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W Nadler

Publications and source records attributed to W Nadler.

15 recordsLinked to original sources
PubMed1999

Theory of the BOLD effect in the capillary region: an analytical approach for the determination of T2 in the capillary network of myocardium.

This article presents an analytical approach for the quantification of the blood oxygen level dependent (BOLD) effect in the capillary region. The capillary geometry of myocardium is considered. The relaxation rate R*2 is determined as a function of the capillary radius Rc, the intracapillary volume fraction RBV, and the diffusion coefficient D. When the intracapillary volume fraction is small, the approximation R*2 = RBV x tau(-1) x (square root of (1+(taudeltaomega)2)-1) is valid, with the correlation time tau = (Rc2/4D) x (absolute value (ln RBV)/(1 - RBV)). The predictions of this model agree well with numerical simulations and experimental data of others and with data recently measured by our group.

Animals↗
PubMed1999

The relationship between the BOLD-induced T(2) and T(2)(*): a theoretical approach for the vasculature of myocardium.

Recently the blood oxygenation level-dependent (BOLD)-related T(2)* of myocardium was derived as an analytical function of intracapillary blood volume, blood oxygenation, and nuclear spin diffusion. The basis of this approach was to approximate the diffusion-induced field fluctuations a nuclear spin is subjected to by strong collision dynamics, i.e., the field fluctuations are uncorrelated. The same analysis is now performed for spin echo experiments that gives myocardial T(2) as a function of the parameters above and the echotime. An analytical relationship between T(2) and T(2)* relaxation is derived. The dependence of T(2) on diffusion, echo time, and blood oxygenation is congruent with simulation and experimental data. Magn Reson Med 42:1004-1010, 1999.

Animals↗
PubMed1998

Testing a new Monte Carlo algorithm for protein folding.

We demonstrate that the recently proposed pruned-enriched Rosenbluth method (PERM) (Grassberger, Phys. Rev. E 56:3682, 1997) leads to extremely efficient algorithms for the folding of simple model proteins. We test it on several models for lattice heteropolymers, and compare it to published Monte Carlo studies of the properties of particular sequences. In all cases our method is faster than the previous ones, and in several cases we find new minimal energy states. In addition to producing more reliable candidates for ground states, our method gives detailed information about the thermal spectrum and thus allows one to analyze thermodynamic aspects of the folding behavior of arbitrary sequences.

Algorithms↗
PubMed1997

Protein folding: optimized sequences obtained by simulated breeding in a minimalist model.

For a minimalist model of protein folding, which we introduced recently, we investigate various methods to obtain folding sequences. A detailed study of random sequences shows that, for this model, such sequences usually do not fold to their ground states during simulations. Straight-forward techniques for the construction of folding sequences, based solely on the target structure, fail. We describe in detail an optimization algorithm, based on genetic algorithms, for the "simulated breeding" of folding sequences in this model. We find that, for any target structure studied, there is not only a single folding sequence but a patch of sequences in sequence space that fold to this structure. In addition, we show that, much as in real proteins, nonhomologous sequences may fold to the same target structure.

Amino Acid Sequence↗
PubMed1996

Nested expression domains for odorant receptors in zebrafish olfactory epithelium.

The mapping of high-dimensional olfactory stimuli onto the two-dimensional surface of the nasal sensory epithelium constitutes the first step in the neuronal encoding of olfactory input. We have used zebrafish as a model system to analyze the spatial distribution of odorant receptor molecules in the olfactory epithelium by quantitative in situ hybridization. To this end, we have cloned 10 very divergent zebrafish odorant receptor molecules by PCR. Individual genes are expressed in sparse olfactory receptor neurons. Analysis of the position of labeled cells in a simplified coordinate system revealed three concentric, albeit overlapping, expression domains for the four odorant receptors analyzed in detail. Such regionalized expression should result in a corresponding segregation of functional response properties. This might represent the first step of spatial encoding of olfactory input or be essential for the development of the olfactory system.

Algorithms↗
PubMed1995

On constructing folding heteropolymers.

Simplified models of the protein-folding process have led to valuable insights into the generic properties of the folding of heteropolymers. On the basis of theoretical arguments, Shakhnovich and Gutin [(1993) Proc. Natl. Acad. Sci. USA 90, 7195-7199] have proposed a specific method to generate folding sequences for one of these. Here we present a model of folding in heteropolymers that is comparable in simplicity but different in spirit to the one studied by Shakhnovich and Gutin. In our model, the proposed recipe for constructing folding sequence fails. We find that, as a rule, the construction of folding sequences is impossible to achieve by looking at the native conformation only. Rather, competing conformations have to be taken into account too. An evolutionary algorithm that generates folding sequences by optimizing both stability of the native state and folding time is described. Remarkably, this algorithm produces, among others, sequences that fold reproducibly to metastable states.

Algorithms↗
PubMed1991

Biological transport processes and space dimension.

We discuss the generic time behavior of reaction-diffusion processes capable of modeling various types of biological transport processes, such as ligand migration in proteins and gating fluctuations in ion channel proteins. The main observable in these two cases, the fraction of unbound ligands and the probability of finding the channel in the closed state, respectively, exhibits an algebraic t-1/2 decay at intermediate times, followed by an exponential cutoff. We provide a simple framework for understanding these observations and explain their ubiquity by showing that these qualitative results are independent of space dimension. We also derive an experimental criterion to distinguish between a one-dimensional process and one whose effective dimension is higher.

Biological Transport↗
PubMed1987

Molecular and stochastic dynamics of proteins.

The rapid fluctuations of protein atoms derived from molecular dynamics simulations can be extrapolated to longer-time motions by effective single-particle stochastic models. This is demonstrated by an analysis of velocity autocorrelation functions for the atoms of lysine side chains in the active site of RNase A. The atomic motions are described by a bounded stochastic model with the friction and noise parameters determined from a molecular dynamics simulation. The low-frequency relaxation behavior is shown to result from collisional damping rather than dephasing. Extrapolation of these results to the quasistochastic motion of the heme group in myoglobin provides an explanation of 57Fe Mössbauer spectroscopic data.

Binding Sites↗
PubMed1985

A model for the lateral diffusion of "stiff" chains in a lipid bilayer.

We present random walk models for the diffusive motion of lipid probe molecules in a lipid bilayer and calculate the diffusion constants for probes spanning the entire bilayer and for probes extending through one lipid layer only. The "stiffness" of such molecules can explain the observed value of 2/3 for the ratio of these diffusion constants.

Diffusion↗
PubMed1984

Theory of Mössbauer spectra of proteins fluctuating between conformational substates.

Mössbauer spectra of 57Fe in proteins fluctuating between different conformational substates are evaluated by means of a two-sided Padée approximation, which can reproduce the low and high frequency dependence of the spectral line shape I(omega) to any desired accuracy. The dynamics of the atom is modeled as Brownian motion in a multiminimum potential and described by a Fokker-Planck equation. The Mössbauer spectrum is expanded in terms of Lorentzian contributions, which can be attributed separately to fluctuations between conformational substates (potential minima) and to relaxation within the substates. In the limit of closely spaced substates, the Mössbauer spectra can be accounted for by an effective diffusion coefficient with Arrhenius-type temperature dependence. We demonstrate that the observed temperature dependence of Mössbauer spectra of proteins [Parak, F., Knapp, E.W. & Kucheida, D. (1982) J. Mol. Biol. 161, 177-194] can be accounted for by stochastic motion in a multiminimum potential.

Binding Sites↗