Noise contribution of the body resistance in partially-depleted SOIMOSFETs

An additional noise component is observed in the noise spectrum of transistors in a partially-depleted (PD) medium-thickness SOI-CMOS technology. We identify the origin of this additional noise in the noisy resistance of the body film. This resistance, coupled to the gate capacitance, forms an RC filter and generates the hump-shape of the additional noise component. Several experimental observations that support this model are presented     

Nonlinear conductivity and current-voltage characteristics of two-dimensional semiconductor superlattices

Electron transport and heating in a two-dimensional semiconductor superlattice with arbitrary orientation of the field (current) relative to the crystallographic axes is investigated in the approximation of constant energy and velocity relaxation times with electron-electron collisions taken into account. The nonlinear conductivity, average electron energies, and interrelationship between field direction and the current excited by it in an unbounded superlattice, as well as the current-voltage characteristics and the transverse electromotive force of a superlattice of finite width are found. Fiz. Tekh. Poluprovodn. 31, 308–310 (March 1997)     

Application of gene gun for local-regional cancer

We studied the in vivo gene transfusion using a gene gun, formerly used in plants and culture cells. The hand-held type gene gun (Helios Gene Gun System) is simple and convenient for effective gene transfection in living animals. This method has some advantages in that there is no need for use of viral vector, independence on the cell cycle and local inducement of plural genes. There is a great possibility for application to local-regional cancer.     

Memory beyond the hippocampus

Cultured hepatocytes of silver eel actively secreted only chylomicron-like lipoprotein. The rate of secretion per mg cellular protein per 24 hr was 2.2 times higher compared with that by yellow eel hepatocytes. Silver eel hepatocytes secreted lipids 2.5 times higher through the lipoprotein than yellow eel hepatocytes. Main lipid was triacylglycerol in either secreted lipoprotein and composition of apolipoproteins of both secreted lipoproteins was the same. The incorporation of 3H-leucine into the lipoprotein secreted by silver eel hepatocytes was 2.4 times higher, but that of 14C-acetate was not significantly different. Protein and lipids composition of plasma lipoproteins of silver eel was significantly higher and lower compared with those of yellow eel, respectively. We suggest that the secreted lipoprotein of silver eel hepatocytes transport much more lipids to other tissues than that of yellow eel hepatocytes.     

Diversity of pituitary cells in primary cell culture. An immunocytochemical study

A bioassay system for rapid detection of carcinogenic agents has been developed using male Fischer 344 rats to bridge the gap between long-term carcinogenicity tests and short-term screening assays. The system, called the medium-term liver bioassay, is fundamentally based on the 2-stage hypothesis of tumor production, employing initiation by diethylnitrosamine (200 mg/kg, i.p.) in the first stage and test chemical administration during the second, in combination with two-thirds partial hepatectomy. It requires only 8 wk for animal experimentation and a further few weeks for quantitative analysis of immunohistochemically demonstrated glutathione S-transferase placental form positive hepatic foci. A total of 291 chemicals/substances have already been analyzed in our laboratory. Among 63 chemicals that were proved to be carcinogenic in the liver of rat and/or mouse, 57 (90%) gave positive results irrespective of their mutagenicity. Negative compounds include peroxisome proliferators and tamoxifen. Even nonhepatocarcinogens were positive at a rate of 24%. Eighty-six percent (12/14) of mouse liver carcinogens were also positive. On the other hand, only 2 out of 45 noncarcinogens showed very weak positivity. Thus, the efficacy of the system for hepatocarcinogens has been well established. This bioassay is increasingly regarded as an appropriate alternative test for carcinogenicity risk assessment and is practically used for a rapid evaluation of hepatocarcinogenicity of chemicals.     

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia

PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.     

The molecular interaction of Fas and FAP-1. A tripeptide blocker of human Fas interaction with FAP-1 promotes Fas-induced apoptosis

Fas (APO-1/CD95), which is a member of the tumor necrosis factor receptor superfamily, is a cell surface receptor that induces apoptosis. A protein tyrosine phosphatase, Fas-associated phosphatase-1 (FAP-1), that was previously identified as a Fas binding protein interacts with the C-terminal 15 amino acids of the regulatory domain of the Fas receptor. To identify the minimal region of the Fas C-terminal necessary for binding to FAP-1, we employed an in vitro inhibition assay of Fas/FAP-1 binding using a series of synthetic peptides as well as a screen of random peptide libraries by the yeast two-hybrid system. The results showed that the C-terminal three amino acids (SLV) of human Fas were necessary and sufficient for its interaction with the third PDZ (GLGF) domain of FAP-1. Furthermore, the direct cytoplasmic microinjection of this tripeptide (Ac-SLV) resulted in the induction of Fas-mediated apoptosis in a colon cancer cell line that expresses both Fas and FAP-1. Since t(S/T)X(V/L/I) motifs in the C termini of several other receptors have been shown to interact with PDZ domain in signal transducing molecules, this may represent a general motif for protein-protein interactions with important biological functions.     

Nuclear waste management in the US: The Nuclear Waste Technical Review Board's perspective

The US program for the management and disposal of commercial spent nuclear fuel and high level waste is in a period of potential programmatic, regulatory, and legislative change. Proposals currently being considered by the US Congress would authorize the development of a storage facility as soon as possible adjacent to the potential repository site at Yucca Mountain. The legislation also would establish regulatory requirements for a permanent repository at an individual dose limit of 1 mSv year⁻¹ (100 mrem year⁻¹) for the average person living near the repository. Concurrently, the fiscal year 1996 appropriation to characterize the Yucca Mountain site has been reduced by approximately 40%. These initiatives portend possible changes in the focus of the US program, including a fundamental shift in priority from permanent disposal to temporary storage, and a change in the approach to licensing a potential repository at the Yucca Mountain site. This paper provides the perspective of the members of the Nuclear Waste Technical Review Board on the impact these developments could have on the future of the US program. It discusses the Board's opinion on how to address the issues these and other developments raise in a way which moves the US civilian radioactive waste management program forward.