Phase I trial of inhaled natural interleukin 2 for treatment of pulmonary malignancy: toxicity, pharmacokinetics, and biological effects

Safety, local and systemic immunomodulation, and tumor response to treatment with aerosolized natural interleukin 2 (nIL-2) applied five times a day were studied in a Phase I trial in 16 patients with pulmonary malignancies refractory to conventional therapy. The toxicity of inhaled nIL-2 was different from that observed after systemic administration. Reversible airway irritation causing a nonproductive cough represented the dose-limiting toxicity. Mild to moderate reduction of the vital capacity and forced expiratory volume (FEV1) with minor effects on relative FEV1, peak expiratory flow, airway resistance, and PaO2 was experienced by individual patients. In 14 patients suffering from pulmonary metastases due to renal cell cancer, one durable complete response, one partial response, and one mixed response were observed. Inhalation of nIL-2 aerosol resulted in a dose-dependent expansion of pulmonary immunocompetent cells in bronchoalveolar lavage fluid. Posttreatment bronchoalveolar lavage showed an activated lymphocyte phenotype with increased HLA-DR expression. The only systemic biological effect detectable in peripheral blood was a marked increase of soluble interleukin 2 receptor serum levels. We conclude that treatment with aerosolized nIL-2 is an effective means for site-specific immunomodulation and deserves further investigation for the treatment of malignant and inflammatory lung disease.     

THE FRACTURE MECHANISM OF 475°C EMBRITTLEMENT IN A DUPLEX STAINLESS STEEL

The mechanism of “475°C embrittlement” of a duplex stainless steel was investigated using finite element modelling of the stress distribution at brittle fracture initiation. Brittle fracture initiated at a critical shear stress, which increased with ferrite hardness. The fracture stress was affected by the duplex microstructure. Fracture was nucleated by deformation twins, which were identified using electron back-scatter diffraction. The ductile-to-brittle fracture transition was sensitive to age-hardening and could be described simply by the effect of age-hardening and test temperature on the yield stress.     

Oscillation of the scattering time in a 2D electron system with oval antidots

Electron scattering by a single barrier is predicted to reveal singularities as the magnetic field is changed, because the number of electron collisions with the barrier dramatically increases as chaotic orbits around the barrier are changed into periodic orbits. To test this experimentally we have measured the magnetoresistance of AlGaAs/GaAs heterostructures with a two-dimensional electron gas and a lateral lattice containing a macroscopic number of oval-shaped antidots fabricated using electron lithography. Reproducible fluctuations in the magnetoresistance are observed at low field, which are due to the oscillations of the number of electron collisions with the antidots. The number of collisions N before the electron escapes from the antidot has been calculated as a function of B in an electric field. The position of the maxima in N(B) obtained from calculations and experiment are in reasonable agreement.     

Mechanical degradation of coating systems in high temperature cyclic oxidation

Cyclic oxidation tests were performed on a large variety of commercially available overlay coatings. The results of cyclic oxidation tests confirmed that the composition of the coating as well as the processing method of the coating can affect the life of the system. Coating life was determined by the time to coating penetration and initiation of substrate attack. As this work was part of a effort to evaluate the relative protectiveness of available coating systems for Industrial Gas Turbine applications at relatively high temperature, an extensive testing programme was undertaken. The different coatings were tested to visual failure. The results presented in this paper concentrate on the surface instability of the coating. Apart from usual oxidation of the coating an additional degradation mechanism was observed. A mechanical effect caused by the instability of the coating as a result of the difference in the thermal coefficient of expansion and mechanical properties between the substrate and coating. This effect, the so-called “rumpling” effect, resulted in a significant reduction in time to penetration and was in some systems the life controlling factor.     

Electroluminescent zinc sulphide devices produced by sol-gel processing

Zinc sulphide thin film electroluminescent devices doped with Mn or Tb have been produced on p-type Si substrates using a process in which doped zinc oxide films are deposited by a sol-gel drain coating method from a solution of zinc acetate containing a manganese or terbium dopant. The films are then converted to ZnS by heating them in an atmosphere containing hydrogen sulphide which replaces the oxygyn with sulphur. The composition, crystalline structure and optical properties of films have shown that complete conversion from the oxide to the sulphide takes place. The luminescent characteristics of the devices so produced have been measured as a function of the doping concentrations, film thickness, insulator thickness and driving voltage and frequency. It has been found that yellow or green luminescence can be obtained using Mn or Tb doping respectively.     

Accurate determination of magnetic field gradients from four pointvector measurements. I. Use of natural constraints on vector dataobtained from a single spinning spacecraft

Cluster introduces a new generation of spacecraft that will measure the spatial gradients of the magnetic field in the Earth's magnetosphere. As gradients require knowledge of differences, small errors resulting from an inadequate knowledge of the orientations, zero levels and the scale factors of the magnetometer sensors affect the calculation of field gradients disproportionately and must be removed with high accuracy. We show that twelve calibration parameters are required for each of the spacecraft (for a total of 48 for the four spacecraft) to correctly infer the measured magnetic fields at each of the spacecraft. By application of a Fourier transform technique, some of the parameters can be recovered. We show that errors in eight of the twelve calibration parameters generate coherent monochromatic signals at the first and the second harmonics of the spin frequency in the despun data. We relate the real and the imaginary parts of the monochromatic signals to the eight calibration parameters. We then present a least squares scheme that improves the eight calibration parameters by iteration until the power of the coherent signal superimposed above the broad-band background is minimized     

Effect of beam voltage on the properties of aluminium nitride prepared by ion beam assisted deposition

The effects of nitrogen-beam voltage on the structure, stress, energy band gap and hardness of AIN thin films deposited on Si (111), Si (100) and sapphire (0001) by ion beam assisted deposition (IBAD) are reported. As the nitrogen-beam voltage was increased from 50 to 200 V, the stress and disorder in the AIN films increased as determined by X-ray diffraction, FTIR and Raman spectroscopy. The preferred orientation of the film's c-axis changed from completely normal to the film at 100 V, to a mixture of normal and in the plane of the film at 200 V. For AIN films deposited under the same conditions, the films were more highly oriented on sapphire (0001) than in Si (111). The hardness of the films increased from 18.2 to 23.7 GPa with the nitrogen-beam voltage, and possible reasons for this change in hardness are considered.     

GABAergic and pallidal terminals in the thalamic reticular nucleus of squirrel monkeys

The ultrastructure of synaptic terminals from the external segment of the globus pallidus and of other synaptic terminals positive for gamma-aminobutyric acid (GABA) was examined in the thalamic reticular nucleus (TRN) of squirrel monkeys. Two GABA-positive terminals types were commonly encountered within the TRN neuropil. The most common type of GABAergic terminals (F terminals) are filled with dispersed pleomorphic synaptic vesicles and clusters of mitochondria. These terminals establish multiple symmetric synapses upon the somata and dendrites of TRN neurons. The external pallidal terminals, labeled with WGA-HRP, arise from thinly myelinated axons and correspond to the medium to large F terminals. A less prevalent population of smaller GABAergic synaptic profiles was also identified. The synaptic profiles in this second group contain considerably fewer pleomorphic synaptic vesicles in small irregular clusters and fewer mitochondria, establish symmetric synapses, are postsynaptic to other axonal terminals, are presynaptic to dendrites and soma, and are unlabeled following pallidal injections of WGA-HRP.