Multifunctional terahertz microscopy for biochemical and chemical imaging and sensing.

Laser-excited terahertz emission microscopy (LTEM) has exhibited great potential for studying the dynamic physical properties of various materials and device evaluation. In this study, an up-to-date version of LTEM, the terahertz chemical microscopy, was developed for biochemical and chemical imaging and sensing. By functionalizing a terahertz semiconductor emitter with an ion-sensitive membrane, a DNA aptamer, and a specific polymer, the change in the terahertz signal amplitude attributed to the surface electrical potential change was successfully detected. Accordingly, the measurement of calcium ions (Ca2+), stress biomarker cortisol, and 2, 4, 6-trinitrotoluene (TNT) explosive was achieved. Measured of charged Ca2+ was via the change in the electrical potential of the ion-sensitive membrane with ion accumulation. For non-charged cortisol and TNT measurements, the surface potential change was recorded by the conformational change of the negatively charged DNA aptamer bound to cortisol and the charge-transfer complex formation between TNT and polyethylenimine polymer, respectively. Moreover, the specificity of this sensing approach was demonstrated by molecular docking and measuring the interfering substances such as sodium ions, potassium ions, brain chemicals histamine and dopamine, and TNT analogues. The results showed that the developed multifunctional terahertz microscopy technique can be used for trace biochemical and chemical sensing via visualization of the terahertz amplitude distribution.

Coherent angular signal amplification using an optical cavity.

Precision angular sensing is an essential technology in physical experiments. Unlike length sensing with a laser beam, it has been thought that sensitivity to the angular motion cannot be enhanced with the help of an optical cavity. A method of angular signal amplification using an optical cavity, called the cavity-amplified angular sensor (CAAS), is proposed. By adjusting or compensating for the Gouy phase of the cavity, the electric field of the laser generated in proportion to the target rotation is coherently stacked in the proposed method. The advantage of this method over other angular sensors is its high sensitivity with the small sensing spot size. Three possible optical configurations are considered, of which two experimentally available ones are investigated. The angular signal amplification is demonstrated for both of them. Based on the theoretical calculation for a realistic model, the fundamental angular sensing noise level is expected to be as low as 10-15rad/Hz1/2, with a 1 mm laser beam size and 10 mW laser power.

Application of long-term collected data for conservation: Spatio-temporal patterns of mortality in Japanese serow.

Monitoring the mortality of wildlife provides basic demographic information to support management plan preparation. The utility of mortality records for conservation measures was investigated in the Japanese serow, focusing on temporal trends and spatial distribution. Using the mortality records of Japanese serow from 2006 to 2018 in Gifu prefecture, cause-specific mortality was categorized into five groups (disease, accident, vehicle collision, parapoxvirus infection, and unknown), and the sex ratios were examined. A state space model was used to analyze the time series for the monthly mortalities, and kernel estimation was used for the spatial distribution of the parapoxvirus infection. Land cover type around the detection point was also reported. Disease, accident, and vehicle collision mortality were similar, and 30% of mortality was of anthropogenic origin. The number of mortality records for males was higher, and the larger home range of males could account for this. The state space model showed moderate increases in monthly mortalities over time and a seasonal variation with the highest level in spring and lowest in winter. Land cover analysis demonstrated a temporal increase in the proportion of human settlement areas, suggesting the change of the Japanese serow habitat. The proximity of Japanese serow to human settlements contributed to increase in mortality records. The point pattern analysis indicated spatial clustering for parapoxvirus infection in the area where an epidemic had occurred in the past. Several measures are recommended; however, mortality records can help develop improved conservation plan.

A comprehensive validation of very early rule-out strategies for non-ST-segment elevation myocardial infarction in emergency departments: protocol for a multicentre prospective cohort study.

