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571.
Nellis DF Ekstrom DL Kirpotin DB Zhu J Andersson R Broadt TL Ouellette TF Perkins SC Roach JM Drummond DC Hong K Marks JD Park JW Giardina SL 《Biotechnology progress》2005,21(1):205-220
A GMP-compliant process is described for producing F5cys-PEG-lipid conjugate. This material fuses with preformed, drug-loaded liposomes, to form "immunoliposomes" that bind to HER2/neu overexpressing carcinomas, stimulates drug internalization, and ideally improves the encapsulated drug's therapeutic index. The soluble, single-chain, variable region antibody fragment, designated F5cys, was produced in E. coli strain RV308 using high-density cultures. Affinity adsorption onto horizontally tumbled Streamline rProtein-A resin robustly recovered F5cys from high-pressure-disrupted, whole-cell homogenates. Two product-related impurity classes were identified: F5cys with mid-sequence discontinuities and F5cys with remnants of a pelB leader peptide. Low-pressure cation exchange chromatography, conducted at elevated pH under reducing conditions, enriched target F5cys relative to these impurities and prepared a C-terminal cysteine for conjugation. Site-directed conjugation, conducted at pH 5.9 +/- 0.1 with reaction monitoring and cysteine quenching, yielded F5cys-MP-PEG(2000)-DSPE. Low-pressure size exclusion chromatography separated spontaneously formed, high-molecular-weight conjugate micelles from low-molecular-weight impurities. When formulated at 1-2 mg/mL in 10 mM trisodium citrate, 10% sucrose (w/v), at pH 6.4 (HCl), the conjugate was stable when stored below -70 degrees C. Six scale-up lots were compared. The largest 40-L culture produced enough F5cys to manufacture 2,085 mg of conjugate, enough to support planned preclinical and future clinical trials. The conjugate was 93% pure, as measured by polyacrylamide gel electrophoresis. Impurities were primarily identified as product-related. Residual endotoxin, rProtein A, and genomic DNA, were at acceptable levels. This study successfully addressed a necessary step in the scale-up of immunoliposome-encapsulated therapeutics. 相似文献
572.
Banana fruit are highly susceptible to chilling injury during low temperature storage. Experiments were conducted to compare ethylene binding during storage at chilling (3 and 8 °C) versus optimum (13 °C) temperatures. The skins of fruit stored at 3 and 8 °C gradually darkened as storage duration increased. This chilling effect was reflected in increasing membrane permeability as shown by increased relative electrolyte leakage from skin tissue. In contrast, banana fruit stored for 8 days at 13 °C showed no chilling injury symptoms. Exposure of banana fruit to the ethylene binding inhibitor 1-methylcyclopropene (1 l l-1 1-MCP) prevented ripening. However, this treatment also enhanced the chilling injury accelerated the occurrence of chilling injury-associated increased membrane permeability. 14C-ethylene release assay showed that ethylene binding by banana fruit stored at low temperature decreased with reduced storage temperature and/or prolonged storage time. Fruit exposed to 1-MCP for 12 h and then stored at 3 or 8 °C exhibited lower ethylene binding than those stored at 13 °C. Thus, chilling injury of banana fruit stored at low temperature is associated with a decrease in ethylene binding. The ability of tissue to respond to ethylene is evidently reduced, thereby resulting in failure to ripen. 相似文献
573.
