U-grooved SIT CMOS technology with 3 fJ and 49 ps (7 mW, 350 fJ)operation

Static induction transistor (SIT) CMOS is analyzed by a circuit simulation method. According to the results, the propagation delay time of the SIT CMOS could be represented as the ratio of the load capacitance to the transconductance. The U-grooved structure plays an important role in the fabrication of MOS SIT with large transconductance and small parasitic capacitance. U-grooved SIT CMOS has been fabricated by anisotropic plasma etching, and its switching speed has been evaluated by a 31-stage ring oscillator. A minimum ρ-τ product of 3 fJ/gate has been obtained for a design rule of 1-μm channel length. A minimum propagation delay time of 49 ps/gate has also been obtained at a dissipation power of 7 mW/gate, which corresponds to a ρ-τ product of 350 fJ/gate     

The switch mechanism of the cell death mode from apoptosis to necrosis in menadione-treated human osteosarcoma cell line 143B cells

Time-dependent changes in the cell death mode from apoptosis to necrosis were studied in cultured 143B cells treated with menadione, an anti-cancerous drug, excluding a possible involvement of "secondary necrosis." The population of apoptotic cells judged by FITC-Annexin V and propidium iodide (PI) double staining reached its maximum at 6 hours after 100 microM menadione treatment followed by an abrupt decrease thereafter, while that of necrotic cells continuously increased reaching 90% at 24 hours. Electron microscopically, cells attached to the culture dish at 6 hours after the treatment consisted of two different types of cells: cells with typical apoptotic features occupying the major population and those with condensed nuclei and swollen cytoplasm. Cells attached to the culture dish at 8 hours after the treatment consisted exclusively of those with condensed nuclei and swollen cytoplasm. Mitochondria in these cells showed various structural changes: those swollen to various degrees with deposition of flocculent densities, or those with highly condensed matrix. Distinct decreases both in intracellular levels of ATP and caspase-3-like activities and remarkable elevations of intracellular levels of superoxide, which were partly suppressed by NAD(P)H oxidase inhibitors, occurred at 6 hours after the treatment. These results may suggest that distinct increases of the intracellular level of superoxide derived from plasma membrane NAD(P)H oxidase besides that from mitochondria have triggered the transition of cell death mode from apoptosis to necrosis. Transition of highly condensed mitochondria to extremely swollen ones may reflect necrotic processes in menadione-treated cells. The present study strongly suggests that time-dependent study is essential using the electron microscopic technique to analyze detailed processes in the changes of the cell death mode.     

Yeast Pho85 kinase is required for proper gene expression during the diauxic shift

The budding yeast Saccharomyces cerevisiae changes its gene expression profile when environmental nutritional conditions are changed. Protein kinases including cyclic AMP-dependent kinase, Snf1 and Tor kinases play important roles in this process. Pho85 kinase, a member of the yeast cyclin-dependent kinase family, is involved in the regulation of phosphate metabolism and reserve carbohydrates, and thus is implicated to function as a nutrient-sensing kinase. Upon depletion of glucose in the medium, yeast cells undergo a diauxic shift, accompanied by a carbon metabolic pathway shift, stimulation of mitochondrial function and downregulation of ribosome biogenesis and protein synthesis. We analysed the effect of a pho85Delta mutation on the expression profiles of the genes in this process to investigate whether Pho85 kinase participates in the yeast diauxy. We found that, in the absence of PHO85, a majority of mitochondrial genes were not properly induced, that proteasome-related and chaperonin genes were more repressed, and that, when glucose was still present in the medium, a certain class of genes involved in ribosome biogenesis (ribosomal protein and rRNA processing genes) was repressed, whereas those involved in gluconeogenesis and the glyoxylate cycle were induced. We also found that PHO85 is required for proper expression of several metal sensor genes and their regulatory genes. These results suggest that Pho85 is required for proper onset of changes in expression profiles of genes responsible for the diauxic shift.     

Ultrastructural basis for the transition of cell death mode from apoptosis to necrosis in menadione-treated osteosarcoma 143B cells

Time-dependent ultrastructural changes of menadione-treated human osteosarcoma 143B cells were correlated with those in their stainability to Annexin V and propidium iodide (PI). Populations of both apoptotic (Annexin V(+)/PI(-)) and necrotic (Annexin V(+)/PI(+)) cells, judged by flow cytometry, began to increase at 2 h after menadione treatment. The former reached a maximum at 6 h followed by abrupt decreases thereafter, while the latter continued to increase. Electron microscopically, cells obtained at 6 h after the menadione treatment consisted of mixed populations of cells with typical apoptotic features and those with a mixture of apoptotic and necrotic features, while cells obtained at 8-24 h consisted exclusively of cells with a mixture of apoptotic and necrotic features. Thus, necrotic cells, as judged by flow cytometry, were in a transitional state of cell death mode from apoptosis to necrosis and are thus designated as 'intermediate cells'. Lack of apoptotic bodies, judged by flow cytometric analysis on sub-G1 nuclei and by electron microscopy in menadione-treated cells, suggested that the transition of cell death mode from apoptosis to necrosis occurred before the apoptotic processes were completed. Effects of N-acetylcysteine and Z-VAD-fmk on menadione-induced ultrastructural changes were also studied.     

