Microwave graph analogs for the voltage drop in three-terminal devices with orthogonal, unitary, and symplectic symmetry.

Transmission measurements through three-port microwave graphs are performed, in analogy to three-terminal voltage drop devices with orthogonal, unitary, and symplectic symmetry. The terminal used as a probe is symmetrically located between two chaotic subgraphs, and each graph is connected to one port, the input and the output, respectively. The analysis of the experimental data clearly exhibits the weak localization and antilocalization phenomena. We find a good agreement with theoretical predictions, provided that the effects of dissipation and imperfect coupling to the ports are taken into account.

Microwave Realization of the Chiral Orthogonal, Unitary, and Symplectic Ensembles.

Random matrix theory has proven very successful in the understanding of the spectra of chaotic systems. Depending on symmetry with respect to time reversal and the presence or absence of a spin 1/2 there are three ensembles, the Gaussian orthogonal (GOE), Gaussian unitary (GUE), and Gaussian symplectic (GSE) one. With a further particle-antiparticle symmetry the chiral variants of these ensembles, the chiral orthogonal, unitary, and symplectic ensembles (the BDI, AIII, and CII in Cartan's notation) appear. We exhibit a microwave setup based on a linear chain of evanescently coupled dielectric cylindrical resonators allowing us to study all three chiral ensembles experimentally. In all cases the predicted repulsion behavior between positive and negative eigenvalues for energies close to zero could be verified.

Spectra and spectral correlations of microwave graphs with symplectic symmetry.

Following an idea by Joyner et al. [Europhys. Lett. 107, 50004 (2014)EULEEJ0295-507510.1209/0295-5075/107/50004], a microwave graph with antiunitary symmetry T obeying T^{2}=-1 has been realized, thus mimicking a spin-1/2 system. The Kramers doublets expected for such systems have been clearly identified and could be lifted by a perturbation which breaks the antiunitary symmetry. The observed spectral level-spacing distribution of the Kramers doublets agreed with the predictions from the Gaussian symplectic ensemble (GSE), expected for chaotic systems with such a symmetry. In addition, we studied the random matrix equivalents of the used graphs both analytically and numerically. Here small deviations from the GSE level-spacing distribution were found, too small to be seen in the experiment but clearly visible in the simulations. Furthermore, results on the two-point correlation function, the spectral form factor, the number variance, and the spectral rigidity are presented, as well as on the transition from Gaussian symplectic to Gaussian orthogonal statistics by continuously changing T from T^{2}=-1 to T^{2}=1.

Microwave Realization of the Gaussian Symplectic Ensemble.

Following an idea by Joyner et al. [Europhys. Lett. 107, 50004 (2014)], a microwave graph with an antiunitary symmetry T obeying T^{2}=-1 is realized. The Kramers doublets expected for such systems are clearly identified and can be lifted by a perturbation which breaks the antiunitary symmetry. The observed spectral level spacings distribution of the Kramers doublets is in agreement with the predictions from the Gaussian symplectic ensemble expected for chaotic systems with such a symmetry.

Microwave experiments in the realm of fidelity.

In this review article, we will demonstrate the power of microwave experiments in the realm of fidelity also known as Loschmidt echoes. As the determination of the fidelity itself is experimentally tedious and error prone, we will introduce the scattering fidelity which under the conditions of chaotic systems and weak coupling approaches the fidelity itself. The main ingredient in fidelity investigations is the type and strength of a perturbation. The perturbations presented here will be both global and local boundary perturbations, as well as local perturber movements but also the change of coupling to the environment. All these perturbations will produce their own fidelity decay as a function of the perturbation strength, which will be discussed in this article.

Lossy chaotic electromagnetic reverberation chambers: Universal statistical behavior of the vectorial field.

The effective Hamiltonian formalism is extended to vectorial electromagnetic waves in order to describe statistical properties of the field in reverberation chambers. The latter are commonly used in electromagnetic compatibility tests. As a first step, the distribution of wave intensities in chaotic systems with varying opening in the weak coupling limit for scalar quantum waves is derived by means of random matrix theory. In this limit the only parameters are the modal overlap and the number of open channels. Using the extended effective Hamiltonian, we describe the intensity statistics of the vectorial electromagnetic eigenmodes of lossy reverberation chambers. Finally, the typical quantity of interest in such chambers, namely, the distribution of the electromagnetic response, is discussed. By determining the distribution of the phase rigidity, describing the coupling to the environment, using random matrix numerical data, we find good agreement between the theoretical prediction and numerical calculations of the response.

