VH-RELATED IDIOTOPES DETECTED BY SITE-DIRECTED MUTAGENESIS

The function of the CD4 cell surface protein as coreceptor on T helper lymphocytes and as receptor for HIV makes this glycoprotein a prime target for an immune intervention with mAb. A detailed understanding of the structural determinants on the therapeutic CD4 mAb that are involved in Ag binding or are recognized by anti-idiotypic mAb (anti-Id) may be important for designing antibodies with optimal therapeutic efficacy. Seven anti-Id raised against the CD4 mAb M-T310 were selected from a large panel with the intention to obtain CD4 mimicking structures with specificity foHr IV gp120. The selected anti-Id did not reacwt ith other CDCspecific mAb cross-blocking M-T310. Among these, mAb MT404, although having the same L chain as M-T310 and a VH region sequence differing onlya t 14 amino acid positions, was not recognized by the anti-Id. MT310 H chain complexed with the J558L L chain reacted with all anti-Id, thus demonstrating that the recognized idiotopes are located within the VH region. To identify the idiotopes of M-T310 seen by the anti-Id, variants of M-T404 containing one or more of the M-T3 1 O-derived substitutions were generated by oligonucleotide-directed mutagenesis. The reactivity pattern of the mutant proteins with the anti-Id demonstrated that the idiotopes reside within the complementarity determining region (CDR) 2 and CDR3 loops of the VH region. A major idiotope was definebdy a single amino acid in CDR2 that was recognized by three anti-Id, whereas the four other anti-Id reacted with determinants of CDR3. Although the performed amino acid substitutions did influence the Id recognition, Ag binding was not significantly affected, suggesting that none of the anti-Id can be considered as a mimicry of the CD4 A

The complexity of lattice knots

AbstractA family of polygonal knots Kn on the cubical lattice is constructed with the property that the quotient of length L(Kn) over the crossing number Cr(Kn) approaches zero as L approaches infinity. More precisely Cr(Kn) = O(L(Kn)43). It is shown that this construction is optimal in the sense that for any knot K on the cubical lattice with length L and Cr crossings Cr ⩽ 3.2L43

Statistical uncertainty of eddy flux–based estimates of gross ecosystem carbon exchange at Howland Forest, Maine

We present an uncertainty analysis of gross ecosystem carbon exchange (GEE) estimates derived from 7 years of continuous eddy covariance measurements of forest-atmosphere CO2fluxes at Howland Forest, Maine, USA. These data, which have high temporal resolution, can be used to validate process modeling analyses, remote sensing assessments, and field surveys. However, separation of tower-based net ecosystem exchange (NEE) into its components (respiration losses and photosynthetic uptake) requires at least one application of a model, which is usually a regression model fitted to nighttime data and extrapolated for all daytime intervals. In addition, the existence of a significant amount of missing data in eddy flux time series requires a model for daytime NEE as well. Statistical approaches for analytically specifying prediction intervals associated with a regression require, among other things, constant variance of the data, normally distributed residuals, and linearizable regression models. Because the NEE data do not conform to these criteria, we used a Monte Carlo approach (bootstrapping) to quantify the statistical uncertainty of GEE estimates and present this uncertainty in the form of 90% prediction limits. We explore two examples of regression models for modeling respiration and daytime NEE: (1) a simple, physiologically based model from the literature and (2) a nonlinear regression model based on an artificial neural network. We find that uncertainty at the half-hourly timescale is generally on the order of the observations themselves (i.e., ∼100%) but is much less at annual timescales (∼10%). On the other hand, this small absolute uncertainty is commensurate with the interannual variability in estimated GEE. The largest uncertainty is associated with choice of model type, which raises basic questions about the relative roles of models and data

Crustal structure beneath the Trondelag Platform and adjacent areas of the Mid-Norwegian margin, as derived from wide-angle seismic and potential field data