Effect of stress on the law of approach to saturation magnetizationin carbon steels

In high fields where the magnetization is approaching saturation, the resolved magnetic polarization I can be expressed by a power series of the inverse of external field H as: I=I_s-b/H ²-c/H³ . . ., or alternatively in terms of the reversible permeability μ_rev=1+(2b/H³+3c/H⁴+ . . .)/μ₀ where I_s is the spontaneous magnetic polarization and b, c, are constants. These equations express the law of approach to saturation magnetization. The coefficient b for a cubic crystal has been deduced as b=0.0762/I_s[K+1.5(λ₁₀₀-λ ₁₁₁)σ]², where σ is the applied stress and others are magnetic constants. The values of reversible permeability μ_rev under biasing field H were measured for carbon steels with applied stresses. The results showed that the square root of 2b changed linearly with the applied stress, The values of magnetic constant K andλ₁₀₀ -λ₁₁₁ were calculated, They agreed with the standard values, but were affected by chemical composition and heat treatment of materials, especially in λ₁₀₀-λ₁₁₁     

An Arabidopsis mutant hypersensitive to red and far-red light signals

A new mutant called psi2 (for phytochrome signaling) was isolated by screening for elevated activity of a chlorophyll a/b binding protein-luciferase (CAB2-LUC) transgene in Arabidopsis. This mutant exhibited hypersensitive induction of CAB1, CAB2, and the small subunit of ribulose-1,5-bisphosphate carboxylase (RBCS) promoters in the very low fluence range of red light and a hypersensitive response in hypocotyl growth in continuous red light of higher fluences. In addition, at high- but not low-light fluence rates, the mutant showed light-dependent superinduction of the pathogen-related protein gene PR-1a and developed spontaneous necrotic lesions in the absence of any pathogen. Expression of genes responding to various hormone and environmental stress pathways in the mutant was not significantly different from that of the wild type. Analysis of double mutants demonstrated that the effects of the psi2 mutation are dependent on both phytochromes phyA and phyB. The mutation is recessive and maps to the bottom of chromosome 5. Together, our results suggest that PSI2 specifically and negatively regulates both phyA and phyB phototransduction pathways. The induction of cell death by deregulated signaling pathways observed in psi2 is reminiscent of retinal degenerative diseases in animals and humans.     

Right ventricular function after aorto-coronary bypass surgery: with relation to the site of right coronary artery occlusion

Postoperative right ventricular function was evaluated serially by thermodilution techniques (REF-1, Edwards Laboratories) in patients who underwent aorto-coronary bypass surgery with uneventful postoperative recovery. The patients were divided into three groups depending on the location of critical stenosis of the right coronary artery. The stenosis was proximal to the right ventricular branch in group I (n = 13), distal to the right ventricular branch but proximal to the acute marginal branch in group II (n = 13) and distal to the acute marginal branch in group III (n = 11). Control (n = 20) consisted of the patients with no significant stenosis of the right coronary artery. Cardiac index, intracardiac pressures and amount of cathecolamin used during postoperative course showed no significant differences among the groups including control. With the use of cathecolamine after surgery, right ventricular ejection fraction (RVEF) rose and right ventricular volumes (RVEDV and RVESV) decreased in all the groups except for group I. These values in group I were unchanged. Thus, there were significant differences in RVEF, RVEDV and RVESV between group I and control. These results mean that right ventricular dysfunction may remain even long after occlusion of the proximal right coronary artery.     

Behavioral recovery in 6-hydroxydopamine-lesioned rats by cotransduction of striatum with tyrosine hydroxylase and aromatic L-amino acid decarboxylase genes using two separate adeno-associated virus vectors

Parkinson's disease (PD) is characterized by the progressive loss of the dopaminergic neurons in the substantia nigra and a severe decrease in dopamine in the striatum. A promising approach to the gene therapy of PD is intrastriatal expression of enzymes in the biosynthetic pathway for dopamine. Tyrosine hydroxylase (TH) catalyzes the synthesis of L-dopa, which must be converted to dopamine by aromatic L-amino acid decarboxylase (AADC). Since the endogenous AADC activity in the striatum is considered to be low, coexpression of both TH and AADC in the same striatal cells would increase the dopamine production and thereby augment the therapeutic effects. In the present study, the TH gene and also the AADC gene were simultaneously transduced into rat striatal cells, using two separate adeno-associated virus (AAV) vectors, AAV-TH and AAV-AADC. Immunostaining showed that TH and AADC were coexpressed efficiently in the same striatal cells in vitro and in vivo. Moreover, cotransduction with these two AAV vectors resulted in more effective dopamine production and more remarkable behavioral recovery in 6-hydroxydopamine (6-OHDA)-lesioned rats, compared with rats receiving AAV-TH alone (p < 0.01). These findings suggest an alternative strategy for gene therapy of PD and indicate that the simultaneous transduction with two AAV vectors can extend their utility for potential gene therapy applications.