11 resultados para Cyclin-Dependent Kinase 4

em Cambridge University Engineering Department Publications Database


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During systemic disease in mice, Salmonella enterica grows intracellularly within discrete foci of infection in the spleen and liver. In concomitant infections, foci containing different S. enterica strains are spatially separated. We have investigated whether functional interactions between bacterial populations within the same host can occur despite the known spatial separation of the foci and independence of growth of salmonellae residing in different foci. In this study we have demonstrated that bacterial numbers of virulent S. enterica serovar Typhimurium C5 strain in mouse tissues can be increased by the presence of the attenuated aroA S. Typhimurium SL3261 vaccine strain in the same tissue. Disease exacerbation does not require simultaneous coinjection of the attenuated bacteria. SL3261 can be administered up to 48 hr after or 24 hr before the administration of C5 and still determine higher tissue numbers of the virulent bacteria. This indicates that intravenous administration of a S. enterica vaccine strain could potentially exacerbate an established infection with wild-type bacteria. These data also suggest that the severity of an infection with a virulent S. enterica strain can be increased by the prior administration of a live attenuated vaccine strain if infection occurs within 48 hr of vaccination. Exacerbation of the growth of C5 requires Toll-like receptor 4-dependent interleukin-10 production with the involvement of both Toll/interleukin-1 receptor-domain-containing adaptor inducing interferon-beta and myeloid differentiation factor 88.

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This paper describes a measurement on a GaAs quantum well waveguide with a high built in field across the quantum wells at a wavelength far from the bandedge. The device structure used for the measurement has been fabricated at STC Technology Ltd and is that of a standard laser ridge structure. In fabrication double heterostructure layers are grown on a [001] n + GaAs substrate, with the active region containing two intrinsic GaAs quantum wells of 10nm thickness separated by 10nm. A 4μm wide ridge is etched to provide transverse optical guiding. The experimental work has involved the use of 1.06μm wavelength light from a Q-switched Nd:YAG laser. Any induced change in refractive index is determined by measuring the change in transmission of the quantum well waveguide Fabry-Perot cavity. The waveguide is placed on a Peltier temperature controller to allow thermal tuning.

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In this paper, we demonstrate for the first time that insulative dielectrophoresis can induce size-dependent trajectories of DNA macromolecules. We experimentally use lambda (48.5 kbp) and T4GT7 (165.6 kbp) DNA molecules flowing continuously around a sharp corner inside fluidic channels with a depth of 0.4 mum. Numerical simulation of the electrokinetic force distribution inside the channels is in qualitative agreement with our experimentally observed trajectories. We discuss a possible physical mechanism for the DNA polarization and dielectrophoresis inside confining channels, based on the observed dielectrophoresis responses due to different DNA sizes and various electric fields applied between the inlet and the outlet. The proposed physical mechanism indicates that further extensive investigations, both theoretically and experimentally, would be very useful to better elucidate the forces involved at DNA dielectrophoresis. When applied for size-based sorting of DNA molecules, our sorting method offers two major advantages compared to earlier attempts with insulative dielectrophoresis: Its continuous operation allows for high-throughput analysis, and it only requires electric field strengths as low as approximately 10 Vcm.

