As an increasing number of non‐cardiac drugs have been reported to cause QT interval prolongation and torsades de pointes (TdP), we extensively studied the utility of atrioventricular (AV) block ...animals as a model to predict their torsadogenic action in human. The present review highlights such in vivo proarrhythmia models. In the case of the canine model, test substances were administered p.o. at conscious state >4 weeks after the induction of AV block, with subsequent Holter ECG monitoring to evaluate drug effects. Control AV block dogs (no pharmacological treatment) survive for several years without TdP attack. For pharmacologically treated dogs, drugs were identified as high, low or no risk. High‐risk drugs induced TdP at 1–3 times the therapeutic dose. Low‐risk drugs did not induce TdP at this dose range, but induced it at higher doses. No‐risk drugs never induced TdP at any dose tested. Electrophysiological, anatomical histological and biochemical adaptations against persistent bradycardia‐induced chronic heart failure were observed in AV block dogs. Recently, we have developed another highly sensitive proarrhythmia model using a chronic AV block cynomolgus monkey, which possesses essentially the same pathophysiological adaptations and drug responses as those demonstrated in the canine model. As a common remodelling process leading to a diminished repolarization reserve may present in patients who experience drug‐induced TdP and in the AV block animals, the in vivo proarrhythmia models described in this review may be useful for predicting the risk of pharmacologically induced TdP in humans.
British Journal of Pharmacology (2008) 154, 1528–1537; doi:fn1; published online 16 June 2008
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Neuronal intranuclear inclusion disease is a neurodegenerative disorder pathologically characterized by eosinophilic hyaline intranuclear inclusions. A high-intensity signal along the ...corticomedullary junction on DWI has been described as a specific MR imaging finding of the cerebrum in neuronal intranuclear inclusion disease. However, MR imaging findings of the cerebellum in neuronal intranuclear inclusion disease have not been fully evaluated. Here, we review MR imaging findings of the cerebellum in a series of 8 patients with pathologically confirmed neuronal intranuclear inclusion disease. The MR imaging results showed cerebellar atrophy (8/8 patients) and high-intensity signal on FLAIR images in the medial part of the cerebellar hemisphere right beside the vermis (the "paravermal area") (6/8) and in the middle cerebellar peduncle (4/8). The paravermal abnormal signals had a characteristic distribution, and they could be an indicator of the diagnosis of neuronal intranuclear inclusion disease even when using the results of past MR imaging examinations in which DWI findings were not examined.
Electroless deposition (ELD) is a well-known method for preparing thin films of metals and their alloys. It is a highly selective method allowing additive patterning of isolated and embedded ...structures on insulating substrates, e.g. glass, plastic or ceramic. It is a relatively low temperature (less than the boiling point of the electrolyte) and low cost process compared to other physical and chemical vapor deposition methods. ELD features uniform and normally conformal deposition (additives may affect its conformality) with low defect density and some unique material properties. In the last 30 years electroless plating of metals (e.g. copper, gold, nickel, cobalt, palladium, iron, silver, etc.) and their alloys, was demonstrated for micro system applications: microelectronics, micro electro mechanics, micro electro optics and micro-fluidics, micro fuel cells, micro batteries etc. Electroless plating was also demonstrated on nano structures, both artificial and natural. In this paper we present a short tribute to the recent advances in electroless plating in the last 30 years. Those advances and innovations are due to the work of many scientists and engineers on a time span started in the 19th century. The progress in electroless plating followed the need and the trend for better metallization technologies for complex structures with critical dimensions that had been shrinking continuously in the last few decades.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Eutectic Ag
3
Sn can grow with a variety of morphologies depending on the solidification conditions and plays an important role in the performance of Pb-free solders. Here, we study morphology ...transitions in the
β
-Sn + Ag
3
Sn eutectic at increasing growth velocity using a combination of real-time X-ray imaging and analytical electron microscopy. Orthorhombic Ag
3
Sn grew as faceted plates or rods with 010 growth direction and (001) as the largest facet in all three eutectic growth morphologies: Irregular plate, broken-lamellar, and rod. Reproducible
β
-Sn + Ag
3
Sn orientation relationships formed for the latter two morphologies. The mechanisms of spacing adjustment and the reversible transition from plate to rod growth are studied for transient solidification after velocity changes. The transition from fully eutectic growth to
β
-Sn dendrites plus eutectic is reasonably reproduced using a competitive growth criterion. At the highest velocities, Ag
3
Sn rods developed perturbations whose break down into particles is discussed in terms of unsteady growth and pinch-off mechanisms.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In situ observations of the reaction between solid Cu in contact with molten Sn–0.7wt.% Cu were achieved using a synchrotron X-ray imaging technique. It was found that, upon wetting, the rapid ...dissolution of Cu adjacent to the solid–liquid interface was followed by near-instantaneous interfacial intermetallic compound (IMC) formation. The kinetics of IMC formation were also elucidated. The results provide direct experimental evidence of the sequence of events in the dissolution reaction and subsequent diffusion, and in particular of the growth mechanisms of the IMC layer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Hydrogen clusters with diameters of a few micrometer range, composed of 10
hydrogen molecules, have been produced for the first time in an expansion of supercooled, high-pressure hydrogen gas into a ...vacuum through a conical nozzle connected to a cryogenic pulsed solenoid valve. The size distribution of the clusters has been evaluated by measuring the angular distribution of laser light scattered from the clusters. The data were analyzed based on the Mie scattering theory combined with the Tikhonov regularization method including the instrumental functions, the validity of which was assessed by performing a calibration study using a reference target consisting of standard micro-particles with two different sizes. The size distribution of the clusters was found discrete peaked at 0.33 ± 0.03, 0.65 ± 0.05, 0.81 ± 0.06, 1.40 ± 0.06 and 2.00 ± 0.13 µm in diameter. The highly reproducible and impurity-free nature of the micron-size hydrogen clusters can be a promising target for laser-driven multi-MeV proton sources with the currently available high power lasers.