INTRODUCTION: Recent advances in troponin sensitivity enabled early and accurate judgement of ruling-out myocardial infarction, especially non-ST elevation myocardial infarction (NSTEMI) in emergency departments (EDs) with development of various prediction-rules and high-sensitive-troponin-based strategies (hs-troponin). Reliance on clinical impression, however, is still common, and it remains unknown which of these strategies is superior. Therefore, our objective in this prospective cohort study is to comprehensively validate the diagnostic accuracy of clinical impression-based strategies, prediction-rules and hs-troponin-based strategies for ruling-out NSTEMIs. METHODS AND ANALYSIS: In total, 1500 consecutive adult patients with symptoms suggestive of acute coronary syndrome will be prospectively recruited from five EDs in two tertiary-level, two secondary-level community hospitals and one university hospital in Japan. The study has begun in July 2018, and recruitment period will be about 1 year. A board-certified emergency physician will complete standardised case report forms, and independently perform a clinical impression-based risk estimation of NSTEMI. Index strategies to be compared will include the clinical impression-based strategy; prediction rules and hs-troponin-based strategies for the following types of troponin (Roche Elecsys hs-troponin T; Abbott ARCHITECT hs-troponin I; Siemens ADVIA Centaur hs-troponin I; Siemens ADVIA Centaur sensitive-troponin I). The reference standard will be the composite of type 1 MI and cardiac death within 30 days after admission to the ED. Outcome measures will be negative predictive value, sensitivity and effectiveness, defined as the proportion of patients categorised as low risk for NSTEMI. We will also evaluate inter-rater reliability of the clinical impression-based risk estimation. ETHICS AND DISSEMINATION: The study is approved by the Ethics Committees of the Kyoto University Graduate School and Faculty of Medicine and of the five hospitals where we will recruit patients. We will disseminate the study results through conference presentations and peer-reviewed journals.

Optical levitation of a mirror for reaching the standard quantum limit.

We propose a new method to optically levitate a macroscopic mirror with two vertical Fabry-Pérot cavities linearly aligned. This configuration gives the simplest possible optical levitation in which the number of laser beams used is the minimum of two. We demonstrate that reaching the standard quantum limit (SQL) of a displacement measurement with our system is feasible with current technology. The cavity geometry and the levitated mirror parameters are designed to ensure that the Brownian vibration of the mirror surface is smaller than the SQL. Our scheme provides a promising tool for testing macroscopic quantum mechanics.

Wetting Induced Oxidation of Pt-based Nano Catalysts Revealed by In Situ High Energy Resolution X-ray Absorption Spectroscopy.

In situ high energy resolution fluorescence detection X-ray absorption spectroscopy (HERFD-XAS) was used to systematically evaluate interactions of H2O and O2 adsorbed on Pt and Pt3Co nanoparticle catalysts in different particle sizes. The systematic increase in oxidation due to adsorption of different species (H2O adsorption

Catalytic Activity of Thiolate-Bridged Diruthenium Complexes Bearing Pendent Ether Moieties in the Oxidation of Molecular Dihydrogen.

Thiolate-bridged diruthenium complexes bearing pendent ethers have been found to work as effective catalysts toward the oxidation of molecular dihydrogen into protons and electrons in water. The pendent ether moiety in the complex plays an important role to facilitate the proton transfer between the metal center and the external proton acceptor.

Blockade of intracellular Zn2+ signaling in the dentate gyrus erases recognition memory via impairment of maintained LTP.

There is no evidence on the precise role of synaptic Zn2+ signaling on the retention and recall of recognition memory. On the basis of the findings that intracellular Zn2+ signaling in the dentate gyrus is required for object recognition, short-term memory, the present study deals with the effect of spatiotemporally blocking Zn2+ signaling in the dentate gyrus after LTP induction and learning. Three-day-maintained LTP was impaired 1 day after injection of clioquinol into the dentate gyrus, which transiently reduced intracellular Zn2+ signaling in the dentate gyrus. The irreversible impairment was rescued not only by co-injection of ZnCl2 , which ameliorated the loss of Zn2+ signaling, but also by pre-injection of Jasplakinolide, a stabilizer of F-actin, prior to clioquinol injection. Simultaneously, 3-day-old space recognition memory was impaired 1 day after injection of clioquinol into the dentate gyrus, but not by pre-injection of Jasplakinolide. Jasplakinolide also rescued both impairments of 3-day-maintained LTP and 3-day-old memory after injection of ZnAF-2DA into the dentate gyrus, which blocked intracellular Zn2+ signaling in the dentate gyrus. The present paper indicates that the blockade and/or loss of intracellular Zn2+ signaling in the dentate gyrus coincidently impair maintained LTP and recognition memory. The mechanism maintaining LTP via intracellular Zn2+ signaling in dentate granule cells, which may be involved in the formation of F-actin, may retain space recognition memory.

