity and frequency differences between the band noise and the sine tone (Experiments 1 and 2). Band noises that were considerably shorter than the sine tone still caused significant overestimations (Experiment 3). A short silent gap between the band noise and the sine tone strongly reduced the amount of overestimation (Experiment 4). Both frozen and nonfrozen band noises yielded overestimations (Experiment 5). Our explanation for the overestimation is that the onset of the sine tone is blurred by the band noise and that such a blurred onset is restored at the level of perceptual organization following rules of a simple auditory grammar. This restoration takes mental processing time, which adds to the perceived duration of the sine tone. We call this illusion time stretching and discuss the notion that subsequent temporal assimilation and/or contrast effects can dilate or compress the amount of stretching.

Nonequilibrium transport properties of quantum dot under a finite bias voltage is investigated using the adaptive time-dependent density matrix renormalization group (TdDMRG) method. The validity of the authors’ previous study was limited for relatively weak coupling parameters because the small scale Kondo energy in the strong coupling regime caused a difficulty. By taking sufficiently long system size, keeping large number of states during the TdDMRG process and utilizing the fourth order Suzuki–Trotter decomposition, we can extend calculations of current–voltage characteristics in the strongly correlated region up to the Wilson ratio R W 1.97 , close to the strong coupling limit. The wide domain of applicability suggests future applications of the method to various nonequilibrium and time-dependent problems.

Time relation among clothing pressure developed at waistband, respiratory movement, and girth of abdomen were investigated. The time constants of 3 sensors to monitor these waves in this measuring system were examined, and were 0.016s, 268.9ms, and 57.0ms corresponded to that order. Therefore, this measuring system for the clothing pressure could sufficiently follow the changes of waistband-pressure which might be caused by either respiratory movements or changes in posture, and the most suitable method to measure the clothing pressure. Subjects were 10 women aged from 20 to 22 years old, and 3 waves measured under 3 conditions : non waistband, wearing waistband with a perfect fitting length and a tight fitting length in free respiration. These waves analyzed by Fourier transform to examine these constitutional frequencies which were 3.85 +/- 0.99s, 3.85 +/- 0.92s, 3.72 +/- 0.85s and nearly equal. By the way, the time lags of peak in girth of abdomen and in respiratory movement were calculated from their cross spectra, the time became significantly late. So, the timing of air flowed into the body became significantly late, because of worn waistband. We distinguish whether the body region influenced by respiratory movement, and have to investigate a permissible limit of the pressure including a change of a respiratory function in the future., Article, SEN-I GAKKAISHI. 66(1):26-33 (2010)

Bradycardia is a trigger of ventricular arrhythmias in patients with arrhythmia including Brugada syndrome and long QT syndrome. The HCN4 channel controls the heart rate, and its mutations predispose to inherited sick sinus syndrome and long QT syndrome associated with bradycardia. We found a 4 base-insertion at the splice donor site of the HCN4 gene in a patient with idiopathic ventricular tachycardia, which was supposed to generate a truncated channel. To investigate the role of the HCN4 channel in ventricular arrhythmia, we introduced a ventricular action potential of I(f) channel produced by HCN4 in a computer simulation model and found that the I(f) channel generated a leaky outward current during the plateau phase of ventricular action potential. Currents through the I(f) channel were suggested to contribute to the shortening of the action potential duration and the prevention of early after-depolarization in bradycardia. These observations suggested that the HCN4 channel played a preventive role in triggering bradycardia-induced ventricular arrhythmias.

To compare the clinical features of aortic stiffness and its contributors between hemodialysis (HD) patients with and those without diabetes, we performed a cross-sectional study of stably treated HD patients (n = 242). Aortic stiffness was assessed by measuring carotid-femoral pulse wave velocity (cfPWV). Annual laboratory data, comorbid conditions, and contributors to cfPWV were compared between HD patients with and those without diabetes. Of the 242 patients, 94 had diabetes. The comparison showed that patients with diabetes had a shorter duration of HD; higher systolic blood pressure (SBP), cfPWV, and rate of macrovascular complications; and lower ankle-brachial blood pressure index and concentrations of serum albumin and calcium. Stepwise multiple regression analysis identified age, duration of HD, SBP, heart rate (HR), and HbA1c as independent determinants of cfPWV in nondiabetic HD patients, while only SBP, HbA1c, and duration of diabetes were independent contributors of cfPWV in HD patients with diabetes. Our results indicate that glucose metabolism plays an important role in the promotion of aortic stiffness in both diabetic and nondiabetic HD patients. In particular, hyperglycemia's effect on aortic compliance in HD patients with diabetes is so strong that it negates the effects of the uremic milieu and aging. Follow-up studies are needed to ascertain whether or not strict diabetes management could improve aortic compliance.

