Oxide thickness dependence of nitridation effects on TDDB characteristics

Wet oxide thicknesses dependence of nitridation effects on electrical characteristics, charge trapping properties and TDDB (Time Dependent Dielectric Breakdown) characteristics have been investigated. It is found that the difference of conduction current between the wet and nitrided wet oxide increases with increasing oxide thickness both for negative and positive bias to the gate until constant current stress is applied. After the stress, with decreasing oxide thickness both in wet and nitrided wet oxide leakage current increases. Up to 60 Å no difference was observed between the wet and nitrided wet oxide but at 50 Å nitrided wet oxide has less increase of current comparing to the wet oxide for the same stress. In wet oxide with increasing stress current density initial hole trap decreases but electron trap increases whereas in nitrided wet oxide has less initial hole trap and also electron trap is less comparing to the wet oxide. Both in wet and nitrided wet oxide for negative bias stress, time to 50 % breakdown decreases with decreasing thickness but at 50 Å a turn-around effect was observed due to nitridation i.e., the 50 % breakdown time is greater for nitrided wet oxide comparing to the wet oxide. On the contrary, for positive bias stress 50 % breakdown time increases with decreasing oxide thickness both in wet and nitrided wet oxide. For positive bias also a turn-around effect is observed at 50 Å i.e., 50% breakdown time is less in nitrided wet oxide comparing to the wet oxide. The improved reliability of nitrided wet oxide at the thin region of 50 Å seems to be due to the increase of more Si---N bond to the interface of oxide and Si comparing to the thick oxide of above 60 Å for the same nitridation conditions.     

Screening the p53 status of human cell lines using a yeast functional assay

We have screened the p53 status of 156 human cell lines, including 142 tumor cell lines from 27 different tumor types and 14 cell lines from normal tissues by using functional analysis of separated alleles in yeast. This assay enables us to score wild-type p53 expression on the basis of the ability of expressed p53 to transactivate the reporter gene HIS3 via the p53-responsive GAL1 promotor in Saccharomyces cerevisiae. Of 142 tumor cell lines, at least 104 lines (73.2%) were found to express the mutated p53 gene: 94 lines (66.2%) were mutated in both alleles, three lines (2.1%) were heterozygous, and no p53 cDNA was amplified from seven lines (4.9%). Of the 14 cell lines originating from normal tissues, all the transformed or immortalized cell lines expressed mutant p53 only. Yeast cells expressing mutant p53 derived from 94 cell lines were analyzed for temperature-sensitive growth. p53 cDNA from eight cell lines showed p53-dependent temperature-sensitive growth, growing at 30 degrees C but not at 37 degrees C. Four temperature-sensitive p53 mutations were isolated: CAT-->CGT at codon 214 (H214R), TAC-->TGC at codon 234 (Y234C), GTG-->ATG at codon 272 (V272M), and GAG-->AAG (E285K). Functionally wild-type p53 was detected in 38 tumor cell lines (26.8%) and all of the diploid fibroblasts at early and late population doubling levels. These results strongly support the previous findings that p53 inactivation is one of the most frequent genetic events that occurs during carcinogenesis and immortalization.     

Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation

We have studied mechanisms by which leptin overexpression, which reduces body weight via anorexic and thermogenic actions, induces triglyceride depletion in adipocytes and nonadipocytes. Here we show that leptin alters in pancreatic islets the mRNA of the genes encoding enzymes of free fatty acid metabolism and uncoupling protein-2 (UCP-2). In animals infused with a recombinant adenovirus containing the leptin cDNA, the levels of mRNAs encoding enzymes of mitochondrial and peroxisomal oxidation rose 2- to 3-fold, whereas mRNA encoding an enzyme of esterification declined in islets from hyperleptinemic rats. Islet UCP-2 mRNA rose 6-fold. All in vivo changes occurred in vitro in normal islets cultured with recombinant leptin, indicating direct extraneural effects. Leptin overexpression increased UCP-2 mRNA by more than 10-fold in epididymal, retroperitoneal, and subcutaneous fat tissue of normal, but not of leptin-receptor-defective obese rats. By directly regulating the expression of enzymes of free fatty acid metabolism and of UCP-2, leptin controls intracellular triglyceride content of certain nonadipocytes, as well as adipocytes.     

