Biomedical subjects

A Heine

Publications and source records attributed to A Heine.

At least 19 recordsLinked to original sources

PubMed2006

Spectral statistics in an open parametric billiard system.

We present experimental results on the eigenfrequency statistics of a superconducting, chaotic microwave billiard containing a rotatable obstacle. Deviations of the spectral fluctuations from predictions based on Gaussian orthogonal ensembles of random matrices are found. They are explained by treating the billiard as an open scattering system in which microwave power is coupled in and out via antennas. To study the interaction of the quantum (or wave) system with its environment, a highly sensitive parametric correlator is used.

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PubMed2005

Experimental investigations of chaos-assisted tunneling in a microwave annular billiard.

We present detailed investigations of the experimental signatures of chaos-assisted tunneling in the two-dimensional annular billiard, as already summarized in Phys. Rev. Lett. 84, 867 (2000). We have performed analog experiments with two-dimensional, electromagnetic resonators allowing for a direct simulation of the corresponding quantum system. Spectra from a superconducting cavity with a high-frequency resolution are combined with electromagnetic intensity distributions of high spatial resolution experimentally determined using a normal conducting twin cavity. Thereby all eigenmodes were obtained with properly identified quantum numbers. Besides distributions of quasi-doublet splittings, which serve as fundamental observables for the tunneling between whispering gallery types of modes, we also focus on the distributions of resonance widths of the doublets. These directly reflect the role of lifetime of certain modes in the tunneling process. Here, as theoretically expected, the class of so-called beach modes is found to play a particular role in mediating between regular and chaotic states to enhance the tunneling strength. This behavior is found in the spectrum and also in the structure of the wave functions.

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PubMed2005

Distribution of resonance strengths in microwave billiards of mixed and chaotic dynamics.

A new measure for statistical properties of the wave function components of quantum systems, the distribution of the product of two partial widths, is introduced. It is tested with data obtained in analog experiments with microwave billiards, where the product of two partial widths equals the resonance strengths in the microwave spectra. The billiards are from the family of the Limaçons, one with chaotic and two with mixed classical dynamics. For completely chaotic systems the partial widths generically obey a Porter-Thomas distribution. We show that in this case the distribution of their product equals a K0 distribution. While we find deviations of the experimental strength distribution from the K0 distribution for the billiards with mixed dynamics, the distributions agree perfectly for the chaotic billiard, when taking into account the experimental threshold of detection in the theoretical description. Hence, the strength distribution provides another stringent test for the connection between statistical properties of systems with classical chaotic dynamics and random matrix theory.

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PubMed2005

Test of a numerical approach to the quantization of billiards.

A method for computing large numbers of eigenvalues of self-adjoint elliptic operators [J. Comput. Phys. 184, 321 (2003)] is tested in numerical studies of the spectral properties of quantum billiards. To this extent, we study a time-reversal invariant quantum billiard of threefold symmetry, that undergoes a transformation in its symmetry properties from C(3v) to C3 . Thereby a transition from Gaussian orthogonal to Gaussian unitary ensemble statistics is observed, verifying earlier experimental indications and theoretical predictions. At the same time our numerical ansatz is shown to be applicable to arbitrary billiard shapes.

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PubMed2004

First experimental evidence for quantum echoes in scattering systems.

A self-pulsing effect termed quantum echoes has been observed in experiments with an open superconducting and a normal conducting microwave billiard whose geometry provides soft chaos, i.e., a mixed phase space portrait with a large stable island. For such systems a periodic response to an incoming pulse has been predicted. Its period has been associated with the degree of development of a horseshoe describing the topology of the classical dynamics. The experiments confirm this picture and reveal the topological information.

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PubMed2004

Encircling an exceptional point.

We calculate analytically the geometric phases that the eigenvectors of a parametric dissipative two-state system described by a complex symmetric Hamiltonian pick up when an exceptional point (EP) is encircled. An EP is a parameter setting where the two eigenvalues and the corresponding eigenvectors of the Hamiltonian coalesce. We show that it can be encircled on a path along which the eigenvectors remain approximately real and discuss a microwave cavity experiment, where such an encircling of an EP was realized. Since the wave functions remain approximately real, they could be reconstructed from the nodal lines of the recorded spatial intensity distributions of the electric fields inside the resonator. We measured the geometric phases that occur when an EP is encircled four times and thus confirmed that for our system an EP is a branch point of fourth order.

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PubMed2003

R-matrix theory of driven electromagnetic cavities.