New 2-pyrone derivatives, dialkyl 3-cyano-6-phenyl-2-oxo-2H-pyran-4-ylmalonates and alkyl 3-cyano-6-phenyl-2-oxo-2H-pyran-4-ylacetates, which were easily prepared by the reaction of 6-aryl-4-methyl-sulfanyl-2-oxo-2H-pyran-3-carbonitriles with active methylene compounds in the presence of potassium carbonate, show fluorescence emission radiation. The light-emitting region of dimethyl 3-cyano-6-(4-N,N-dimethylamino)styryl-2-oxo-2H-pyran-4-ylmalonate (7h) was 620 nm in dichloromethane, making this compound a typical red fluorescent compound. Methyl 8-hydroxy-6-methyl-1-oxo-3-phenyl-1H-pyrano-[3,4-c]pyridine-5-carboxylate deriv-atives also showed fluorescence in the solid state. This is the first example of fluorescence in fused 2-pyrone derivatives.

In this short note, I review the Bank of Japan (BOJ)'s monetary policy since its exit from the so-called quantitative easing regime early in 2006. The major characteristic of the policy stance during the period, called Strategy 2 below, has been to adjust the policy interest rate gradually upward in response to a healthy real economy despite stagnant behaviour in consumer prices. Such a policy stance can be contrasted with a hypothetical strategy, Strategy 1, whereby the BOJ would have kept the policy rate at lower levels, possibly at 0%, until inflation starts to show an upward trend more clearly. The two strategies are compared on many fronts with particular attention to well-known recent empirical regularities about inflation – a smaller response of inflation to output and larger uncertainties about the response. Various comparisons of the two strategies offered here, although far from conclusive, tend to support Strategy 1 over Strategy 2. In my discussion of the two strategies, I also comment on some of the major features of the Nishimura article in this issue.

Background— Autopsy-negative sudden unexplained death, including sudden infant death syndrome, can be caused by cardiac channelopathies such as Brugada syndrome (BrS). Type 1 BrS, caused by mutations in the SCN5A -encoded sodium channel, accounts for ≈20% of BrS. Recently, a novel mutation in the glycerol-3-phosphate dehydrogenase 1–like gene ( GPD1-L ) disrupted trafficking of SCN5A in a multigenerational family with BrS. We hypothesized that mutations in GPD1-L may be responsible for some cases of sudden unexplained death/sudden infant death syndrome. Methods and Results— Using denaturing high-performance liquid chromatography and direct DNA sequencing, we performed comprehensive open-reading frame/splice site mutational analysis of GPD1-L on genomic DNA extracted from necropsy tissue of 83 unrelated cases of sudden unexplained death (26 females, 57 males; average age, 14.6±10.7 years; range, 1 month to 48 years). A putative, sudden unexplained death–associated GPD1-L missense mutation, E83K, was discovered in a 3-month-old white boy. Further mutational analysis was then performed on genomic DNA derived from a population-based cohort of 221 anonymous cases of sudden infant death syndrome (84 females, 137 males; average age, 3±2 months; range, 3 days to 12 months), revealing 2 additional mutations, I124V and R273C, in a 5-week-old white girl and a 1-month-old white boy, respectively. All mutations occurred in highly conserved residues and were absent in 600 reference alleles. Compared with wild-type GPD1-L, GPD1-L mutations coexpressed with SCN5A in heterologous HEK cells produced a significantly reduced sodium current ( P P Conclusions— The present study is the first to report mutations in GPD1-L as a pathogenic cause for a small subset of sudden infant death syndrome via a secondary loss-of-function mechanism whereby perturbations in GPD1-L precipitate a marked decrease in the peak sodium current and a potentially lethal BrS-like proarrhythmic substrate.

