Phage-display selection of a human single-chain fv antibody highly specific for melanoma and breast cancer cells using a chemoenzymatically synthesized G(M3)-carbohydrate antigen

Overexpression of the cell-surface glycosphingolipid G(M3) is associated with a number of different cancers, including those of the skin, colon, breast, and lung. Antibodies against the G(M3) epitope have potential application as therapeutic agents in the treatment of these cancers. We describe the chemoenzymatic synthesis of two G(M3)-derived reagents and their use in the panning of a phage-displayed human single-chain Fv (scFv) antibody library derived from the blood of cancer patients. Three scFv-phage clones, GM3A6, GM3A8, and GM3A15, were selected for recombinant expression and were characterized using BIAcore and flow cytometry. BIAcore measurements using the purified, soluble scFvs yielded dissociation constants (K(d)) ranging from 4.2 x 10(-7) to 2.1 x 10(-5) M. Flow cytometry was used to evaluate the ability of each scFv to discriminate between normal human cells (human dermal fibroblast, HDFa), melanoma cells (HMV-1, M21, and C-8161), and breast cancer cells (BCM-1, BCM-2, and BMS). GM3A6 displayed cross-reactivity with normal cells, as well as tumor cells, and GM3A15 possessed little or no binding activity toward any of the cell lines tested. However, GM3A8 bound to five of the six tumor cell lines and showed no measurable reactivity against the HDFa cells. Hence, we have demonstrated that a synthetic G(M3) panning reagent can be used to isolate a fully human scFv that is highly specific for native G(M3) on the surface of tumor cells. The result is a significant step toward effective immunotherapies for the treatment of cancer.     

A Model of the Dynamics of the Third World War — An Exercise in Technology Transfer

The paper discusses two scenarios for a Third World War in Europe, and argues that it is often convenient to supplement a scenario by a formal model. The problems of creating such a model are examined, and a model is formulated for land, air, and sea combat in Europe and the Atlantic, using the System Dynamics approach, which has not hitherto been widely employed for military analysis.The model confirms the results of the two scenarios, and its use for the analysis of alternative force configurations is illustrated. Some implications in the interpretation of Soviet military literature are discussed, and the paper ends with speculations on the role and value of such models.     

Laser ultrasonic surface wave inspection of alumina ceramics of varying density

In this paper, the surface acoustic wave velocity results acquired from the inspection of specially manufactured and characterised alumina ceramic materials are presented. Ultrasonic velocity data of alumina-based ceramics in the range 60-100% theoretical density was generated utilising non-contacting laser-ultrasonic measurements based on laser generation and detection of surface acoustic waves with the objective of creating a routine technique for industrial advanced alumina inspection. With linear fitting the surface acoustic wave velocity data serves as a calibration graph for using laser ultrasonics for routine monitoring of alumina. A second laser ultrasonic technique based on the laser generation and foil transducer detection of surface acoustic waves was used to validate the surface acoustic wave velocities measured by the laser generation/detection technique.     

Highly efficient dual head 100 mJ TEM00 Nd:YAG Oscillator

A diode-pumped, Q-switched Nd:YAG laser employing a dual-pump zig-zag slab head scheme in an unstable resonator configuration for use in space-based planetary altimetry or atmospheric LIDAR is described. The pump heads are aligned orthogonally to each other, producing a symmetric overall thermal lens that eliminates the need for an intracavity cylindrical lens and aperture. This laser has demonstrated over 100 mJ in Q-switched operation with high optical efficiency (24%), good beam quality, high pointing stability, and large operational margins for multi-billion shot lifetimes.     

TIRF microscopy as a screening method for non-specific binding on surfaces

We report a method for studying nanoparticle-biosensor surface interactions based on total internal reflection fluorescence (TIRF) microscopy. We demonstrate that this simple technique allows for high throughput screening of non-specific adsorption (NSA) of nanoparticles on surfaces of different chemical composition. Binding events between fluorescent nanoparticles and functionalized Zeonor? surfaces are observed in real-time, giving a measure of the attractive or repulsive properties of the surface and the kinetics of the interaction. Three types of coatings have been studied: one containing a polymerized aminosilane network with terminal -NH(2) groups, a second film with a high density of -COOH surface groups and the third with sterically restraining branched poly(ethylene)glycol (PEG) functionality. TIRF microscopy revealed that the NSA of nanoparticles with negative surface charge on such modified coatings decreased in the following order -NH(2)>-branched PEG>-COOH. The surface specificity of the technique also allows discrimination of the degree of NSA of the same surface at different pH.     

The impact of the natural sciences on archaeology

This article reviews some of the applications of physics to the solution of archaeological problems. The use of magnetic, resistivity and electromagnetic surveying techniques for the location of buried features is described. Various methods of age determination are outlined while the problems associated with radiocarbon dating of organic material and thermoluminescent dating of pottery are discussed in detail. The techniques, including petrological examination, chemical analysis and isotopic analysis, employed in the physical examination of archaeological artefacts are described. Examples of the application of these techniques in establishing the source of the raw materials used in pottery, metal and stone implements and in elucidating the techniques of manufacture of pottery and metal objects are also given.