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1.
Activity-directed synthesis (ADS) is a structure-blind, functional-driven molecular discovery approach. In this Concept, four case studies highlight the general applicability of ADS and showcase its flexibility to support different medicinal chemistry strategies. ADS deliberately harnesses reactions with multiple possible outcomes, and allows many chemotypes to be evaluated in parallel. Resources are focused on bioactive molecules, which emerge in tandem with associated synthetic routes. Some of the future challenges for ADS are highlighted, including the realisation of an autonomous molecular discovery platform. The prospects for ADS to become a mainstream lead generation approach are discussed. 相似文献
2.
Predicting Forest Age Classes from High Spatial Resolution Remotely Sensed Imagery Using Voronoi Polygon Aggregation 总被引:1,自引:0,他引:1
Efficient identification of forest age is useful for forest management and ecological applications. Here we propose a user-assisted method for determining forest age using high spatial resolution remotely sensed imagery. This method requires individual trees to be extracted from imagery and represented as points. We use a local maximum filter to generate points that are converted to Voronoi polygons. Properties of the Voronoi polygons are correlated with forest age and used to aggregate points (trees) into areas (stands) based on three forest age classes. Accuracy of the aggregation ranges from approximately 68% to 78% and identification of the mature class is more consistent and accurate than the younger classes. 相似文献
3.
MC Jacobson E Franssen BD Birt MJ Davidson RW Gilbert 《Canadian Metallurgical Quarterly》1997,26(3):171-179
The aim of this study was to investigate the effect of the absence of elongate spermatids (ES) from the rat seminiferous epithelium on the quantitative secretion and synthesis of the three major Sertoli cell secretory proteins--SGP-1, SGP-2 and CP-2. Seminiferous tubules (ST) were isolated (a) from normal 28-day-old rats, in which the most mature germ cell type is the round spermatid, (b) from normal adult rats at stages IX-XIV of the spermatogenic cycle, i.e. after spermiation, or at stages I-V and VI-VIII, when ES are still attached to the Sertoli cell, and (c) at stages VI-VIII from normal adult rats and from rats treated with methoxyacetic acid (MAA) in order to specifically deplete ES at these stages. Two-dimensional SDS PAGE combined with computerized image analysis was used to analyse 35S-methionine-labelled intracellular and secreted proteins. In the case of SGP-1 and SGP-2, almost all of the protein synthesized by ST was secreted. The total amount of both SGP-1 and CP-2 secreted by unstaged ST from immature rats was significantly lower than that secreted by unstaged ST from adult rats. The total amount of SGP-1 and CP-2 secreted by adult ST at stages IX-XIV of the spermatogenic cycle also declined dramatically compared to ST at earlier stages. The proportion of the total CP-2 synthesized by ST which was secreted also declined in all situations in which ES were absent from the seminiferous epithelium. The synthesis of only SGP-2 was changed by ES depletion from ST at stages VI-VIII, which was almost doubled compared to synthesis of this protein by ST from control rats. Our results suggest strongly that the secretion of SGP-1 and SGP-2 is via the constitutive pathway, and that regulation of these two proteins by ES is at the level of protein synthesis. In contrast, the regulation of CP-2 by ES is predominantly at the level of secretion, suggesting that this protein is secreted via a regulated pathway. Our findings add to the evidence showing that ES play a major role in the regulation of Sertoli cell function. 相似文献
4.
IG Sumner A Vaughan R Eisenthal RW Pickersgill AJ Owen PW Goodenough 《Canadian Metallurgical Quarterly》1993,1164(3):243-251
Papaya proteinase omega (pp omega) has been purified from dried latex both by immunoaffinity and traditional methods. Kinetic analysis revealed that (1), the pp omega-catalysed hydrolysis of N-benzoyl-L-arginine p-nitroanilide (BApNA) has a lower specificity (kcat/Km) than the same reaction catalysed by papain; (2), the pp omega-catalysed hydrolysis of a tripeptide substrate having phenylalanine at the second position (S2-site) showed a more similar specificity to that catalysed by papain; (3), the significant difference between the two enzymes is that steady state kinetics with both L-BApNA and a tripeptide enables the identification in pp omega of other ionizations affecting binding. The active sites of papain and pp omega can therefore be distinguished by pH-dependence of kcat/Km. 相似文献
5.
