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The recording performance of a new prototype magnetic tape based on perpendicularly oriented strontium ferrite particles is investigated using a 29 nm wide tunneling magnetoresistive reader. At a linear density of 702 kbpi, a post-detection byte-error rate of 2.8e-2 is demonstrated based on measured recording data and a software read channel. The read channel uses a 64-state implementation of an extended version of a data-dependent noise-predictive maximum-likelihood detection scheme that tracks the first and second order statistics of the data-dependent noise. At the demonstrated post-detection byte-error rate, a post-error-correction-coding byte-error rate of less than 1e-20 can be achieved using an iterative decoding architecture. To facilitate aggressive track-density scaling, we made multiple advances in the area of track following. First, we developed a new timing-based servo pattern and implemented a novel quad channel averaging scheme. Second, we developed a new field programmable gate array prototyping platform to enable the implementation of quad channel averaging. Third, we enhanced our low disturbance tape transport with a pair of 20 mm diameter air bearing tape guides and a prototype track-following actuator. Fourth, we developed a novel low friction tape head and finally, we designed a set of tape speed optimized track-following controllers using the model-based H∞ design framework. Combining these technologies, we achieved a position error signal (PES) characterized by a standard deviation ≤ 3.18 nm over a tape speed range of 1.2 to 4.1 m/s. This magnitude of PES in combination with a 29 nm wide reader enables reliable recording at a track width of 56.2 nm corresponding to a track density of 451.9 ktpi, for an equivalent areal density of 317.3 Gb/in2.

The pharmacological activity of DSP-6952, a novel compound was investigated, compared to that of clinically efficacious gastrointestinal (GI) prokinetic 5-hydroxytryptamine 4 (5-HT 4 ) receptor agonists. DSP-6952 had a strong affinity of K i = 51.9 nM for 5-HT 4(b) receptor, and produced contraction in the isolated guinea pig colon with EC 50 of 271.6 nM and low intrinsic activity of 57%, similar to tegaserod and mosapride. In the development of the 5-HT 4 receptor agonists, cardiovascular risk was deliberately evaluated, because some related prokinetics were reported to cause with cardiovascular adverse events, such as ventricular arrhythmias or ischemia. DSP-6952 showed minimal effects up to 100 μM in human ether-a-go-go-related gene (hERG) channels or guinea pig cardiomyocytes. In telemetered conscious monkeys, DSP-6952 did not affect blood pressure or any electrocardiogram (ECG) up to 180 mg/kg, p.o.; however, DSP-6952 transiently increased heart rate, as well as in anesthetized dogs. The positive chronotropic effects of DSP-6952 were completely antagonized by a 5-HT 4 receptor antagonist, and another 5-HT 4 receptor agonist, TD-5108 also increased heart rate. These effects are considered a class effect seen in clinically developing and marketed 5-HT 4 receptor agonists, and have not been regarded as a critical issue in clinical use. DSP-6952 did not induce contraction in the rabbit coronary artery up to 100 μM, which differed from tegaserod or sumatriptan. These results show that DSP-6952 does not have cardiac ischemic risk via coronary vasoconstriction. In conclusion, DSP-6952 is a promising GI prokinetic compound with partial 5-HT 4 receptor agonistic activity as well as a favorable cardiovascular safety profile.

