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.

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.

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.

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.

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.

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.

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.

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).

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).

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.

Torsion-bar antenna for low-frequency gravitational-wave observations.

We propose a novel type of gravitational-wave antenna, formed by two bar-shaped test masses and laser-interferometric sensors to monitor their differential angular fluctuations. This antenna has a fundamental sensitivity to low-frequency signals below 1 Hz, even with a ground-based configuration. In addition, it is possible to expand the observation band to a lower limit determined by the observation time, by using modulation and up-conversion of gravitational-wave signals by rotation of the antenna. The potential sensitivity of this antenna is superior to those of current detectors in a 1 mHz-10 Hz frequency band and is sufficient for observations of gravitational waves radiated from in-spiral and merger events of intermediate-mass black holes.

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.

Attenuation of hippocampal mossy fiber long-term potentiation by low micromolar concentrations of zinc.

The role of zinc in long-term potentiation (LTP) at hippocampal mossy fiber synapses is controversial because of the contrary results obtained when using zinc chelators. On the basis of the postulation that exogenous zinc enhances the action of zinc released from mossy fibers, mossy fiber LTP after tetanic stimulation (100 Hz, 1 sec) was checked in the presence of exogenous zinc at low micromolar concentrations. Mossy fiber LTP was significantly attenuated in the presence of 5-30 microM ZnCl(2), and the amplitude of field excitatory postsynaptic potentials 60 min after tetanic stimulation was decreased to almost the basal level. Mossy fiber LTP was also attenuated in the presence of 5 microM ZnCl(2) 5 min after tetanic stimulation. The present study is the first to demonstrate that low micromolar concentrations of zinc attenuate mossy fiber LTP. When mossy fiber LTP was induced in the presence of CaEDTA and ZnAF-2 DA, a membrane-impermeable and a membrane-permeable zinc chelator, respectively, extracellular and intracellular chelation of zinc enhanced a transient posttetanic potentiation (PTP) without altering LTP. It is likely that zinc released by tetanic stimulation is immediately taken up into the mossy fibers and attenuates mossy fiber PTP. These results suggest that attenuation of PTP rather than LTP at mossy fiber synapses is a more physiological role for endogenous zinc. Targeting molecules of zinc in mossy fiber LTP seem to be different between during and after LTP induction because of the differential synaptic activity between them.

[Drug delivery to the colon using novel one-step, dry-coated tablets (OSDrC)].

One-step dry-coated tablets (OSDrC), which are useful as colon-targeting drugs, were prepared using Eudragit L 100-55 (Eud-L) and chitosan (Chit) as an outer layer. The lag time of OSDrC with an outer layer of Eud-L : Chit at a ratio of 3 : 1 in each test medium was greater than the gastric emptying time in the first fluid simulating the stomach and was greater than the small intestine transit time in phosphate buffer (pH 7.4) simulating the small intestine. Drug-release profiles of OSDrC were evaluated under test conditions considering the amount of gastric acid and bile acid, as well as the amount of fluid in the colon. The lag time of OSDrC was greater than the gastric emptying time in test medium simulating the stomach and greater than the small intestine transit time in test medium simulating the small intestine, although it was affected by the amount of gastric acid and bile acid. Drug release from OSDrC was completed within the colonic transit time in the test medium simulating the colon, although it was affected by the amount of fluid in the colon. Therefore the prepared OSDrC were found to permit drug delivery to the colon.

Development and evaluation of a novel dry-coated tablet technology for pellets as a substitute for the conventional encapsulation technology.

Pellet formulations as represented by multiparticulate systems are often contained in hard capsules. We examined the use of a different approach to the making of compressed tablets containing pellets, OSDRC-technology. OSDRC-technology employs a double-structure punch (center punch and outer punch) allowing for dry-coated tablets to be assembled in a single run. We examined the effects of the thickness of the outer punch, formability of pellets, and diameter of tablets on pellet filling. The results revealed that thinner outer punches are not always better for filling small tablets with large amounts of pellets. We considered that this was because the core pellets spread in a cone shape within the formulating tablets at filling, requiring a thickness of the outer punch and a particle density of the diluents at which pellets would not exude from the formulating tablets. It was suggested that the formability of core pellets affects the maximum number of layers of pellets, and higher formability would yield better results. However, we found that pellets with poor formability (tensile strength of < or =2 kPa) could be used in tablets. For the tablets, the larger the diameter, the greater the maximum number of layers. We considered this to be due to the friction between the pellets and punch wall. We concluded that OSDRC-technology could be applied to capsule-like forms containing pellets > or =50 wt% through an unconventional approach.