The outer mid-Norwegian margin is characterized by strong breakup magmatism and has been extensively surveyed. The crustal structure of the inner continental shelf, however, is less studied, and its relation to the onshore geology, Caledonian structuring, and breakup magmatism remains unclear. Two Ocean Bottom Seismometer profiles were acquired across the Trøndelag Platform in 2003, as part of the Euromargins program. Additional-land stations recorded the marine shots. The P-wave data were modeled by ray-tracing, supported by gravity modeling. Older multi-channel seismic data allowed for interpretation of stratigraphy down to the top of the Triassic. Crystalline basement velocity is ~6 km s-1 onshore. Top basement is difficult to identify offshore, as velocities (5.3-5.7 km s-1) intermediate between typical crystalline crust and Mesozoic sedimentary strata appear 50-80 km from the coast. This layer thickens towards the Klakk-Ytreholmen Fault Complex and predates Permian and later structur-ing. The velocities indicate sedimentary rocks, most likely Devonian. Onshore late- to post-Caledonian detachments have been proposed to extend offshore, based on the magnetic anomaly pattern. We do not find the expected correlation between upper basement velocity structure and detachments. However, there is a distinct, dome-shaped lower-crustal body with a velocity of 6.6-7.0 km s-1. This is thickest under the Froan Basin, and the broad magnetic anomaly used to delineate the detachments correlates with this. The proposed offshore continuation of the detachments thus appears- unreliable. While we find indications of high density and velocity (~7.2 km s-1) lower crust under the Rås Basin, similar to the proposed igneous underplating of the outer margin, this is poorly constrained near the end of our profiles. The gravity field indicates that this body may be continuous from the pre-breakup basement structures of the Utgard High to the Frøya High, suggesting that it could be an island arc or oceanic terrane-accreted during the Caledonian orogeny. Thus, we find no clear evidence of early Cenozoic igneous underplating of the inner part of the shelf

Laplacian modes probing gauge fields

We show that low-lying eigenmodes of the Laplace operator are suitable to represent properties of the underlying SU(2) lattice configurations. We study this for the case of finite temperature background fields, yet in the confinement phase. For calorons as classical solutions put on the lattice, the lowest mode localizes one of the constituent monopoles by a maximum and the other one by a minimum, respectively. We introduce adjustable phase boundary conditions in the time direction, under which the role of the monopoles in the mode localization is interchanged. Similar hopping phenomena are observed for thermalized configurations. We also investigate periodic and antiperiodic modes of the adjoint Laplacian for comparison. In the second part we introduce a new Fourier-like low-pass filter method. It provides link variables by truncating a sum involving the Laplacian eigenmodes. The filter not only reproduces classical structures, but also preserves the confining potential for thermalized ensembles. We give a first characterization of the structures emerging from this procedure.Comment: 43 pages, 26 figure

Design and control of spin gates in two quantum dots arrays

We study the spin-spin interaction between quantum dots coupled through a two dimensional electron gas with spin-orbit interaction. We show that the interplay between transverse electron focusing and spin-orbit coupling allows to dynamically change the symmetry of the effective spin-spin Hamiltonian. That is, the interaction can be changed from Ising-like to Heisenberg-like and vice versa. The sign and magnitude of the coupling constant can also be tuned.Comment: 4 pages, 3 figure

Joint modeling of ChIP-seq data via a Markov random field model

Chromatin ImmunoPrecipitation-sequencing (ChIP-seq) experiments have now become routine in biology for the detection of protein-binding sites. In this paper, we present a Markov random field model for the joint analysis of multiple ChIP-seq experiments. The proposed model naturally accounts for spatial dependencies in the data, by assuming first-order Markov dependence and, for the large proportion of zero counts, by using zero-inflated mixture distributions. In contrast to all other available implementations, the model allows for the joint modeling of multiple experiments, by incorporating key aspects of the experimental design. In particular, the model uses the information about replicates and about the different antibodies used in the experiments. An extensive simulation study shows a lower false non-discovery rate for the proposed method, compared with existing methods, at the same false discovery rate. Finally, we present an analysis on real data for the detection of histone modifications of two chromatin modifiers from eight ChIP-seq experiments, including technical replicates with different IP efficiencies

Tunneling limit of heavy-fermion point contacts

We present results for a multichannel tunneling model that describes point-contact spectra between a metallic tip and a superconducting heavy-fermion system. We calculate tunneling spectra both in the normal and superconducting state. In point-contact and scanning tunneling spectroscopy many heavy-fermion materials, like CeCoIn5, exhibit an asymmetric differential conductance, dI/dV, combined with a strongly suppressed Andreev reflection signal in the superconducting state. For Andreev reflection to occur a junction has to be in the highly transparent limit. Here we focus on the opposite limit, namely that of low transparency leading to BCS-like dI/dV curves. We discuss the consequences of a multichannel tunneling model for CeCoIn5 assuming itinerant electron bands and localized f electrons.Comment: Contribution at SCES-201

Local demands on sterile neutrinos

In a model independent manner, we explore the local implications of a single neutrino oscillation measurement which cannot be reconciled within a three-neutrino theory. We examine this inconsistency for a single region of baseline to neutrino energy $L/E$. Assuming that sterile neutrinos account for the anomaly, we find that the {\it local} demands of this datum can require the addition to the theory of one to three sterile neutrinos. We examine the constraints which can be used to determine when more than one neutrino would be required. The results apply only to a given region of $L/E$. The question of the adequacy of the sterile neutrinos to satisfy a global analysis is not addressed here. Finally, using the results of a 3+2 analysis, we indicate values for unknown mixing matrix elements which would require two sterile neutrinos due to local demands only.Comment: 11 pages, 1 figure, discussion adde