Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance.

Resulting from impaired collagen turnover, fibrosis is a hallmark of adipose tissue (AT) dysfunction and obesity-associated insulin resistance (IR). Prolidase, also known as peptidase D (PEPD), plays a vital role in collagen turnover by degrading proline-containing dipeptides but its specific functional relevance in AT is unknown. Here we show that in human and mouse obesity, PEPD expression and activity decrease in AT, and PEPD is released into the systemic circulation, which promotes fibrosis and AT IR. Loss of the enzymatic function of PEPD by genetic ablation or pharmacological inhibition causes AT fibrosis in mice. In addition to its intracellular enzymatic role, secreted extracellular PEPD protein enhances macrophage and adipocyte fibro-inflammatory responses via EGFR signalling, thereby promoting AT fibrosis and IR. We further show that decreased prolidase activity is coupled with increased systemic levels of PEPD that act as a pathogenic trigger of AT fibrosis and IR. Thus, PEPD produced by macrophages might serve as a biomarker of AT fibro-inflammation and could represent a therapeutic target for AT fibrosis and obesity-associated IR and type 2 diabetes.

Fingerprints of slingshot non-sequential double ionization on two-electron probability distributions.

We study double ionization of He driven by near-single-cycle laser pulses at low intensities at 400 nm. Using a three-dimensional semiclassical model, we identify the pathways that prevail non-sequential double ionization (NSDI). We focus mostly on the delayed pathway, where one electron ionizes with a time-delay after recollision. We have recently shown that the mechanism that prevails the delayed pathway depends on intensity. For low intensities slingshot-NSDI is the dominant mechanism. Here, we identify the differences in two-electron probability distributions of the prevailing NSDI pathways. This allows us to identify properties of the two-electron escape and thus gain significant insight into slingshot-NSDI. Interestingly, we find that an observable fingerpint of slingshot-NSDI is the two electrons escaping with large and roughly equal energies.

Slingshot Nonsequential Double Ionization as a Gate to Anticorrelated Two-Electron Escape.

At intensities below the recollision threshold, we show that recollision-induced excitation with one electron escaping fast after recollision and the other electron escaping with a time delay via a Coulomb slingshot motion is one of the most important mechanisms of nonsequential double ionization (NSDI), for strongly driven He at 400 nm. Slingshot NSDI is a general mechanism present for a wide range of low intensities and pulse durations. Anticorrelated two-electron escape is its striking hallmark. This mechanism offers an alternative explanation of anticorrelated two-electron escape obtained in previous studies.

Non-sequential double ionization with near-single cycle laser pulses.

A three-dimensional semiclassical model is used to study double ionization of Ar when driven by a near-infrared and near-single-cycle laser pulse for intensities ranging from 0.85 × 1014 W/cm2 to 5 × 1014 W/cm2. Asymmetry parameters, distributions of the sum of the two electron momentum components along the direction of the polarization of the laser field and correlated electron momenta are computed as a function of the intensity and of the carrier envelope phase. A very good agreement is found with recently obtained results in kinematically complete experiments employing near-single-cycle laser pulses. Moreover, the contribution of the direct and delayed pathways of double ionization is investigated for the above observables. Finally, an experimentally obtained anti-correlation momentum pattern at higher intensities is reproduced with the three-dimensional semiclassical model and shown to be due to a transition from strong to soft recollisions with increasing intensity.

Interaction of molecular nitrogen with free-electron-laser radiation.

We compute molecular continuum orbitals in the single center expansion scheme. We then employ these orbitals to obtain molecular Auger rates and single-photon ionization cross sections to study the interaction of N2 with Free-Electron-Laser (FEL) pulses. The nuclei are kept fixed. We formulate rate equations for the energetically allowed molecular and atomic transitions and we account for dissociation through additional terms in the rate equations. Solving these equations for different parameters of the FEL pulse, allows us to identify the most efficient parameters of the FEL pulse for obtaining the highest contribution of double core hole states (DCH) in the final atomic ion fragments. Finally we identify the contribution of DCH states in the electron spectra and show that the DCH state contribution is more easily identified in the photo-ionization rather than the Auger transitions.

