p53 gene therapy in vivo of herpatocellular and liver metastatic colorectal cancer

Tumor suppressor genes such as p53 contribute to the oncogenic process via loss-of-function mechanisms such as genetic mutation or complex formation with other cellular or viral proteins. p53 is mutated in approximately 50% of human tumors and has an important role in the genesis or progression of both colorectal and hepatocellular cancers. Colorectal cancer is leading cause of cancer mortality in the United States, whereas hepatocellular cancer is the leading worldwide cause of cancer death; the liver is a primary site of morbidity in both diseases. Because systemic tumor suppressor gene therapy is currently not feasible, we have chosen to develop a regional form of such therapy directed at primary or metastatic liver neoplasms. Gene replacement therapy with p53 is a promising new strategy to treat advanced human cancers.     

Multiple-gate SOI MOSFETs: device design guidelines

This paper describes computer simulations of various SOI MOSFETs with double and triple-gate structures, as well as gate-all-around devices. The concept of a triple-gate device with sidewalls extending into the buried oxide (hereby called a "/spl Pi/-gate" or "Pi-gate" MOSFET) is introduced. The Pi-gate device is simple to manufacture and offers electrical characteristics similar to the much harder to fabricate gate-all-around MOSFET. To explore the optimum design space for four different gate structures, simulations were performed with four variable device parameters: gate length, channel width, doping concentration, and silicon film thickness. The efficiency of the different gate structures is shown to be dependent of these parameters. The simulation results indicate that the the Pi-gate device is a very promising candidate for future nanometer MOSFET applications.     

Structural evaluation of thermal stratification for PWR surge line

Recent observations at operating plants and subsequent US NRC requirements have identified flow stratification in surge lines as a phenomenon that must be considered in the design basis of surge lines. To address these concerns, the stratified loading conditions were included in the design of YGN 3 and 4 surge line as a design basis transient and pipe temperature and displacement measurement were taken during YGN 3 pre-core hot functional testing to determine the degree of surge line flow stratification. The measured displacements and temperatures were extensively reviewed and evaluated in detail: (1) to verify the validity of the thermal hydraulic model used to predict the pipe top-to-bottom temperature differentials; (2) to analytically correlate measured surge line temperatures and displacements; and (3) to confirm the validity of the stratified flow analysis procedure. This paper shows that the stratified flow phenomenon is generic and therefore generic loadings can be developed and evaluated for the surge line analyses.     

C-t analysis of MOS capacitors under constant current stress

The effect of high oxide field stress is studied using capacitance-time (C-t) measurements of MOS capacitors. The stress results in parallel shifts of the C-t curve along the time axis. The flatband voltage shift ΔV_FB obtained from the initial deep depletion capacitance C(t=0⁺) follows the same trend as that from the high-frequency C-V characteristics. However, the discrepancy between the two flatband voltages becomes larger as the stress increases due to the effect of interface charges on C-t characteristics. The flatband voltage difference is converted to interface trap density, showing a steady increase of interface trap density with stress, similar to that from low-frequency C-V measurements     

Hepatotoxin (microcystin) and neurotoxin (anatoxin-a) contained in natural blooms and strains of cyanobacteria from Japanese freshwaters

Amounts of hepatotoxic microcystin and neurotoxic anatoxin-a were estimated in natural blooms and strains of cyanobacteria from freshwaters in Japan. A simultaneous analysis method of anatoxin-a and microcystin was applied to natural bloom samples, which has been dominated by several species and the strains of cyanobacteria which produced simultaneously both toxins. The natural blooms examined in the present study were mainly composed of Anabaena and Oscillatoria, but most also contained Microcystis and other cyanobacteria. Only one sample was almost unialgal, Anabaena spiroides, collected from Lake Sagami. The toxins in 14 samples collected from nine different natural blooms during 1988-1992 were identified as microcystins-RR, -YR, and -LR; desmethyl-7-microcystin-LR (7-DMLR); and anatoxin-a. Microcystins were the main toxins contained in these natural blooms, with anatoxin-a not being detected or of very little quantity. 7-DMLR was detected in samples only from Lake Kasumigaura. Five strains of Anabaena isolated from waters in Japan produced a small amount of anatoxin-a, but no microcystins. One half of the strains of Microcystis produced microcystins and/or anatoxin-a. This is the first study showing Microcystis producing both anatoxin-a and microcystins.     

Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.     

Oxidative regeneration of sulfided sorbent by H2S without emission of SO2

Much SO₂, another perilous air pollutant, was emitted during the oxidative regeneration of sulfided sorbent by H₂S. In order to prevent emission of SO₂, we carried out oxidative regeneration with the physical mixture of CaO and sulfided sorbent and investigated the effect of regeneration temperature and oxygen concentration on the reactivity of CaO with S0₂. The effluent gases were analyzed by G.C. and the properties of sorbent were characterized by XRD. SEM, TG/DTA and EPMA. Deterioration of reactivity of CaO with S0₂ resulted in increment of emission of SO₁₂ due to the structural changes of CaO above 750°C and that at 850°C was more severe. Furthermore EPMA and XRD analysis revealed that product layer diffusion through the solid product, CaSO₄, was the rate limiting step for CaO sulfidation. The reaction of CaO w:.th SO₂ was first order approximately and that was accelerated by high O₂ concentration.     

Overview of ship-design expert systems

Expert systems constitute a branch of artificial intelligence, and their unique characteristics enable computer systems to perform at the level of a human expert by the use of algorithms that can capture domain-specific knowledge. Through an extensive survey of research about ship-design expert systems, we conclude that although development and implementation of expert systems for ship design offer substantial barriers, the shipbuilding industry needs them nonetheless. We examine the major reasons that use of expert systems in this industry has lagged behind. These include the problems of integration with existing computer-aided design systems, problems of knowledge representation and sizable development costs. We discuss in detail some key factors that can lead to the solution of these problems.