Nonhydrolyzable Heptose Bis- and Monophosphate Analogues Modulate Pro-inflammatory TIFA-NF-κB Signaling

d -Glycero-d -manno-heptose-1β,7-bisphosphate (HBP) and d -glycero-d -manno-heptose-1β-phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells through the activation of the TIFA-dependent NF-κB pathway. To better understand structure-based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA-NF-κB signal axis was evaluated in vivo at a low-nanomolar concentration (6 nM) and compared to that of the natural metabolites. Our data showed that three phosphonate analogues had similar stimulatory activity to HBP, whereas two phosphonates antagonized HBP-induced TIFA-NF-κB signaling. These results open new horizons for the design of pro-inflammatory and innate immune modulators that could be used as vaccine adjuvant.     

An evolutionary algorithm for large traveling salesman problems

This work proposes an evolutionary algorithm, called the heterogeneous selection evolutionary algorithm (HeSEA), for solving large traveling salesman problems (TSP). The strengths and limitations of numerous well-known genetic operators are first analyzed, along with local search methods for TSPs from their solution qualities and mechanisms for preserving and adding edges. Based on this analysis, a new approach, HeSEA is proposed which integrates edge assembly crossover (EAX) and Lin-Kernighan (LK) local search, through family competition and heterogeneous pairing selection. This study demonstrates experimentally that EAX and LK can compensate for each other's disadvantages. Family competition and heterogeneous pairing selections are used to maintain the diversity of the population, which is especially useful for evolutionary algorithms in solving large TSPs. The proposed method was evaluated on 16 well-known TSPs in which the numbers of cities range from 318 to 13509. Experimental results indicate that HeSEA performs well and is very competitive with other approaches. The proposed method can determine the optimum path when the number of cities is under 10,000 and the mean solution quality is within 0.0074% above the optimum for each test problem. These findings imply that the proposed method can find tours robustly with a fixed small population and a limited family competition length in reasonable time, when used to solve large TSPs.     

Reliability investigation of 0.07-/spl mu/m InGaAs-InAlAs-InP HEMT MMICs with pseudomorphic In/sub 0.75/Ga/sub 0.25/As channel

The authors have investigated the reliability performance of G-band (183 GHz) monolithic microwave integrated circuit (MMIC) amplifiers fabricated using 0.07-/spl mu/m T-gate InGaAs-InAlAs-InP HEMTs with pseudomorphic In/sub 0.75/Ga/sub 0.25/As channel on 3-in wafers. Life test was performed at two temperatures (T/sub 1/ = 200 /spl deg/C and T/sub 2/ = 215 /spl deg/C), and the amplifiers were stressed at V/sub ds/ of 1 V and I/sub ds/ of 250 mA/mm in a N/sub 2/ ambient. The activation energy is as high as 1.7 eV, achieving a projected median-time-to-failure (MTTF) /spl ap/ 2 /spl times/ 10/sup 6/ h at a junction temperature of 125 /spl deg/C. MTTF was determined by 2-temperature constant current stress using /spl Delta/G/sub mp/ = -20% as the failure criteria. The difference of reliability performance between 0.07-/spl mu/m InGaAs-InAlAs-InP HEMT MMICs with pseudomorphic In/sub 0.75/Ga/sub 0.25/As channel and 0.1-/spl mu/m InGaAs-InAlAs-InP HEMT MMICs with In/sub 0.6/Ga/sub 0.4/As channel is also discussed. The achieved high-reliability result demonstrates a robust 0.07-/spl mu/m pseudomorphic InGaAs-InAlAs-InP HEMT MMICs production technology for G-band applications.     

Quantitative analysis of ephedrines in urine by HPLC

Simultaneous determination of six ephedrines in urine sample has been achieved by high performance liquid chromatography on a Lichrospher RP-18 column, using methylamphetamine as internal standard. The 6 ephedrines are well separated in 25 minutes with resolution better than 1.8. This method has high recovery, selectivity and reproducibility, and the linearity is satisfactory from 1.5 micrograms/ml to 25 micrograms/ml with correlation coefficients better than 0.999.     

Synthesis of Hexp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->O) (CH2)7 CH3 probes for exploration of the substrate specificity of glycosyltransferases: Part II, Hex = 3-O-methyl-beta-D-Gal, 3-deoxy-beta-D-Gal, 3-deoxy-3-fluoro-beta-D-Gal, 3-amino-3-deoxy-beta-D-Gal, beta-D-Gul, alpha-L-Alt, or beta-L-Gal

Seven analogues of the trisaccharide beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->O)(CH 2)7CH3 have been synthesized as potential substrates for glycosyltransferases involved in the chain-termination of N-acetyllactosamine-type N-glycans. These compounds include: 3-O-methyl-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp -(1-->O) (CH2)7CH3, 3-deoxy-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1 -->O) (CH2)7CH3, 3-deoxy-3-fluoro-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-M anp- (1-->O)(CH2)7Ch3, 3-amino-3-deoxy-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Ma np- (1-->O)(CH2)7CH3, beta-D-Gulp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-- >O)(CH2)7CH3, beta-L-Galp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->O)(CH 2)7CH3, and alpha-L-Altp-(1-->4)-beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1- ->O) (CH2)7CH3. All trisaccharides were obtained by condensation of suitably modified glycosyl donors based on imidates or thioglycosides with the same disaccharide acceptor, octyl 3,4,6-tri-O-benzyl-2-O-(3,6-di-O-benzyl-2-deoxy-2-phthalimido-beta-D- glucopyranosyl)-alpha-D-mannopyranoside, followed by deprotection.