Ectopic foci from pulmonary veins (PVs) comprise the main trigger associated with the initiation of atrial fibrillation (AF). An abrupt anatomical narrow-to-wide transition, modeled as in vitro geometrical patterning with similar configuration in the present study, is located at the junction of PVs and the left atrium (LA). Complex cellular composition, i.e., constituent cell heterogeneity, is also observed in PVs and the PVs-LA junction. High frequency triggers accompanied with anatomical irregularity and constituent cell heterogeneity provoke impaired conduction, a prerequisite for AF genesis. However, few experiments investigating the effects of these factors on electrophysiological properties using human-based cardiomyocytes (CMs) with atrial properties have been reported. The aim of the current study was to estimate whether geometrical patterning and constituent cell heterogeneity under high frequency stimuli undergo conduction disturbance utilizing an in vitro two-dimensional (2D) monolayer preparation consisting of atrial-like CMs derived from human induced pluripotent stem cells (hiPSCs) and atrial fibroblasts (Fbs). We induced hiPSCs into atrial-like CMs using a directed cardiac differentiation protocol with the addition of all-trans retinoic acid (ATRA). The atrial-like hiPSC-derived CMs (hiPSC-CMs) and atrial Fbs were transferred in defined ratios (CMs/Fbs: 100%/0% or 70%/30%) on manually fabricated plates with or without geometrical patterning imitating the PVs-LA junction. High frequency field stimulation emulating repetitive ectopic foci originated in PVs were delivered, and the electrical propagation was assessed by optical mapping. We generated high purity CMs with or without the ATRA application. ATRA-treated hiPSC-CMs exhibited significantly higher atrial-specific properties by immunofluorescence staining, gene expression patterns, and optical action potential parameters than those of ATRA-untreated hiPSC-CMs. Electrical stimuli at a higher frequency preferentially induced impaired electrical conduction on atrial-like hiPSC-CMs monolayer preparations with an abrupt geometrical transition than on those with uniform geometry. Additionally, the application of human atrial Fbs to the geometrically patterned atrial-like hiPSC-CMs tended to further deteriorate the integrity of electrical conduction compared with those using the atrial-like hiPSC-CM alone preparations. Thus, geometrical narrow-to-wide patterning under high frequency stimuli preferentially jeopardized electrical conduction within in vitro atrial-like hiPSC-CM monolayers. Constituent cell heterogeneity represented by atrial Fbs also contributed to the further deterioration of conduction stability.

The pharmacological activity of DSP-6952, a novel compound was investigated, compared to that of clinically efficacious gastrointestinal (GI) prokinetic 5-hydroxytryptamine

Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K(+) channel and Ca(2+) channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2min every 10min for 30min after drug exposure for the vehicle and each drug concentration. IKr and IKs blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca(2+) channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the IKr blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential.

In order to detect and track the small magnet embedded in the vicinity of a target tumor during surgical operation, a magnetic navigation system based on the three-dimensional measurement with micro-fluxgate magnetic sensors was developed. In this paper, we present an image overlay method for superimposing the magnet marker, which is localized by the magnetic navigation system, on the 2D endoscopic view. To evaluate the performance of the proposed system and its applicability in clinical use, we set up an in vivo experiment, in which the surgeons used the system to perform a thoracoscopic surgery on a pig. As a result, the surgeons could operate the partial resection of the target area, which corresponded to the tumor lesions, of the pig lung easily and safely under the guidance of the magnetic navigation system.

In this paper, we report mechanical properties of ZrO2-MgO substrate for thin film magnetic head. Two mechanical properties were measured. One is the tribological property and the other is the slicing resistance. In the tribological property test(so-called "Shoe-Shine Test"), the ZrO2-MgO material showed good result compared with the current material (Al2O3-TiC), and also gave no damages against the magnetic media.On the other hand, the slicing resistance for ZrO2-MgO substrate with less than 84% MgO content was higher two times than for the current material. The sample containing more than 90% MgO, however, showed the same slicing resistance as for the current material. These phenomena were accommodated by the distribution of ZrO2 grains, so that, the low slicing resistance was thought to be due to the separation of each ZrO2 grain. This was also confirmed by measuring the thermal conductivity.

The fracture toughness (KIC) on the major planes of single crystal silicon was measured by the controlled surface flaw (CSF) and indentation fracture (IF) methods at high temperatures. The KIC values obtained by the CSF method for the surface orientations {100}, {110}, {111} and {112} of silicon up to about 500°C decreased with increasing temperature. In the low temperature region, the linear decrease of KIC for {110}, {111}, and {112}, excepting for {100}, was explained on the basis of an elastic model. The KIC values for {100}, {110}, {111} and {112} planes of silicon increased rapidly over the temperatures of 500, 600, 700 and 800°C, respectively.It was found that the rapid KIC increase for those planes of silicon at the individual critical temperatures was attributable to extensive plastic yielding in the vicinity of the crack tips relating the Schmid factor and numbers of slip systems for each planes. The KIC values obtained by the IF method in the range from 400 to 600°C were larger than those obtained by the CSF method for all planes. The trend of increase in KIC values by the former method in the high temperature region agreed with that by the later method.

