Direct observation of topological magnon polarons in a multiferroic material.

Magnon polarons are novel elementary excitations possessing hybrid magnonic and phononic signatures, and are responsible for many exotic spintronic and magnonic phenomena. Despite long-term sustained experimental efforts in chasing for magnon polarons, direct spectroscopic evidence of their existence is hardly observed. Here, we report the direct observation of magnon polarons using neutron spectroscopy on a multiferroic Fe2Mo3O8 possessing strong magnon-phonon coupling. Specifically, below the magnetic ordering temperature, a gap opens at the nominal intersection of the original magnon and phonon bands, leading to two separated magnon-polaron bands. Each of the bands undergoes mixing, interconverting and reversing between its magnonic and phononic components. We attribute the formation of magnon polarons to the strong magnon-phonon coupling induced by Dzyaloshinskii-Moriya interaction. Intriguingly, we find that the band-inverted magnon polarons are topologically nontrivial. These results uncover exotic elementary excitations arising from the magnon-phonon coupling, and offer a new route to topological states by considering hybridizations between different types of fundamental excitations.

Magnon mode transition in real space.

Spin excitation of an ilmenite FeTiO3 powder sample is measured by time-of-flight inelastic neutron scattering. The dynamic magnetic pair-density function DM(r, E) is obtained from the dynamic magnetic structure factor SM(Q, E) by the Fourier transformation. The real space spin dynamics exhibit magnon mode transitions in the spin-spin correlation with increasing energy from no-phase-shift to π-phase-shift. The mode transition is well reproduced by a simulation using the reciprocal space magnon dispersions. This analysis provides a novel opportunity to study the local spin dynamics of various magnetic systems.

The ω3 scaling of the vibrational density of states in quasi-2D nanoconfined solids.

The vibrational properties of crystalline bulk materials are well described by Debye theory, which successfully predicts the quadratic ω2 low-frequency scaling of the vibrational density of states. However, the analogous framework for nanoconfined materials with fewer degrees of freedom has been far less well explored. Using inelastic neutron scattering, we characterize the vibrational density of states of amorphous ice confined inside graphene oxide membranes and we observe a crossover from the Debye ω2 scaling to an anomalous ω3 behaviour upon reducing the confinement size L. Additionally, using molecular dynamics simulations, we confirm the experimental findings and prove that such a scaling appears in both crystalline and amorphous solids under slab-confinement. We theoretically demonstrate that this low-frequency ω3 law results from the geometric constraints on the momentum phase space induced by confinement along one spatial direction. Finally, we predict that the Debye scaling reappears at a characteristic frequency ω× = vL/2π, with v the speed of sound of the material, and we confirm this quantitative estimate with simulations.

Fluorometric sensing of biogenic amines with aggregation-induced emission-active tetraphenylethenes.

A fluorometric sensor for detection and identification of biogenic amines with carboxylic acid modified tetraphenylethenes (TPEs) based on aggregation-induced emission (AIE) is reported. A mixture of the carboxylic acid substituted TPE and biogenic amines displayed a blue emission on aggregation, which serves as a "turn-on" fluorescent sensor for the amines, the degree of fluorescence enhancement being dependent on the amine. The chromic responses were utilized to distinguish the amines. A fluorometric sensor array of three TPEs with carboxylic acid groups was shown to identify accurately 10 different amines, including biogenic amines. The response patterns were systematically classified by using linear discriminant analysis (LDA) with 98% classification accuracy. Additional information on the concentration of histamine in a "tuna fish matrix" as an example was assessed by the further analysis of the fluorescence intensity, demonstrating a test for food freshness and quality.

Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity.

