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排序方式: 共有236条查询结果,搜索用时 328 毫秒
21.
22.
Comeau S Rainville S Baldwin W Austin E Gerstenberger S Cross C Wong WH 《Biofouling》2011,27(3):267-274
The recent spread of dreissenid mussels to various bodies of water in the western US has sparked interest by many state and federal agencies to develop protocols to stop further expansion. Quagga mussels (Dreissena rostriformis bugensis) are of particular importance as they are currently the most widespread dreissenid species in the region. This project examined the susceptibility of quagga mussels to hot-water sprays at different temperatures and durations of spray contact at Lake Mead (Nevada-Arizona, USA). Emersed adult quagga mussels were exposed to hot-water sprays at 20, 40, 50, 54, 60, 70, and 80°C for 1, 2, 5, 10, 20, 40, 80, and 160?s. Sprays at ≥60°C for 5?s were shown to be 100% lethal. Sprays of 54°C for 10?s, 50°C for 20?s, and 40°C for 40?s also resulted in 100% mortality. A spray temperature of 60°C for 5?s is recommended for mitigating fouling by quagga mussels. 相似文献
23.
Neitz RJ Konradi AW Sham HL Zmolek W Wong K Qin A Lorentzen C Nakamura D Quinn KP Sauer JM Powell K Ruslim L Chereau D Ren Z Anderson J Bard F Yednock TA Griswold-Prenner I 《Bioorganic & medicinal chemistry letters》2011,21(12):3726-3729
In this Letter, we describe the evolution of selective JNK3 inhibitors from 1, that routinely exhibit >10-fold selectivity over JNK1 and >1000-fold selectivity over related MAPKs. Strong SAR was found for substitution of the naphthalene ring, as well as for inhibitors adopting different central scaffolds. Significant potency gains were appreciated by inverting the polarity of the thione of the parent triazolothione 1, resulting in potent compounds with attractive pharmacokinetic profiles. 相似文献
24.
Han KP Zhu X Liu B Jeng E Kong L Yovandich JL Vyas VV Marcus WD Chavaillaz PA Romero CA Rhode PR Wong HC 《Cytokine》2011,56(3):804-810
IL-15, a promising cytokine for treating cancer and viral diseases, is presented in trans by the IL-15 receptor (IL-15R) alpha-chain to the IL-15Rβγc complex displayed on the surface of T cells and natural killer (NK) cells. We previously reported that an asparagine to aspartic acid substitution at amino acid 72 (N72D) of IL-15 provides a 4-5-fold increase in biological activity compared to the native molecule. In this report, we describe Chinese hamster ovary (CHO) cell expression of a soluble complex (IL-15 N72D:IL-15RαSu/Fc) consisting of the IL-15 N72D superagonist and a dimeric IL-15Rα sushi domain-IgG1 Fc fusion protein. A simple but readily scalable affinity and ion exchange chromatography method was developed to highly purify the complex having both IL-15 binding sites fully occupied. The immunostimulatory effects of this complex were confirmed using cell proliferation assays. Treatment of mice with a single intravenous dose of IL-15N72D:IL-15RαSu/Fc resulted in a significant increase in CD8+ T cells and NK cells that was not observed following IL-15 treatment. Pharmacokinetic analysis indicated that the complex has a 25-h half-life in mice which is considerably longer than <40-min half-life of IL-15. Thus, the enhanced activity of the IL-15N72D:IL-15RαSu/Fc complex is likely the result of the increased binding activity of IL-15N72D to IL-15Rβγc, optimized cytokine trans-presentation by the IL-15RαSu domain, the dimeric nature of the cytokine domain and its increased in vivo half-life compared to IL-15. These findings indicate that this IL-15 superagonist complex could serve as a superior immunostimulatory therapeutic agent. 相似文献
25.
Zhao C Sham HL Sun M Stoll VS Stewart KD Lin S Mo H Vasavanonda S Saldivar A Park C McDonald EJ Marsh KC Klein LL Kempf DJ Norbeck DW 《Bioorganic & medicinal chemistry letters》2005,15(24):7604-5503
As part of our efforts to identify potent HIV-1 protease inhibitors that are active against resistant viral strains, structural modification of the azacyclic urea (I) was undertaken by incorporating acyl groups as P1′ ligands. The extensive SAR study has yielded a series of N-acyl azacyclic ureas (II), which are highly potent against both wild-type and multiple PI-resistant viral strains. 相似文献
26.
Synthesis and evaluation of urea-based indazoles as melanin-concentrating hormone receptor 1 antagonists for the treatment of obesity 总被引:1,自引:0,他引:1
Souers AJ Gao J Wodka D Judd AS Mulhern MM Napier JJ Brune ME Bush EN Brodjian SJ Dayton BD Shapiro R Hernandez LE Marsh KC Sham HL Collins CA Kym PR 《Bioorganic & medicinal chemistry letters》2005,15(11):2752-2757
A series of urea-based N-1-(2-aminoethyl)-indazoles was synthesized and evaluated for melanin-concentrating hormone receptor 1 (MCHr1) antagonism in both binding and functional assays. Several compounds that acted as MCHr1 antagonists were identified, and optimization afforded a compound with excellent binding affinity, good functional potency, and oral efficacy in a chronic model for weight loss in diet-induced obese mice. 相似文献
27.