Evidence for a T-shape break-up pattern in the triple photoionization of Li.

We examine the angular distributions of all three electrons ionized from Li by a single photon near the triple ionization threshold using a fully quantum-mechanical treatment. We find strong evidence for a T-shape break-up pattern at a 5 eV excess energy as previously predicted by quasiclassical simulations [A. Emmanouilidou and J. M. Rost, J. Phys. B 39, 4037 (2006); A. Emmanouilidou, P. Wang, and J. M. Rost, Phys. Rev. Lett. 100, 063002 (2008)]. This finding is in conflict with the expected Wannier break-up dynamics of three electrons moving at mutual angles of 120°, which is expected to hold at energies a few eV above threshold. We use our quantum-mechanical approach to explore the physical mechanisms behind this unusual break-up configuration.

Partitioning the phase space in a natural way for scattering systems.

In this paper, we demonstrate a recent procedure for the construction of a symbolic dynamics for open systems by applying it to a model potential, the driven inverted Gaussian, which has proven very useful in describing laser-atom interaction. The symbolic dynamics and the corresponding partition of the Poincaré map are natural from the point of view of an asymptotic observer since the resulting branching tree coincides with the one extracted from the scattering functions. In general, the whole procedure is approximate because it only describes the globally unstable part of the chaotic invariant set, that is, the part that can be seen by an asymptotic observer in scattering data. It ignores Kolmogorov-Arnold-Moser islands and their fractal surroundings.

Construction of a natural partition of incomplete horseshoes.

We present a method for constructing a partition of an incomplete horseshoe in a Poincare map. The partition is based only on the unstable manifolds of the outermost fixed points and eventually their limits. Consequently, this partition becomes natural from the point of view of asymptotic scattering observations. The symbolic dynamics derived from this partition coincides with the one derived from the hierarchical structure of the singularities of the scattering functions.

Classical scattering for a driven inverted Gaussian potential in terms of the chaotic invariant set.

We study the classical electron scattering from a driven inverted Gaussian potential, an open system, in terms of its chaotic invariant set. This chaotic invariant set is described by a ternary horseshoe construction on an appropriate Poincaré surface of section. We find the development parameters that describe the hyperbolic component of the chaotic invariant set. In addition, we show that the hierarchical structure of the fractal set of singularities of the scattering functions is the same as the structure of the chaotic invariant set. Finally, we construct a symbolic encoding of the hierarchical structure of the set of singularities of the scattering functions and use concepts from the thermodynamical formalism to obtain one of the measures of chaos of the fractal set of singularities, the topological entropy.

Steering an eigenstate to a destination

The control of time evolution of a quantum state under various physical constraints is investigated and solved in the context of a two-level system. We have discovered a general scheme of steering an eigenenergy state to a destination without net nonadiabatic transitions, and we discuss how the result may be tested and utilized in practice.

Detection of benign or malignant origin of ascites with combined indirect immunoperoxidase assays of carcinoembryonic antigen and lysozyme.

The indirect immunoperoxidase method was used to study the presence of the intracellular carcinoembryonic antigen (CEA) and lysozyme (LZ) in alcohol-fixed cytologic smears of peritoneal fluids from 2 patients with chronic active hepatitis, 31 patients with liver cirrhosis and 7 patients with malignant liver disease. In the two patients with hepatitis, LZ was positive in both CEA was positive in one and negative in the other. Of the 31 patients with liver cirrhosis, 21 (67.5%) were LZ positive, 27 (87%) were CEA negative and only 4 (13%) were CEA positive. Of the seven patients with malignant disease, six were CEA positive and six were LZ negative. It is of interest that 23 of 24 (96%) LZ-positive results and 28 of 29 (97%) CEA-negative results corresponded to negative cytologic diagnoses for malignancy. Cytologic diagnosis of "reactive mesothelial cells" seemed to correlate better (71%) with CEA-negative and LZ-positive results. The data suggest that the investigation of CEA and LZ in the cells of peritoneal fluids appears to have promise as an adjunct to cytology in differentiating benign from malignant origins of the fluid.