Aggravation of left ventricular dysfunction in patients with biopsy-proven cardiac human herpesvirus A and B infection.

BACKGROUND: Human herpesvirus 6 (HHV-6) A and B are lymphotropic viruses with life-long persistence, primarily associated with non-cardiac diseases, and discussed as a possible etiologic factor of myocarditis and cardiomyopathy. OBJECTIVE: To analyze the long-term spontaneous course of cardiac patients suffering from suspected inflammatory cardiomyopathy (CMi) with persisting HHV-6 A and B infections by follow-up biopsies. STUDY DESIGN: We prospectively evaluated patients (n=73) with biopsy-proven viral HHV-6 A and B infection in endomyocardial biopsies (EMBs), followed up by reanalysis of EMBs and left ventricular ejection fraction (LV-EF) measurements after a median period of 8.8 months (range 4-73 months). Beyond, we studied HHV-6 prevalence in isolated peripheral blood cells (PBCs) and HHV-6 species in EMBs. HHV-6 species-specific cellular infection sites within the myocardium were identified by immunohistochemistry (IHC). RESULTS: We identified 73 patients with cardiac HHV-6 A and B persistence or newly detected in follow-up EMB (95.0% B). Proof of HHV-6 in PBCs was primarily associated with A. Persistence of cardiac HHV-6 B genome was significantly associated with cardiac dysfunction at follow-up (LV-EF deteriorated from 58.2±16.0 to 51.8±17.2%, p<0.001), and LV improvement was observed when HHV-6 B persistence resolved (LV-EF increased from 54.9±15.4 to 60.7±13.1%, p<0.001). CONCLUSIONS: Persistence of cardiac HHV-6 B genomes was significantly associated with cardiac dysfunction, and hemodynamic parameters improved in association with HHV-6 B clearance.

Analyses of germline, chromosomally integrated human herpesvirus 6A and B genomes indicate emergent infection and new inflammatory mediators.

Human herpesvirus-6A (HHV-6A) is rarer than HHV-6B in many infant populations. However, they are similarly prevalent as germline, chromosomally integrated genomes (ciHHV-6A/B). This integrated form affects 0.1-1 % of the human population, where potentially virus gene expression could be in every cell, although virus relationships and health effects are not clear. In a Czech/German patient cohort ciHHV-6A was more common and diverse than ciHHV-6B. Quantitative PCR, nucleotide sequencing and telomeric integration site amplification characterized ciHHV-6 in 44 German myocarditis/cardiomyopathy and Czech malignancy/inflammatory disease (MI) patients plus donors. Comparisons were made to sequences from global virus reference strains, and blood DNA from childhood-infections from Zambia (HHV-6A mainly) and Japan (HHV-6B). The MI cohort were 86 % (18/21) ciHHV-6A, the cardiac cohort 65 % (13/20) ciHHV-6B, suggesting different disease links. Reactivation was supported by findings of 1) recombination between ciHHV-6A and HHV-6B genes in 20 % (4/21) of the MI cohort; 2) expression in a patient subset, of early/late transcripts from the inflammatory mediator genes chemokine receptor U51 and chemokine U83, both identical to ciHHV-6A DNA sequences; and 3) superinfection shown by deep sequencing identifying minor virus-variants only in ciHHV-6A, which expressed transcripts, indicating virus infection reactivates latent ciHHV-6A. Half the MI cohort had more than two copies per cell, median 5.2, indicative of reactivation. Remarkably, the integrated genomes encoded the secreted-active form of virus chemokines, rare in virus from childhood-infections. This shows integrated virus genomes can contribute new human genes with links to inflammatory pathology and supports ciHHV-6A reactivation as a source for emergent infection.

Experimental Width Shift Distribution: A Test of Nonorthogonality for Local and Global Perturbations.

The change of resonance widths in an open system under a perturbation of its interior has been recently introduced by Fyodorov and Savin [Phys. Rev. Lett. 108, 184101 (2012)] as a sensitive indicator of the nonorthogonality of resonance states. We experimentally study universal statistics of this quantity in weakly open two-dimensional microwave cavities and reverberation chambers realizing scalar and electromagnetic vector fields, respectively. We consider global as well as local perturbations, and also extend the theory to treat the latter case. The influence of the perturbation type on the width shift distribution is more pronounced for many-channel systems. We compare the theory to experimental results for one and two attached antennas and to numerical simulations with higher channel numbers, observing a good agreement in all cases.

Improved diagnosis of idiopathic giant cell myocarditis and cardiac sarcoidosis by myocardial gene expression profiling.

AIMS: Improvement of clinical diagnostics of idiopathic giant cell myocarditis (IGCM) and cardiac sarcoidosis (CS), two frequently fatal human myocardial diseases. Currently, IGCM and CS are diagnosed based on differential patterns of inflammatory cell infiltration and non-caseating granulomas in histological sections of endomyocardial biopsies (EMBs), after heart explantation or postmortem. We report on a method for improved differential diagnosis by myocardial gene expression profiling in EMBs. METHODS AND RESULTS: We examined gene expression profiles in EMBs from 10 patients with histopathologically proven IGCM, 10 with CS, 18 with active myocarditis (MCA), and 80 inflammation-free control subjects by quantitative RT-QPCR. We identified distinct differential profiles that allowed a clear discrimination of tissues harbouring giant cells (IGCS, CS) from those with MCA or inflammation-free controls. The expression levels of genes coding for cytokines or chemokines (CCL20, IFNB1, IL6, IL17D; P < 0.05), cellular receptors (ADIPOR2, CCR5, CCR6, TLR4, TLR8; P < 0.05), and proteins involved in the mitochondrial energy metabolism (CPT1, CYB, DHODH; P < 0.05) were deregulated in 2- to 300-fold, respectively. Bioinformatic analyses and correlation of the gene expression data with immunohistochemical findings provided novel information regarding the differential cellular and molecular pathomechanisms in IGCM, CS, and MCA. CONCLUSION: Myocardial gene expression profiling is a reliable method to predict the presence of multinuclear giant cells in the myocardium, even without a direct histological proof, in single small EMB sections, and thus to reduce the risk of sampling errors. This profiling also facilitates the discrimination between IGCM and CS, as two different clinical entities that require immediate and tailored differential therapy.

First experimental realization of the Dirac oscillator.

We present the first experimental microwave realization of the one-dimensional Dirac oscillator, a paradigm in exactly solvable relativistic systems. The experiment relies on a relation of the Dirac oscillator to a corresponding tight-binding system. This tight-binding system is implemented as a microwave system by a chain of coupled dielectric disks, where the coupling is evanescent and can be adjusted appropriately. The resonances of the finite microwave system yield the spectrum of the one-dimensional Dirac oscillator with and without a mass term. The flexibility of the experimental setup allows the implementation of other one-dimensional Dirac-type equations.

Experimental observation of a fundamental length scale of waves in random media.

Waves propagating through a weakly scattering random medium show a pronounced branching of the flow accompanied by the formation of freak waves, i.e., extremely intense waves. Theory predicts that this strong fluctuation regime is accompanied by its own fundamental length scale of transport in random media, parametrically different from the mean free path or the localization length. We show numerically how the scintillation index can be used to assess the scaling behavior of the branching length. We report the experimental observation of this scaling using microwave transport experiments in quasi-two-dimensional resonators with randomly distributed weak scatterers. Remarkably, the scaling range extends much further than expected from random caustics statistics.

A distinct subgroup of cardiomyopathy patients characterized by transcriptionally active cardiotropic erythrovirus and altered cardiac gene expression.

Recent studies have detected erythrovirus genomes in the hearts of cardiomyopathy and cardiac transplant patients. Assessment of the functional status of viruses may provide clinically important information beyond detection of the viral genomes. Here, we report transcriptional activation of cardiotropic erythrovirus to be associated with strongly altered myocardial gene expression in a distinct subgroup of cardiomyopathy patients. Endomyocardial biopsies (EMBs) from 415 consecutive cardiac erythrovirus (B19V)-positive patients with clinically suspected cardiomyopathy were screened for virus-encoded VP1/VP2 mRNA indicating transcriptional activation of the virus, and correlated with cardiac host gene expression patterns in transcriptionally active versus latent infections, and in virus-free control hearts. Transcriptional activity was detected in baseline biopsies of only 66/415 patients (15.9 %) harbouring erythrovirus. At the molecular level, significant differences between cardiac B19V-positive patients with transcriptionally active versus latent virus were revealed by expression profiling of EMBs. Importantly, latent B19V infection was indistinguishable from controls. Genes involved encode proteins of antiviral immune response, B19V receptor complex, and mitochondrial energy metabolism. Thus, functional mapping of erythrovirus allows definition of a subgroup of B19V-infected cardiomyopathy patients characterized by virus-encoded VP1/VP2 transcripts and anomalous host myocardial transcriptomes. Cardiac B19V reactivation from latency, as reported here for the first time, is a key factor required for erythrovirus to induce altered cardiac gene expression in a subgroup of cardiomyopathy patients. Virus genome detection is insufficient to assess pathogenic potential, but additional transcriptional mapping should be incorporated into future pathogenetic and therapeutic studies both in cardiology and transplantation medicine.

Experimental observation of the spectral gap in microwave n-disk systems.

Symmetry reduced three-disk and five-disk systems are studied in a microwave setup. Using harmonic inversion the distribution of the imaginary parts of the resonances is determined. With increasing opening of the systems, a spectral gap is observed for thick as well as for thin repellers and for the latter case it is compared with the known topological pressure bounds. The maxima of the distributions are found to coincide for a large range of the distance to radius parameter with half of the classical escape rate. This confirms theoretical predictions based on rigorous mathematical analysis for the spectral gap and on numerical experiments for the maxima of the distributions.

miRNA as activity markers in Parvo B19 associated heart disease.

Parvovirus B19 is a frequent virus detected in endomyocardial biopsies of patients with clinically suspected myocarditis or dilated cardiomyopathy (DCM). Viruses often cause a more symptomatic disease with increased tissue injury if they become reactivated. A disease-specific differential expression of microRNAs (miRNAs) has been described in the regulation of replicating viruses. Analyzing patients with latent and reactivated B19V infection, we found 29 differentially regulated miRNAs and, in order to test whether predicted genes are differentially expressed, selected mRNAs were tested by TaqMan-QPCR.

Weyl asymptotics: from closed to open systems.

We present microwave experiments on the symmetry reduced five-disk billiard studying the transition from a closed to an open system. The measured microwave reflection signal is analyzed by means of the harmonic inversion and the counting function of the resulting resonances is studied. For the closed system this counting function shows the Weyl asymptotic with a leading exponent equal to 2. By opening the system successively this exponent decreases smoothly to a noninteger value. For the open systems the extraction of resonances by the harmonic inversion becomes more challenging and the arising difficulties are discussed. The results can be interpreted as a first experimental indication for the fractal Weyl conjecture for resonances.

Fractalkine in human inflammatory cardiomyopathy.

BACKGROUND: Cardiac inflammation is important for the prognosis of patients with inflammatory cardiomyopathy (CMi), but the mechanisms leading to it are not fully elucidated. OBJECTIVE: To study the role of fractalkine (CX3CL1) in chemotactic and adhesive properties of peripheral blood mononuclear cells (PBMCs) in patients with CMi. METHODS AND RESULTS: Patients with enterovirus (EV)-positive CMi, patients with virus-negative CMi, patients with parvovirus B19 (B19) genomes with low intramyocardial inflammation and patients without cardiac inflammation and viral infection in the endomyocardial biopsy (EMB) were enrolled (n=10/group). The expression of CX3CL1 and monocyte chemoattractant protein (MCP-1) in EMBs was significantly increased in EV-positive and virus-negative patients with CMi in contrast to controls and B19-positive patients (EV+ vs controls: CX3CL1-area fraction (AF) % 0.078±0.012 vs 0.009±0.003 p<0.05; MCP-1-AF % 0.093±0.023 vs 0.011±0.009). The receptor (CX3CR1)-mediated chemotaxis was increased twofold in PBMCs in comparison with those of controls. The MCP-1 secretion was 3.1-fold higher in PBMCs from EV-positive patients compared with controls, and this elevation was further increased by CX3CL1 in EV-positive patients. No significant CX3CL1-mediated MCP-1 increase was seen in PBMCs from healthy controls. Moreover, spontaneously beating neonatal rat cardiomyocytes exposed to CX3CL1 exhibited an attenuated positive chronotropic response to ß-adrenergic stimulation with isoproterenol. CONCLUSION: The cardiac and plasma CX3CL1/CX3CR1 system is upregulated in CMi and this affects the functional potential of PBMCs. Moreover, a direct cardiodepressive effect of CX3CL1 in cardiac tissue was demonstrated since neonatal cardiomyocytes exhibited an attenuated positive chronotropic response to ß-adrenergic stimulation.