The MROI fringe tracker: Laboratory tracking with ICONN

The loop is closed on ICONN, the Magdalena Ridge Observatory Interferometer fringe tracker. Results from laboratory experiments demonstrating ICONN's ability to track realistic, atmospheric-like path difference perturbations in real-time are shown. Characterizing and understanding the behavior and limits of ICONN in a controlled environment are key for reaching the goals of the MROI. The limiting factors in the experiments were found to be the light delivery system and temporary path length correction mechanism; not the on-sky components of ICONN. ICONN was capable of tracking fringes with a coherence loss below 5%; this will only improve in its final deployment.The Magdalena Ridge Observatory Interferometer is funded by the US Department of Transportation, the State of New Mexico, and New Mexico Tech with previous funding from the Navy Research Laboratory (NRL, agreement no. N00173-01-2-C902).This is the final version of the article, also available from SPIE at http://proceedings.spiedigitallibrary.org/proceeding.aspx?articleid=1891933. Copyright 2014 Society of Photo Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited. http://dx.doi.org/10.1117/12.205560

Lattice worldline representation of correlators in a background field

We use a discrete worldline representation in order to study the continuum limit of the one-loop expectation value of dimension two and four local operators in a background field. We illustrate this technique in the case of a scalar field coupled to a non-Abelian background gauge field. The first two coefficients of the expansion in powers of the lattice spacing can be expressed as sums over random walks on a d-dimensional cubic lattice. Using combinatorial identities for the distribution of the areas of closed random walks on a lattice, these coefficients can be turned into simple integrals. Our results are valid for an anisotropic lattice, with arbitrary lattice spacings in each direction.Comment: 54 pages, 14 figure

Sozialstaatliche Kürzungspolitik in Deutschland: Nur eine Mär? Eine quantitative Gesetzgebungsanalyse 1974–2014

Quantitative analyses on welfare state dynamics have to cope with the “dependent variable problem”, as studies on social spending reach different conclusions than analyses of replacement rate data. This article suggests a way around this problem by presenting results from a fine-grained analysis of welfare state legislation in Germany between 1974 and 2014. We show that the German welfare state has seen both cuts and expansions occur in all decades. Moreover, we show by means of a regression analysis that partisan politics play a role. Supporting the “Nixon-in-China”-thesis, social democratic governments are associated with a higher probability of cutbacks – especially in times of budgetary pressure – whereas expansions are more likely under Christian democratic governments

The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis

Tofisopam is a member of the 2,3-benzodiazepine compound family which is marketed for the treatment of anxiety in some European countries. In contrast to classical 1,4-benzodiazepines, the compound does not bind to the benzodiazepine binding site of the γ-aminobutyric acid receptor and its psychopharmacological profile differs from such compounds. In addition to anxiolytic properties, antipsychotic effects are reported. We now show that tofisopam, 50 mg/kg intraperitoneally (i.p.), administered in parallel to repeated doses of dizocilpine 0.2 mg/kg i.p. can ameliorate dizocilpine-induced prolongation of immobility, which is considered to be a model of negative symptoms of psychosis. We further show that tofisopam acts as an isoenzyme-selective inhibitor of phosphodiesterases (PDEs) with highest affinity to PDE-4A1 (0.42 μM) followed by PDE-10A1 (0.92 μM), PDE-3 (1.98 μM) and PDE-2A3 (2.11 μM). The data indicate that tofisopam is an interesting candidate for the adjuvant treatment of psychosis with focus on negative symptoms. Combined partial inhibition of PDE-4 and PDE-10 as well as PDE-2 may be the underlying mechanism to this activity. Due to the good safety profile of tofisopam as evident from long-term use of this agent in patients, it may be concluded that dual or triple inhibition of PDE isoenzymes with additive or synergistic effects may be an interesting approach to pharmacological activity, resulting in active compounds with beneficial safety profile. Dose-limiting side effects such as emesis induced by selective inhibition of PDE-4 may be prevented by such strategies

Ska3 Ensures Timely Mitotic Progression by Interacting Directly With Microtubules and Ska1 Microtubule Binding Domain

The establishment of physical attachment between the kinetochore and dynamic spindle microtubules, which undergo cycles of polymerization and depolymerization generating straight and curved microtubule structures, is essential for accurate chromosome segregation. The Ndc80 and Ska complexes are the major microtubule-binding factors of the kinetochore responsible for maintaining chromosome-microtubule coupling during chromosome segregation. We previously showed that the Ska1 subunit of the Ska complex binds dynamic microtubules using multiple contact sites in a mode that allows conformation-independent binding. Here, we show that the Ska3 subunit is required to modulate the microtubule binding capability of the Ska complex (i) by directly interacting with tubulin monomers and (ii) indirectly by interacting with tubulin contacting regions of Ska1 suggesting an allosteric regulation. Perturbing either the Ska3-microtubule interaction or the Ska3-Ska1 interactions negatively influences microtubule binding by the Ska complex in vitro and affects the timely onset of anaphase in cells. Thus, Ska3 employs additional modulatory elements within the Ska complex to ensure robust kinetochore-microtubule attachments and timely progression of mitosis

Cyclic AMP Control Measured in Two Compartments in HEK293 Cells: Phosphodiesterase KM Is More Important than Phosphodiesterase Localization

The intracellular second messenger cyclic AMP (cAMP) is degraded by phosphodiesterases (PDE). The knowledge of individual families and subtypes of PDEs is considerable, but how the different PDEs collaborate in the cell to control a cAMP signal is still not fully understood. In order to investigate compartmentalized cAMP signaling, we have generated a membrane-targeted variant of the cAMP Bioluminiscence Resonance Energy Transfer (BRET) sensor CAMYEL and have compared intracellular cAMP measurements with it to measurements with the cytosolic BRET sensor CAMYEL in HEK293 cells. With these sensors we observed a slightly higher cAMP response to adenylyl cyclase activation at the plasma membrane compared to the cytosol, which is in accordance with earlier results from Fluorescence Resonance Energy Transfer (FRET) sensors. We have analyzed PDE activity in fractionated lysates from HEK293 cells using selective PDE inhibitors and have identified PDE3 and PDE10A as the major membrane-bound PDEs and PDE4 as the major cytosolic PDE. Inhibition of membrane-bound or cytosolic PDEs can potentiate the cAMP response to adenylyl cyclase activation, but we see no significant difference between the potentiation of the cAMP response at the plasma membrane and in cytosol when membrane-bound and cytosolic PDEs are inhibited. When different levels of stimulation were tested, we found that PDEs 3 and 10 are mainly responsible for cAMP degradation at low intracellular cAMP concentrations, whereas PDE4 is more important for control of cAMP at higher concentrations