Dispersion of Rod-like Particles of Nafion in Salt-Free Water/1-Propanol and Water/Ethanol Solutions.

The dispersion of perfluorinated sulfonic acid ionomers in catalyst inks is an important factor controlling the performance of catalyst layers in membrane electrode assemblies of proton exchange membrane fuel cells (PEMFCs). The effect of water/alcohol composition on the dispersion of H-Nafion in water/1-propanol and water/ethanol solutions was studied by dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and (19)F nuclear magnetic resonance ((19)F NMR) spectroscopy. Hydrodynamic radii calculated from DLS decay profiles and the radii and interparticle distance of rod-like particles derived from SAXS profiles showed almost the same dependence on alcohol concentration. 1-Propanol was more effective than ethanol to induce changes in the characteristic lengths of the rod-like particles. The motional narrowing in the (19)F NMR spectra by addition of 1-propanol indicates selective solvation of the rod-like particles. We suppose this might have decreased their radii and induced their elongation, which eventually led to extension of the ordered regions as observed in the hydrodynamic radii. Our study helps to clarify the dispersion of Nafion in aqueous alcohol solutions, which has implications for the performance of PEMFCs.

Intracellular Zn(2+) signaling in the dentate gyrus is required for object recognition memory.

The role of perforant pathway-dentate granule cell synapses in cognitive behavior was examined focusing on synaptic Zn(2+) signaling in the dentate gyrus. Object recognition memory was transiently impaired when extracellular Zn(2+) levels were decreased by injection of clioquinol and N,N,N',N'-tetrakis-(2-pyridylmethyl) ethylendediamine. To pursue the effect of the loss and/or blockade of Zn(2+) signaling in dentate granule cells, ZnAF-2DA (100 pmol, 0.1 mM/1 µl), an intracellular Zn(2+) chelator, was locally injected into the dentate molecular layer of rats. ZnAF-2DA injection, which was estimated to chelate intracellular Zn(2+) signaling only in the dentate gyrus, affected object recognition memory 1 h after training without affecting intracellular Ca(2+) signaling in the dentate molecular layer. In vivo dentate gyrus long-term potentiation (LTP) was affected under the local perfusion of the recording region (the dentate granule cell layer) with 0.1 mM ZnAF-2DA, but not with 1-10 mM CaEDTA, an extracellular Zn(2+) chelator, suggesting that the blockade of intracellular Zn(2+) signaling in dentate granule cells affects dentate gyrus LTP. The present study demonstrates that intracellular Zn(2+) signaling in the dentate gyrus is required for object recognition memory, probably via dentate gyrus LTP expression.

Enhanced susceptibility to spontaneous seizures of noda epileptic rats by loss of synaptic zn(2+).

Zinc homeostasis in the brain is associated with the etiology and manifestation of epileptic seizures. Adult Noda epileptic rats (NER, >12-week-old) exhibit spontaneously generalized tonic-clonic convulsion about once a day. To pursue the involvement of synaptic Zn(2+) signal in susceptibility to spontaneous seizures, in the present study, the effect of zinc chelators on epileptogenesis was examined using adult NER. Clioquinol (CQ) and TPEN are lipophilic zinc chelotors, transported into the brain and reduce the levels of synaptic Zn(2+). The incidence of tonic-clonic convulsion was markedly increased after i.p. injection of CQ (30-100 mg/kg) and TPEN (1 mg/kg). The basal levels of extracellular Zn(2+) measured by ZnAF-2 were decreased before tonic-clonic convulsion was induced with zinc chelators. The hippocampal electroencephalograms during CQ (30 mg/kg)-induced convulsions were similar to those during sound-induced convulsions in NER reported previously. Exocytosis of hippocampal mossy fibers, which was measured with FM4-64, was significantly increased in hippocampal slices from CQ-injected NER that did not show tonic-clonic convulsion yet. These results indicate that the abnormal excitability of mossy fibers is induced prior to epileptic seizures by injection of zinc chelators into NER. The incidence of tonic-clonic convulsion induced with CQ (30 mg/kg) was significantly reduced by co-injection with aminooxyacetic acid (5-10 mg/kg), an anticonvulsant drug enhancing GABAergic activity, which did not affect locomotor activity. The present paper demonstrates that the abnormal excitability in the brain, especially in mossy fibers, which is potentially associated with the insufficient GABAergic neuron activity, may be a factor to reduce the threshold for epileptogenesis in NER.

