Ultrasonic characterization of the pulmonary venous wall: echographic and histological correlation

Background: Pulmonary vein isolation with radiofrequency catheter ablation techniques is used to prevent recurrences of human atrial fibrillation. Visualization of the architecture at the venoatrial junction could be crucial for these ablative techniques. Our study assesses the potential for intravascular ultrasound to provide this information. Methods and Results: We retrieved 32 pulmonary veins from 8 patients dying from noncardiac causes. We obtained cross-sectional intravascular ultrasound (IVUS) images with a 3.2F, 30-MHz ultrasound catheter at intervals on each vein. Histological cross-sections at the intervals allowed comparisons with ultrasonic images. The pulmonary venous wall at the venoatrial junction revealed a 3-layered ultrasonic pattern. The inner echogenic layer represents both endothelium and connective tissue of the media (mean maximal thickness, 1.4±0.3 mm). The middle hypoechogenic stratum corresponds to the sleeves of left atrial myocardium surrounding the external aspect of the venous media. This layer was thickest at the venoatrial junction (mean maximal thickness, 2.6±0.8 mm) and decreased toward the lung hilum. The outer echodense layer corresponds to fibro-fatty adventitial tissue (mean maximal thickness, 2.15±0.36 mm). We found a close agreement among the IVUS and histological measurements for maximal luminal diameter (mean difference, -0.12±1.3 mm) and maximal muscular thickness (mean difference, 0.17±0.13 mm) using the Bland and Altman method. Conclusions: Our experimental study demonstrates for the first time that IVUS images of the pulmonary veins can provide information on the distal limits and thickness of the myocardial sleeves and can be a valuable tool to help accurate targeting during ablative procedures

Resonant dipole-dipole interaction in the presence of dispersing and absorbing surroundings

Within the framework of quantization of the macroscopic electromagnetic field, equations of motion and an effective Hamiltonian for treating both the resonant dipole-dipole interaction between two-level atoms and the resonant atom-field interaction are derived, which can suitably be used for studying the influence of arbitrary dispersing and absorbing material surroundings on these interactions. The theory is applied to the study of the transient behavior of two atoms that initially share a single excitation, with special emphasis on the role of the two competing processes of virtual and real photon exchange in the energy transfer between the atoms. In particular, it is shown that for weak atom-field interaction there is a time window, where the energy transfer follows a rate regime of the type obtained by ordinary second-order perturbation theory. Finally, the resonant dipole-dipole interaction is shown to give rise to a doublet spectrum of the emitted light for weak atom-field interaction and a triplet spectrum for strong atom-field interaction.Comment: 15 pages, 1 figure, RevTE

Human papillomavirus 16 E6 induces FoxM1B in oral keratinocytes through GRHL2

High-risk human papillomavirus (HPV) is a major risk factor for oral and pharyngeal cancers (OPCs), yet the detailed mechanisms by which HPV promotes OPCs are not understood. Forkhead box M1B (FoxM1B) is an oncogene essential for cell cycle progression and tumorigenesis, and it is aberrantly overexpressed in many tumors. We previously showed that FoxM1B was the putative target of an epithelial-specific transcription factor, Grainyhead-like 2 (GRHL2). In the current study, we demonstrate that HPV type 16 (HPV-16) E6 induces FoxM1B in human oral keratinocytes (HOKs) and tonsillar epithelial cells (TECs) in part through GRHL2. FoxM1B was barely detectable in cultured normal human oral keratinocytes (NHOKs) and progressively increased in immortalized HOKs harboring HPV-16 genome (HOK-16B) and tumorigenic HOK-16B/BaP-T cells. Retroviral expression of HPV-16 E6 and/or E7 in NHOKs, TECs, and hypopharyngeal carcinoma cells (FaDu) revealed induction of FoxM1B and GRHL2 by the E6 protein but not E7. Both GRHL2 and FoxM1B were strongly induced in the epidermis of HPV-16 E6 transgenic mice and HPVoral squamous cell carcinomas. Ectopic expression of FoxM1B led to acquisition of transformed phenotype in HOK-16B cells. Loss of FoxM1B by lentiviral short hairpin RNA vector or chemical inhibitor led to elimination of tumorigenic characteristics of HOK-16B/BaP-T cells. Luciferase reporter assay revealed that GRHL2 directly bound and regulated the FoxM1B gene promoter activity. Using epithelial-specific Grhl2 conditional knockout mice, we exposed wild-type (WT) and Grhl2 KO mice to 4-nitroquinolin 1-oxide (4-NQO), which led to induction of FoxM1B in the tongue tissues and rampant oral tumor development in the WT mice. However, 4-NQO exposure failed to induce tongue tumors or induction of FoxM1B expression in Grhl2 KO mice. Collectively, these results indicate that HPV-16 induces FoxM1B in part through GRHL2 transcriptional activity and that elevated FoxM1B level is required for oropharyngeal cancer development

Noncommutative quantum mechanics and Bohm's ontological interpretation

We carry out an investigation into the possibility of developing a Bohmian interpretation based on the continuous motion of point particles for noncommutative quantum mechanics. The conditions for such an interpretation to be consistent are determined, and the implications of its adoption for noncommutativity are discussed. A Bohmian analysis of the noncommutative harmonic oscillator is carried out in detail. By studying the particle motion in the oscillator orbits, we show that small-scale physics can have influence at large scales, something similar to the IR-UV mixing

Rapid optimization of drug combinations for the optimal angiostatic treatment of cancer.