Granulomatous lesions were observed in the swim bladder, kidney, spleen and gills of two farmed Japanese pufferfish (Takifugu rubripes) infected with Mycobacterium chelonae. Three types of lesions ...were noted: unencapsulated clusters of epithelioid cells without central necrosis (type 1), encapsulated granulomas without central necrosis (type 2) and encapsulated granulomas with central necrosis (type 3). Type 3 lesions occurred most frequently in the swim bladder, while type 1 and type 2 lesions occurred frequently in the kidney and spleen, and the gills exhibited mostly type 1 lesions. This suggests that the lesions in the swim bladder were more fully developed than those occurring elsewhere and that the swim bladder may be more susceptible to infection with M. chelonae. This is the first report describing the histopathological features of M. chelonae infection in Tetraodontidae.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Background Forced oscillometry is a non-invasive method to measure respiratory resistance and reactance. In this study, we investigated the characteristics of measurements obtained with an ...impulse oscillation system (IOS) for patients with interstitial lung disease (ILD). Method IOS and spirometry were performed in 64 ILD patients, 54 asthma patients, 49 chronic obstructive pulmonary disease (COPD) patients, and 29 controls. Respiratory resistance and reactance were assessed as measurements averaged over several tidal breaths (whole-breath analysis) and as measurements separately averaged during inspiration and expiration (inspiratory–expiratory analysis). Results Whole-breath IOS analyses for ILD patients showed increased resistance at 5 Hz and decreased reactance at 5 Hz (X5) compared with controls, although these features were also found in asthma and COPD patients. Inspiratory–expiratory analysis demonstrated that the changes in X5 and reactance area (AX) between inspiration and expiration (ΔX5 and ΔAX, respectively) were significantly different from those in asthma patients, COPD patients, and controls. However, multiple linear regression analysis showed that the presence of ILD was independently associated with ΔX5, but not with ΔAX. Furthermore, ΔX5 was inversely correlated with vital capacity and diffusing capacity of carbon monoxide in ILD patients. Conclusions Our results suggest that ΔX5 is a characteristic feature of IOS measurements in ILD patients, which is clearly different from those in asthma and COPD patients. This within-breath X5 change in ILD might be associated with its severity and physiological abnormality, although further studies are needed to investigate its cause.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
► Semi-solid ultra steel was deformed during time resolved synchrotron X-ray imaging. ► Globule rearrangement involving dilation was the main deformation mechanism. ► Agglomeration influenced ...rearrangement by increasing the effective size of structural units.
The dynamics of globule motion are studied in situ during the deformation of globular semi-solid steel (Fe–2C–0.9Mn–0.5Si in mass%). Samples with globular morphology and 55–65% effective solid fraction were deformed in direct shear at a shear rate of ∼10
−3
s
−1 during time-resolved synchrotron X-ray imaging. Globule rearrangement involving dilation was the main deformation mechanism. Agglomeration is shown to significantly influence rearrangement by increasing the effective size of structural units.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Metastable Sn-NiSn4 eutectic can form in electronic solder joints and is a reliability concern. Here the competition between stable Sn-Ni3Sn4 and metastable Sn-NiSn4 eutectic growth is studied during ...unidirectional solidification. The stable and metastable eutectic points are measured, the dynamics of eutectic growth and the transition between the two eutectics is investigated by synchrotron radiography, and the crystallography of eutectic growth is measured by EBSD. It is shown that the Sn-Ni3Sn4 eutectic has a highly irregular morphology with diverging and converging rods because monoclinic Ni3Sn4 grows only along 010 without a reproducible orientation relationship (OR) with Sn. The metastable Sn-NiSn4 eutectic has a more regular broken-lamellar morphology and a reproducible OR with Sn. The critical velocity between the two eutectics is less than 1 μm/s which is discussed in terms of the small temperature difference between the two eutectic points and the kinetic growth advantages of the metastable eutectic.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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