Design of Trehalose-Based Amide/Sulfonamide C-type Lectin Receptor Signaling Compounds

Mincle agonists have been shown to induce inflammatory cytokine production, such as tumor necrosis factor-alpha (TNF) and promote the development of a Th1/Th17 immune response that might be crucial to development of effective vaccination against pathogens such as Mycobacterium tuberculosis. As an expansion of our previous work, a library of 6,6′-amide and sulfonamide α,α-d -trehalose compounds with various substituents on the aromatic ring was synthesized efficiently in good to excellent yields. These compounds were evaluated for their ability to activate the human C-type lectin receptor Mincle by the induction of cytokines from human peripheral blood mononuclear cells. A preliminary structure–activity relationship (SAR) of these novel trehalose diamides and sulfonamides revealed that aryl amide-linked trehalose compounds demonstrated improved activity and relatively high potency cytokine production compared to the Mincle ligand trehalose dibehenate adjuvant (TDB) and the natural ligand trehalose dimycolate (TDM) inducing dose-dependent and human-Mincle-specific stimulation in a HEK reporter cell line.     

Morphological evolution of edge-hillocks on single-crystal films having anisotropic drift-diffusion under the capillary and electromigration forces

The morphological evolution of hillocks at the unpassivated sidewalls of single-crystal metallic thin film interconnects is investigated via computer simulations using the free-moving boundary value problem. The effect of drift-diffusion anisotropy on the development of surface topographical scenarios is fully explored under the action of electromigration and capillary forces, utilizing numerous combinations of the surface texture, the drift-diffusion anisotropy and the direction of the applied electric field. The simulation studies yield analytical relationships for the velocity of the surface solitary waves and the drift velocity of electromigration-induced internal voids as a function of the applied current densities, which contain intrinsic and structural properties of the single-crystal thin films. The threshold value of the applied current density, above which electromigration-induced internal voids can be formed and may cause the catastrophic failure of interconnects by breaching, also appears explicitly in this relationship.     

Self Assembly of Polymer Structures Induced by Electric Field

A method has been developed for fabricating polymer microstructures based on electric field induced self assembly and pattern formation. A dielectric fluid placed in between two conductive plates experience a force in an applied electric field gradient across the plates, which can induce a diffusive surface instability and self construction of the fluid surface. This process is exploited for the fabrication of self assembled polymer microstructures as well as replicated patterns through the use of pre-patterned plates or electrodes. FEM simulation is used to decide the minimum wavelength and electric gradient distribution of polymer structures. A variety of structures in the micron and nanometer scales including bio-fluidic MEMS, polymer optoelectronic devices can be fabricated using this method.     

Constructing Pseudo-Random Permutations with a Prescribed Structure

We show how to construct pseudo-random permutations that satisfy a certain cycle restriction, for example that the permutation be cyclic (consisting of one cycle containing all the elements) or an involution (a self-inverse permutation) with no fixed points. The construction can be based on any (unrestricted) pseudo-random permutation. The resulting permutations are defined succinctly and their evaluation at a given point is efficient. Furthermore, they enjoy a fast forward property, i.e. it is possible to iterate them at a very small cost. Received 10 August 2000 and revised 30 September 2000 Online publication 9 April 2001     

Collaborative detection and mitigation of DDoS in software-defined networks

The Journal of Supercomputing - This research presents the detection and mitigation of distributed denial of service (DDoS) in software defined networks (SDN). The proposed method consists of three...     

Randomized range-maxima in nearly-constant parallel time

Given an array ofn input numbers, therange-maxima problem is that of preprocessing the data so that queries of the type what is the maximum value in subarray [i..j] can be answered quickly using one processor. We present a randomized preprocessing algorithm that runs inO(log^* n) time with high probability, using an optimal number of processors on a CRCW PRAM; each query can be processed in constant time by one processor. We also present a randomized algorithm for a parallel comparison model. Using an optimal number of processors, the preprocessing algorithm runs inO( (n)) time with high probability; each query can be processed inO ( (n)) time by one processor. (As is standard, (n) is the inverse of Ackermann function.) A constant time query can be achieved by some slowdown in the performance of the preprocessing stage.     

The Role of Rigid Residues in Modulating TEM-1 β-Lactamase Function and Thermostability

The relationship between protein motions (i.e., dynamics) and enzymatic function has begun to be explored in β-lactamases as a way to advance our understanding of these proteins. In a recent study, we analyzed the dynamic profiles of TEM-1 (a ubiquitous class A β-lactamase) and several ancestrally reconstructed homologues. A chief finding of this work was that rigid residues that were allosterically coupled to the active site appeared to have profound effects on enzyme function, even when separated from the active site by many angstroms. In the present work, our aim was to further explore the implications of protein dynamics on β-lactamase function by altering the dynamic profile of TEM-1 using computational protein design methods. The Rosetta software suite was used to mutate amino acids surrounding either rigid residues that are highly coupled to the active site or to flexible residues with no apparent communication with the active site. Experimental characterization of ten designed proteins indicated that alteration of residues surrounding rigid, highly coupled residues, substantially affected both enzymatic activity and stability; in contrast, native-like activities and stabilities were maintained when flexible, uncoupled residues, were targeted. Our results provide additional insight into the structure-function relationship present in the TEM family of β-lactamases. Furthermore, the integration of computational protein design methods with analyses of protein dynamics represents a general approach that could be used to extend our understanding of the relationship between dynamics and function in other enzyme classes.     

Investigation of bio-ethanol steam reforming over cobalt-based catalysts

The catalytic performance of cobalt catalysts supported on γ-Al₂O₃, TiO₂, ZrO₂ were studied for bio-ethanol steam reforming (BESR) reaction. The supported catalysts (10 wt%Co) were prepared by impregnation and characterized through Thermogravimetric analysis (TGA), H₂ chemisorption, laser Raman Spectroscopy, Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS), and temperature-programmed reaction (TPRxn). The metallic cobalt sites were found to correlate with the BESR reaction activity. The reaction and H₂ chemisorption showed that ZrO₂ supported catalyst showed the best dispersion and best catalytic activity. Over the 10% Co/ZrO₂ catalyst, using a H₂O:EtOH:inert molar ratio of 10:1:75 and a GHSV = 5000 h⁻¹, 100% ethanol conversion and a yield of 5.5 mol H₂/mol EtOH were obtained at 550 °C and atmospheric pressure.     

High-Temperature Stiffness and Damping Measurements to Monitor the Glassy Intergranular Phase in Liquid-Phase-Sintered Silicon Carbides

Detailed stiffness and internal friction ( Q ⁻¹) versus temperature curves were obtained for liquid-phase-sintered silicon carbides using advanced resonant beam analysis up to 1400°C. As-sintered materials display a stable Q ⁻¹-peak near 1100°C, superimposed on an increasing background. The change of stiffness associated with the damping peak is quantitatively related to the amount of matter in pockets of the amorphous intergranular phase in which the refractory SiC matrix grains are embedded. The successful removal of the amorphous pockets by annealing at 1900°C is deduced from the disappearance of the damping peak and confirmed with transmission electron microscopy.