Atmospheric chemistry of diazomethane – an experimental and theoretical study

The kinetics of the O₃, OH and NO₃ radical reactions with diazomethane were studied in smog chamber experiments employing long-path FTIR and PTR-ToF-MS detection. The rate coefficients were determined to be k _CH2NN+O3?=?(3.2?±?0.4)?×?10^?17 and k _CH2NN+OH?=?(1.68?±?0.12)?×?10^?10 cm³ molecule^?1 s^?1 at 295?±?3?K and 1013?±?30 hPa, whereas the CH₂NN?+?NO₃ reaction was too fast to be determined in the static smog chamber experiments. Formaldehyde was the sole product observed in all the reactions. The experimental results are supported by CCSD(T*)-F12a/aug-cc-pVTZ//M062X/aug-cc-pVTZ calculations showing the reactions to proceed exclusively via addition to the carbon atom. The atmospheric fate of diazomethane is discussed.     

Azasugar inhibitors as pharmacological chaperones for Krabbe disease

Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe a new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.     

Towards Treating Correlations in Bose Condensates

 We use the adiabatic hyperspheric expansion and the Faddeev decomposition of the wave function with only s-waves. We derive for a fixed hyperradius an integro-differential equation for the angular eigenvalue and wave function. The correlations lower the interaction energy for N = 20 by about a factor of 5. Received October 22, 2001; accepted for publication November 5, 2001     

Time delay as a key to apoptosis induction in the p53 network

A feedback mechanism that involves the proteins p53 and mdm2, induces cell death as a controlled response to severe DNA damage. A minimal model for this mechanism demonstrates that the response may be dynamic and connected with the time needed to translate the mdm2 protein. The response takes place if the dissociation constant k between p53 and mdm2 varies from its normal value. Although it is widely believed that it is an increase in k that triggers the response, we show that the experimental behaviour is better described by a decrease in the dissociation constant. The response is quite robust upon changes in the parameters of the system, as required by any control mechanism, except for few weak points, which could be connected with the onset of cancer. Received 8 May 2002 / Received in final form 9 July 2002 Published online 17 September 2002     

Note on a conjecture of toft

A conjecture of Toft [17] asserts that any 4-critical graph (or equivalently, every 4-chromatic graph) contains a fully odd subdivision ofK ₄. We show that if a graphG has a degree three nodev such thatG-v is 3-colourable, then eitherG is 3-colourable or it contains a fully oddK ₄. This resolves Toft's conjecture in the special case where a 4-critical graph has a degree three node, which is in turn used to prove the conjecture for line-graphs. The proof is constructive and yields a polynomial algorithm which given a 3-degenerate graph either finds a 3-colouring or exhibits a subgraph that is a fully odd subdivision ofK ₄. (A graph is 3-degenerate if every subgraph has some node of degree at most three.)     

Adaptive application of operators in standard representation

Recently adaptive wavelet methods have been developed which can be shown to exhibit an asymptotically optimal accuracy/work balance for a wide class of variational problems including classical elliptic boundary value problems, boundary integral equations as well as certain classes of noncoercive problems such as saddle point problems. A core ingredient of these schemes is the approximate application of the involved operators in standard wavelet representation. Optimal computational complexity could be shown under the assumption that the entries in properly compressed standard representations are known or computable in average at unit cost. In this paper we propose concrete computational strategies and show under which circumstances this assumption is justified in the context of elliptic boundary value problems. Dedicated to Charles A. Micchelli on the occasion of his 60th birthday Mathematics subject classifications (2000) 41A25, 41A46, 65F99, 65N12, 65N55. This work has been supported in part by the Deutsche Forschungsgemeinschaft SFB 401, the first and third author are supported in part by the European Community's Human Potential Programme under contract HPRN-CT-202-00286 (BREAKING COMPLEXITY). The second author acknowledges the financial support provided through the European Union's Human Potential Programme, under contract HPRN-CT-2002-00285 (HASSIP) and through DFG grant DA 360/4–1.     

Design and Cold Tests of Asymmetric Quasioptical Resonators

This paper presents the design and test of asymmetric quasioptical resonators for gyrotron applications, where most of the diffraction output coupling comes from the smaller of two mirrors. A computer code based on scalar diffraction theory is used to calculate the resonator losses and the electric field near the mirrors. Resonators with mirror separations approaching confocal have reduced side lobes in the diffraction patterns, which should allow for better power transmission and focusing. Cold tests have been performed at 94 and 141 GHz to measure the quality factor of the asymmetric resonators as a function of mirror separation and mirror misalignment. Typical resonator parameters include 65 cm mirror separation, 1-3% output coupling and 85% of the losses from the small mirror. A half-symmetric resonator with one flat and one curved mirror has also been investigated. The calculated values of Q are in reasonably good agreement with the cold test measurements.