Drug combinations can improve angiostatic cancer treatment efficacy and enable the reduction of side effects and drug resistance. Combining drugs is non-trivial due to the high number of possibilities. We applied a feedback system control (FSC) technique with a population-based stochastic search algorithm to navigate through the large parametric space of nine angiostatic drugs at four concentrations to identify optimal low-dose drug combinations. This implied an iterative approach of in vitro testing of endothelial cell viability and algorithm-based analysis. The optimal synergistic drug combination, containing erlotinib, BEZ-235 and RAPTA-C, was reached in a small number of iterations. Final drug combinations showed enhanced endothelial cell specificity and synergistically inhibited proliferation (p < 0.001), but not migration of endothelial cells, and forced enhanced numbers of endothelial cells to undergo apoptosis (p < 0.01). Successful translation of this drug combination was achieved in two preclinical in vivo tumor models. Tumor growth was inhibited synergistically and significantly (p < 0.05 and p < 0.01, respectively) using reduced drug doses as compared to optimal single-drug concentrations. At the applied conditions, single-drug monotherapies had no or negligible activity in these models. We suggest that FSC can be used for rapid identification of effective, reduced dose, multi-drug combinations for the treatment of cancer and other diseases

Spinor condensates and light scattering from Bose-Einstein condensates

These notes discuss two aspects of the physics of atomic Bose-Einstein condensates: optical properties and spinor condensates. The first topic includes light scattering experiments which probe the excitations of a condensate in both the free-particle and phonon regime. At higher light intensity, a new form of superradiance and phase-coherent matter wave amplification were observed. We also discuss properties of spinor condensates and describe studies of ground--state spin domain structures and dynamical studies which revealed metastable excited states and quantum tunneling.Comment: 58 pages, 33 figures, to appear in Proceedings of Les Houches 1999 Summer School, Session LXXI

Quasars and their host galaxies

This review attempts to describe developments in the fields of quasar and quasar host galaxies in the past five. In this time period, the Sloan and 2dF quasar surveys have added several tens of thousands of quasars, with Sloan quasars being found to z>6. Obscured, or partially obscured quasars have begun to be found in significant numbers. Black hole mass estimates for quasars, and our confidence in them, have improved significantly, allowing a start on relating quasar properties such as radio jet power to fundamental parameters of the quasar such as black hole mass and accretion rate. Quasar host galaxy studies have allowed us to find and characterize the host galaxies of quasars to z>2. Despite these developments, many questions remain unresolved, in particular the origin of the close relationship between black hole mass and galaxy bulge mass/velocity dispersion seen in local galaxies.Comment: Review article, to appear in Astrophysics Update

(Sub)mm Interferometry Applications in Star Formation Research

This contribution gives an overview about various applications of (sub)mm interferometry in star formation research. The topics covered are molecular outflows, accretion disks, fragmentation and chemical properties of low- and high-mass star-forming regions. A short outlook on the capabilities of ALMA is given as well.Comment: 20 pages, 7 figures, in proceedings to "2nd European School on Jets from Young Star: High Angular Resolution Observations". A high-resolution version of the paper can be found at http://www.mpia.de/homes/beuther/papers.htm

Active Galactic Nuclei at the Crossroads of Astrophysics

Over the last five decades, AGN studies have produced a number of spectacular examples of synergies and multifaceted approaches in astrophysics. The field of AGN research now spans the entire spectral range and covers more than twelve orders of magnitude in the spatial and temporal domains. The next generation of astrophysical facilities will open up new possibilities for AGN studies, especially in the areas of high-resolution and high-fidelity imaging and spectroscopy of nuclear regions in the X-ray, optical, and radio bands. These studies will address in detail a number of critical issues in AGN research such as processes in the immediate vicinity of supermassive black holes, physical conditions of broad-line and narrow-line regions, formation and evolution of accretion disks and relativistic outflows, and the connection between nuclear activity and galaxy evolution.Comment: 16 pages, 5 figures; review contribution; "Exploring the Cosmic Frontier: Astrophysical Instruments for the 21st Century", ESO Astrophysical Symposia Serie

Observing Supermassive Black Holes across cosmic time: from phenomenology to physics

In the last decade, a combination of high sensitivity, high spatial resolution observations and of coordinated multi-wavelength surveys has revolutionized our view of extra-galactic black hole (BH) astrophysics. We now know that supermassive black holes reside in the nuclei of almost every galaxy, grow over cosmological times by accreting matter, interact and merge with each other, and in the process liberate enormous amounts of energy that influence dramatically the evolution of the surrounding gas and stars, providing a powerful self-regulatory mechanism for galaxy formation. The different energetic phenomena associated to growing black holes and Active Galactic Nuclei (AGN), their cosmological evolution and the observational techniques used to unveil them, are the subject of this chapter. In particular, I will focus my attention on the connection between the theory of high-energy astrophysical processes giving rise to the observed emission in AGN, the observable imprints they leave at different wavelengths, and the methods used to uncover them in a statistically robust way. I will show how such a combined effort of theorists and observers have led us to unveil most of the SMBH growth over a large fraction of the age of the Universe, but that nagging uncertainties remain, preventing us from fully understating the exact role of black holes in the complex process of galaxy and large-scale structure formation, assembly and evolution.Comment: 46 pages, 21 figures. This review article appears as a chapter in the book: "Astrophysical Black Holes", Haardt, F., Gorini, V., Moschella, U and Treves A. (Eds), 2015, Springer International Publishing AG, Cha