Li Q Woods KW Wang W Lin NH Claiborne A Gu WZ Cohen J Stoll VS Hutchins C Frost D Rosenberg SH Sham HL 《Bioorganic & medicinal chemistry letters》2005,15(8):2033-2039
Beginning with the structure of tipifarnib (1), a series of inhibitors of FTase have been synthesized by transposition of the D-ring to the imidazole and subsequent modification of the 2-quinolone motif. The compounds in the new series may be achiral and have structural features that allow for analogs that are difficult or impossible to make in the tertiary carbon-based tipifarnib series. The most potent compound (4d) is 4 times more active in vitro against FTase than tipifarnib. 相似文献
28.
The interactions of microfibril-associated glycoprotein (MAGP)-2 have been investigated with fibrillins and fibrillin-containing microfibrils. Solid phase binding assays were conducted with recombinant fragments covering fibrillin-1 and most of fibrillin-2. MAGP-2, and its structure relative MAGP-1, were found to bind two fragments spanning the N-terminal half of fibrillin-1 and an N-terminal fragment of fibrillin-2. Blocking experiments indicated that MAGP-2 had a binding site(s) close to the N terminus of the fibrillin-1 molecule that was distinct from that for MAGP-1 and an additional, more central binding site(s) that may be shared by the two MAGPs. Immunogold labeling of developing nuchal ligament tissue showed that MAGP-2 had regular covalent and periodic (about 56 nm) association with fibrillin-containing microfibrils of elastic fibers in this tissue. Further analysis of isolated microfibrils indicated that MAGP-2 was attached at two points along the microfibril substructure, "site 1" on the "beads" and "site 2" at the "shoulder" of the interbead region close to where the two "arms" fuse. In contrast, MAGP-1 was located only on the beads. Comparison of the MAGP-2 binding data with known fibrillin epitope maps of the microfibrils showed that site 1 correlated with the N-terminal MAGP-2 binding region, and site 2 correlated with the second, more central, MAGP-2 binding region on the fibrillin-1 molecule. Of particular note, immunolabeling at site 2 was markedly decreased, relative to that at site 1, on extended microfibrils with bead-to-bead periods over 90 nm, suggesting that site 2 may move toward the beads when the microfibril is stretched. The study points to MAGP-2 being an integral component of some populations of fibrillin-containing microfibrils. Moreover, the identification of multiple MAGP-binding sequences on fibrillins supports the concept that MAGPs may function as molecular cross-linkers, stabilizing fibrillin monomers in folded conformation within or between the microfibrils, and thus MAGPs may be implicated in the modulation of the elasticity of these structures. 相似文献
29.
Zhang D Zhou W Yin C Chen W Ozawa R Ang LH Anandan L Aigaki T Hing H 《Genesis (New York, N.Y. : 2000)》2006,44(4):189-201
Despite the identification of a number of guidance molecules, a comprehensive picture has yet to emerge to explain the precise anatomy of the olfactory map. From a misexpression screen of 1,515 P{GS} lines, we identified 23 genes that, when forcibly expressed in the olfactory receptor neurons, disrupted the stereotyped anatomy of the Drosophila antennal lobes. These genes, which have not been shown previously to control olfactory map development, encode novel proteins as well as proteins with known roles in axonal outgrowth and cytoskeletal remodeling. We analyzed Akap200, which encodes a Protein Kinase A-binding protein. Overexpression of Akap200 resulted in fusion of the glomeruli, while its loss resulted in misshapen and ectopic glomeruli. The requirement of Akap200 validates our screen as an effective approach for recovering genes controlling glomerular map patterning. Our finding of diverse classes of genes reveals the complexity of the mechanisms that underlie olfactory map development. 相似文献
30.
We proposed that Rangia cuneata (Sowerby, 1831) is an important estuarine bivalve with ecological significance in three coastal lakes in Barataria Bay, Gulf
of Mexico—Lake Cataouatche, Lake Salvador and Lac des Allemands. Our goals were to determine the abundance and distribution
of Rangia in these lakes and to measure clearance times to elucidate its potential impacts on phytoplankton communities. The estimated
average densities of R. cuneata in Lake Cataouatche, Lake Salvador, and Lac des Allemands were 63, 157, and 107 individuals m−2, respectively, which is 30% lower than that observed in nearby Lake Pontchartrain. The size of clams in Lake Salvador was
between 4 and 50 mm, while individuals in Lake Cataouatche and Lac des Allemands were mostly >20 mm. We postulate that a relatively
infrequent large tropical storm transported the larvae from Lake Salvador to the other two lakes 1 year before our sampling
to create this size difference. The clams were up to 99.9% of the total benthic biomass in Lake Salvador, 15.9% in Lake Cataouatche,
and 40.0% in Lac des Allemands. The R. cuneata biomass values were between 16.2 and 27.6 g m−2 and the clearance times were 1.0–1.5 days. The clearance times are among the highest previously reported for coastal bivalve
communities, which were from cooler climates. The results demonstrate that Rangia can be a critical part of the ecological processes in shallow water systems of the Gulf of Mexico. 相似文献