Evaluation of a novel sugar coating method for moisture protective tablets.

A novel method of manufacturing one-step dry-coated (OSDRC) tablets, which we recently invented, was used to produce sugar-coated tablets protected from moisture without the need for a conventional complicated sugar coating process. Amorphous sucrose was selected for the outer layer of the OSDRC tablets as sugar-coated layer. The isothermal crystallization behavior and characteristics such as water vapor permeability, tensile strength, and disintegration time of compressed amorphous sucrose were investigated. Water vapor adsorption measurements showed the crystallization behavior of amorphous tablets to be similar to that of amorphous powder, although it was affected by compression pressure. We found that the crystallized amorphous sucrose after compression at 200 MPa was moisture protective, and the water vapor permeability coefficient was decreased to 1/2000 or less compared with a tablet prepared with a lactose-microcrystalline cellulose (MCC) mixture, hydroxypropylmethylcellulose (HPMC), and sucrose crystal. The water vapor permeability and physicochemical characteristics were influenced by the amorphous content or additive content. It was confirmed that a new sugar-coated tablet using amorphous sucrose and OSDRC technology was moisture protective, therefore, it was concluded that the novel sugar coating method was very useful to obtain a moisture protective tablet.

[Preparation and release profile of colon-targeting drug delivered as novel one-step dry-coated tablets (OSDrC)].

One-Step Dry-Coated tablets (OSDrC) of a colon-targeting drug were prepared using Eudragit L 100-55 (Eud-L) and chitosan (Chit) as the outer layer. Lag time in the 1st fluid, which simulated the stomach, was affected by differences in the pores occurring as a result of Chit dissolution. The dissolution rate of Chit was decreased by the addition of Eud-L. On the other hand, lag times in phosphate buffer (pH 7.4) simulating the small intestine, and in the 2nd fluid simulating the colon, were affected by differences in the pores occurring as a result of Eud-L dissolution and Chit swelling. The lag time of OSDrC with an outer layer of Eud-L:Chit at a ratio of 3:1 in each test medium was greater than the gastric emptying time in the 1st fluid and the small intestine transit time in phosphate buffer (pH 7.4). Furthermore, lag times were similar when test media were changed sequentially. Therefore, it is possible to deliver colon-targeting drugs as OSDrC with an outer layer of Eud-L:Chit at 3:1.

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

Evaluation of novel one-step dry-coated tablets as a platform for delayed-release tablets.

Using a novel one-step dry-coated tablets (OSDRC) manufacturing method, which we have recently invented, we evaluated the possibility of its application to delayed-release tablets. The manufacturing method for OSDRC is different from conventional methods in that dry-coated tablets can be made with only one process. One of the major advantages of OSDRC is that we can expect to produce tablets, which always contain the core exactly in the center of the whole tablet. This characteristic means that the thickness of outer layer is constantly uniform, which is difficult to achieve with the conventional dry-coated tablets. The effects of different outer layer thicknesses and various compression pressures were examined using HPMC to evaluate OSDRC applicability to delayed-release tablets. We proved that the lag-time can be adjusted only by changing the thickness of the outer layer without any arrangement of its ingredients, which is quite different from the conventional approach. Further, the lag-time of each OSDRC prepared in the 100-200 MPa compression pressure range was almost the same, indicating the lag-time of OSDRC under these compression pressures does not vary. The release rate of the drug (acetaminophen) from the OSDRC with 0.5 and 1.0 mm outer layer thicknesses was almost constant independent of compression pressure. On the other hand, the release rate of the OSDRC with a 2.0 mm outer layer thickness was delayed compared to that of other thicknesses. That is, in the tablets with 2.0 mm outer layer thickness, the release rate declined since its outer layer thickness was sufficient to form a gel-layer. In conclusion, OSDRC could be a platform for delayed-release tablets, which do not utilize the conventional method used for dry-coated tablets.