Introduction Long QT Syndrome (LQTS) is an inherited disorder characterized by prolonged QT intervals and life-threatening polymorphic ventricular tachyarrhythmias. LQT1 caused by KCNQ1 mutations is the most common form of LQTS. Methods and results Patients diagnosed with LQTS were screened for disease-associated mutations in KCNQ1, KCNH2, KCNE1, KCNE2, KCNJ2, and SCN5A. A novel mutation was identified in KCNQ1 caused by a three-base deletion at the position 824-826, predicting a deletion of phenylalanine at codon 275 in segment 5 of KCNQ1 (DeltaF275). Wild-type (WT) and DeltaF275-KCNQ1 constructs were generated and transiently transfected together with a KCNE1 construct in CHO-K1 cells to characterize the properties of the slowly activating delayed rectifier current (IKs) using conventional whole-cell patch-clamp techniques. Cells transfected with WT-KCNQ1 and KCNE1 (1:1.3 molar ratio) produced slowly activating outward current with the characteristics of IKs. Tail current density measured at -40 mV following a two-second step to +60 mV was 381.3 +/- 62.6 pA/pF (n = 11). Cells transfected with DeltaF275-KCNQ1 and KCNE1 exhibited essentially no current. (Tail current density: 0.8 +/- 2.1 pA/pF, n = 11, P = 0.00001 vs WT). Cotransfection of WT- and DeltaF275- KCNQ1 (50/50), along with KCNE1, produced little to no current (tail current density: 10.3 +/- 3.5 pA/pF, n = 11, P = 0.00001 vs WT alone), suggesting a potent dominant negative effect. Immunohistochemistry showed normal membrane trafficking of DeltaF275-KCNQ1. Conclusion Our data suggest that a DeltaF275 mutation in KCNQ1 is associated with a very potent dominant negative effect leading to an almost complete loss of function of IKs and that this defect underlies a LQT1 form of LQTS.

Polysubstituted pyridine derivatives were synthesized by the reaction of ketene dithioacetal, 3,3-bis(methylsulfanyl)methylenemalononitrile 1b, with a variety of active methylene compounds in the presence of either sodium hydroxide or potassium hydroxide as a base in DMSO. This reaction was carried out under economical one-pot reaction conditions (cheap catalyst and solvent) and solved the problem of the odor of methanethiol, commonly derived from reactions of ketene dithioacetals. This is a significant enhancement of GSC (green and sustainable chemistry) in the field of ketene dithioacetal chemistry.

Aortic pulse wave velocity (Ao-PWV) and ankle-brachial blood pressure index (ABPI) are significant prognostic factors in patients with end-stage renal disease (ESRD). Diabetes mellitus (DM) promotes changes in arterial walls, including marked increases in Ao-PWV and decreases in ABPI. To determine the prevalence of peripheral arterial occlusive disease (PAOD) as well as the clinical variables useful in predicting these changes in nondiabetic patients with ESRD undergoing hemodialysis (HD), we performed a cross-sectional study in a cohort of 143 patients. Ao-PWV and ABPI were measured simultaneously and compared with several annual biochemical measurements and other clinical variables. The prevalence of PAOD in our cohort was 30.5%. In univariate regression analysis, Ao-PWV correlated positively with age, heart rate (HR), blood pressure (BP), pulse pressure (PP) and HbA1c, and negatively with serum albumin and ABPI. ABPI correlated negatively with age, HD duration, systolic BP, PP, low-density lipoprotein (LDL) cholesterol and hypersensitive C-reactive protein (hs-CRP), and positively with serum albumin and bone mineral density. In a step-down multiple regression analysis, HbA1c was identified as an independent determinant of Ao-PWV along with age, HD duration, HR and mean BP, while hs-CRP was an independent contributor to ABPI along with age, HD duration, PP and LDL cholesterol. Our results suggest that HD promotes aortic wall stiffness and PAOD progression. We recommend the monitoring of HbA1c to allow the prediction of aortic wall stiffness in nondiabetic ESRD patients. Our results did not confirm the influence of insulin resistance on the development of arterial sclerosis lesions.

A sonochemistry process reforms heavy fuel oil or solid fuel into lighter liquid fuel. The sonochemistry is originated from the behavior of acoustic cavitation bubbles; the nucleation, growth, and violent collapse. Here, an instantaneous hot spot region with local temperature of several thousand Kelvin and pressure of several hundred Mega-Pascal is generated by the cavitation bubble collapse. This hot-spot causes the decomposition of carbon bond and the removal of nitrogen, aromatic series. The rate of sonochemical reaction is affected by vapor pressure of fuel, and thus is decreased for heavy fuels. Therefore, the authors have proposed the application of sonochemistry into heavy fuel oil mixed with higher volatility fuels, because the mixed fuels can improve volatility characteristics due to formation of two-phase region including both vapor and liquid phases. In this paper, the cavitation behavior of mixed fuel is clarified and the result shows that high efficiency fuel reformulation is accomplished by applying sonochemistry to mixed fuel.

