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 greenhouse effect; Impact upon and the role to be played by construction

The authors highlight several possible ways in which the construction industry could lower present emissions of the greenhouse gas, carbon dioxide. It is an excellent discussion document and is recommended reading.     

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.     

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     

The Effect of Organic Ligands on the Rate of Loss of Phenylmercuric Nitrate into Rubber Closures and Plastic Containers

The effect of the presence of various organic compounds containing a variety of functional groups on the rate of loss of phenylmericuric (PM) nitrate into plastic containers and rubber closures has been investigated. The presence of organic compounds profoundly influenced the loss of the phenylmercuric nitrate, that loss being dependent upon their chemical structure and concentration. This effect explains the unpredictability of the loss of PM nitrate into polymer matrices from pharmaceutical products.     

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.