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We study the dissociation of preformed bivalent ligand-bivalent receptor aggregates in solution, where the ligand is a symmetric bivalent hapten with two identical 2,4-dinitrophenyl (DNP) groups and the receptor is a fluorescein-labeled monoclonal anti-DNP IgE. We promote dissociation in two ways: by the addition of high concentrations of a monovalent hapten that competes for IgE binding sites with the bivalent hapten and by the addition of high concentrations of unlabeled IgE that binds almost all ligand binding sites that dissociate from labeled IgE. We investigate both theoretically and experimentally the two types of dissociation and find them to be quite different. Theory predicts that their kinetics will depend differently on the fundamental rate constants that characterize binding and aggregation. Using monovalent ligand to promote dissociation, we find that the fraction of labeled IgE sites bound to bivalent ligand decays with a slow and fast component. The fast decay corresponds to the dissociation of a singly bound DNP hapten. The interpretation of the slow decay depends on the detailed way in which ligand-receptor aggregates break up. We show that one possible explanation of these data is that small stable rings form before the addition of monovalent ligand. Other possible explanations are also presented.

Fluorescence measurements are among the most powerful methods for investigating structure and structural changes on cell surfaces. The basic strength of this method is that nanomolar concentrations of fluorophores can be detected in the presence of a high level of background noise provided by the cells. An ideal fluorescent probe absorbs and emits at wavelengths not in common with the cellular components, has a high quantum yield, and can be placed specifically into a location such that it is sensitive to the structural aspect of interest. Recently there has been a great expansion in the commercial availability of fluorescent probes with a broad range of fluorescent properties and reactive groups for conjugation (e.g., Haugland, 1989). The requirement for specific placement on a macromolecular/cellular complex remains the most challenging experimentally. In this regard, specific ligands and specific monoclonal antibodies that can be fluorescently modified are valuable reagents. In this chapter we describe our use of quantitative fluorescence measurements to investigate the binding properties of cell surface receptors.

A simple, inexpensive, non-magnetizable, pulsatile air-driven pump has been devised for use in magnetic resonance environments. The pump has a variable stroke volume and stroke rate, is easily cleaned and sterilized, requires relatively small priming volumes and causes no observable hemolysis when blood is used as the perfusate. This device is usable for phantoms, isolated organs or in situ preparations.

Ten gated cardiac software phantoms, representing normal and abnormal clinical conditions, were transferred to 9 different computer systems and tested with 11 cardiac programmes. Problems of inappropriate data format were encountered when analysing the phantoms on other systems. The global left ventricular ejection fraction (LVEF) values resulting from the different programmes were compared. Significant programme differences were found, the programmes falling generally into two groups. Few LVEF outlier values were identified. Full functional assessment of cardiac phantoms requires a set of different views which together form the phantom. Application of software phantoms for programme assessment and training requires prudence and attention to the acquired data format, frame time, and gating method for the appropriate use of phantoms.

This article outlines an approach, based on ecosystem services, for assessing the trade-offs inherent in managing humans embedded in ecological systems. Evaluating these trade-offs requires an understanding of the biophysical magnitudes of the changes in ecosystem services that result from human actions, and of the impact of these changes on human welfare. We summarize the state of the art of ecosystem services–based management and the information needs for applying it. Three case studies of Long Term Ecological Research (LTER) sites—coastal, urban, and agricultural—illustrate the usefulness, information needs, quantification possibilities, and methods for this approach. One example of the application of this approach, with rigorously established service changes and valuations taken from the literature, is used to illustrate the potential for full economic valuation of several agricultural landscape management options, including managing for water quality, biodiversity, and crop productivity.

Recent models of adaptation to climate change have allowed economic agents perfect foresight about future climatic conditions. We argue that it is time to move beyond assumptions of perfect foresight to consider the impacts of changing climate predictability on adaptation dynamics. An option value investment model is used to illustrate the impact of one significant determinant of predictability - climate variability - on the timing of adaptation. Decreased predictability leads to postponed adaptation and increased pre-adaptation damage costs, indicating that estimates of the damage reductions to be gained through adaptation based on perfect foresight have been excessively optimistic.

China's projected oil import requirements and greenhouse gas emissions from energy consumption will dominate the international oil market and environmental agendas. As a result of these energy requirements, China has recently expanded development of domestic oil supplies and coal production. Effectively limiting greenhouse gas emmissions will require a sustained international effort to increased energy efficiency and market reform in China.

The analysis of shallow p‐n junctions by standard secondary ion mass spectrometry with oxygen primary ion bombardment can be significantly enhanced in two ways. The sensitivity can be increased about 100‐fold by using both instrumental means and chemical modification (in situ oxidation). The depth resolution can be improved about twofold in many cases (e.g., for B), by phenomena accompanying oxidation. It is known that chemical segregation of As may adversely affect depth resolution, so analyses for different elements must be treated on a case‐by‐case basis.

