An optimized derivative of an endogenous CXCR4 antagonist prevents atopic dermatitis and airway inflammation

Aberrant CXCR4/CXCL12 signaling is involved in many pathophysiological processes such as cancer and inflammatory diseases. A natural fragment of serum albumin, named EPI-X4, has previously been identified as endogenous peptide antagonist and inverse agonist of CXCR4 and is a promising compound for the development of improved analogues for the therapy of CXCR4-associated diseases. To generate optimized EPI-X4 derivatives we here performed molecular docking analysis to identify key interaction motifs of EPI-X4/CXCR4. Subsequent rational drug design allowed to increase the anti-CXCR4 activity of EPI-X4. The EPI-X4 derivative JM#21 bound CXCR4 and suppressed CXCR4-tropic HIV-1 infection more efficiently than the clinically approved small molecule CXCR4 antagonist AMD3100. EPI-X4 JM#21 did not exert toxic effects in zebrafish embryos and suppressed allergen-induced infiltration of eosinophils and other immune cells into the airways of animals in an asthma mouse model. Moreover, topical administration of the optimized EPI-X4 derivative efficiently prevented inflammation of the skin in a mouse model of atopic dermatitis. Thus, rationally designed EPI-X4 JM#21 is a novel potent antagonist of CXCR4 and the first CXCR4 inhibitor with therapeutic efficacy in atopic dermatitis. Further clinical development of this new class of CXCR4 antagonists for the therapy of atopic dermatitis, asthma and other CXCR4-associated diseases is highly warranted

Modeling, optimizing and simulating robot calibration with accuracy improvement

This work describes techniques for modeling, optimizing and simulating calibration processes ofrobots using off-line programming. The identification of geometric parameters of the nominalkinematic model is optimized using techniques of numerical optimization of the mathematicalmodel. The simulation of the actual robot and the measurement system is achieved by introducingrandom errors representing their physical behavior and its statistical repeatability. An evaluationof the corrected nominal kinematic model brings about a clear perception of the influence ofdistinct variables involved in the process for a suitable planning, and indicates a considerableaccuracy improvement when the optimized model is compared to the non-optimized one

Die Pflanzengesellschaften Niedersachsens. Bestandsentwicklung, Gefaehrdung und Schutzprobleme Moosgesellschaften

With the contribution of U. Drehwald: Zur Syntaxonomie und Synsystematik der niedersaechsischen Moosgesellschaften (Syntaxonomy and synsystematics of moss populations in Lower Saxony)Available from TIB Hannover: RA 4507(20,9) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Transition to metallization in warm dense helium-hydrogen mixtures using stochastic density functional theory within the Kubo-Greenwood formalism

The Kubo-Greenwood (KG) formula is often used in conjunction with Kohn-Sham (KS) density functional theory (DFT) to compute the optical conductivity, particularly for warm dense matter. For applying the KG formula, all KS eigenstates and eigenvalues up to an energy cutoff are required and thus the approach becomes expensive, especially for high temperatures and large systems, scaling cubically with both system size and temperature. Here, we develop an approach to calculate the KS conductivity within the stochastic DFT framework, which requires knowledge only of the KS Hamiltonian but not its eigenstates and values. We show that the computational effort associated with the method scales linearly with system size and reduces in proportion to the temperature, unlike the cubic increase with traditional deterministic approaches. In addition, we find that the method allows an accurate description of the entire spectrum, including the high-frequency range, unlike the deterministic method which is compelled to introduce a high-frequency cutoff due to memory and computational time constraints. We apply the method to helium-hydrogen mixtures in the warm dense matter regime at temperatures of ∼60kK and find that the system displays two conductivity phases, where a transition from nonmetal to metal occurs when hydrogen atoms constitute ∼0.3 of the total atoms in the system

Die Pflanzengesellschaften Niedersachsens. Bestandsentwicklung, Gefaehrdung und Schutzprobleme Salzpflanzengesellschaften der Meereskueste und des Binnenlandes. Wasser- und Sumpfpflanzengesellschaften des Suesswassers

Available from TIB Hannover: RA 4507(20,7-8) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman