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On the face of it, the directors of new large scientific projects have an impossible task. They have to make technical decisions about sciences in which they have never made a research contribution—sciences in which they have no contributory expertise. Furthermore, these decisions must be accepted and respected by the scientists who are making research contributions. The problem is discussed in two interviews conducted with two directors of large scientific projects. The paradox is resolved for the managers by their use of interactional and referred expertise. The same analysis might be applicable to management in general. An Appendix, co-authored with Jeff Shrager, compares the notion of referred expertise with contributory expertise.  相似文献   
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Eight bobcat kittens were fitted with a specially designed harness system supporting a radio transmitter. These kittens were the youngest known to be radio-instrumented. This system was used successfully through two seasons, from June 1989 to January 1991. Litters of kittens were located soon after birth for weighing, marking, and aging (by tooth eruption). During the first year when kittens were at least eight weeks old and six weeks old the second year, attempts were made to radio-instrument kittens in each litter. This harness system allowed litters to be located periodically until their death or dispersal. We were able to collect important data during the most crucial and least known weeks of the lives of bobcat kittens.  相似文献   
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The species composition of periphyton and benthic insect communities and abundances of common taxa (&;gt;0.1&;#37; of individuals) were examined during snow-free months in Convict Creek, a permanent snowmelt- and spring-fed stream in the Sierra Nevada of California. The communities were highly diverse. The most abundant taxa in the periphyton were diatoms ( Achnanthes minutissima, Cocconeis placentula lineata, Cymbella microcephala, C. sinuata, Fragilaria construens, F. crotonensis , Navicula spp., Synedra acus , and S. rumpens ), except in late spring and summer when several seasonal blue-green algae ( Chamaesiphon incrustans, Lyngbya spp. and Oscillatoria spp.) are at their maximum densities. Most common periphyton taxa vary systematically in abundance with season, but relative abundances of taxa also appear to be influenced by streambed scouring and by concentrations of ambient nutrients. Data on population densities and length frequencies of larval and nymphal stages of common benthic insects and occurrences of pupal and adult stages were examined to determine life history patterns. Taxa hatching in winter and spring and abundant as immatures in late spring include ephemeropterans ( Epeorus longimanus, Drunella flavilinea , and Caudatella heterocaudata ), plecopterans ( Calineuria californica, Doroneuria baumanni, and Pteronarcys princeps ) and dipterans ( Cryptolabis sp.). Common taxa hatching in late spring or summer are the plecopteran Malenka ( californica? ) and the trichopterans Arctopsyche grandis and Rhyacophila acropedes . Several bivoltine and multivoltine ephemeropterans ( Baetis devinctus and B. tricaudatus ) and dipterans ( Simulium spp. and Chironomidae) have summer cohorts. Taxa hatching in late summer or autumn and most abundant in autumn include ephemeropterans ( Baetis spp., Ephemerella infrequens, Epeorus dulciana, Ironodes lepidus , and Paraleptophlebia pallipes ), trichopterans ( Hydropsyche oslari, Lepidostoma spp., Glossosoma califica, Micrasema sp., Brachycentrus americanus, Neophylax sp., and Rhyacophila vaccua ) and dipterans ( Antocha monticola, Pericoma sp., and Chironomidae). Major recurring events that may influence life history patterns and structure of the benthic insect community are (1) near-freezing, nighttime winter water temperatures and occasional anchor ice, (2) a prolonged period of high discharge in late spring and early summer (3) a brief summer, and (4) a prolonged period of moderate stream discharge in autumn when the substratum is stable and food is abundant.  相似文献   
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The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. It is currently believed that four to six crypt stem cells reside at the +4 position immediately above the Paneth cells in the small intestine; colon stem cells remain undefined. Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49) was selected from a panel of intestinal Wnt target genes for its restricted crypt expression. Here, using two knock-in alleles, we reveal exclusive expression of Lgr5 in cycling columnar cells at the crypt base. In addition, Lgr5 was expressed in rare cells in several other tissues. Using an inducible Cre knock-in allele and the Rosa26-lacZ reporter strain, lineage-tracing experiments were performed in adult mice. The Lgr5-positive crypt base columnar cell generated all epithelial lineages over a 60-day period, suggesting that it represents the stem cell of the small intestine and colon. The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers.  相似文献   