Giant calcifying epithelioma of Malherbe (pilomatrixoma): imaging features

We present a case of giant calcifying epithelioma of Malherbe (pilomatrixoma) in the right upper arm of a 62-year-old man. It measured 18 x 12 x 8 cm in size, making it the largest of all the cases reported previously. CT clearly demonstrated a well-defined, subcutaneous mass with amorphous calcifications. The mass showed intermediate signal intensity on T2*-weighted MR images and slight contrast uptake on contrast-enhanced MR images. Histopathologically, this tumor showed no aggressive or malignant nature. The patient is without evidence of recurrence or metastasis 3 years following the resection.     

A modularized framework for solving an economic–environmental power generation mix problem

This paper presents a modularized simulation modelling framework for evaluating the impacts on economic cost and CO₂ emissions resulting from the introduction of a solid oxide fuel cell (SOFC) system into the existing mix of centralized power generation technologies in Japan. The framework is comprised of three parts: a dual‐objective linear programming model that solves the generation best‐mix problem for the existing power generation technologies; a nonlinear SOFC system model in which the economic cost and CO₂ emissions by the SOFC system can be calculated; and the Queuing Multi‐Objective Optimizer (QMOO), a multi‐objective evolutionary algorithm (MOEA) developed at the EPFL in Switzerland as the overall optimizer of the combined power supply system. Thus, the framework integrates an evolutionary algorithm that is more suitable for handling nonlinearities with a calculus‐based method that is more efficient in solving linear programming problems. Simulation experiments show that the framework is successful in solving the stated problem. Moreover, the three components of the modularized framework can be interconnected through a platform‐independent model integration environment. As a result, the framework is flexible and scalable, and can potentially be modified and/or integrated with other models to study more complex problems. Copyright © 2004 John Wiley & Sons, Ltd.     

Induction of apoptosis in HEp-2 cells by infection with herpes simplex virus type 2

Although herpes simplex virus type 1 (HSV-1) does not induce apoptosis in infected HEp-2 cells, herpes simplex virus type 2 (HSV-2) did induce apoptosis in a small but significant fraction of the same cells. Apoptosis was not observed in Vero or HeLa cells infected with HSV-2. In addition, HSV-2 infection in the presence of cycloheximide induced extensive apoptosis of HEp-2 or HeLa cells.     

Concentration-dependent block of sodium current in guinea pig ventricular myocytes by a class III antiarrhythmic agent, MS-551

The 32P-post-labelling assay for DNA adduct quantification gives the opportunity to examine endogenous exposure to DNA reactive compounds. Most human biomonitoring studies applied white blood cells (WBC) or cells obtained by broncho-alveolar lavages (BAL) as source of DNA, but still it is not clear what cell type represents the most reliable indicator for exposure to cigarette smoke-associated genotoxins. At first, we examined DNA adduct levels by means of nuclease P1 (NP1) enriched 32P-post-labelling in separated WBC subpopulations after in vitro incubations for 18 h with 10 microM benzo[a]pyrene (B[a]P). DNA adduct levels were highest in monocytes (10.7 +/- 2.9 adducts/10(8) nucleotides, n = 8), followed by lymphocytes (5.9 +/- 1.7, n = 8), and granulocytes (0.5 +/- 0.2, n = 8). Secondly, aromatic-DNA adduct levels were determined in BAL cells and WBC-subsets from (non-)smoking volunteers. In smoking individuals, adduct levels were in the ranking order: BAL cells (3.7 +/- 1.0, n = 5) > monocytes (2.0 +/- 0.5, n = 8) > or = lymphocytes (1.6 +/- 0.4, n = 8) > granulocytes (0.8 +/- 0.2, n = 8) by NP1-enrichment and monocytes (9.0 +/- 3.2, n = 5) > or = lymphocytes (8.0 +/- 2.1, n = 6) > granulocytes (2.1 +/- 0.3, n = 7) by butanol-enriched 32P-post-labelling. Aromatic-DNA adduct levels were significantly higher in WBC-subsets of smokers as compared with non-smokers, except for DNA adducts in granulocytes using butanol enrichment. Thirdly, dose-response relationships were investigated in mononuclear white blood cells (MNC, i.e. monocytes plus lymphocytes) and BAL-cells of a larger group of smoking individuals (n = 78). Adduct levels in MNC were related to daily exposure to cigarette-tar (r = 0.31, P < 0.01). Adduct levels in BAL cells seemed to be correlated with pack-years, but after correction for age this relationship was lost. Butanol extraction resulted in 5-6-fold higher DNA adduct levels in MNC, whereas butanol extraction of BAL-DNA of the same individuals yielded only 2-fold higher adduct levels. The two enrichment procedures of 32P-post-labelling were correlated in BAL cells (r = 0.86, P < 0.001, n = 12). We conclude that particularly MNC are good surrogates for the detection of smoking-related DNA adducts.     