New limit on Lorentz violation using a double-pass optical ring cavity.

A search for Lorentz violation in electrodynamics was performed by measuring the resonant frequency difference between two counterpropagating directions of an optical ring cavity. Our cavity contains a dielectric element, which makes our cavity sensitive to the violation. The laser frequency is stabilized to the counterclockwise resonance of the cavity, and the transmitted light is reflected back into the cavity for resonant frequency comparison with the clockwise resonance. This double-pass configuration enables a null experiment and gives high common mode rejection of environmental disturbances. We found no evidence for odd-parity anisotropy at the level of δc/c ≲ 10(-14). Within the framework of the standard model extension, our result put more than 5 times better limits on three odd-parity parameters κ(o+)(JK) and a 12 times better limit on the scalar parameter κ(tr) compared with the previous best limits.

Detecting nonculturable bacteria in the active mycorrhizal zone of the pine mushroom Tricholoma matsutake.

The fungus Tricholoma matsutake forms an ectomycorrhizal relationship with pine trees. Its sporocarps often develop in a circle, which is commonly known as a fairy ring. The fungus produces a solid, compact, white aggregate of mycelia and mycorrhizae beneath the fairy ring, which in Japanese is called a 'shiro'. In the present study, we used soil dilution plating and molecular techniques to analyze the bacterial communities within, beneath, and outside the T. matsutake fairy ring. Soil dilution plating confirmed previous reports that bacteria and actinomycetes are seldom present in the soil of the active mycorrhizal zone of the T. matsutake shiro. In addition, the results showed that the absence of bacteria was strongly correlated with the presence of T. matsutake mycorrhizae. The results demonstrate that bacteria, especially aerobic and heterotrophic forms, and actinomycetes, are strongly inhibited by T. matsutake. Indeed, neither bacteria nor actinomycetes were detected in 11.3% of 213 soil samples from the entire shiro area by culture-dependent methods. However, molecular techniques demonstrated that some bacteria, such as individual genera of Sphingomonas and Acidobacterium, were present in the active mycorrhizal zone, even though they were not detected in soil assays using the dilution plating technique.

Involvement of N-methyl-D-aspartate receptor subunits in zinc-mediated modification of CA1 long-term potentiation in the developing hippocampus.

Zinc is an endogenous N-methyl-D-aspartate (NMDA) receptor blocker. It is possible that zinc-mediated modification of hippocampal CA1 long-term potentiation (LTP) is linked to the expression of NMDA receptor subunits, which varies with postnatal development. In the present study, the effect of ZnCl(2) and CaEDTA, a membrane-impermeable zinc chelator, on CA1 LTP induction was examined in hippocampal slices from immature (3-week-old) and young (6-week-old) rats. Tetanus (10-100 Hz, 1 sec)-induced CA1 LTP was more greatly enhanced in 3-week-old rats. CA1 LTP was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist, and CaEDTA in 3-week-old rats, as in the case of 6-week-old rats reported previously. In 3-week-old rats, on the other hand, 5 µM ZnCl(2) attenuated NMDA receptor-mediated EPSPs more than in 6-week-old rats and significantly attenuated CA1 LTP. Moreover, 5 µM ZnCl(2) significantly attenuated CA1 LTP in the presence of (2R,4S)-4-(3-phosphonopropyl)-2-piperidinecarboxylic acid (PPPA), an NR2A antagonist, in 3-week-old rats, but not that in the presence of ifenprodil, an NR2B antagonist, suggesting that zinc-mediated attenuation of CA1 LTP is associated with the preferential expression of NR2B subunit in 3-week-old rats. In 6-week-old rats, however, 5 µM ZnCl(2) significantly potentiated CA1 LTP and also CA1 LTP in the presence of PPPA. The present study demonstrates that endogenous zinc may participate in the induction of CA1 LTP. It is likely that the changes in expression of NMDA receptor subunits are involved in the zinc-mediated modification of CA1 LTP in the developing hippocampus.