We develop a theory of out-of-equilibrium transport phenomena in a magnetic field based on the self-consistent perturbation theory within the weak correlation regime. Magnetization vanishes in the limit of large bias voltage. The differential conductance splits into double peaks with increasing a magnetic field. The threshold field of the split is reduced when the correlation effect is increased.

The absorption and fluorescent properties of newly synthesized 5-aryl-2,2′-bipyridyls were examined both in solution and in the solid state. The 6-methoxy derivatives 5a–5c have weak fluorescence, ...

The effect of noise and presentation level on the perception of English consonants by native listeners and non-native listeners were examined. English words contrasting in /r/–/l/, /b/–/v/ and /s/–/th/ sounds, which are known to be difficult to distinguish for native speakers of Japanese, were presented to both native speakers of American English (AE listeners) and those of Japanese (J) in white noise and in pink noise at sytematically changed signal-to-noise ratios (SNR). Words were also presented at various presentation levels. The effects of noise and presentation level differed by phonetic contrast and language group. The /b/–/v/ and /s/–/th/ contrasts were more affected by noise at high SNRs, while /r/–/l/ was tolerant for noise when the SNR was higher than −3 dB. The presentation level affected AE listeners’ identification of /b/–/v/, but not of other contrasts. J listeners’ perception was affected less than that of AE listeners, possibly because the flooring effect for J listeners’ identification performance was low, even for original stimuli.

In strongly correlated systems, some of the low-energy excitations are enhanced. In geometrically frustrated systems, due to the absence of long-range order, there remains (pseudo-) degeneracy associated with the low-energy excitations at low temperatures. Lifting of degeneracy in both Mott insulating systems and itinerant electron systems are discussed by considering the pyrochlore lattice as an example.

Dimethyl acetylenedicarboxylate (DMAD) is a very important and useful reagent for the preparation of dimethyl heterocyclic-o-dicarboxylates, which are key intermediates in the synthesis of fused pyridazine derivatives. The synthesis of thiopyranes by the Diels-Alder reaction of dithiocarboxylate derivatives, synthesis of various cyclazines by [2 + 8] cycloaddition reactions, and synthesis of dimethyl pyrazolo[3,4-b]pyridine-5,6-dicarboxylates and polycyclic heterocycles containing the 1,6-naphthyridine ring system by the reaction of o-aminonitrile compounds with DMAD are described here.

Fitz-Hugh-Curtis症候群は,性感染症を原因とする肝周囲炎である.クラミジア・トラコマティス感染症による本症候群の3例を報告する.年齢は25～36歳の女性で,いずれも右上腹部痛を主訴に来院した.全例ともに血清クラミジアIgA, IgG抗体が上昇していた.腹部超音波検査では, 2症例で肝右葉表面に腹水と思われる低エコー域を認めたが, Morison窩には認めなかった.また,超音波プローブで肝表面を圧迫すると全例に圧痛が増強した.腹部CT検査では,全例に肝右葉表面に腹水が確認されたが,やはりMorison窩には認めなかった.さらに,造影CT検査を施行した1例では,肝被膜の濃染像を認めた.以上の所見は,クラミジア肝周囲炎を診断する上で重要な所見と考えられた.なお,全例ともに抗生剤により軽快した.最近,クラミジア感染症は増加傾向にあり,若い女性の右上腹部痛の診断には,本症候群を念頭に置くことが重要と考えられる.

Our auditory system has to organize and to pick up a target sound with many components, sometimes rejecting irrelevant sound components, but sometimes forming multiple streams including the target stream. This situation is well described with the concept of auditory scene analysis. Research on speech perception in noise is closely related to auditory scene analysis. This paper briefly reviews the concept of auditory scene analysis and previous and ongoing research on speech perception in noise, and discusses the future direction of research. Further experimental investigations are needed to understand our perceptual mechanisms better.

We investigate nonequilibrium transport through a dot in a finite magnetic field in a weak correlation regime by using the self-consistent perturbation theory in the Keldysh formalism. Separation of the density of states between the up and down spins becomes smaller gradually and ends up with the Zeeman energy as increasing the bias voltage. Concerning the differential conductance the zero-bias peak splits into two peaks when magnetic field is increased. The critical field for the splitting decreases as the Coulomb interaction is increased.