Fracture toughness (KIC) values were measured on the major planes of single-crystal silicon using the controlled surface flaw (CSF) and indentation fracture (IF) methods at room temperature. The values of KIC on the surface orientations {100}, {110}, {111} and {112} obtained by the CSF method were found to be 1.13, 1.12-1.14, 1.18 and 1.11-1.18MPa·m0.5, respectively. It was found that these KIC values increased slightly with increasing the Young's modulus perpendicular to the fracture surfaces. Though KIC values obtained by the IF method, on the other hand, were scattered significantly (0.82-1.18MPa·m0.5), its Young's modulus dependence was similar to that obtained by CSF method.

In this study, the effects of atropine sulfate (atropine) on swallowing and cough reflex were evaluated in the two experimental models in conscious dogs. To evaluate the effects of atropine on swallowing, 1 mL of marker (contrast medium) was injected into the pharynx under X-ray exposure to induce swallowing. Baclofen, used as a positive control, caused marker congestion in the upper esophagus. In our experimental model, atropine (0.02 and 0.1 mg /kg, i.v.) dose-dependently increased not only the number of marker congestions but also that of the swallows. In addition, atropine significantly shortened the onset of first swallowing. In the evaluation of atropine effects on electrically evoked cough reflex induced by two electrodes implanted into the trachea, atropine strongly inhibited the number of coughs at 0.01 or 0.05 mg/kg accompanied with 0.01 or 0.05 mg/kg per hour (i.v.), respectively. These findings indicate that atropine has the potential of causing aspiration pneumonia through induction of swallowing disorder and inhibition of the cough reflex. Keywords:: swallowing disorder, inhibition of cough reflex, anti-cholinergic agent, dog, aspiration pneumonia

The mechanical, physical, and tribological properties of ZrO2‐Y2O3‐Ta2O5 have been investigated in this article. Under noncontact conditions, the frictional coefficient of the composite was found to be less than 50% of the Al2O3‐TiC material. And, under contact conditions, the damage against the media was less than 0.2 dB, comparable to the ferrite material. The slicing resistance of this material rapidly changed from 1 to 3 mol % Ta2O5 because of its fracture mode. It was found that addition of Ta2O5 stabilizes the tetragonal phase which was found to be unchanged by aging at 200 °C.

To investigate the effect of α- and β-Si3N4 content on the thermal conductivity of silicon nitride ceramics, six samples containing various quantities of α-Si3N4 were prepared by the reaction bonding process and the thermal conductivity of the reaction bonded Si3N4 (RBSN) was measured by the transient hot wire method at various temperatures from room temperature to 1000°C. The RBSN samples containing 1, 25, 33, 45, 55 and 66% α-Si3N4 were produced by nitriding the compacts of pure silicon powder in a nitrogen atmosphere at 1480°C for prescribed periods. Bulk density, true density and total porosity of samples were 2.51±0.02g/cm3, 3.08±0.03g/cm3 and 18.6±1.0%, respectively, regardless of the α-content. No significant change in microstructure of RBSN samples was observed by scanning electron microscopy With an increase in the content of α-Si3N4, the thermal conductivity (λ) of BRSN samples decreased from λ=17.4Wm-1K-1 for the sample with α-Si3N4 of 1% (viz. consisted mainly of β-Si3N4) to λ=9.3Wm-1K-1 for that of 66%. It was considered that the α-Si3N4 solid solutions by which the thermo-elastic wave carrying the heat energy in the non-electro-conductive solid materials such as Si3N4 ceramics is scattered, might be formed with the impurities included in silicon powder as a starting material. The thermal conductivity of all RBSN samples decreased simply with increasing temperature due to the increase of the mutual scattering of the thermo-elastic wave, and the decreasing rate of thermal conductivity for the RBSN with lower α-contents was found to be larger than that for those with higher α-contents.