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.     

Synthesis, absolute configuration, and analysis of malathion, malaoxon, and isomalathion enantiomers

Syntheses of the enantiomers of malathion, malaoxon, and isomalathion are reported herein. Malathion enantiomers were prepared from (R)- or (S)-malic acid in three steps. Enantiomers of malathion were converted to the corresponding enantiomers of malaoxon in 52% yield by oxidation with monoperoxyphthalic acid, magnesium salt. The four isomalathion stereoisomers were prepared via two independent pathways using strychnine to resolve the asymmetric phosphorus moiety. The absolute configurations of the four stereoisomers of isomalathion were determined by X-ray crystallographic analysis of an alkaloid salt precursor. A high-performance liquid chromatography technique was developed to resolve the four stereoisomers of isomalathion, and to determine their stereoisomeric ratios.     

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.     

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     

Psychosocial experiences influence functioning: new risks, new outcomes

A 34-year-old Japanese woman developed spiking fever, splenomegaly, arthritis, neutrophilia, hyperferritinaemia (22517 ng/ml), elevated C-reactive protein (9.1 mg/ml) and severe thrombocytopenia (1.7 x 10(4)/microl). The patient had depressed antithrombin III activity and abnormally high concentrations of both fibrin degradation products and thrombin-antithrombin complexes. This condition was resistant to high-dose prednisolone therapy (120 mg/day) and non-steroidal anti-inflammatory drugs. We initiated oral methotrexate therapy (7.5 mg/week, orally) with a favourable outcome. The patient's spiking fever subsided on the first day of methotrexate administration. Elevated levels of ferritin and C-reactive protein in the sera rapidly normalised. Methotrexate rapidly improved the disease state which suggested that methotrexate act via modulation of cytokine production or secretion.     

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.     

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.     

Synthesis of nitrogen incorporated diamond-like carbon thin films using microwave surface-wave plasma CVD

Nitrogenated diamond-like (DLC:N) carbon thin films have been deposited by microwave surface wave plasma chemical vapor deposition on silicon and quartz substrates, using argon gas, camphor dissolved in ethyl alcohol composition and nitrogen as plasma source. The deposited DLC:N films were characterized for their chemical, optical, structural and electrical properties through X-ray photoelectron spectroscopy, UV/VIS/NIR spectroscopy, Raman spectroscopy, atomic force microscope and current–voltage characteristics. Optical band gap decreased (2.7 to 2.4 eV) with increasing Ar gas flow rate. The photovoltaic measurements of DLC:N / p-Si structure show that the open-circuit voltage (V_oc) of 168.8 mV and a short-circuit current density (J_sc) of 8.4 μA/cm² under light illumination (AM 1.5 100 mW/cm²). The energy conversion efficiency and fill factor were found to be 3.4 × 10^{− 4}% and 0.238 respectively.     

Transfer learning in deep neural network-based receiver coil sensitivity map estimation

Magnetic Resonance Materials in Physics, Biology and Medicine - The success of parallel Magnetic Resonance Imaging algorithms like SENSitivity Encoding (SENSE) depends on an accurate estimation of...