Several illusory phenomena in auditory perception are accounted for by using the event construction model presented by Nakajima et al. (2000) in order to explain the gap transfer illusion. This model assumes that onsets and offsets of sounds are detected perceptually as if they were independent auditory elements. They are connected to one another according to the proximity principle to constitute auditory events. This model seems to contribute to a general cross-modal theory of perception where the idea of edge integration plays an important role. Potential directions in which we can connect the present paradigm with speech perception are indicated, and possibilities to improve artificial auditory environments are suggested.

Objective. – The function of the C-terminus region of the human ether-a-go-go related gene (HERG) has not been well characterized except for its involvement in trafficking. To understand further the role of C-terminus region, we performed a functional analysis of a novel frameshift mutation (1122fs/147) identified in a Japanese long QT syndrome 2 (LQT2) patient who had recurrent episodes of syncope. Methods. – Wild type (WT) and mutant HERG plasmids were transfected into human embryonic kidney (HEK-293) cells, and whole-cell current was recorded by the patch-clamp technique. Confocal microscopy was performed to examine the membrane distribution of channel protein using a green fluorescent protein tagged to the N-terminus of HERG. Results. – The mutant 1122fs/147 alone could express current, but reduced density by 74% of control. No dominant negative effect was noted with co-expression of WT and 1122fs/147. Activation and deactivation time constants were not changed, while inactivation was accelerated in 1122fs/147 compared to WT, and V1/2 of steady-state inactivation curve shifted by 11 mV in the negative direction. Current density of 1123stop mutant revealed 49% reduction compared to WT and showed no shift in steady-state inactivation. Confocal microscopy revealed reduced protein expression on the cell surface both in 1122fs/147 and 1123stop mutants compared to WT. Conclusion. – Frameshift mutation at the C-terminus region with additional 147 amino acids evoked a loss of function of the HERG channel. A negative shift in steady-state inactivation induced by the additional 147 amino acids and trafficking defect contribute to a reduced current amplitude of 1122fs/147.

We construct a microscopic Hamiltonian for the ferromagnetism of UGe 2 by taking account of the orbital degeneracy of the 5-f electrons and investigate possible phases by the Hartree–Fock approximation. We reduce the number of mean values to be determined by assuming the magnetic orders where the coplanar magnetic moments perpendicular to the c -axis constitute an a -axis moment as a whole. Because of the orbital degeneracy, the anisotropies of the crystalline electric field term and the hopping term competes with each other. Moreover occupation number in each atomic orbit is sensitive to the relation between the crystalline electric field and the Coulomb interaction. In consequence, a rich ground state phase diagram with various different ferromagnetic orders is obtained.

Hyperpolarization-activated cyclic nucleotide-gated channel 4 gene HCN4 is a pacemaker channel that plays a key role in automaticity of sinus node in the heart, and an HCN4 mutation was reported in a patient with sinus node dysfunction. Expression of HCN4 in the heart is, however, not confined to the sinus node cells but is found in other tissues, including cells of the conduction system. On the other hand, mutations in another cardiac ion channel gene, SCN5A, also cause sinus node dysfunction as well as other cardiac arrhythmias, including long QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, and progressive cardiac conduction disturbance. These observations imply that HCN4 abnormalities may be involved in the pathogenesis of various arrhythmias, similar to the SCN5A mutations. In this study, we analyzed patients suffering from sinus node dysfunction, progressive cardiac conduction disease, and idiopathic ventricular fibrillation for mutations in HCN4. A missense mutation, D553N, was found in a patient with sinus node dysfunction who showed recurrent syncope, QT prolongation in electrocardiogram, and polymorphic ventricular tachycardia, torsade de pointes. In vitro functional study of the D553N mutation showed a reduced membranous expression associated with decreased If currents because of a trafficking defect of the HCN4 channel in a dominant-negative manner. These data suggest that the loss of function of HCN4 is associated with sinus nodal dysfunction and that a consequence of pacemaker channel abnormality might underlie clinical features of QT prolongation and polymorphic ventricular tachycardia developed under certain conditions.

Based on the recent approach to the Kondo effect in a dot with a finite bias voltage by using the perturbation theory, we discuss the new peak found in the differential conductance, in addition to the zero-bias peak. The new peak originate from the splitting of the Kondo resonance under a finite voltage which may be measured by the recent proposed three-terminal quantum dot.

