Radiation-inducible TNF-alpha gene expression under stress-inducible promoter gadd 153 for cancer therapy

We demonstrated the effectiveness of radiation-inducible expression of the TNF-alpha gene for cancer therapy in vitro. The TNF-alpha gene under the control of the stress-inducible promoter, gadd 153, was introduced into the human glioma cell line, U251-SP. Without cobalt-60 gamma irradiation, no cytotoxicity against the transfected cells was observed. When the transfected cells were irradiated with 10 or 20 gray (Gy), the gadd 153 promoter was highly induced and the expression level of TNF-alpha increased. Five days after the irradiation, the TNF-alpha productions of each cell irradiated with 10 and 20 Gy were 30 and 100 times higher than the basal level, respectively. The cytotoxicities against the transfected cells 5 d after irradiation with 10 and 20 Gy were 79% or 91%, respectively, which are much higher than those against the nontransfected cells that were irradiated at the same dose (43% and 78%, respectively). These results demonstrate that the gadd 153-TNF-alpha system may be an effective tool for radiosurgery of malignant brain tumors.     

Dimeric C34 Derivatives Linked through Disulfide Bridges as New HIV-1 Fusion Inhibitors

C34, a 34-mer fragment peptide, is contained in the HIV-1 envelope protein gp41. A dimeric derivative of C34 linked through a disulfide bridge at its C terminus was synthesized and found to display potent anti-HIV activity, comparable with that of a previously reported PEGylated dimer of C34REG. The reduction in the size of the linker moiety for dimerization was thus successful, and this result might shed some light on the mechanism of the suppression of six-helix bundle formation by these C34 dimeric derivatives. Addition of a Gly-Cys(CH₂CONH₂)-Gly-Gly motif at the N-terminal position of a C34 monomeric derivative significantly increased the anti-HIV-1 activity. This moiety functions as a new pharmacophore, and this might provide a useful insight into the design of potent HIV-1 fusion inhibitors.     

LiF enhanced nucleation of the low temperature microcrystalline silicon prepared by plasma enhanced chemical vapour deposition

A 15-nm lithium fluoride (LiF) thin film evaporated on glass substrate is shown to enhance the nucleation of microcrystalline Si grown by plasma enhanced chemical vapour deposition at the amorphous/microcrystalline boundary conditions. The effect is more pronounced at low substrate temperatures, nucleation density being 10 times higher at ∼ 80 °C. The effect is ascribed to the ionic chemical nature of LiF, the low work function material used in organic electronic devices, and we propose its use for micro patterning crystalline Si regions in otherwise amorphous Si film.     

Development of high temperature gas-cooled reactor (HTGR) fuel in Japan

This paper describes experiences and present status of research and development works for the high temperature gas-cooled reactor (HTGR) fuel in Japan. Recently, Very High Temperature Reactor (VHTR) is evaluated highly worldwide, and is a principal candidate for the Generation IV reactor systems. In Japan, HTGR fuel fabrication technologies have been developed through the High Temperature Engineering Test Reactor (HTTR) project in Japan Atomic Energy Agency since 1960’s. In total about 2 tons of uranium of the HTTR fuel has been fabricated successfully and its excellent quality has been confirmed through the long-term high temperature operation. Based on the HTTR fuel technologies, SiC TRISO fuel has been newly developed for burnup extension targeted VHTR. For ZrC-TRISO coated fuel as an advanced fuel designs, R&Ds for fabrication and inspection have been carried out in JAEA. The irradiation with the Japanese uniform stoichiometric ZrC coating has been completed in the cooperation with Oak Ridge National Laboratory of the United States.     

Larval osmeterial secretions of the swallowtails (Papilio)

The larval osmeterial secretions of sixPapilio species examined displayed a remarkable qualitative change at the fourth larval ecdysis. The secretions of 4th (penultimate) instar larvae ofP. machaon, P. memnon, P. helenus, P. bianor, andP. maackii principally comprised mono- and/or sesquiterpenoids. The compounds identified from these species included -pinene, sabinene, -myrcene, limonene, -phellandrene, (Z)--ocimene, (E)--ocimene, -elemene, -caryophyllene, (E)--farnesene, -selinene, (E,E)--farnesene, germacrene-A, germacrene-B, caryophyllene oxide, methyl 3-hydroxy-n-butyrate, and acetic acid. In contrast, the secretion of 4th larval instar ofP. xuthus, although containing similar terpenic compounds, was accompanied by large amounts of aliphatic acids and their esters: isobutyric acid, 2-methylbutyric acid, methyl isobutyrate and methyl 2-methylbutyrate. On the other hand, the osmeterial secretions of 5th (last) instar larvae varied little in quality among the six species, and the identified compounds consisted of isobutyric acid, 2-methylbutyric acid, methyl isobutyrate, ethyl isobutyrate, methyl 2-methylbutyrate, ethyl 2-methylbutyrate, and isovaleric acid, the last of which was specific toP. bianor andP. maackii. The chemical alteration of osmeterial exudate synchronized at the final larval ecdysis with the larval morphological change (particularly in body coloration) that appears to be of defensive significance against predators.     