MA Steller KJ Gurski M Murakami RW Daniel KV Shah E Celis A Sette EL Trimble RC Park FM Marincola 《Canadian Metallurgical Quarterly》1998,4(9):2103-2109
Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease. 相似文献
6.
Replacement of missing teeth with fixed bridgework often involves producing full crown retainers on teeth on both sides of an edentulous space. Unfortunately, this approach can result in the destruction of much healthy tooth tissue, and the clinician must balance the benefits of replacing missing teeth with the amount of tooth preparation required. Current thinking in restorative dentistry places the preservation of tooth tissue at a premium, and most practitioners are happy to use techniques that embrace this philosophy. Because of this, cantilever bridges have an increasing role in dental practice, where the replacement for a missing tooth or teeth has one or more abutments on only one side of the edentulous space, being unsupported at the other. Cantilever bridges fall into several types, depending on the number of abutments and types of retainers. This article describes the various cantilever bridge designs, considers the biomechanics of these restorations, and provides guidelines for their clinical use. 相似文献
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9.
We have used a variety of methods to characterize the genome of the archaeon Methanosarcina thermophila TM-1. Pulsed-field gel analysis indicates a genome size of 2.8 Mb. We have constructed a bacterial artificial chromosome (BAC) library of M. thermophila and have used it to generate physical maps for this organism. The library is made up of 384 clones with an average insert size of 58 kb representing 8.0 genome equivalents. The utility of the library for low-resolution physical mapping was shown by identifying NotI linking clones and using these to order the NotI macrorestriction fragments of M. thermophila into a 2.8 Mb map. Hybridization of nine single copy genes and a 16S rRNA sequence to these macrorestriction fragments forms the basis for the first genetic map in this organism. High-resolution physical maps, consisting of overlapping clones, have been created using HindIII fingerprints of BAC clones. In this way, we identified a minimal path of five clones that span a 270 kb NotI fragment. The ease of manipulating BAC clones makes the BAC system an excellent choice for the construction of low-resolution and high-resolution physical and genetic maps of archaeal genomes. It also provides a substrate for future genome-sequencing efforts. 相似文献
10.
Comparison of two methods of surfactant administration and the effect on dosing-associated hypoxemia
M Nelson JJ Nicks MA Becker LA Vrlenich V Bhatt-Mehta RE Schumacher 《Canadian Metallurgical Quarterly》1997,17(6):450-454
OBJECTIVE: The purpose of our study was to test the hypothesis that surfactant dosing through a proximal sideport adapter on an endotracheal tube leads to more dosing-associated hypoxemia compared with a method of dosing that uses a double-lumen endotracheal tube. STUDY DESIGN: Using adequate sample size to compare significant changes in O2 saturation (power > 0.8, alpha < 0.05) we enrolled 36 infants with respiratory distress syndrome in this randomized trial. A 10% change in O2 saturation was considered clinically significant. Nineteen infants received 38 doses of surfactant through the sideport adapter. Seventeen infants received 31 doses of surfactant through the nonventilation lumen of a double-lumen endotracheal tube. Two main outcome measures were assessed: time-averaged O2 saturation values 30 minutes after dosing and the largest absolute fall in O2 saturation for each patient. RESULTS AND CONCLUSIONS: Time-averaged O2 saturation measures were higher in the proximal sideport group (p = 0.02), but the magnitude of difference was probably not clinically significant. No significant difference was detected between groups when we compared largest absolute drop in O2 saturation. Secondary analyses found no effect of birth weight or dose number (second vs third dose) on either outcome measure. 相似文献