Lurasidone [(3aR,4S,7R,7aS)-2-[(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexylmethyl]hexahydro-4,7-methano-2H-isoindole-1,3-dione hydrochloride; SM-13496] is an azapirone derivative and a novel antipsychotic candidate. The objective of the current studies was to investigate the in vitro and in vivo pharmacological properties of lurasidone. Receptor binding affinities of lurasidone and several antipsychotic drugs were tested under comparable assay conditions using cloned human receptors or membrane fractions prepared from animal tissue. Lurasidone was found to have potent binding affinity for dopamine D(2), 5-hydroxytryptamine 2A (5-HT(2A)), 5-HT(7), 5-HT(1A), and noradrenaline alpha(2C) receptors. Affinity for noradrenaline alpha(1), alpha(2A), and 5-HT(2C) receptors was weak, whereas affinity for histamine H(1) and muscarinic acetylcholine receptors was negligible. In vitro functional assays demonstrated that lurasidone acts as an antagonist at D(2) and 5-HT(7) receptors and as a partial agonist at the 5-HT(1A) receptor subtype. Lurasidone showed potent effects predictive of antipsychotic activity, such as inhibition of methamphetamine-induced hyperactivity and apomorphine-induced stereotyped behavior in rats, similar to other antipsychotics. Furthermore, lurasidone had only weak extrapyramidal effects in rodent models. In animal models of anxiety disorders and depression, treatment with lurasidone was associated with significant improvement. Lurasidone showed a preferential effect on the frontal cortex (versus striatum) in increasing dopamine turnover. Anti-alpha(1)-noradrenergic, anticholinergic, and central nervous system (CNS) depressant actions of lurasidone were also very weak. These results demonstrate that lurasidone possesses antipsychotic activity and antidepressant- or anxiolytic-like effects with potentially reduced liability for extrapyramidal and CNS depressant side effects.

High-energy spin fluctuation in low-Tc iron-based superconductor LaFePO0.9.

Spin fluctuations are widely believed to play an important role in the superconducting mechanisms of unconventional high temperature superconductors. Spin fluctuations have been observed in iron-based superconductors as well. However, in some iron-based superconductors such as LaFePO0.9, they have not been observed by inelastic neutron scattering (INS). LaFePO0.9 is an iron-based superconductor with a low superconducting transition temperature (Tc = 5 K), where line nodes are observed in the superconducting gap function. The line-node symmetry typically originates from sign reversal of the order parameter in spin-fluctuation-mediated superconductivity. This contradiction has been a long-standing mystery of this superconductor. Herein, spin fluctuations were found at high energies such as 30-50 meV with comparable intensities to an optimally doped LaFeAs(O, F). Based on this finding, the line-node symmetry can be explained naturally as spin-fluctuation-mediated superconductivity.

Elastic and dynamical structural properties of La and Mn-doped SrTiO3 studied by neutron scattering and their relation with thermal conductivities.

The electron-doped SrTiO3 exhibits good thermoelectric properties, which makes this material a promising candidate of an n-type oxide thermoelectric device. Recent studies indicated that only a few percent co-doping of La and Mn in SrTiO3 substantially reduces the thermal conductivity, thereby greatly improving the thermoelectric figure of merit at room temperature. Our time-of-flight neutron scattering studies revealed that by doping both La and Mn into SrTiO3, the inelastic scattering spectrum shows a momentum-independent increase in the low-energy spectral weight approximately below 10 meV. The increase in the low-energy spectral weight exhibits a clear correlation with thermal conductivity. The correlation is attributed to dynamical and local structural fluctuations caused by the Jahn-Teller instability in Mn3+ ions coupled with the incipient ferroelectric nature of SrTiO3, as the origin of the low thermal conductivity.

Retreat from Stress: Rattling in a Planar Coordination.

Thermoelectric devices convert heat flow to charge flow, providing electricity. Materials for highly efficient devices must satisfy conflicting requirements of high electrical conductivity and low thermal conductivity. Thermal conductivity in caged compounds is known to be suppressed by a large vibration of guest atoms, so-called rattling, which effectively scatters phonons. Here, the crystal structure and phonon dynamics of tetrahedrites (Cu,Zn)12 (Sb,As)4 S13 are studied. The results reveal that the Cu atoms in a planar coordination are rattling. In contrast to caged compounds, chemical pressure enlarges the amplitude of the rattling vibration in the tetrahedrites so that the rattling atom is squeezed out of the planar coordination. Furthermore, the rattling vibration shakes neighbors through lone pairs of the metalloids, Sb and As, which is responsible for the low thermal conductivity of tetrahedrites. These findings provide a new strategy for the development of highly efficient thermoelectric materials with planar coordination.

