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991.
Henry Murillo David W.A. Hunt Sherah L. VanLaerhoven 《Biocontrol Science and Technology》2012,22(2):125-134
The fecundity and life table parameters of Campoletis sonorensis females were measured using thirty 4-day-old Trichoplusia ni larvae daily at 24°C, 60% RH and a photoperiod of 12 h L:12 h D. The mean longevity was 34.5±2.8 days, the mean oviposition period was 22.7±1.9 days, and the mean constant oviposition period and the mean post-oviposition period were 15.9±1.3 and 11.9±2.2 days, respectively. The mean realised fecundity and the mean fertility differed significantly at 66.9±7.8 and 60.4±7.8 parasitoids per female, respectively. The mean sex ratio for the mean oviposition period (23 days) was 0.13±0.07, indicating a highly female biased ratio. The life table parameters were: intrinsic rate of natural increase (r m), 0.135 female/day; gross reproductive rate (GRR), 50.30; net reproductive rate (R o), 49.96; finite capacity for increase (λ), 1.14 female/day; mean generation time (T), 28.97 days; doubling time (DT), 5.13; capacity for increase (r c), 0.33; and cohort generation time (T c), 11.69. Campoletis sonorensis may be a suitable candidate for a biocontrol program of T. ni populations mostly because the primary selection criterion, rm , obtained for this parasitoid can be similar to or larger than the rate obtained for T. ni. 相似文献
992.
Zificsak CA Gingrich DE Breslin HJ Dunn DD Milkiewicz KL Theroff JP Thieu TV Underiner TL Weinberg LR Aimone LD Albom MS Mason JL Saville L Husten J Angeles TS Finn JP Jan M O'Kane TM Dobrzanski P Dorsey BD 《Bioorganic & medicinal chemistry letters》2012,22(1):133-137
The elaboration of a novel scaffold for the inhibition of JAK2 and FAK kinases was targeted in order to provide a dual inhibitor that could target divergent pathways for tumor cell progression. 相似文献
993.
Hunt T Atherton-Watson HC Axford J Collingwood SP Coote KJ Cox B Czarnecki S Danahay H Devereux N Howsham C Hunt P Paddock V Paisley D Young A 《Bioorganic & medicinal chemistry letters》2012,22(2):929-932
We report the identification of a novel series of human epithelial sodium channel (ENaC) blockers that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride. Following a rational design hypothesis a series of quaternary amines were prepared and evaluated for their ability to block ion transport via ENaC in human bronchial epithelial cells (HBECs). Compound 11 has an IC(50) of 200nM and is efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED(50) of 44μgkg(-1) at 1h. As such, pyrazinoyl quaternary amines represent the first examples of a promising new class of human ENaC blockers. 相似文献
994.
Liang G Aldous S Merriman G Levell J Pribish J Cairns J Chen X Maignan S Mathieu M Tsay J Sides K Rebello S Whitely B Morize I Pauls HW 《Bioorganic & medicinal chemistry letters》2012,22(2):1049-1054
A solid phase combinatorial library was designed based on X-ray structures and in-silico models to explore an inducible S4+ pocket, which is formed by a simple side-chain rotation of Tyr95. This inducible S4+ pocket is unique to β-tryptase and does not exist for other trypsin-like serine proteases of interest. Therefore, inhibitors utilizing this pocket have inherent advantages for being selective against other proteases in the same family. A member of this library was found to be a potent and selective β-tryptase inhibitor with a suitable pharmacokinetic profile for further clinical evaluation. 相似文献
995.
996.
997.
Jason Gavin Juan F. Marquez Ruiz Kinga Kedziora Henry Windle Dermot P. Kelleher John F. Gilmer 《Bioorganic & medicinal chemistry letters》2012,22(24):7647-7652
This Letter generalizes the metabolism of the azo class of compounds by Clostridium perfringens, an anaerobe found in the human colon. A recently reported 5-aminosalicylic acid-based prednisolone prodrug was shown to release the drug when incubated with the bacteria, while the para-aminobenzoic acid (PABA) based analogue did not. Instead, it showed a new HPLC peak with a relatively close retention time to the parent which was identified by LCMS as the partially reduced hydrazine product. This Letter investigates azoreduction across a panel of substrates with varying degrees of electronic and steric similarity to the PABA-based compound. Azo compounds with an electron donating group on the azo-containing aromatic ring showed immediate disproportionation to their parent amines without any detection of hydrazine intermediates by HPLC. Compounds containing only electron withdrawing groups are partially and reversibly reduced to produce a stable detectable hydrazine. They do not disproportionate to their parent amines, but regenerate the parent azo compound. This incomplete reduction is relevant to the design of azo-based prodrugs and the toxicology of azo-based dyes. 相似文献
998.
Heads JT Adams R D'Hooghe LE Page MJ Humphreys DP Popplewell AG Lawson AD Henry AJ 《Protein science : a publication of the Protein Society》2012,21(9):1315-1322
The stability of therapeutic antibodies is a prime pharmaceutical concern. In this work we examined thermal stability differences between human IgG1 and IgG4 Fab domains containing the same variable regions using the thermofluor assay. It was found that the IgG1 Fab domain is up to 11°C more stable than the IgG4 Fab domain containing the same variable region. We investigated the cause of this difference with the aim of developing a molecule with the enhanced stability of the IgG1 Fab and the biological properties of an IgG4 Fc. We found that replacing the seven residues, which differ between IgG1 C(H) 1 and IgG4 C(H) 1 domains, while retaining the native IgG1 light-heavy interchain disulfide (L-H) bond, did not affect thermal stability. Introducing the IgG1 type L-H interchain disulfide bond (DSB) into the IgG4 Fab resulted in an increase in thermal stability to levels observed in the IgG1 Fab with the same variable region. Conversely, replacement of the IgG1 L-H interchain DSB with the IgG4 type L-H interchain DSB reduced the thermal stability. We utilized the increased stability of the IgG1 Fab and designed a hybrid antibody with an IgG1 C(H) 1 linked to an IgG4 Fc via an IgG1 hinge. This construct has the expected biophysical properties of both the IgG4 Fc and IgG1 Fab domains and may therefore be a pharmaceutically relevant format. 相似文献
999.
Background
Agricultural tractor overturns without rollover protective structures are the leading cause of farm fatalities in the United States. To our knowledge, no studies have incorporated the spatial scan statistic in identifying high-risk areas for tractor overturns. The aim of this study was to determine whether tractor overturns cluster in certain parts of Kentucky and identify factors associated with tractor overturns.Methods
A spatial statistical analysis using Kulldorff''s spatial scan statistic was performed to identify county clusters at greatest risk for tractor overturns. A regression analysis was then performed to identify factors associated with tractor overturns.Results
The spatial analysis revealed a cluster of higher than expected tractor overturns in four counties in northern Kentucky (RR = 2.55) and 10 counties in eastern Kentucky (RR = 1.97). Higher rates of tractor overturns were associated with steeper average percent slope of pasture land by county (p = 0.0002) and a greater percent of total tractors with less than 40 horsepower by county (p<0.0001).Conclusions
This study reveals that geographic hotspots of tractor overturns exist in Kentucky and identifies factors associated with overturns. This study provides policymakers a guide to targeted county-level interventions (e.g., roll-over protective structures promotion interventions) with the intention of reducing tractor overturns in the highest risk counties in Kentucky. 相似文献1000.