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981.
Reeves WH Skryabin DV Biancalana F Knight JC Russell PS Omenetto FG Efimov A Taylor AJ 《Nature》2003,424(6948):511-515
Photonic crystal fibres (PCFs) offer greatly enhanced design freedom compared to standard optical fibres. For example, they allow precise control of the chromatic dispersion (CD) profile--the frequency dependence of propagation speed--over a broad wavelength range. This permits studies of nonlinear pulse propagation in previously inaccessible parameter regimes. Here we report on spectral broadening of 100-fs pulses in PCFs with anomalously flat CD profiles. Maps of the spectral and spatio-temporal behaviour as a function of power show that dramatic conversion (to both longer and shorter wavelengths) can occur in remarkably short lengths of fibre, depending on the magnitude and shape of the CD profile. Because the PCFs used are single-mode at all wavelengths, the light always emerges in a fundamental guided mode. Excellent agreement is obtained between the experimental results and numerical solutions of the nonlinear wave equation, indicating that the underlying processes can be reliably modelled. These results show how, through appropriate choice of CD, nonlinearities can be efficiently harnessed to generate laser light at new wavelengths. 相似文献
982.
Artemisinins target the SERCA of Plasmodium falciparum 总被引:1,自引:0,他引:1
Eckstein-Ludwig U Webb RJ Van Goethem ID East JM Lee AG Kimura M O'Neill PM Bray PG Ward SA Krishna S 《Nature》2003,424(6951):957-961
Artemisinins are extracted from sweet wormwood (Artemisia annua) and are the most potent antimalarials available, rapidly killing all asexual stages of Plasmodium falciparum. Artemisinins are sesquiterpene lactones widely used to treat multidrug-resistant malaria, a disease that annually claims 1 million lives. Despite extensive clinical and laboratory experience their molecular target is not yet identified. Activated artemisinins form adducts with a variety of biological macromolecules, including haem, translationally controlled tumour protein (TCTP) and other higher-molecular-weight proteins. Here we show that artemisinins, but not quinine or chloroquine, inhibit the SERCA orthologue (PfATP6) of Plasmodium falciparum in Xenopus oocytes with similar potency to thapsigargin (another sesquiterpene lactone and highly specific SERCA inhibitor). As predicted, thapsigargin also antagonizes the parasiticidal activity of artemisinin. Desoxyartemisinin lacks an endoperoxide bridge and is ineffective both as an inhibitor of PfATP6 and as an antimalarial. Chelation of iron by desferrioxamine abrogates the antiparasitic activity of artemisinins and correspondingly attenuates inhibition of PfATP6. Imaging of parasites with BODIPY-thapsigargin labels the cytosolic compartment and is competed by artemisinin. Fluorescent artemisinin labels parasites similarly and irreversibly in an Fe2+-dependent manner. These data provide compelling evidence that artemisinins act by inhibiting PfATP6 outside the food vacuole after activation by iron. 相似文献
983.
Insect behaviour: reversal of sex roles in nuptial feeding 总被引:1,自引:0,他引:1
984.
It has been a long-standing goal to detect the effects of quantum mechanics on a macroscopic mechanical oscillator. Position measurements of an oscillator are ultimately limited by quantum mechanics, where 'zero-point motion' fluctuations in the quantum ground state combine with the uncertainty relation to yield a lower limit on the measured average displacement. Development of a position transducer, integrated with a mechanical resonator, that can approach this limit could have important applications in the detection of very weak forces, for example in magnetic resonance force microscopy and a variety of other precision experiments. One implementation that might allow near quantum-limited sensitivity is to use a single electron transistor (SET) as a displacement sensor: the exquisite charge sensitivity of the SET at cryogenic temperatures is exploited to measure motion by capacitively coupling it to the mechanical resonator. Here we present the experimental realization of such a device, yielding an unequalled displacement sensitivity of 2 x 10(-15) m x Hz(-1/2) for a 116-MHz mechanical oscillator at a temperature of 30 mK-a sensitivity roughly a factor of 100 larger than the quantum limit for this oscillator. 相似文献
985.
986.
987.
988.
Higgins JM 《Cellular and molecular life sciences : CMLS》2003,60(3):446-462
The haspins constitute a newly defined protein family containing a distinctive C-terminal eukaryotic protein kinase domain and divergent N termini. Haspin homologues are found in animals, plants and fungi, suggesting an origin early in eukaryotic evolution. Most species have a single haspin homologue. However, Saccharomyces cerevisiae has two such genes, while Caenorhabditis elegans has at least three haspin homologues and approximately 16 haspin-related genes. Mammalian haspin genes have features of retrogenes and are strongly expressed in male germ cells and at lower levels in some somatic tissues. They encode nuclear proteins with serine/threonine kinase activity. Murine haspin is reported to inhibit cell cycle progression in cell lines. One of the S. cerevisiae homologues, ALK1, is a member of the CLB2 gene cluster that peaks in expression at M phase and thus may function in mitosis. Therefore, the haspins are an intriguing group of kinases likely to have important roles during or following both meiosis and mitosis. 相似文献
989.
Targeting of the Akt/PKB kinase to the actin skeleton 总被引:2,自引:0,他引:2
Cenni V Sirri A Riccio M Lattanzi G Santi S de Pol A Maraldi NM Marmiroli S 《Cellular and molecular life sciences : CMLS》2003,60(12):2710-2720
Serine/threonine kinase Akt/PKB intracellular distribution undergoes rapid changes in response to agonists such as Platelet-derived growth factor (PDGF) or Insulin-like growth factor (IGF). The concept has recently emerged that Akt subcellular movements are facilitated by interaction with nonsubstrate ligands. Here we show that Akt is bound to the actin skeleton in in situ cytoskeletal matrix preparations from PDGF-treated Saos2 cells, suggesting an interaction between the two proteins. Indeed, by immunoprecipitation and subcellular fractioning, we demonstrate that endogenous Akt and actin physically interact. Using recombinant proteins in in vitro binding and overlay assays, we further demonstrate that Akt interacts with actin directly. Expression of Akt mutants strongly indicates that the N-terminal PH domain of Akt mediates this interaction. More important, we show that the partition between actin bound and unbound Akt is not constant, but is modulated by growth factor stimulation. In fact, PDGF treatment of serum-starved cells triggers an increase in the amount of Akt associated with the actin skeleton, concomitant with an increase in Akt phosphorylation. Conversely, expression of an Akt mutant in which both Ser473 and Thr308 have been mutated to alanine completely abrogates PDGF-induced binding. The small GTPases Rac1 and Cdc42 seem to facilitate actin binding, possibly increasing Akt phosphorylation.Received 10 September 2003; accepted 25 September 2003 相似文献
990.
Kamath RS Fraser AG Dong Y Poulin G Durbin R Gotta M Kanapin A Le Bot N Moreno S Sohrmann M Welchman DP Zipperlen P Ahringer J 《Nature》2003,421(6920):231-237