The resonances of cylindrical symmetric microwave cavities are analyzed in R-matrix theory, which transforms the input channel conditions to the output channels. Single and interfering double resonances are studied and compared with experimental results obtained with superconducting microwave cavities. Because of the equivalence of the two-dimensional Helmholtz and the stationary Schrödinger equations, the results give insight into the resonance structure of regular and chaotic quantum billiards.

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PubMed2003

Observation of a chiral state in a microwave cavity.

A microwave experiment has been realized to measure the phase difference of the oscillating electric field at two points inside the cavity. The technique has been applied to a dissipative resonator which exhibits a singularity-called exceptional point-in its eigenvalue and eigenvector spectrum. At the singularity, two modes coalesce with a phase difference of pi/2. We conclude that the state excited at the singularity has a definitive chirality.

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PubMed2003

Phase shift experiments identifying Kramers doublets in a chaotic superconducting microwave billiard of threefold symmetry.

The spectral properties of a two-dimensional microwave billiard showing threefold symmetry have been studied with a new experimental technique. This method is based on the behavior of the eigenmodes under variation of a phase shift between two input channels, which strongly depends on the symmetries of the eigenfunctions. Thereby a complete set of 108 Kramers doublets has been identified by a simple and purely experimental method. This set clearly shows Gaussian unitary ensemble statistics, although the system is time-reversal invariant.

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PubMed2002

Experimental test of a trace formula for a chaotic three-dimensional microwave cavity.

We have measured resonance spectra in a superconducting microwave cavity with the shape of a three-dimensional generalized Bunimovich stadium billiard and analyzed their spectral fluctuation properties. The experimental length spectrum exhibits contributions from periodic orbits of nongeneric modes and from unstable periodic orbits of the underlying classical system. It is well reproduced by our theoretical calculations based on the trace formula derived by Balian and Duplantier for chaotic electromagnetic cavities.

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PubMed2001

Engagement of the Fc epsilon RI stimulates the production of IL-16 in Langerhans cell-like dendritic cells.

Preferential uptake and presentation of IgE-bound allergens by epidermal Langerhans cells (LC) via the high affinity IgE receptor, FcepsilonRI, is regarded as an important mechanism in the induction of cutaneous inflammation in atopic dermatitis. Here, we show that activation of monocyte-derived LC-like dendritic cells (LLDC) through engagement of FcepsilonRI induces the expression of IL-16, a chemoattractant factor for dendritic cells, CD4+ T cells, and eosinophils. We found that ligation of FcepsilonRI on LLDC derived from atopic dermatitis patients that express high levels of FcepsilonRI increases IL-16 mRNA expression and storage of intracellular IL-16 protein and enhances the secretion of mature IL-16 in a biphasic manner. An early release of IL-16 (peak at 4 h) is independent of protein synthesis, while a more delayed release (peak at 12 h) requires protein synthesis and occurs subsequent to the induction of IL-16 mRNA and intracellular accumulation of pro-IL-16. There was evidence that LLDC use caspase-1 to process IL-16, as inhibition of caspase-1, but not of caspase-3, partially prevented the release of IL-16 in response to ligation of FcepsilonRI. In an in vivo model of IgE-dependent LC activation, the atopy patch test, positive skin reactions were also associated with the induction of IL-16 in epidermal dendritic cells. These data indicate that IL-16 released from LC after allergen-mediated activation through FcepsilonRI may link IgE-driven and cellular inflammatory responses in diseases such as atopic dermatitis.

Caspase 1↗

PubMed2001

Structural basis for a disfavored elimination reaction in catalytic antibody 1D4.

Murine antibody 1D4 selectively catalyzes a highly disfavored beta-elimination reaction. Crystal structures of unliganded 1D4 and 1D4 in complex with a transition-state analog (TSA) have elucidated a possible general base mode of catalysis. The structures of the unliganded and liganded Fabs were determined to 1.80 and 1.85 A resolution, respectively. The structure of the complex reveals a binding pocket with high shape complementarity to the TSA, which is recruited to coerce the substrate into the sterically demanding, eclipsed conformation that is required for catalysis. A histidine residue and two water molecules are likely involved in the catalysis. The structure supports either a concerted E2 or stepwise E1cB-like mechanism for elimination. Finally, the liganded 1D4 structure shows minor conformational rearrangements in CDR H2, indicative of induced-fit binding of the hapten. 1D4 has pushed the boundaries of antibody-mediated catalysis into the realm of disfavored reactions and, hence, represents an important milestone in the development of this technology.