We investigated the temperature-dependent Hall resistance and magnetization of the semiconductor/ferromagnetic hybrid structure of GaAs:MnAs granular films under dark and laser irradiated conditions. Under the laser irradiation with the energy above the band gap energy of GaAs, negative large Hall resistance due to the anomalous Hall effect was observed below the blocking temperature T b of the MnAs clusters. The intrinsic photo-induced magnetization of the MnAs clusters was, however, hardly observed. These results indicate that the blocking phenomena correlate with the photo-induced anomalous Hall resistance of the GaAs:MnAs granular films. Therefore, the magnetic interaction between the photo-induced carriers and the blocked magnetization of the MnAs clusters plays an important role in the photo-induced phenomena in the GaAs:MnAs granular films.

With the Finite temperature Density Matrix Renormalization Group method (FT-DMRG), we depeloped a method to calculate thermo-dynamical quantities and the conductance of a quantum dot system. Conductance is written by the local density of states on the dot. The density of states is calculated with the numerical analytic continuation from the thermal Green's function which is obtained directly from the FT-DMRG. Typical Kondo behaviors in the quantum dot system are observed conveniently by comparing the conductance with the magnetic and charge susceptibilities: Coulomb oscillation peaks and the unitarity limit. We discuss advantage of this method compared with others., Comment: 14 pages, 13 fiures

Dilated cardiomyopathy is characterized by ventricular dilation with systolic dysfunction of cardiac muscle. Recent genetic studies have revealed that mutations in genes for cytoskeleton proteins distributed in the Z-disc and/or intercalated discs of the cardiac muscle are major predictors of cardiomyopathy. However, as mutations in these genes can account for only a part of the patient population, there should be another disease-causing gene(s) for cardiomyopathy. Cypher/ZASP appears to be an ideal candidate for the cardiomyopathy causative gene, because Cypher/ZASP encodes a Z-disc associated protein, and recent studies have demonstrated that Cypher/ZASP knock-out mice develop cardiomyopathy. In this study, we searched for sequence variations in Cypher/ZASP in 96 unrelated Japanese patients with dilated cardiomyopathy. A D626N mutation located within the third LIM domain was identified in a familial case but not found in the unrelated controls. A family study of the patient showed that all affected siblings tested had the same mutation. Clinical information of the affected family members suggested that the mutation was associated with late onset cardiomyopathy. To reveal the biochemical changes due to the mutation, we performed a yeast two-hybrid assay and a pull-down assay. It was demonstrated by both assays that the D626N mutation of Cypher/ZASP increased the affinity of the LIM domain for protein kinase C, suggesting a novel biochemical mechanism of the pathogenesis of dilated cardiomyopathy.

The interference effect of nonspeech and speech in short-term auditory memory was investigated with an experiment paradigm proposed by Deutsch [Science, 168, 1604–1605 (1970)], in which test tones, separated by a 5-s retention interval, were interpolated with six other sounds. In Experiment 1, the test tones were pure tones. The interpolated sounds were pure tones and naturally spoken digits by a female and a male. Nine participants were tested for (1) pure-test-tone pitch recognition, (2) serial recall of the interpolated spoken digits, and (3) both tasks (1) and (2). Pitch recognition errors were significantly increased in task (3) compared to task (1), and the digit recall errors were also significantly increased in task (3). In Experiment 2, the test tones were eight-component harmonic complex tones. The interpolated sounds were eight-component harmonic complex tones, and naturally spoken digits by a male. Twelve participants were tested for the corresponding task conditions as in Experiment 1. Significant increases in the errors of pitch recognition and of digit recall were observed when both tasks were required. These results suggest that speech can interfere with tone pitch in short-term auditory memory, and that pitch salience plays a crucial role in the interference.

The objectives of the study were to clarify the relationship between blood pressure and mortality from stroke, heart disease, cardiovascular diseases and all causes of death among representative population of Japanese and to estimate category-specific excess mortality from stroke due to blood pressure (BP) level. The study design comprised a retrospective cohort study using the 1980 National Survey on Cardiovascular Diseases and identification of underlying causes of death using national vital statistics data. In 1994, a 14-year follow-up cohort study was conducted among participants of the National Survey on Cardiovascular Diseases in 1980, randomly selected from the Japanese population. With a collaboration of 300 public health centres, which had conducted the original survey in 1980, 91.4% of the participants of the original survey could be followed up. Total observed person-years were 53948 for men and 70932 for women. During follow-up, 1327 deaths were observed. BP levels were significantly related to mortality from strokes, cardiovascular diseases and all causes of death for both sexes (P

