Klaus Holliger

Human anti-self antibodies with high specificity from phage display libraries

Recently we demonstrated that human antibody fragments with binding activities against foreign antigens can be isolated from repertoires of rearranged V‐genes derived from the mRNA of peripheral blood lymphocytes (PBLs) from unimmunized humans. The heavy and light chain V‐genes were shuffled at random and cloned for display as single‐chain Fv (scFv) fragments on the surface of filamentous phage, and the fragments selected by binding of the phage to antigen. Here we show that from the same phage library we can make scFv fragments encoded by both unmutated and mutated V‐genes, with high specificities of binding to human self‐antigens. Several of the affinity purified scFv fragments were shown to be a mixture of monomers and dimers in solution by FPLC gel filtration and the binding kinetics of the dimers were determined using surface plasmon resonance (k(on) = 10(5)‐10(6) M‐1s‐1, k(off) = 10(−2)s‐1 and Ka = 10(7) M‐1). The kinetics of association are typical of known Ab‐protein interactions, but the kinetics of dissociation are relatively fast. For therapeutic application, the binding affinities of such antibodies could be improved in vitro by mutation and selection for slower dissociation kinetics.

Application of a new 2D time-domain full-waveform inversion scheme to crosshole radar data

Crosshole radar tomography is a useful tool in diverse investigations in geology, hydrogeology, and engineering. Conventional tomograms provided by standard ray-based techniques have limited resolution, primarily because only a fraction of the information contained in the radar data i.e., thefirst-arrivaltimesandmaximumfirst-cycleamplitudesis included in the inversion. To increase the resolution of radar tomograms,wehavedevelopedaversatilefull-waveforminversion scheme that is based on a finite-difference time-domain solution of Maxwell’s equations. This scheme largely accountsforthe3Dnatureofradar-wavepropagationandincludes an efficient method for extracting the source wavelet from the radar data.After demonstrating the potential of the newschemeontworealisticsyntheticdatasets,weapplyitto two crosshole field data sets acquired in very different geologic/hydrogeologic environments. These are the first applications of full-waveform tomography to observed crosshole radar data.The resolution of all full-waveform tomograms is showntobemarkedlysuperiortothatoftheassociatedraytomograms. Small subsurface features a fraction of the dominant radar wavelength and boundaries between distinct geological/hydrological units are sharply imaged in the fullwaveformtomograms.

A stochastic view of lower crustal fabric based on evidence from the Ivrea Zone

Despite its complicated history the Ivrea Zone is considered to be a representative surface exposure of extended continental crust. We have digitized two standard 1:25,000 geological maps from this area and evaluated their structural statistics. Because of the subvertical orientation of the Ivrea Zone these maps can be considered as small-scale cross sections through the lower continental crust. The autocorrelation functions of the digitized lithologies measured from these maps show a clear self-similar or fractal rather than a Gaussian or deterministic trend. We found that an anisotropic von Karman correlation function with an aspect ratio around 4 and a Hurst number of 0.3, corresponding to a fractal dimension of 2.7, matches the observed data. Our results represent an explicit confirmation of previous indirect evidence for the fractal nature of lithospheric heterogeneities and provide the means to construct realistic crustal-scale seismic models of Ivrea-type lower continental crust.

Full-Waveform Inversion of Crosshole Radar Data Based on 2-D Finite-Difference Time-Domain Solutions of Maxwell's Equations

Crosshole radar techniques are important tools for a wide range of geoscientific and engineering investigations. Unfortunately, the resolution of crosshole radar images may be limited by inadequacies of the ray tomographic methods that are commonly used in inverting the data. Since ray methods are based on high-frequency approximations and only account for a small fraction of the information contained in the radar traces, they are restricted to resolving relatively large-scale features. As a consequence, the true potential of crosshole radar techniques has yet to be realized. To address this issue, we introduce a full-waveform inversion scheme that is based on a finite-difference time-domain solution of Maxwells equations. We benchmark our new scheme on synthetic crosshole data generated from suites of increasingly complex models. The full-waveform tomographic images accurately reconstruct the following: (1) the locations, sizes, and electrical properties of isolated subwavelength objects embedded in homogeneous media; (2) the locations and sizes of adjacent subwavelength objects embedded in homogeneous media; (3) abrupt media boundaries and average and stochastic electrical property variations of heterogeneous layered models; and (4) the locations, sizes, and electrical conductivities of water-filled tunnels and closely spaced subwavelength pipes embedded in heterogeneous layered models. The new scheme is shown to be remarkably robust to the presence of uncorrelated noise in the radar data. Several limitations of the full-waveform tomographic inversion are also identified. For typical crosshole acquisition geometries and parameters, small resistive bodies and small closely spaced dielectric objects may be difficult to resolve. Furthermore, electrical property contrasts may be underestimated. Nevertheless, the full-waveform inversions usually provide substantially better results than those supplied by traditional ray methods.