Animals↗

PubMed2001

Observation of covalent intermediates in an enzyme mechanism at atomic resolution.

In classical enzymology, intermediates and transition states in a catalytic mechanism are usually inferred from a series of biochemical experiments. Here, we derive an enzyme mechanism from true atomic-resolution x-ray structures of reaction intermediates. Two ultra-high resolution structures of wild-type and mutant d-2-deoxyribose-5-phosphate (DRP) aldolase complexes with DRP at 1.05 and 1.10 angstroms unambiguously identify the postulated covalent carbinolamine and Schiff base intermediates in the aldolase mechanism. In combination with site-directed mutagenesis and (1)H nuclear magnetic resonance, we can now propose how the heretofore elusive C-2 proton abstraction step and the overall stereochemical course are accomplished. A proton relay system appears to activate a conserved active-site water that functions as the critical mediator for proton transfer.

Aldehyde-Lyases↗

PubMed2001

Crystal structure of a cocaine-binding antibody.

Murine monoclonal antibody GNC92H2 was elicited by active immunization with a cocaine immunoconjugate and binds free cocaine with excellent specificity and moderate affinity. Improvement of affinity, as well as humanization of GNC92H2, would be advantageous in immunopharmacotherapy for cocaine addiction, and for emergency cases of drug overdose. Toward this end, the crystal structure of an engineered murine-human chimeric Fab of GNC92H2 complexed with cocaine was determined at 2.3 A resolution. Structural analysis reveals a binding pocket with high shape and charge complementarity to the cocaine framework, which explains the specificity for cocaine, as opposed to the pharmacologically inactive cocaine metabolites. Importantly, the structure provides a foundation for mutagenesis to enhance the binding affinity for cocaine and potent cocaine derivatives, such as cocaethylene, and for additional humanization of the antibody.

Animals↗

PubMed2001

First experimental test of a trace formula for billiard systems showing mixed dynamics.

In general, trace formulas relate the density of states for a given quantum mechanical system to the properties of the periodic orbits of its classical counterpart. Here we report for the first time on a semiclassical description of microwave spectra taken from superconducting billiards of the Limaçon family showing mixed dynamics in terms of a generalized trace formula derived by Ullmo et al. [Phys. Rev. E 54, 136 (1996)]. This expression not only describes mixed-typed behavior but also the limiting cases of fully regular and fully chaotic systems and thus presents a continuous interpolation between the Berry-Tabor and Gutzwiller formulas.

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PubMed2001

Experimental observation of the topological structure of exceptional points.

We report on a microwave cavity experiment where exceptional points (EPs), which are square root singularities of the eigenvalues as function of a complex interaction parameter, are encircled in the laboratory. The real and imaginary parts of an eigenvalue are given by the frequency and width of a resonance and the eigenvectors by the field distributions. Repulsion of eigenvalues--always associated with EPs--implies frequency anticrossing (crossing) whenever width crossing (anticrossing) is present. The eigenvalues and eigenvectors are interchanged while encircling an EP, but one of the eigenvectors undergoes a sign change which can be discerned in the field patterns.

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PubMed2000

Using antibody catalysis to study the outcome of multiple evolutionary trials of a chemical task.

Catalytic aldolase antibodies generated by immunization with two different, but structurally related, beta-diketone haptens were cloned and sequenced to study similarities and differences between independently evolved catalysts. Kinetic and sequence analysis coupled with mutagenesis, structural, and modeling studies reveal that the defining event in the evolution of these catalysts was a somatic mutation that placed a lysine residue in a deep, yet otherwise unrefined, hydrophobic pocket. We suggest that covalent chemistries may be as readily selected from the immune repertoire as the traditional noncovalent interactions that have formed the basis of immunochemistry until this time. Further, we believe that these experiments recapitulate the defining events in the evolution of nature's enzymes, particularly as they relate to chemical mechanism, catalytic promiscuity, and gene duplication.

Amino Acid Sequence↗

PubMed2000

First experimental evidence for chaos-assisted tunneling in a microwave annular billiard

We report on first experimental signatures for chaos-assisted tunneling in a two-dimensional annular billiard. Measurements of microwave spectra from a superconducting cavity with high frequency resolution are combined with electromagnetic field distributions experimentally determined from a normal conducting twin cavity with high spatial resolution to resolve eigenmodes with properly identified quantum numbers. Distributions of quasidoublet splittings serve as basic observables for the tunneling between whispering gallery-type modes localized to congruent, but distinct tori which are coupled weakly to irregular eigenstates associated with the chaotic region in phase space.

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