Gene therapy for lung cancer

Gene therapy has received considerable attention and some speculation as to its value. Although few patients have been treated, the preliminary results of the phase I lung cancer gene therapy clinical trials are very promising. Clinically relevant basic research in the molecular pathogenesis and immunology of lung cancer is progressing. As improved vector technologies are developed, new opportunities will be available to initiate lung cancer gene therapy trials that are based on a more detailed understanding of lung cancer biology. In conclusion, although important biologic and technical questions remain unanswered, recent research suggests that gene therapy will have a profound impact on lung cancer treatment.     

Toxin gene-mediated growth inhibition of lung adenocarcinoma in an animal model of pleural malignancy

Transduction of malignant cells with toxin genes provides a novel strategy by which to promote tumor cell destruction. Whereas the capacity of the toxin gene/prodrug combination cytosine deaminase/fluorocytosine to inhibit growth of human metastatic pulmonary adenocarcinoma cell lines in vitro is established, the in vivo efficacy of this binary system has not yet been determined. For the development of toxin gene therapy for the treatment of lung adenocarcinoma metastatic to the pleural space, a reliable, disease-specific model is required. The serosa of the rat small intestine resembles the basal lamina of the pleura and provides the basis for a more convenient model than direct injection of tumor into the pleural space. Adenocarcinoma cells are inoculated into everted denuded rat intestine configured as a sac. Immunocytochemical and histological analyses show rapid cell growth with characteristics that mimic nodular metastatic intrapleural disease. In the context of this model, systemically delivered fluorocytosine significantly inhibits the growth of cytosine deaminase-expressing human lung adenocarcinoma cells. The dosing schedule required 30 days; neither addition of an enzyme inhibitor that increases the half-life of fluorocytosine nor intralumenal drug delivery is effective in shortening (to 15 days) the protocol. We conclude that CD continues to hold promise as a toxin gene for lung adenocarcinoma gene therapy, and that prolonged prodrug administration may be required for maximum efficacy.     

Passage of fission fragments through thin film plastic scintillators

The slowing down of fission fragments from the spontaneous fission of ²⁵²Cf has been studied in the self-supporting thin films of plastic scintillator NE 102A, using a surface barrier detector. The measured residual energies and hence the energy losses of the mean light and heavy fragments after passing through the thin films of thickness ranging from ～-100 to 1200 μg/cm² of NE 102A are reported. These measurements were carried down to 20.0 MeV and ～- 14.0 MeV for light and heavy fragments respectively. The shape spectrum parameters from the slowed spectra are determined. The measured energy straggling parameters obtained from these spectra show a maximum around 300 μg/cm² of NE 102A and the energy bunching effect due to fission fragments is observed in thicker plastic scintillator films (>300 μg/cm²). The stopping power obtained from these measurements is compared with the theoretical predictions.     

Novice errors in conceptual database design

Conceptual and logical database modelling are difficult tasks for designers, and the potential for committing and correcting errors is significant. This paper reports on two laboratory experiments that investigated the underlying causes of errors committed by novice designers engaged in conceptual database modelling tasks. These causes can be traced to combinatorial complexity of the task, biases resulting from misapplication of heuristics, and incomplete knowledge about database design. The most common error was that subjects translated their initial understanding of the application into final database structures and did not consider alternative hypotheses and solutions. The paper includes recommendations to reduce the occurrence of errors.     

Analysis of thick functionally graded plates by using higher-order shear and normal deformable plate theory and MLPG method with radial basis functions

Infinitesimal deformations of a functionally graded thick elastic plate are analyzed by using a meshless local Petrov–Galerkin (MLPG) method, and a higher-order shear and normal deformable plate theory (HOSNDPT). Two types of Radial basis functions RBFs, i.e. Multiquadrics and Thin Plate Splines, are employed for constructing the trial solutions, while a fourth-order Spline function is used as the weight/test function over a local subdomain. Effective material moduli of the plate, made of two isotropic constituents with volume contents varying only in the thickness direction, are computed using the Mori–Tanaka homogenization technique. Computed results for a simply supported aluminum/ceramic plate are found to agree well with those obtained analytically. Results for a plate with two opposite edges free and the other two simply supported agree very well with those obtained by analyzing three-dimensional deformations of the plate by the finite element method. The distributions of the deflection and stresses through the plate thickness are also presented for different boundary conditions. It is found that both types of basis functions give accurate values of plate deflection, but the multiquadrics give better values of stresses than the thin plate splines.     

Numerical solution of three-dimensional entrance flow of a bingham material through noncircular ducts

A finite difference analysis is made of three-dimensional entrance flows for an incompressible Bingham fluid in noncircular ducts. Approximate mathematical models are considered for rectangular and triangular ducts, and solutions are obtained assuming a uniform inlet velocity distribution for different values of Bingham number. The axial and transverse velocities, the entrance length and the pressure development have been calculated using a digital computer.     

High Resolution Synchrotron X-Radiation Diffraction Imaging of Crystals Grown in Microgravity and Closely Related Terrestrial Crystals

Irregularities in three crystals grown in space and in four terrestrial crystals grown under otherwise comparable conditions have been observed in high resolution diffraction imaging. The images provide important new clues to the nature and origins of irregularities in each crystal. For two of the materials, mercuric iodide and lead tin telluride, more than one phase (an array of non diffracting inclusions) was observed in terrestrial samples; but the formation of these multiple phases appears to have been suppressed in directly comparable crystals grown in microgravity. The terrestrial seed crystal of triglycine sulfate displayed an unexpected layered structure, which propagated during directly comparable space growth. Terrestrial Bridgman regrowth of gallium arsenide revealed a mesoscopic structure substantially different from that of the original Czochralski material. A directly comparable crystal is to be grown shortly in space.     

The effects of thermal history and composition on the hot ductility of low carbon steels

The hot tensile test was used to investigate the effects of certain key variables on the hot ductility of low carbon steels. A transition from high to low ductility occurred at about 2200°F (1204°C) during continuous cooling of both wrought and cast specimens of low carbon steel after relatively brief exposure to temperatures above 2400°F (1316°C). The observed loss in ductility on cooling below 2200°F (1204°C): (a) increased with decreasing manganese-sulfur ratios, (b) was minimized by appropriate variations in thermal history. Metallographic and fractographic examination of the tensile specimens after thermal cycling indicated that this low ductility below 2200°F (1204°C) resulted from microcracking associated with (Mn, Fe)S precipitates found at the austenite grain boundaries. The results of this investigation help explain why different levels of hot ductility are observed in low carbon steels and what steps can be taken to improve this ductility.