Geometric Singular Perturbation Theory for Systems with Symmetry

Journal of Dynamics and Differential Equations - In this paper we focus on a class of symmetric vector fields in the context of singularly perturbed fast-slow dynamical systems. Our main question...     

Application of TiO2-nanotubes/PbO2 as an anode for the electrochemical elimination of Acid Red 1 dye

Journal of Solid State Electrochemistry - In this study, galvanostatic electrolysis, through the use of the platinum supported on Ti (Ti/Pt) and Ti/TiO2-nanotubes/PbO2 anodes, was conducted in an...     

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.     

Stereocontrolled spirocyclic bislactams derived from pyroglutamic acid

The synthesis of rigid spirocyclic bislactams derived from pyroglutamic acid has been established.     

Stability results for Mountain Pass and Linking type solutions of semilinear problems involving Dirichlet forms

Some stability results for Mountain Pass and Linking type solutions of semilinear problems involving a very general class of Dirichlet forms are stated. The non linear terms are supposed to have a suitable superlinear growth and the family of Dirichlet forms is required to be dominated from below and from above by a fixed diffusion type form. Some concrete examples are also given.     

An Application of Branch and Cut to Open Pit Mine Scheduling

The economic viability of the modern day mine is highly dependent upon careful planning and management. Declining trends in average ore grades, increasing mining costs and environmental considerations will ensure that this situation will remain in the foreseeable future. The operation and management of a large open pit mine having a life of several years is an enormous and complex task. Though a number of optimization techniques have been successfully applied to resolve some important problems, the problem of determining an optimal production schedule over the life of the deposit is still very much unresolved. In this paper we will critically examine the techniques that are being used in the mining industry for production scheduling indicating their limitations. In addition, we present a mixed integer linear programming model for the scheduling problems along with a Branch and Cut solution strategy. Computational results for practical sized problems are discussed.