Tandospirone potentiates the fluoxetine-induced increases in extracellular dopamine via 5-HT(1A) receptors in the rat medial frontal cortex.

Recent clinical studies suggest that 5-HT(1A) receptor agonists, including buspirone, may have an antidepressant effect and potentiate the efficacy of selective serotonin reuptake inhibitors (SSRI) in major depressive disorders. In the present study, we investigated the effect of tandospirone, a highly potent and selective 5-HT(1A) receptor agonist, on dopamine release and potentiation of fluoxetine-induced dopamine outflow in the medial frontal cortex using microdialysis in freely moving rats. Intraperitoneal injection of tandospirone (5 mg/kg) increased dopamine release to about 190% of basal levels. Pretreatment with the selective 5-HT(1A) receptor antagonist, WAY 100635 (1mg/kg), blocked the effect of tandospirone. Local application of WAY 100635 (10 microM) via microdialysis probe antagonized the increase in dopamine release in the medial frontal cortex induced by systemic injection of tandospirone. Fluoxetine (10 mg/kg) also increased dopamine release in the medial frontal cortex, to 200% of basal levels, and the simultaneous administration of tandospirone and fluoxetine increased the release to 380%. These results indicate that tandospirone potentiates the fluoxetine-induced increase in dopamine release via 5-HT(1A) receptors in the rat medial frontal cortex, and suggest that tandospirone may have therapeutic potential for the treatment of depression.

In vitro and in vivo antagonistic activities of SM-31900 for the NMDA receptor glycine-binding site.

The purpose of this study was to clarify the in vitro pharmacological profile and the in vivo activity of (3S)-7-chloro-3-[2-((1R)-1-carboxyethoxy)-4-aminomethylphenyl]aminocarbonylmethyl-1,3,4,5-tetrahydrobenz[c,d]indole-2-carboxylic acid hydrochloride (SM-31900). SM-31900 inhibited the binding of [3H]glycine and [3H]5,7-dichlorokynurenic acid, radioligands for the N-methyl-D-aspartate (NMDA) receptor glycine-binding site, to rat brain membranes in a competitive manner, with K(i) values of 11+/-2 and 1.0+/-0.1 nM, respectively, and completely prevented the binding of [3H]dizocilpine (MK-801), a radioligand for the NMDA receptor channel site. In cultures of rat cortical neurons, SM-31900 markedly prevented the neuronal cell death induced by transient exposure to glutamate, in a concentration-dependent manner. Its neuroprotective potency was much stronger than those of other glycine-binding site antagonists (4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline (L-689,560), 5,7-dichlorokynurenic acid, and 7-chlorokynurenic acid). Furthermore, SM-31900 showed anticonvulsant activity when administered systemically, unlike other antagonists. These data indicate that SM-31900 is a systemically active antagonist with high affinity for the NMDA receptor glycine-binding site.

A case of antiphospholipid syndrome with cutaneous ulcer and intrauterine fetal growth retardation.

A 28-year-old patient presented with severe intrauterine fetal growth retardation (IUGR) at 34 weeks' gestation. There was a prior history of a recurrent cutaneous ulcer on the left thigh. Serological tests for IgG anticardiolipin antibody were positive. A live premature male infant was delivered by an urgent cesarean section because of fetal distress. Histopathological examination revealed that the causes of the cutaneous ulcer and IUGR were thrombosis of the small blood vessels and placental infarction, respectively. Early diagnosis and proper treatment are important in the management of the antiphospholipid syndrome.

[Practical chemistry education provided by team-based learning (TBL) and peer evaluation].