High-resolution physical mapping in Pennisetum squamulatum reveals extensive chromosomal heteromorphism of the genomic region associated with apomixis
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Akiyama Y Conner JA Goel S Morishige DT Mullet JE Hanna WW Ozias-Akins P 《Plant physiology》2004,134(4):1733-1741
Gametophytic apomixis is asexual reproduction as a consequence of parthenogenetic development of a chromosomally unreduced egg. The trait leads to the production of embryos with a maternal genotype, i.e. progeny are clones of the maternal plant. The application of the trait in agriculture could be a tremendous tool for crop improvement through conventional and nonconventional breeding methods. Unfortunately, there are no major crops that reproduce by apomixis, and interspecific hybridization with wild relatives has not yet resulted in commercially viable germplasm. Pennisetum squamulatum is an aposporous apomict from which the gene(s) for apomixis has been transferred to sexual pearl millet by backcrossing. Twelve molecular markers that are linked with apomixis coexist in a tight linkage block called the apospory-specific genomic region (ASGR), and several of these markers have been shown to be hemizygous in the polyploid genome of P. squamulatum. High resolution genetic mapping of these markers has not been possible because of low recombination in this region of the genome. We now show the physical arrangement of bacterial artificial chromosomes containing apomixis-linked molecular markers by high resolution fluorescence in situ hybridization on pachytene chromosomes. The size of the ASGR, currently defined as the entire hemizygous region that hybridizes with apomixis-linked bacterial artificial chromosomes, was estimated on pachytene and mitotic chromosomes to be approximately 50 Mbp (a quarter of the chromosome). The ASGR includes highly repetitive sequences from an Opie-2-like retrotransposon family that are particularly abundant in this region of the genome. 相似文献
574.
Light induces phenylpropanoid metabolism in Arabidopsis roots 总被引:1,自引:0,他引:1
575.
Randolph JT Sauer DR Haviv F Nilius AM Greer J 《Bioorganic & medicinal chemistry letters》2004,14(6):1599-1602
Antibacterial SAR for a series of macrolides derived from erythromycin A that are potent LHRH antagonists was developed in an attempt to eliminate the antibiotic activities of these compounds. Increasing the size of the alkyl substituents on the desosamine 3'-amine resulted in potent LHRH antagonists that were inactive against staphylococcal bacteria strains, and were significantly (>10-fold) less active against streptococcal bacteria strains. Complete elimination of antibacterial activities could be achieved by replacement of one or both methyl groups on the 3'-amine with a large alkyl substituent. 相似文献
576.
Herzog B Hall RK Wang XL Waltner-Law M Granner DK 《Molecular endocrinology (Baltimore, Md.)》2004,18(4):807-819
577.
Weiss LW Wood LE Fry AC Kreider RB Relyea GE Bullen DB Grindstaff PD 《Journal of strength and conditioning research / National Strength & Conditioning Association》2004,18(4):765-770
Strength augmentation has been demonstrated in resistance-trained men subsequent to 4 days of training abstinence. However, this phenomenon was exhibited in an unusual circumstance in which the exercise test (seated heel raise) primarily involved an isolated skeletal muscle (soleus) that is normally comprised almost exclusively of 1 fiber type. It is unclear if similar results would be found for aggregate muscle actions. Therefore, a comparable study was designed with this in mind. Subjects were apparently healthy, young, strength-trained men (n = 25). All performed various tests of bench press strength at the beginning of their last standardized dynamic constant external resistance (DCER) training session. Subjects were subsequently randomly assigned to 1 of 4 groups and repeated the identical tests at intervals of either 2, 3, 4, or 5 days with no intervening training. Strength tests consisted of 1 repetition maximum (1RM) concentric-only isokinetic bench presses performed at 1.49 and 0.37 m.s(-1) as well as a 1RM DCER bench press. Measures of peak force and power were obtained from the isokinetic tests and maximum load from the DCER test. Results were expressed in both absolute and relative (to body weight) terms. Subsequent to the 4 abstinence intervals, groups performed similarly (p > 0.05) for all dependent variables. Concurrently, however, a small effect size (ES) was found for the group having a 4-day respite for both absolute and relative expressions of peak force and power at the slowest isokinetic bench press velocity. A small ES was also identified for the group having 2 days of rest for relative peak force at the slowest isokinetic test velocity and for relative DCER strength. Therefore, modest and transient strength augmentation appears likely in aggregate muscle actions following 2-4 days of training abstinence in resistance-trained men, but only at relatively slow velocities. 相似文献
578.