Integration of diverse physical-property models: Subsurface zonation and petrophysical parameter estimation based on fuzzy c-means cluster analyses

Inversions of an individual geophysical data set can be highly nonunique, and it is generally difficult to determine petrophysical parameters from geophysical data. We show that both issues can be addressed by adopting a statistical multiparameter approach that requires the acquisition, processing, and separate inversion of two or more types of geophysical data. To combine information contained in the physical-property models that result from inverting the individual data sets and to estimate the spatial distribution of petrophysical parameters in regions where they are known at only a few locations, we demonstrate the potential of the fuzzy c -means (FCM) clustering technique. After testing this new approach on synthetic data, we apply it to limited crosshole georadar, crosshole seismic, gamma-log, and slug-test data acquired within a shallow alluvial aquifer. The derived multiparameter model effectively outlines the major sedimentary units observed in numerous boreholes and provides plausible estimates ...

Prestack depth migration of primary and surface-related multiple reflections: Part I — Imaging

Surface-related multiples (i.e., all seismic waves reflected at the free surface at least once) often severely contaminate seismic recordings. Because conventional imaging techniques require input data that consist of primary reflections only, significant processing effort is commonly dedicated to attenuating multiples prior to migration. On the other hand, surface-related multiples provide additional illumination of the subsurface and, therefore, should not be considered as noise. We present a prestack depth-migration method that allows primary and multiple reflections to be imaged simultaneously. Depth imaging using primary and multiple reflections (DIPMR) involves decomposing the datainto upgoing and downgoing wave constituents, followed by downward extrapolation. Artifacts generated by interference of upgoing and downgoing events not associated with the same subsurface reflection points (crosstalk) are attenuated by using a 2D deconvolution imaging condition. In contrast to existing methods, DIPMR doe...

Finite-difference modeling of electromagnetic wave propagation in dispersive and attenuating media

Realistic modeling of electromagnetic wave propagation in the radar frequency band requires a full solution of Maxwell’s equations as well as an adequate description of the material properties. We present a finite‐difference time‐domain (FDTD) solution of Maxwell’s equations that allows accounting for the frequency dependence of the dielectric permittivity and electrical conductivity typical of many near‐surface materials. This algorithm is second‐order accurate in time and fourth‐order accurate in space, conditionally stable, and computationally only marginally more expensive than its standard equivalent without frequency‐dependent material properties. Empirical rules on spatial wavefield sampling are derived through systematic investigations of the influence of various parameter combinations on the numerical dispersion curves. Since this algorithm intrinsically models energy absorption, efficient absorbing boundaries are implemented by surrounding the computational domain by a thin (⩽2 dominant waveleng...

Numerical modeling of borehole georadar data

High-frequency electromagnetic (EM) wave propagation phenomena associated with borehole georadar experiments are complex. To improve our understanding of the governing physical processes, we present a finite-difference solution of Maxwells equations in cylindrical coordinates. This approach allows us to model the full EM wavefield associated with borehole georadar experiments and to assess the adequacy of ray-based methods currently used to interpret the observed amplitudes. Our results indicate that because shallow boreholes are often water filled, the finite length of the boreholes as well as changes in material properties along a borehole wall can have major effects on the amplitude behavior of borehole georadar data. As a result of waveguide phenomena, the radiation pattern of a vertical electric dipole source located in a water-filled borehole may be distorted significantly with respect to the corresponding reference radiation pattern in a homogeneous medium. Even greater distortions of the radiation pattern result when the electric dipole source is located near material boundaries or near the upper or lower end of a borehole. This study indicates that some of the basic assumptions of conventional ray-based amplitude tomography often are not fulfilled for borehole georadar data and that the derived constraints on the attenuation and conductivity structure should be regarded as qualitative in nature. The algorithm and the results presented in this study do, however, offer the perspective to alleviate some of these inherent problems and thus help to make ray-based georadar attenuation tomography a more reliable and effective tool for probing the shallow subsurface.

The crust as a heterogeneous "optical" medium" or "crocodiles in the mist"

Abstract Based on petrophysical data, geologic maps, and a well log, we present statistical descriptions of likely upper-, middle-, and lower-crustal rocks to characterize the fine-scale heterogeneity observed in crustal exposures and inferred from deep-crustal seismic data. The statistical models, developed for granitic and metamorphic upper crust, and for an extended metamorphic lower crust, are used to construct whole-crustal models of seismic velocity heterogenity. We present finite-difference synthetic CMP data from several models which compare favorably with field data. The statistical models also permit classification of the seismic reflection experiment and the crustal heterogeneity according to scattering regime. The “optical”, or scattering properties of importance for classification are the velocity fluctuation intensity, the horizontal and vertical correlation lengths of the medium, the correlation function of the medium, and the velocity population function. For the crustal properties we measured, the bandwidth of a typical deep crustal experiment overlaps from the weak to the strong scattering regime, with implications for crustal seismic data processing and imaging. Notably, deep-crustal signals are likely to have experienced multiple scattering, making common seismic imaging techniques of questionable value. Moreover, the details of the unmigrated CMP stacked section bears little resemblance to the underlying medium.

Modal fields: A new method for characterization of random seismic velocity heterogeneity

Geologically and petrophysically constrained synthetic random velocity fields are important tools for exploring (through the application of numerical codes) the seismic response of small-scale lithospheric heterogeneities. Statistical and geophysical analysis of mid- and lower-crustal exposures has demonstrated that the probability density function for some seismic velocity fields is likely to be discrete rather than continuous. We apply the term “modal” fields to describe fields of this sort. This letter details a methodology for generating synthetic modal fields which satisfy the von Karman covariance function. In addition, we explore some of the mathematics of “modality”, and define a modality parameter which quantifies the variation between end members binary and continuous fields.