SrCu 2( BO 3)2 is a new two-dimensional spin gap system and the magnetic behaviour of this compound is explained well by the two-dimensional orthogonal dimer Heisenberg model. Recently several excitations have been observed by inelastic neutron scattering and other experiments. We study features of these excitations by Lanczos method and perturbation technique. A triplet excitation has an almost localised nature. This localised character is observed as an almost flat band in neutron scattering. On the other hand, bound states of two triplet excitations, which have dispersive character, are stable in contrast to ordinary magnetic systems. We calculate the dynamic structure factor by a Lanczos method in finite systems and compare our results with experiments.

In this review, we summarize the present status of theories of the spin fluctuation (SF) mechanism in explaining anomalous or non-Fermi liquid behaviours and unconventional superconductivity (SC) in strongly correlated electron systems around the antiferromagnetic (AF) quantum critical point. We refer to the high-Tc cuprates, two-dimensional organic compounds and heavy electron systems. We argue that the SF theories are successful in explaining at least the essential part of the problems, indicating that AF SF is the common origin of SC in these systems. This review is concluded by several comments on remaining problems which may require some additions to the SF theory, like the pseudo-gap phenomena observed in the hole-underdoped cuprates.

In order to investigate electronic properties of recently discovered heavy fermion superconductors CeTIn 5 (T = Ir and Co), we employ the relativistic linear augmented-plane-wave (RLAPW) method to clarify the energy band structures and Fermi surfaces of those materials. The obtained energy bands mainly due to the large hybridization between Ce 4 f and In 5 p states well reproduce the Fermi surfaces consistent with the de Haas-van Alphen experimental results. However, when we attempt to understand magnetism and superconductivity in CeTIn 5 from the microscopic viewpoint, the energy bands obtained in the RLAPW method are too complicated to analyze the system by further including electron correlations. Thus, it is necessary to prepare a more simplified model, keeping correctly the essential characters of the energy bands obtained in the band-structure calculation. For the purpose, we construct a tight-binding model for CeTIn 5 by including f – f and p – p hoppings as well as f – p hybridization, which are ex...

The magnetic properties of SrCu2 (BO3)2 are reviewed from a theoretical point of view. SrCu2 (BO3)2 is a new two-dimensional spin gap system and its magnetic properties are well described by a spin-1/2 antiferromagnetic Heisenberg model of the orthogonal dimer lattice. The model has a dimer singlet ground state whose exactness was proven by Shastry and Sutherland for a topologically equivalent model more than 20 years ago. The exactness of the ground state is maintained even if interlayer couplings are introduced for SrCu2 (BO3)2. In the two-dimensional model, quantum phase transitions take place between different ground states for which three phases are expected: a gapped dimer singlet state, a plaquette resonating valence bond state and a gapless magnetic ordered state. Analysis of the experimental data shows that the dimer singlet ground state is realized in SrCu2 (BO3)2. The orthogonality of the dimer bonds, which is the underlying symmetry of the exactness of the ground state, also leads to an unusual property of elementary excitations, namely the almost localized nature of the triplet excitations. Application of an external magnetic field changes the density of the triplet excitations. In general, there is competition between kinetic energies and interaction energies between triplets. The almost localized nature of the triplets makes it easy to form regular lattices. In fact, at certain densities, where the commensurability energy is significant, the triplet excitations form superstructures and plateaux appear at 1/2, 1/3, 1/4 and 1/8 in the magnetization curve. In high-magnetic-field experiments, magnetic plateaux at magnetizations of 1/3, 1/4 and 1/8 have been observed. Translational symmetry of the lattice is spontaneously broken at the plateaux, except for the 1/2 plateau. The 1/3 and 1/4 plateaux are expected to have magnetic superstructures of stripe form while the 1/2 plateau has a square unit cell and the 1/8 plateau a rhomboid cell. Especially at the 1/8 plateau, nuclear magnetic resonance experiments indicate the presence of at least 11 distinct Cu sites with different spin polarizations, which is the first evidence of breaking of the translational symmetry at the plateau phase. The spin texture calculated on the basis of a Heisenberg model with adiabatic spin–phonon coupling is consistent with the experimental results.