Significance of serum glucocorticoid and chelatable zinc in depression and cognition in zinc deficiency.

Dietary zinc deficiency elicits neuropsychological symptoms and cognitive dysfunction. To pursue the mechanisms of these symptoms, in the present study, the relationship among serum glucocorticoid, chelatable zinc in the synaptic cleft and brain function based on behavior was examined in young rats fed a zinc-deficient diet for 4 weeks. Serum glucocorticoid level was significantly increased in zinc-deficient rats. However, the induction of in vivo dentate gyrus LTP and object recognition memory were not affected in zinc-deficient rats. Chelatable zinc levels were decreased in the stratum lucidum of the hippocampal CA3, but not in the molecular layer of the dentate gyrus. It is reported that dentate gyrus LTP and object recognition memory are affected in clioquinol (30mg/kg)-administered rats, in which chelatable zinc is significantly decreased in the molecular layer of the dentate gyrus. Thus, the significant decrease in chelatable zinc in the molecular layer of the dentate gyrus may be required for object recognition memory deficit in zinc deficiency. On the other hand, the time of grooming in the open-field test was decreased in zinc-deficient rats. Immobility time in the forced swim test was increased in zinc-deficient rats, but not in clioquinol-administered rats, in which chelatable zinc was more markedly decreased than in zinc-deficient rats, suggesting that the lack of chelatable zinc does not increase depression-like behavior. These results suggest that the chronic increase in serum glucocorticoid level is involved in the increase in depression-like behavior rather than the decrease in chelatable zinc after 4-week zinc deficiency.

Transient increase in Zn2+ in hippocampal CA1 pyramidal neurons causes reversible memory deficit.

The translocation of synaptic Zn(2+) to the cytosolic compartment has been studied to understand Zn(2+) neurotoxicity in neurological diseases. However, it is unknown whether the moderate increase in Zn(2+) in the cytosolic compartment affects memory processing in the hippocampus. In the present study, the moderate increase in cytosolic Zn(2+) in the hippocampus was induced with clioquinol (CQ), a zinc ionophore. Zn(2+) delivery by Zn-CQ transiently attenuated CA1 long-term potentiation (LTP) in hippocampal slices prepared 2 h after i.p. injection of Zn-CQ into rats, when intracellular Zn(2+) levels was transiently increased in the CA1 pyramidal cell layer, followed by object recognition memory deficit. Object recognition memory was transiently impaired 30 min after injection of ZnCl(2) into the CA1, but not after injection into the dentate gyrus that did not significantly increase intracellular Zn(2+) in the granule cell layer of the dentate gyrus. Object recognition memory deficit may be linked to the preferential increase in Zn(2+) and/or the preferential vulnerability to Zn(2+) in CA1 pyramidal neurons. In the case of the cytosolic increase in endogenous Zn(2+) in the CA1 induced by 100 mM KCl, furthermore, object recognition memory was also transiently impaired, while ameliorated by co-injection of CaEDTA to block the increase in cytosolic Zn(2+). The present study indicates that the transient increase in cytosolic Zn(2+) in CA1 pyramidal neurons reversibly impairs object recognition memory.

Preparation and evaluation of orally rapidly disintegrating tablets containing taste-masked particles using one-step dry-coated tablets technology.

In this study, in order to address the problems with manufacturing orally rapidly disintegrating tablets (ODT) containing functional (taste masking or controlled release) coated particles, such as the low compactability of coated particles and the rupture of coated membrane during compression, a novel ODT containing taste-masked coated particles (TMP) in the center of the tablets were prepared using one-step dry-coated tablets (OSDrC) technology. As a reference, physical-mixture tablets (PM) were prepared by a conventional tableting method, and the properties of the tablets and the effect of compression on the characteristics of TMP were evaluated. OSDrC was found to have higher tensile strength and far lower friability than PM, but the oral disintegration time of OSDrC is slightly longer than that of PM following high compression pressure. Consequently, OSDrC approaches the target tablet properties of ODT, whereas PM does not. The deformation of TMP in OSDrC due to compression is slight, and the release rate of acetaminophen (AAP) from OSDrC is the same as from TMP. However, TMP on the surface of PM are considerably deformed, and the release rate of AAP from PM is faster than from TMP. These findings suggest that OSDrC technology is a useful approach for preparing ODT containing functional coated particles. Furthermore, we demonstrate that the elastic recovery of tablets can affect differences in the properties of OSDrC, PM and placebo tablets (PC).