Feeder components and instrumentation for the JT-60SA magnet system

The modifying of the JT-60U magnet system to the superconducting coils is progressing as a satellite facility for ITER by both parties of Japanese government and European commission in the Broader Approach agreement. The magnet system requires current supplies of 25.7 kA for 18 TF coils and of 20 kA for 4 CS modules and 6 EF coils. The magnet system generates an average heat load of 3.2 kW at 4 K to the cryogenic system. The feeder components connected to the power supply provide current supply. The cooling pipes connected to the cryogenic system provide coolant supply. The instrumentation of the JT-60SA magnet system is used for its operation.     

The relationship between the molecular weight and the critical miscibility composition of a solvent-nonsolvent-terpolymer system

A theoretical equation for the dependence of the apparent molecular weight measured by light scattering on the solvent used has been derived with regard to the composition heterogeneity. Terpolymers corresponding to a partial azeotrope were synthesized from styrene, acrylonitrile, and methyl methacrylate with mole fractions of 0.55, 0.16, and 0.29, respectively. The molecular weight measured by light scattering was found to be independent of the solvent used. Therefore the terpolymer was concluded to be apparently homogeneous in composition. The relationship between the molecular weight M of the terpolymer and the volume fraction of the nonsolvent γ in the solvent mixture at the precipitation point in a butanone-methanol-terpolymer system was experimentally proved to follow the equation where γ₀ and b′ are constants. Between the molecular weight and the limiting viscosity number [η] of the terpolymer the following relationships are valid at 35°C: and      

A 500-MHz pipelined burst SRAM with improved SER immunity

This paper describes a 0.25-μm, 64 K×36 bit pipelined burst SRAM using a 6.156-μm² cell. It realizes over 500-MHz operation using a lower cost double metal process, Internal 16 K×144 organization by T-shaped bit line array reduces 20% of latency, 20% of active power, and 8.5% of die size. The low power also enables us to use lower cost thin quad flat type packages. Our solution to the soft error problem, a shallow triple well structure and four-transistor cell with stacked capacitor, improved soft error rate by 3.5 orders of magnitude compared with the conventional SRAM cell     

Adenovirally expressed basic fibroblast growth factor rescues photoreceptor cells in RCS rats

OBJECTIVE: To examine the efficacy of an antileukocyte adhesion antibody (anti-CD18) as an adjuvant for delayed (2 hours and 4 hours) thrombolytic therapy (recombinant human tissue plasminogen activator [rt-PA]) in middle cerebral artery occlusion (MCAO) in rats. BACKGROUND: Thrombolytic therapy with rt-PA is limited in its application by a short therapeutic window. METHODS: Male Wistar rats were subjected to MCAO by a single fibrin-rich clot. The rats were assigned to the following experimental groups: Experiment 1 (treatment 2 hours after embolization), 1) rt-PA, 2) anti-CD18 antibody, 3) rt-PA and anti-CD18 antibody, 4) immunoglobulin (Ig) G, and 5) vehicle; Experiment 2 (treatment 4 hours after occlusion), 1) rt-PA alone, 2) rt-PA and anti-CD18 antibody, and 3) nontreated control group. Neurologic deficits, infarction volume, hemorrhage, and brain myeloperoxidase (MPO) immunoreactivity were measured. Results: Administration of rt-PA and anti-CD18 antibody 2 hours later reduced significantly (p < 0.05) the infarct volume and improved neurologic deficits compared with the vehicle-treated group. Treatment with rt-PA alone improved neurologic deficits significantly and reduced mean infarct volume compared with the vehicle-treated group. However, treatment with anti-CD18 antibody neither reduced infarct volume nor improved neurologic deficits compared with the IgG-treated group. The combination of rt-PA and anti-CD18 antibody treatment at 4 hours reduced significantly the infarct volume and MPO immunoreactive cells compared with rt-PA treatment alone at 4 hours, and reduced neurologic deficits compared with rt-PA treatment alone and compared with the nontreated animals. CONCLUSIONS: The combination of antileukocyte adhesion antibody and thrombolytic therapy may increase the therapeutic window for the treatment of stroke.     

Persistence and partitioning of eight selected pharmaceuticals in the aquatic environment: Laboratory photolysis, biodegradation, and sorption experiments

We selected eight pharmaceuticals with relatively high potential ecological risk and high consumption—namely, acetaminophen, atenolol, carbamazepine, ibuprofen, ifenprodil, indomethacin, mefenamic acid, and propranolol—and conducted laboratory experiments to examine the persistence and partitioning of these compounds in the aquatic environment. In the results of batch sunlight photolysis experiments, three out of eight pharmaceuticals—propranolol, indomethacin, and ifenprodil—were relatively easily photodegraded (i.e., half-life < 24 h), whereas the other five pharmaceuticals were relatively stable against sunlight. The results of batch biodegradation experiments using river water suggested relatively slow biodegradation (i.e., half-life > 24 h) for all eight pharmaceuticals, but the rate constant was dependent on sampling site and time. Batch sorption experiments were also conducted to determine the sorption coefficients to river sediments and a model soil sample. The determined coefficients (K_d values) were much higher for three amines (atenolol, ifenprodil, and propranolol) than for neutral compounds or carboxylic acids; the K_d values of the amines were comparable to those of a four-ring polycyclic aromatic hydrocarbon (PAH) pyrene. The coefficients were also higher for sediment/soil with higher organic content, and the organic carbon-based sorption coefficient (log K_oc) showed a poor linear correlation with the octanol-water distribution coefficient (log D_ow) at neutral pH. These results suggest other sorption mechanisms—such as electrochemical affinity, in addition to hydrophobic interaction—play an important role in sorption to sediment/soil at neutral pH.