The purpose of this paper is to present the concept and design of Technical Listening Training, a systematic education program designed to allow prospective acoustic engineers and sound designers to enhance their auditory sensitivity. Sound professionals should have the ability to express auditory differences using appropriate technical terms for the physical properties of sounds. Furthermore, they should be able to imagine the sounds when given the acoustic properties of the sounds. Training starts with a discrimination task for pitch, loudness, and timbre in order to increase sensitivity to auditory differences. This is followed by instruction on sound property identification to improve students’ ability to correlate auditory impressions with the physical properties of the sound, thereby allowing them to imagine the sound. Through Technical Listening Training, students improve their sound sensitivity and understanding of the relationship between acoustic properties and auditory impression.

There have been many studies investigating the association between gene polymorphisms and coronary artery disease (CAD) including myocardial infarction (MI), and some studies have shown that certain gene polymorphisms are associated with CAD/MI. However, the results of the association have sometimes been controversial. The reason may be that the contribution of genetic risk factors to CAD/MI varies depending on the ethnic, environmental, and habitual backgrounds, and differs between males and females. In this study, we analyzed 17 polymorphisms in 12 candidate genes for MI in 136 patients and 200 to 235 controls, and found that there is a significant association of MI with the polymorphisms in the genes for E-selectin and CD14 receptor. To further explore the association, we investigated the C-260 T polymorphism in the promoter region of the CD14 gene in 502 MI patients and 527 control subjects. The genotype distributions of the CD14 polymorphism were as follows: patients; T/T 32.5%, C/T 48.2%, C/C 19.3%, and controls; T/T 25.4%, C/T 52.8%, C/C 21.8%. The frequencies of the T/T homozygotes were significantly higher in the patients (OR = 1.41, P = 0.013) than in the control group, confirming the association of CD14 polymorphism with MI in Japanese. Stratification analyses further demonstrated that the association was more prominent in females and in patients with a relatively low body mass index, suggesting that the contribution of the CD14-linked genetic risk to MI differs with respect to gender and habitual background.

The free-living nematode, Caenorhabditis elegans (C. elegans) was adopted as a multicellular biosensor of biological toxicity from alkylphenols and organotin compounds. Alkylphenols were found to affect reproduction at lower doses than indicated by the acute toxicity assay. In particular, nonylphenol altered the reproduction rate of C. elegans at a dose 10- to 100-fold lower than the 50% lethal concentration (LC50). A comparison of the number of viable worms and eggs suggested that alkylphenols and organotin compounds possess hatching toxicity. A 0.1 μM dose of organotin compounds caused a significant decrease, in the order of 20-50%, in reproduction of the worms, and an abnormal male: hermaphrodite ratio was observed. C. elegans therefore appears to represent a potent and sensitive organism with which to evaluate the biological effects of chemicals. In particular, the sensitivity of reproduction as an endpoint is highly useful for assessing the sublethal effects of chemicals., Journal of Health Science v.48(6) p.555-559, 2002

We describe a novel approach to evaluating the respiratory toxicity of chemicals in the free-living nematode Caenorhabditis elegans. Using DOX-96KT, a general purpose, multi-channel dissolved oxygen (DO) measuring system, we measured the DO concentration in culture media containing C. elegans exposed to chemicals to assay for respiratory toxicity. The current value, which is an index of the dissolved oxygen concentration in culture media, was measured every 10 sec for 30 min at 24°C. We focused on the respiration levels of the exposed worms between 500 and 1800 sec. This method produces results that are similar to the computer tracking system measuring behavioral toxicity. Since it can do multiple dilution series tests at a given time, it is useful for concentration-activity correlation studies. This novel technique is not only an alternative to the computer tracking system for measuring behavioral toxicity but also a rapid sublethal toxicity test for chemical hazard assessment., Journal of Health Science v.48(3) p.269-272, 2002

Yb4As3 is a unique 4f compound having Yb3+ chains below the charge-ordering temperature T c =290 K . The Yb3+ chains are believed to be responsible for the most part of anomalous properties this material shows at low temperatures. First a microscopic Hamiltonian is derived for the Yb3+ chains from its structure and the crystal-field wave functions to show that a staggered g tensor and a staggered Dzyaloshinsky–Moriya (DM) term are present. This Hamiltonian naturally explains the energy gap formed for the magnetic field applied perpendicular to the chain. There are some experimental features, which cannot be explained by the single-chain Hamiltonian and may be due to interchain couplings. It is pointed out that the interchain DM interaction should be nonzero and may lead to an upturn of susceptibility observed at low temperatures for the magnetic field parallel to the chain.