Effect of Abscisic Acid on Banana Fruit Ripening in Relation to the Role of Ethylene 总被引:7,自引:0,他引:7
Abstract
The role of abscisic acid (ABA) in banana fruit ripening was examined with the ethylene binding inhibitor, 1-methylcyclopropene
(1-MCP). ABA (0, 10−5, 10−4, or 10−3 mol/L) was applied by vacuum infiltration into fruit. 1-MCP (1 μL/L) was applied by injecting a measured volume of stock
gas into sealed glass jars containing fruit. Fruit ripening, as judged by ethylene evolution and respiration associated with
color change and softening, was accelerated by 10−4 or 10−3 mol/L ABA. ABA at 10−5 mol/L had no effect. The acceleration of ripening by ABA was greater at 10−3 mol/L than at 10−4 mol/L. ABA-induced acceleration of banana fruit ripening was not observed in 1-MCP treated fruit, especially when ABA was
applied after exposure to 1-MCP. Thus, ABA's promotion of ripening in intact banana fruit is at least partially mediated by
ethylene. Exposure of ABA-treated fruit to 0.1 μL/L ethylene for 24 h resulted in increased ethylene production and respiration,
and associated skin color change and fruit softening. Control fruit (no ABA) was unresponsive to similar ethylene treatments.
The data suggest that ABA facilitates initiation and progress in the sequence of ethylene-mediated ripening events, possibly
by enhancing the sensitivity to ethylene.
Received 29 January 1999; accepted 16 January 2000 相似文献
579.
Mohammed H Roberts DL Copley M Hammond M Nichols SC Mitchell JP 《AAPS PharmSciTech》2012,13(3):875-882
Current pharmacopeial methods for testing dry powder inhalers (DPIs) require that 4.0 L be drawn through the inhaler to quantify aerodynamic particle size distribution of “inhaled” particles. This volume comfortably exceeds the internal dead volume of the Andersen eight-stage cascade impactor (ACI) and Next Generation pharmaceutical Impactor (NGI) as designated multistage cascade impactors. Two DPIs, the second (DPI-B) having similar resistance than the first (DPI-A) were used to evaluate ACI and NGI performance at 60 L/min following the methodology described in the European and United States Pharmacopeias. At sampling times ≥2 s (equivalent to volumes ≥2.0 L), both impactors provided consistent measures of therapeutically important fine particle mass (FPM) from both DPIs, independent of sample duration. At shorter sample times, FPM decreased substantially with the NGI, indicative of incomplete aerosol bolus transfer through the system whose dead space was 2.025 L. However, the ACI provided consistent measures of both variables across the range of sampled volumes evaluated, even when this volume was less than 50% of its internal dead space of 1.155 L. Such behavior may be indicative of maldistribution of the flow profile from the relatively narrow exit of the induction port to the uppermost stage of the impactor at start-up. An explanation of the ACI anomalous behavior from first principles requires resolution of the rapidly changing unsteady flow and pressure conditions at start up, and is the subject of ongoing research by the European Pharmaceutical Aerosol Group. Meanwhile, these experimental findings are provided to advocate a prudent approach by retaining the current pharmacopeial methodology.KEY WORDS: cascade impactor, compendial method, dry powder inhaler, sample volume 相似文献
580.
Given the physiological limits to egg size, large-bodied non-avian dinosaurs experienced some of the most extreme shifts in size during postnatal ontogeny found in terrestrial vertebrate systems. In contrast, mammals--the other dominant vertebrate group since the Mesozoic--have less complex ontogenies. Here, we develop a model that quantifies the impact of size-specific interspecies competition on abundances of differently sized dinosaurs and mammals, taking into account the extended niche breadth realized during ontogeny among large oviparous species. Our model predicts low diversity at intermediate size classes (between approx. 1 and 1000 kg), consistent with observed diversity distributions of dinosaurs, and of Mesozoic land vertebrates in general. It also provides a mechanism--based on an understanding of different ecological and evolutionary constraints across vertebrate groups--that explains how mammals and birds, but not dinosaurs, were able to persist beyond the Cretaceous-Tertiary (K-T) boundary, and how post-K-T mammals were able to diversify into larger size categories. 相似文献