Upper limit on gravitational wave backgrounds at 0.2 Hz with a torsion-bar antenna.

We present the first upper limit on gravitational wave (GW) backgrounds at an unexplored frequency of 0.2 Hz using a torsion-bar antenna (TOBA). A TOBA was proposed to search for low-frequency GWs. We have developed a small-scaled TOBA and successfully found Ω(gw)(f)<4.3×10(17) at 0.2 Hz as demonstration of the TOBA's capabilities, where Ω(gw)(f) is the GW energy density per logarithmic frequency interval in units of the closure density. Our result is the first nonintegrated limit to bridge the gap between the LIGO band (around 100 Hz) and the Cassini band (10(-6)-10(-4) Hz).

Zinc-mediated attenuation of hippocampal mossy fiber long-term potentiation induced by forskolin.

The rise in presynaptic calcium induced by high-frequency stimulation activates the calcium-calmodulin-sensitive adenylyl cyclase (AC) 1 followed by the induction of long-term potentiation (LTP) at the hippocampal mossy fiber-CA3 synapse. Zinc is released with glutamate from mossy fiber terminals. However, the role of the zinc in mossy fiber LTP is controversial. In the present study, the mechanism of zinc-mediated attenuation of mossy fiber LTP was examined in that induced by forskolin, an AC activator. Mossy fiber LTP induced by tetanic stimulation (100 Hz for 1 s) was attenuated in the presence of 5 microM ZnCl(2), whereas that induced by forskolin under test stimulation (0.1 Hz) was not attenuated. Forskolin-induced mossy fiber LTP was attenuated by perfusion with 100 microM ZnCl(2) prior to the induction. However, the zinc (100 microM) pre-perfusion did not attenuate mossy fiber LTP induced by Sp-cAMPS, an activator of protein kinase A, under test stimulation. Zinc is necessary to be taken up into mossy fiber boutons for effectively inhibiting AC activity. In hippocampal slices labeled with ZnAF-2 DA, a membrane-permeable zinc indicator, intracellular ZnAF-2 signal was increased during tetanic stimulation in the presence of 5 microM ZnCl(2), but not under test stimulation. Intracellular ZnAF-2 signal was increased under test stimulation in the presence of 100 microM ZnCl(2). These results suggest that zinc taken up into mossy fibers attenuates forskolin-induced mossy fiber LTP via inhibition of AC activity. The significance of endogenous zinc uptake by mossy fibers is discussed focused on tetanus-induced mossy fiber LTP.

Differential effects of zinc influx via AMPA/kainate receptor activation on subsequent induction of hippocampal CA1 LTP components.

Zinc potentiates the induction of NMDA receptor-dependent hippocampal CA1 long-term potentiation (LTP) at low micromolar concentrations, while excessive zinc attenuates it. Homeostasis of synaptic zinc is critical for LTP induction. In the present study, LTP at hippocampal CA1 synapses was analyzed focused on the timing and level of zinc influx into hippocampal cells in hippocampal slices from young rats. Zinc (100 microM) perfusion increased intracellular zinc level and subsequently attenuated CA1 LTP induced by tetanic stimuli at 100 Hz for 1s, which was completely inhibited in the presence of 50 microM APV, an NMDA receptor antagonist. When 10 microM CNQX, an AMPA/kainate receptor antagonist, which reduced zinc influx into hippocampal cells, was perfused prior to the zinc perfusion, the attenuation of CA1 LTP by the zinc perfusion was restored. These results suggest that facilitated zinc influx into hippocampal cells via AMPA/kainate receptor activation is an event to attenuate subsequent induction of NMDA receptor-dependent CA1 LTP. On the other hand, the zinc pre-perfusion also attenuated CA1 LTP induced by 200-Hz tetanus, but not NMDA receptor-independent CA1 LTP induced by 200-Hz tetanus in the presence of APV, suggesting that the induction of NMDA receptor-independent CA1 LTP is less susceptibility to the facilitated zinc influx into hippocampal CA1 cells. Zinc influx via AMPA/kainate receptor activation may differentially act on subsequent induction of CA1 LTP components.