An acoustic sensor, useful as an ultrasonic transducer, microphone or hydrophone, uses an optical lever to amplify the motion of the sensor surface and convert it to an electrical signal for image processing. A beam of light (15) from a laser is directed at an oblique angle onto a reflective surface (13) coupled to a sensor membrane (31). The reflected light (16) strikes a position-sensitive light detector (PSD) (17) generating an electrical signal indicating the position of the light spot on the PSD (17). When an acoustic wave strikes the sensor membrane (31), the small movements of the reflective surface (13) result in large motions of the spot of light on the PSD (17), thereby amplifying the acoustic signal. Also disclosed is a multi-element sensor array suitable for linear array or phased array imaging. Three approaches are disclosed for increasing the sensitivity by optical amplification: 1) the vibrating mirror (46) is part of a cantilever that increases the angular deflection of the incident light beam (15); 2) a stationary mirror (M2) is positioned approximately parallel to the vibrating mirror surface; the reflected light beam is reflected back onto the vibrating mirror (M1), and picks up another increment of the acoustic signal with each reflection; 3) the effective movement of the optical lever is increased within a small volume by the use of two stationary mirrors (M3, M4) to increase the path length from the vibrating mirror (M1) to the position-sensitive detector (17). Two chopped light beams may be directed at a single vibrating surface (M1), and phase-locked loop circuitry used to reduce the signal-to-noise ratio.

Structural interactions between IgE and its high-affinity receptor have been investigated with the methods of fluorescence resonance energy transfer and genetic engineering. The results indicate that IgE has a bent conformation when bound to receptor on the cell surface and that the site of interaction is contained in the Cε2 and Cε3 domains; the C-terminal domain, Cε4, is not required for binding. Cross-linking of IgE-receptor complexes is required for signal transduction across the plasma membrane. Binding studies with defined bivalent ligands indicate that structural and/or kinetic features determine the functional effectiveness of the cross-linked states.

Interfaces formed by tin and palladium deposition on the (110) face of tin dioxide, SnO2 (a semiconductor due to native defects), have been studied from coverages of 0.05 monolayer (ML) to over 10 ML. The structural, chemical, electronic, and electrical properties of the surfaces were characterized primarily by low‐energy electron diffraction (LEED), x‐ray photoelectron spectroscopy, ultraviolet photoemission spectroscopy, and a retractable four‐point conductivity probe. Modifications of the substrate by oxidation, annealing, and ion bombardment treatments produced three different substrate structures which were used to examine the interface abruptness and the metallization due to Sn and Pd. The deposition of Sn produced an increased surface conductivity on the ordered substrates due to the formation of donor states (oxygen vacancies) at the surface. The deposition of Pd results in the growth of a metallic layer beginning at 1–5 ML, depending upon the surface oxygen concentration. The metallic conductivity rapidly increases with Pd coverage and by 10 ML, LEED reveals microcrystallites in azimuthal registry with the substrate. In contrast, the development of metallic conductivity is relatively slow for the disordered Sn multilayers.

Recent advances in computer processing of images and the development of electronic x-ray detectors have made possible the development of digital radiographic techniques, which offer great potential for the analysis of paintings. The ability to distinguish very small differences in x-ray attenuation characteristics provides the possibility of quantitative analysis of pigment structures. The very sophisticated image processing techniques that have been developed for the space industry and medicine also may be applied to the analysis of paintings through the use of the digital radiographic images. In this communication, digital fluoroscopy, scanned projection radiography, and scanned point-source methods will be described. The virtues and limitations of each are noted. An initial experience with two of these methods will be the major subject of this communication.

Lacerations of the profundus tendon distal to the superficialis insertion can be treated by advancement of the proximal cut end of the tendon to its insertion. In the English-language literature, limits cited for the distance a profundus tendon can be safely advanced vary from 0.75 to 2.5 cm and appear to be based on clinical impressions. Our cadaver model suggested the degree of tendon advancement tolerable was 1 cm. A delicate balance exists in the profundus tendon system, and this should be considered when surgical advancement is contemplated.

CAMAC has been used for data acquisition and control of nuclear measurement systems in the Vanderbilt University Nuclear Medicine Laboratory for approximately two years. The implementation of the CAMAC crate controller used with a PDP/9 computer is described. Data are acquired from three types of devices. These include a stationary multi-probe system, a computer driven scanner and a dual probe scanner not under computer control. Future extensions of our system are discussed, including the collection of data from higher data rate instruments (Anger-type scintillation camera) as well as computer networking. The CAMAC system required a higher initial dollar investment when compared to a single dedicated scanner interface. However, it provided a much more versatile and more easily expanded system. When a second device is added, we found that the use of CAMAC can be defended successfully on a cost basis alone. The CAMAC standard allows the replication of systems by laboratories without the large investments in time and money usually needed to interface specialized measurement systems to computers. The modularity permits orderly growth of systems and protects against obsolescence. Almost any standard would be better than no standard, and we plan to use CAMAC for all applications where data-transmission-rate requirements permit. We hope that users in the nonnuclear field will come to utilize CAMAC in their measurement and data reduction systems where similar benefits should be obtained.