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Qu X  Wen JD  Lancaster L  Noller HF  Bustamante C  Tinoco I 《Nature》2011,475(7354):118-121
The ribosome translates the genetic information encoded in messenger RNA into protein. Folded structures in the coding region of an mRNA represent a kinetic barrier that lowers the peptide elongation rate, as the ribosome must disrupt structures it encounters in the mRNA at its entry site to allow translocation to the next codon. Such structures are exploited by the cell to create diverse strategies for translation regulation, such as programmed frameshifting, the modulation of protein expression levels, ribosome localization and co-translational protein folding. Although strand separation activity is inherent to the ribosome, requiring no exogenous helicases, its mechanism is still unknown. Here, using a single-molecule optical tweezers assay on mRNA hairpins, we find that the translation rate of identical codons at the decoding centre is greatly influenced by the GC content of folded structures at the mRNA entry site. Furthermore, force applied to the ends of the hairpin to favour its unfolding significantly speeds translation. Quantitative analysis of the force dependence of its helicase activity reveals that the ribosome, unlike previously studied helicases, uses two distinct active mechanisms to unwind mRNA structure: it destabilizes the helical junction at the mRNA entry site by biasing its thermal fluctuations towards the open state, increasing the probability of the ribosome translocating unhindered; and it mechanically pulls apart the mRNA single strands of the closed junction during the conformational changes that accompany ribosome translocation. The second of these mechanisms ensures a minimal basal rate of translation in the cell; specialized, mechanically stable structures are required to stall the ribosome temporarily. Our results establish a quantitative mechanical basis for understanding the mechanism of regulation of the elongation rate of translation by structured mRNAs.  相似文献   
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Molecular mechanism of anaerobic ammonium oxidation   总被引:7,自引:0,他引:7  
Two distinct microbial processes, denitrification and anaerobic ammonium oxidation (anammox), are responsible for the release of fixed nitrogen as dinitrogen gas (N(2)) to the atmosphere. Denitrification has been studied for over 100 years and its intermediates and enzymes are well known. Even though anammox is a key biogeochemical process of equal importance, its molecular mechanism is unknown, but it was proposed to proceed through hydrazine (N(2)H(4)). Here we show that N(2)H(4) is produced from the anammox substrates ammonium and nitrite and that nitric oxide (NO) is the direct precursor of N(2)H(4). We resolved the genes and proteins central to anammox metabolism and purified the key enzymes that catalyse N(2)H(4) synthesis and its oxidation to N(2). These results present a new biochemical reaction forging an N-N bond and fill a lacuna in our understanding of the biochemical synthesis of the N(2) in the atmosphere. Furthermore, they reinforce the role of nitric oxide in the evolution of the nitrogen cycle.  相似文献   
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Templates are widely used to arrange molecular components so they can be covalently linked into complex molecules that are not readily accessible by classical synthetic methods. Nature uses sophisticated templates such as the ribosome, whereas chemists use simple ions or small molecules. But as we tackle the synthesis of larger targets, we require larger templates-which themselves become synthetically challenging. Here we show that Vernier complexes can solve this problem: if the number of binding sites on the template, n(T), is not a multiple of the number of binding sites on the molecular building blocks, n(B), then small templates can direct the assembly of relatively large Vernier complexes where the number of binding sites in the product, n(P), is the lowest common multiple of n(B) and n(T) (refs 8, 9). We illustrate the value of this concept for the covalent synthesis of challenging targets by using a simple six-site template to direct the synthesis of a 12-porphyrin nano-ring with a diameter of 4.7?nm, thus establishing Vernier templating as a powerful new strategy for the synthesis of large monodisperse macromolecules.  相似文献   
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