Proteases are known to be involved in the apoptotic pathway. We report here that benzyloxycarbonyl (Z)-Leu-Leu-leucinal(ZLLLal), a leupeptin analogue, can induce apoptosis in MOLT-4 and L5178Y cells. ZLLLal is a cell-permeant inhibitor of proteasome. Among the protease inhibitors tested, only calpain inhibitor I (acetyl-Leu-Leu-norleucinal) and ZLLLal caused a marked induction of apoptosis in MOLT-4 cells. In contrast Z-Leu-leucinal, a specific inhibitor of calpain, did not induce apoptosis. When MOLT-4 cells were incubated in the presence of ZLLLal, p53 accumulated in the cells. These results strongly suggest that inhibition of proteasome induces p53-dependent apoptosis and that proteasome can protect cell from apoptosis.

Discrete element method (DEM) is a useful tool for obtaining details of mixing processes at a particle scale. It has been shown to satisfactorily describe the flow structure developed in bladed mixers. Here, the advantage is taken of the microstructure gained from DEM to evaluate how best to quantify the microstructure created by mixing. A particle-scale mixing index (PSMI) is defined based on coordination numbers to represent the structure of a particle mixture. The mixture quality is then analyzed qualitatively and quantitatively in three different ways: a macroscopic mixing index based on the conventional approach, coordination number, and PSMI. Their effectiveness is examined based on DEM data generated for different particle loading arrangements and binary mixtures of particles with various volume fractions, size ratios, and density ratios. Unlike the two other methods, PSMI reveals in a straightforward manner whether a binary mixture of different particles is mixing or segregating over time, while being able to detect particle-scale structural changes accompanying the mixing or segregation processes in all the mixtures investigated. Moreover, PSMI is promising in that it is not influenced by the size and number of samples, which afflict conventional mixing indexes.

The contribution of indirect action mediated by OH radicals to cell inactivation by ionizing radiations was evaluated for photons over the energy range from 12.4 keV to 1.25 MeV and for heavy ions over the linear energy transfer (LET) range from 20 keV/microm to 440 keV/microm by applying competition kinetics analysis using the OH radical scavenger DMSO. The maximum level of protection provided by DMSO (the protectable fraction) decreased with decreasing photon energy down to 63% at 12.4 keV. For heavy ions, a protectable fraction of 65% was found for an LET of around 200 keV/microm; above that LET, the value stayed the same. The reaction rate of OH radicals with intracellular molecules responsible for cell inactivation was nearly constant for photon inactivation, while for the heavy ions, the rate increased with increasing LET, suggesting a reaction with the densely produced OH radicals by high-LET ions. Using the protectable fraction, the cell killing was separated into two components, one due to indirect action and the other due to direct action. The inactivation efficiency for indirect action was greater than that for direct action over the photon energy range and the ion LET range tested. A significant contribution of direct action was also found for the increased RBE in the low photon energy region.

Reliable, noninvasive imaging modalities to characterize plaque components are clinically desirable for detecting unstable coronary plaques, which cause acute coronary syndrome. Although recent clinical developments in computed tomography (CT) have enabled the visualization of luminal narrowing and calcified plaques in coronary arteries, the identification of noncalcified plaque components remains difficult. Phase-contrast X-ray CT imaging has great potentials to reveal the structures inside biological soft tissues, because its sensitivity to light elements is almost 1,000 times greater than that of absorption-contrast X-ray imaging. Moreover, a specific mass density of tissue can be estimated using phase-contrast X-ray CT. Ex vivo phase-contrast X-ray CT was performed using a synchrotron radiation source (SPring-8, Japan) to investigate atherosclerotic plaque components of apolipoprotein E-deficient mice. Samples were also histologically analyzed. Phase-contrast X-ray CT at a spatial resolution of 10 -20 m revealed atherosclerotic plaque components easily, and thin fibrous caps were detected. The specific mass densities of these plaque components were quantitatively estimated. The mass density of lipid area was significantly lower (1.011 Ϯ 0.001766 g/ml) than that of smooth muscle area or collagen area (1.057 Ϯ 0.001407 and 1.080 Ϯ 0.001794 g/ml, respectively). Moreover, the three-dimensional assessment of plaques could provide their anatomical information. Phasecontrast X-ray CT can estimate the tissue mass density of atherosclerotic plaques and detect lipid-rich areas. It can be a promising noninvasive technique for the investigation of plaque components and detection of unstable coronary plaques. synchrotron radiation; atherosclerotic plaque component; tissue-mass density of plaque component ATHEROSCLEROSIS IS A SYSTEMIC disease in which the clinical manifestations weakly correlate with its extent and with the severity of luminal stenosis. Coronary plaque disruption and subsequent thrombosis in coronary atherosclerosis lead to a potentially life-threatening disease, acute coronary syndrome (11,15). Clinical evidence suggests that atherosclerotic plaque components are important predictors of plaque stability and clinical events. The risk of plaque rupture appears to depend on the plaque components rather than the severity of stenosis.Most ruptures occur in "unstable" plaques containing a soft lipid-rich core, covered by a thin and inflamed cap of fibrous tissue (39).Invasive techniques, such as coronary angiography, intravascular ultrasound, and optical coherent tomography, can reveal the luminal diameter or stenosis, wall thickness, and plaque volume and components (16). However, to detect an unstable plaque that leads to acute coronary syndrome, reliable, noninvasive imaging modalities for the characterization of plaque components are clinically desirable. Currently, two emerging and promising techniques, namely, computed tomography (CT) and magnetic resonance imaging (MRI), are widely accepted by the medic...