A technique for correction of motion between images which are obtained in high‐speed digital subtraction or cine angiographic acquisitions is being tested. The method is based on the application of quadratic polynomial equations which transform one image so that it matches a reference image.Images which have been processed in this manner can be summed to improve the signal‐to‐noise ratios over individual images. The technique for motion correction currently being tested uses operator interaction to establish the appropriate polynomial transformation. An operator selects fiducial (reference) points on an image which will be the reference. Then he selects the corresponding fiducial points on the image to be processed. The algorithm calculates the coefficients of a pair of quadratic polynomial equations and applies them to each pixel in the image. Results demonstrate the application of the technique in phantoms and in digitized cine angiograms.

For monovalent ligands interacting with cell surface receptors we have directly observed the functional dependence of the forward rate constant on the number of receptors per cell (N). The experimental system we studied consisted of monovalent ligand, 2,4-dinitrophenyl (DNP)-aminocaproyl-L-tyrosine (DCT), binding to bivalent, monoclonal anti-DNP immunoglobulin E (IgE) anchored to its high affinity receptor on rat basophilic leukemia (RBL) cells. To measure the fractional occupation of antibody combining sites by DNP we employed a recently developed fluorescence technique (Erickson, J., Kane, B. Goldstein, D. Holowka, and B. Baird, 1986, Mol. Immunol., 72:769-781). Our results are well fitted by the equation (Berg and Purcell, 1977, Biophys. J., 20:193-219) konc = 4 pi DaN kappa on/[4 pi Da + N kappa on] where konc is the forward rate constant for binding to the cell, D is the diffusion constant of the ligand, a is the radius of the cell, and kappa on is the intrinsic forward rate constant describing a single IgE combining site-DNP interaction. If D is fixed at 10(-5) cm2/s, the best fit of accumulated data predicts an average cell radius of approximately 4 microns and kappa on of approximately 1.8 x 10(-13) cm3/s [1.1 x 10(8)(M . s)-1]; both in excellent agreement with RBL cell size and the single-site forward rate constant for the binding of DCT to IgE in solution, respectively. We believe this is the first report of experimental evidence that directly illustrates the effect of surface density in determining the rates of binding for small molecules to membrane receptors.

The increasing cost of software and hardware for complex acquisition and control systems has made it desirable to implement small stand alone systems with less complex software and more versatile hardware. This paper discusses two applications of an autonomous CAMAC crate based on an LSI-11 controller. The first application is an EKG gated single probe system for cardiac ejection fraction measurement. The second is the control system for a rectilinear scanner in a low level counting facility.

Two inexpensive automatic sample changers for use with automatic-cycling multichannel analyzers are described. Both small dry samples and small liquid samples can be used.

The philosophy and general test methods that can be used on a routine basis to assure the quality of medical imaging systems are summarized in this article. Quality assurance must be observed throughout the entire imaging process from the initial order for a particular procedure to the generation, interpretation, and reporting of results. Key areas of concern include the optimization of the decision process (selection of the proper imaging procedure or sequence of procedures); the utilization of contrast agents, pharmaceuticals (including radiopharmaceuticals), and pharmacologically enhanced imaging procedures; the biodistribution and dosimetry; and the possible side effects of external agents.

The data acquired by the new medical imaging techniques, in many ways, exceeded our ability to properly store, transmit and use the images produced. As diagnostic imaging procedures become progressively less invasive and traumatic, they are being applied to a much larger patient population. The decrease in memory and other instrumentation costs, along with expanded technological capability of computer systems, has provided medicine an opportunity to create network systems for the storage, processing, recall, and remote location of these diagnostic images. Therefore, problems of access and confidentiality have become increasingly important. This communication will consider certain medical, legal, and ethical aspects of these technologies of data acquisition, storage, manipulation and retrieval.

The ability of a series of bivalent haptens to bind and cross-link immunoglobulin E (IgE) in solution and on the surface of cells was examined. Several short (less than 30 A) dinitrophenyl (DNP) haptens were found to bind tightly to and cross-link a monoclonal anti-DNP IgE in solution, but these failed to trigger substantial release of 3H-serotonin from sensitized rat basophilic leukemia (RBL) cells or rat peritoneal mast cells. A longer bivalent hapten, approximately 50 A in length, consisting of two DNP-aminocaproyl-L-tyrosine (DCT) groups coupled to the alpha-amino groups of L-cystine was synthesized and characterized. This bivalent hapten [(DCT)2-cystine], binds very tightly to the same monoclonal anti-DNP IgE in solution and cross-links these antibodies to form higher mol. wt aggregates as judged by gel filtration and binding studies. It also stimulates degranulation of both RBL and mast cells sensitized with two different monoclonal anti-DNP IgE antibodies, with the mast cells exhibiting generally greater responsiveness to this ligand. The (DCT)2-cystine bivalent hapten appears to have the structural features necessary for carrying out detailed binding studies with receptor-bound IgE on the cell surface.

