Investigation of Relationships between Grain Structure and Inhomogeneous Deformation by Means of Laboratory-Based Multimodal X-Ray Tomography: Strain Accuracy Analysis

Experimental Mechanics - The internal strain distribution developing during plastic deformation is important for understanding the mechanical properties of polycrystalline materials. Such...     

Sufficient Conditions for a Digraph to be Supereulerian

A (di)graph is supereulerian if it contains a spanning eulerian sub(di)graph. This property is a relaxation of hamiltonicity. Inspired by this analogy with hamiltonian cycles and by similar results in supereulerian graph theory, we analyze a number of sufficient Ore type conditions for a digraph to be supereulerian. Furthermore, we study the following conjecture due to Thomassé and the first author: if the arc‐connectivity of a digraph is not smaller than its independence number, then the digraph is supereulerian. As a support for this conjecture we prove it for digraphs that are semicomplete multipartite or quasitransitive and verify the analogous statement for undirected graphs.     

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.     

Preparation and Characterization of Activated Carbon from Microwave and Conventional Heated Almond Shells Using Phosphoric Acid Activation

Activated carbon production from almond shells using phosphoric acid activation agent was achieved by applying both conventional heating and microwave heating in succession. The morphology and surface properties of activated carbon were studied using thermogravimetric and differential gravimetric analysis, Fourier-transform infrared spectroscopy, scanning electron microscopy, and Brunauer–Emmett–Teller analysis. A surface area of 1128 m²/g was achieved by optimizing the microwave power (500?W), microwave application time (15?minutes), conventional heating time (45?minutes), conventional heating temperature (500?°C), and the phosphoric acid:sample ratio (0.7:1). An adsorption capacity of methylene blue of 148?mg/g and an iodine value of 791?mg/g was obtained for the prepared activated carbon.     

Influence functions and efficiencies of the canonical correlation and vector estimates based on scatter and shape matrices

In this paper, the influence functions and limiting distributions of the canonical correlations and coefficients based on affine equivariant scatter matrices are developed for elliptically symmetric distributions. General formulas for limiting variances and covariances of the canonical correlations and canonical vectors based on scatter matrices are obtained. Also the use of the so-called shape matrices in canonical analysis is investigated. The scatter and shape matrices based on the affine equivariant Sign Covariance Matrix as well as the Tyler's shape matrix serve as examples. Their finite sample and limiting efficiencies are compared to those of the Minimum Covariance Determinant estimators and S-estimator through theoretical and simulation studies. The theory is illustrated by an example.     

A normalizing system of natural deduction for intuitionistic linear logic

 The main result of this paper is a normalizing system of natural deduction for the full language of intuitionistic linear logic. No explicit weakening or contraction rules for -formulas are needed. By the systematic use of general elimination rules a correspondence between normal derivations and cut-free derivations in sequent calculus is obtained. Normalization and the subformula property for normal derivations follow through translation to sequent calculus and cut-elimination. Received: 10 October 2000 / Revised version: 26 July 2001 / Published online: 2 September 2002 Mathematics Subject Classification (2000): 03F52, 03F05 Keywords or phrases: Linear logic – Natural deduction – General elimination rules     

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     

On-line cysteine modification for protein analysis: new probes for electrochemical tagging nanospray mass spectrometry

A series of electrogenerated selective electrophiles based on substituted benzoquinones has been characterized as tags for l-cysteine and cysteine residues in proteins. The electrophiles are generated electrochemically from the corresponding hydroquinones. It is shown from mass spectrometry analysis that the electrogenerated benzoquinone can tag the biomolecules. The rate constants pertaining to the addition of l-cysteine onto the electrogenerated benzoquinones have been determined using electrochemical techniques. The substitution patterns have been unraveled leading to the assessment of site-specific rate constants. It is shown that the rate constants are primarily dependent on the electronic nature of the substituents as expressed by the Hammett substitution constant. The apparent tagging yields observed for l-cysteine in nanospray mass spectrometry experiments do not correspond to the yields expected from the electrochemical study, as the ionisation efficiencies are highly dependent on the tag. Finally, the on-line tagging has been tested using β-lactoglobulin A and myoglobin. Based on these results, it is concluded that the tagging reaction is selective towards cysteine when it takes place in the nanospray interface. The results show that the methodology presented can be used for a rapid characterization and identification of reactive sites in biomolecules.