Learning chemistry is cumulative: basic knowledge and chemical calculation skills are required to gain understanding of higher content. However, we often suffer from students' lack of learning skills to acquire these concepts. One of the reasons is the lack of adequate training in the knowledge and skills of chemistry, and one of the reasons for this lack is the lack of adequate evaluation of training procedures and content. Team-based learning (TBL) is a strong method for providing training in the knowledge and skills of chemistry and reaffirms the knowledge and skills of students of various levels. In our faculty, TBL exercises are provided for first-year students concurrently with lectures in physical chemistry and analytical chemistry. In this study, we researched the adoption of a peer evaluation process for this participatory learning model. Questionnaires taken after TBL exercises in the previous year showed a positive response to TBL. Further, a questionnaire taken after TBL exercises in the spring semester of the current year also yielded a positive response not only to TBL but also to peer evaluation. In addition, a significant correlation was observed between the improvement of students' grades in chemistry classes and the feeling the percentage (20%) of peer evaluation in overall evaluation low (logistic regression analysis, p=0.022). On the basis of the findings, we argue that TBL provides a generic, practical learning environment including an effective focus on learning strategy and evaluation of knowledge, skills, and attitudes, and studies on the educational effects of TBL and peer evaluation.

Lurasidone in the treatment of schizophrenia: a 6-week, placebo-controlled study.

RATIONALE: There is an unmet need in the treatment of schizophrenia for effective medications with fewer adverse effects. OBJECTIVE: This study aims to evaluate the efficacy and safety of lurasidone, an atypical antipsychotic, for the treatment of schizophrenia. METHODS: Patients with an acute exacerbation of schizophrenia were randomized to 6 weeks of double-blind treatment with once-daily, fixed-dose lurasidone 40 mg (N = 50), lurasidone 120 mg (N = 49), or placebo (N = 50). The primary efficacy measure was mean change from baseline to day 42 (last observation carried forward) in the Brief Psychiatric Rating Scale derived (BPRSd) from the Positive and Negative Syndrome Scale (PANSS). RESULTS: Mean change in BPRSd was significantly greater in patients receiving lurasidone 40 and 120 mg/day versus placebo (-9.4 and -11.0 versus -3.8; p = 0.018 and 0.004, respectively). Treatment with lurasidone 120 mg/day was superior to placebo across all secondary measures, including PANSS total (p = 0.009), PANSS positive (p = 0.005), PANSS negative (p = 0.011), and PANSS general psychopathology (p = 0.023) subscales and Clinical Global Impression of Severity (CGI-S; p = 0.001). Treatment with lurasidone 40 mg/day was superior to placebo on the PANSS positive subscale (p = 0.018) and CGI-S (p = 0.002). The most common adverse events for patients receiving lurasidone were nausea (16.2 versus 4.0 % for placebo) and sedation (16.2 versus 10.0 % for placebo). Minimal changes in weight, cholesterol, triglyceride, and glucose levels were observed. CONCLUSIONS: In this study, which was limited by a relatively high discontinuation rate, lurasidone provided effective treatment for patients with acute exacerbation of chronic schizophrenia and had minimal effects on weight and metabolic parameters.

Mode-distribution analysis of quasielastic neutron scattering and application to liquid water.

A quasielastic neutron scattering (QENS) experiment is a particular technique that endeavors to define a relationship between time and space for the diffusion dynamics of atoms and molecules. However, in most cases, analyses of QENS data are model dependent, which may distort attempts to elucidate the actual diffusion dynamics. We have developed a method for processing QENS data without a specific model, wherein all modes can be described as combinations of the relaxations based on the exponential law. By this method, we can obtain a distribution function B(Q,Γ), which we call the mode-distribution function (MDF), to represent the number of relaxation modes and distributions of the relaxation times in the modes. The deduction of MDF is based on the maximum entropy method and is very versatile in QENS data analysis. To verify this method, reproducibility was checked against several analytical models, such as that with a mode of distributed relaxation time, that with two modes closely located, and that represented by the Kohlrausch-Williams-Watts function. We report the first application to experimental data of liquid water. In addition to the two known modes, the existence of a relaxation mode of water molecules with an intermediate time scale has been discovered. We propose that the fast mode might be assigned to an intermolecular motion and the intermediate motion might be assigned to a rotational motion of the water molecules instead of to the fast mode.

[Adaptation of peer evaluation to small group discussion (SGD) and its validity for summative evaluation].

We adopted peer evaluation (mutual evaluation between students) for small group discussion (SGD) among first graders. The peer evaluation criteria were 5 grade scales for 5 fields: "preparation," "remark," "listening," "activeness," and "role." A comparison with tutor evaluation clarified the validity of peer evaluation for summative evaluation. Although the average of peer evaluation (4.2 (4.0-4.4)) was higher than that of tutor evaluation (3.8 (3.7-4.1)) (p=0.0601, Mann-Whitney U test), the value of the correlation coefficient between peer evaluation and summative evaluation of SGD (average 0.35 (0.12-0.54)) was almost the same as that of the coefficient between tutor evaluation and summative evaluation of SGD (average 0.36 (0.24-0.42)) (p=0.6761, Mann-Whitney U test). Principal component analysis showed that the tutor could not evaluate "remark" and "listening" independently, while students evaluate "listening" independently from other evaluation criteria. The combination of peer and tutor evaluation may be multilateral evaluation for SGD. The questionnaire about peer evaluation for students showed that they recognized the value of peer evaluation and favorably accepted its use.

Fluorescence turn-on sensing of lectins with mannose-substituted tetraphenylethenes based on aggregation-induced emission.

The synthesis of mannose-substituted tetraphenylethenes (TPEs) and their aggregation-induced emission (AIE) behavior, induced by interactions with concanavalin A (Con A), are reported. A mixture of the mannose-TPE conjugates and Con A in a buffer solution displays an intense blue emission on agglutination within a few seconds, which serves as a "turn-on" fluorescent sensor for lectins. The sensing is also selective: the conjugates act as a sensor for Con A, but do not sense a galactose-binding lectin, PNA. Con A-recognition is not affected even in the presence of other proteins in a mixture. The conjugates also exhibit high sensitivity to detect Con A. An increased sensitivity of the conjugates results if mannopyranoside substituents are linked to the TPE-core unit with a flexible chain and/or when the number of mannose residues increases.

Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled trial.

OBJECTIVE: Lurasidone is a novel psychotropic agent with high affinity for D(2) and 5-HT(2A) receptors, as well as for receptors implicated in the enhancement of cognition and mood and the reduction of negative symptoms (5-HT(7), 5-HT(1A), and alpha(2c)). The objective of the study was to evaluate the safety and efficacy of lurasidone in patients hospitalized for an acute exacerbation of DSM-IV-defined schizophrenia. METHOD: Patients were randomly assigned to 6 weeks of double-blind treatment with a fixed dose of lurasidone 80 mg (N = 90, 75.6% male, mean age = 39.7 years, mean baseline score on the Brief Psychiatric Rating Scale derived from the Positive and Negative Syndrome Scale [BPRSd] = 55.1) or placebo (N = 90, 77.8% male, mean age = 41.9 years, mean BPRSd score = 56.1). The primary efficacy measure was the BPRSd. The study was conducted from May to December 2004. RESULTS: At day 42, last-observation-carried-forward endpoint, treatment with lurasidone was associated with significant improvement compared to placebo on the BPRSd (least squares mean +/- SE = -8.9 +/- 1.3 vs. -4.2 +/- 1.4; p = .012), as well as on all secondary efficacy measures, including the PANSS total score (-14.1 +/- 2.1 vs. -5.5 +/- 2.2; p = .004) and the PANSS positive (-4.3 +/- 0.7 vs. -1.7 +/- 0.7; p = .006), negative (-2.9 +/- 0.5 vs. -1.3 +/- 0.5; p = .025), and general psychopathology (-7.0 +/- 1.1 vs. -2.7 +/- 1.2; p = .0061) subscales. Significant improvement was seen as early as day 3, based on BPRSd, PANSS, and Clinical Global Impressions-Severity of Illness assessments. Treatment with lurasidone was generally well tolerated and was not associated with adverse changes in metabolic or electrocardiogram parameters. There were no clinically significant differences between lurasidone and placebo in objective measures of extrapyramidal symptoms. CONCLUSIONS: The results of this study suggest that the novel psychotropic agent lurasidone is a safe and effective treatment for patients with an acute exacerbation of schizophrenia. TRIAL REGISTRATION: (ClinicalTrials.gov) Identifier: NCT00088634.