The location of the brain's symmetry axis on computerized tomography (CT) images was mathematically formulated. A series of computer programs were written to "peel off" the skull and artifacts external to the skull. Image lines were then tested for right-left symmetry and in each line a pixel was selected which best represented the center of symmetry of the skull contents. The resultant calculated symmetry line of images with and without pathology was comparable to the visually determined symmetry axis. This method permits computed screening for right-left asymmetry.

We have developed a method for use in investigating factors controlling the binding and cross-linking by bivalent haptens of immunoglobulin E (IgE) bound to receptors on rat basophilic leukemia (RBL) cells. This method employs monoclonal anti-2,4-dinitrophenyl (DNP) IgE that is labeled with fluorescein-5-isothiocyanate (FITC), and it measures FITC quenching that accompanies DNP occupation of the antibody combining sites in a titration experiment. The validity of this approach is demonstrated using the monovalent hapten DNP- l -lysine. The affinity constant for this ligand obtained by the FITC quenching method is compared with those obtained with previously established methods: equilibrium dialysis and quenching of endogenous tryptophan for IgE in solution and [3H]-DNP- l -lysine binding to IgE on cells. The FITC quenching method has been used to carry out a detailed study of the binding of monovalent DNP-aminocapryol l -tyrosine (DCT) and bivalent (DCT)2-cystine to FITC-IgE and its Fab fragments in solution. Intrinsic (K) and cross-linking (Kx) affinity constants are obtained by analyzing the binding curves in terms of simple equilibrium equations. With these DCT haptens the ability of this method to assess hapten binding and cross-linking of IgE bound to receptors on RBL cells is shown.

The authors describe a method for digitizing diagnostic ultrasonic data using a system originally constructed for use with radioisotope scan data. A commercial ultrasonic unit drives the transducer and amplifies the preliminary echo signal. The output signals from the ultrasonic unit are fed to a programmable digital logic interface coupled to a 4,096-word memory. The data can then be transferred directly to a PDP-9 computer for data manipulation or to computer-compatible magnetic tape for permanent storage.

"The benefits and risks of any particular GM crop depend on the interactions of its ecological functions and natural history with the agroecosystem and ecosystems within which it is embedded. These evolutionary and ecological factors must be considered when assessing GM crops. We argue that the assessment of GM crops should be broadened to include alternative agricultural practices, ecosystem management, and agricultural policy. Such an assessment would be facilitated by a clearer understanding of the indirect costs of agriculture and the ecological services that support it. The benefits of GM crops should be compared to those of other means of agricultural intensification such as organic farming, integrated pest management, and agricultural policy reform. A gradual and cautious approach to the use of GM crops that relies on a truly comprehensive risk assessment could allow people to reap substantial benefits from GM crops while mitigating their serious risks."

NUCLEAR magnetic resonance (NMR) imaging is a technique by which the quantitative analysis of a biological structure or tissue sample may be determined. The various approaches to be discussed in this article all depend on the fact that certain atomic nuclei behave as small magnets. When these nuclei are placed in static magnetic fields, some will align themselves in the direction of the field. In this configuration they will rotate about the field direction (precess) at a frequency that is dependent on the strength of the applied magnetic field (Bo). If in this circumstance these aligned and precessing nuclei are exposed to an alternating magnetic field (radio frequency [RF]) of the same frequency, some of these nuclei will be forced from their equilibrium state to a higher energy level. When the interrogating RF is removed, the excited nuclei will emit the added energy and return to their former state. The

To determine the most stable mode of internal fixation for the pathologic femoral shaft fracture with extensive cortical destruction, 2 fixation techniques incorporating methylmethacrylate were compared. Osteotomies through standardized cortical defects were created in intact embalmed femora to simulate a standard pathologic fracture. Fixation obtained with either intramedullary Schneider rods or 28-hold ASIF plates, both using bone cement, was compared in torsion and bending. In torsion, plate-fixed femora failed at a mean load of 71.2 newton-meters compared to 26.8 newton-meters for the Schneider rod counterparts. In bending, plate-fixed bones at a mean load of 8133.9 newtons compared to 1921.4 newtons for rod-fixed femora. Fixation with double plates and methylmethacrylate was clearly more stable and allowed for immediate pain-free ambulation.