Effects of short duration morning bright light in healthy elderly. II: sleep and motor activity

Subjective sleep feelings and motor activity were measured in seven healthy elderly subjects for 6 days. The subjects were exposed to bright light (6000 lux) for 30 min in the morning or instructed to sit in front of a desktop lighting device without light. The average level of motor activity during the night was significantly decreased in the bright light condition, compared with the controlled condition. However, daytime motor activity did not show significant differences between the two conditions. From these findings, even a short duration of morning bright light is effective in maintaining sleep without changing daytime activity.     

Small cell lung cancer associated with subacute sensori-motor neuropathy in a patient whose symptoms subsided during chemotherapy

A 71-year-old man was referred to us with diplopia, left peripheral facial nerve dysfunction, ataxic gait and dysesthesia of the extremities. Neurological examination revealed mild reduction of sensation to pinprick and light touch in the left dominant lower leg. His standing position was wide based, and he showed Romberg's sign. The patient also presented signs of left peripheral facial, bilateral abducent, and left oculomotor nerve dysfunction. Serum levels of CEA, CA 19-9, and proGRP were high. 67Gallium scintigraphy showed an accumulation of radioactivity at the hilum of the right lung, and the findings of bronchofiberscopy were compatible with the diagnosis of small cell lung cancer. Because the symptoms gradually worsened to the point that the patient could not move by himself, chemotherapy and radiotherapy were initiated 3 months after the onset of symptoms. While under chemotherapy, symptoms of neuropathy subsided and the patient was able to walk with the aid of a walking stick. Although all symptoms were indicative of carcinomatous neuropathy, no antineuronal antibodies were detected in the patient's serum by immunohistochemical techniques. However, because the lung cancer deteriorated gradually despite therapy, the patient died of respiratory failure. At autopsy, tumor metastases were found in the pericardium, left lung, both adrenal glands, right hilum lymph nodes, and mediasternal lymph nodes. No microscopic signs of metastases were found in the frontal, parietal, temporal, or occipital lobes, or in the basal ganglia, thalamus, midbrain, pons, cerebellar vermis and hemispheres, or upper medulla. Histopathologically, there was no degeneration of neuronal cell bodies in cerebellar or cervical dorsal root ganglia; however, almost total loss of myelinated fibers or variegated demyelination of myelinated fibers was observed in the anterior, lateral and posterior funiculus at both cervical segments of the spinal cord. The number of myelinated fibers was smaller in the 5th and 6th cervical left ventral roots. The reason why the patient's symptoms subsided during chemotherapy was probably a suppression of antineuronal antigen by chemotherapy and the repair of myelinated fibers.     

Expression of costimulatory molecules, B7-1 and B7-2 on human gastric carcinoma

Costimulation of T cells via B7-1 and B7-2 molecules on a tumor has been shown to be important for eliciting cell-mediated antitumor immunity. We studied the surface expression of B7-1 and B7-2 in 24 cases of gastric carcinoma from the primary locus, 20 cases of metastatic carcinoma from malignant ascites, 20 cases of benign gastric mucosa and 7 gastric carcinoma cell lines by two-color flow cytometry with mAb CD80 and CD86. The B7-1 and B7-2 molecules were expressed by 6 cell lines, and 1 cell line showed the predominant expression of B7-2 but not B7-1. Almost all patients with primary gastric carcinoma and benign gastric mucosa showed high levels of expression of the B7-1 and B7-2, revealing approximately 40%-60% positive cells. However, the percentage of B7-1-positive cells of poorly differentiated primary carcinomas was significantly lower than that of well-differentiated carcinoma and normal mucosa (P < 0.01). Furthermore, all of the metastatic carcinoma cells revealed consistently very low or undetectable levels of expression of the B7-1 molecule, only 8% (mean) of cells being positive, despite showing higher levels of B7-2 expression. Thus, it seems likely that decreased or deleted expression of B7-1 correlates with the grade of tumor differentiation, tumor progression and metastasis. These results suggest that the B7-1 molecule on the gastric carcinoma bearing CD80+CD86+ is abrogated during tumor invasion and/or metastasis, and the tumor finally acquires the CD80-CD86+ phenotype. Consequently, inadequate B7-1 costimulation may contribute to the escape of tumors from destruction by the host's immune system.