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We have investigated a resonant refractive nonlinearity in a semiconductor waveguide by measuring intensity dependent phase shifts and bias-dependent recovery times. The measurements were performed on an optimized 750-μm-long AR coated buried heterostructure MQW p-i-n waveguide with a bandedge at 1.48 μm. Figure 1 shows the experimental arrangement. The mode-locked color center laser was tuned to 50 meV beyond the bandedge and 8 ps pulses with peak incident power up to 57 W were coupled into the waveguide. Some residual bandtail absorption remains at this wavelength and this is sufficient to cause carriers to be photogenerated and these give rise to a refractive nonlinearity, predominantly by plasma and bandfilling effects. A Fabry-Perot interferometer is used to measure the spectrum of the light which exits the waveguide. The nonlinearity within the guide causes self phase modulation (SPM) of the light and a study of the spectrum allows information to be recovered on the magnitude and recovery time of the nonlinear phase shift with a reasonable degree of accuracy. SPM spectra were recorded for a variety of pulse energies coupled into he unbiased waveguide. Figure 2 shows the resultant phase shift measured from the SPM spectra as a function of pulse energy. The relationship is a linear one, indicating that no saturation of the nonlinearity occurs for coupled pulse energies up to 230 pJ. A π phase shift, the minimum necessary for an all-optical switch, is obtained for a coupled pulse energy of 57 pJ while the maximum phase shift, 4 π, was measured for 230 pJ. The SPM spectra were highly asymmetric with pulse energy shifted to higher frequencies. Such spectra are characteristic of a slow, negative nonlinearity. This relatively slow speed is expected for the unbiased guide as the recovery time will be of the order of the recombination time of the photogenerated electrons, about 1 ns for InGaAsP material. In order to reduce the recovery time of the nonlinearity, it is necessary to remove the photogenerated carriers from the waveguide by a process other than recombination. One such technique is to apply a reverse bias to the waveguide in order to sweep the carriers out. Figure 3 shows the effect on the recovery time of the nonlinearity of applying reverse bias to the waveguide for 230 pJ coupled power. The recovery time was reduced from one much longer than the length of the pulse, estimated to be about 1 ns, at zero bias to 18 ± 3 ps for a bias voltage greater than -4 V. This compares with a value of 24 ps obtained in a bulk waveguide.

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The Arabidopsis genome contains a highly complex and abundant population of small RNAs, and many of the endogenous siRNAs are dependent on RNA-Dependent RNA Polymerase 2 (RDR2) for their biogenesis. By analyzing an rdr2 loss-of-function mutant using two different parallel sequencing technologies, MPSS and 454, we characterized the complement of miRNAs expressed in Arabidopsis inflorescence to considerable depth. Nearly all known miRNAs were enriched in this mutant and we identified 13 new miRNAs, all of which were relatively low abundance and constitute new families. Trans-acting siRNAs (ta-siRNAs) were even more highly enriched. Computational and gel blot analyses suggested that the minimal number of miRNAs in Arabidopsis is approximately 155. The size profile of small RNAs in rdr2 reflected enrichment of 21-nt miRNAs and other classes of siRNAs like ta-siRNAs, and a significant reduction in 24-nt heterochromatic siRNAs. Other classes of small RNAs were found to be RDR2-independent, particularly those derived from long inverted repeats and a subset of tandem repeats. The small RNA populations in other Arabidopsis small RNA biogenesis mutants were also examined; a dcl2/3/4 triple mutant showed a similar pattern to rdr2, whereas dcl1-7 and rdr6 showed reductions in miRNAs and ta-siRNAs consistent with their activities in the biogenesis of these types of small RNAs. Deep sequencing of mutants provides a genetic approach for the dissection and characterization of diverse small RNA populations and the identification of low abundance miRNAs.

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A temperature-dependent mobility model in amorphous oxide semiconductor (AOS) thin film transistors (TFTs) extracted from measurements of source-drain terminal currents at different gate voltages and temperatures is presented. At low gate voltages, trap-limited conduction prevails for a broad range of temperatures, whereas variable range hopping becomes dominant at lower temperatures. At high gate voltages and for all temperatures, percolation conduction comes into the picture. In all cases, the temperature-dependent mobility model obeys a universal power law as a function of gate voltage. © 2011 IEEE.

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Theories of instrumental learning are centred on understanding how success and failure are used to improve future decisions. These theories highlight a central role for reward prediction errors in updating the values associated with available actions. In animals, substantial evidence indicates that the neurotransmitter dopamine might have a key function in this type of learning, through its ability to modulate cortico-striatal synaptic efficacy. However, no direct evidence links dopamine, striatal activity and behavioural choice in humans. Here we show that, during instrumental learning, the magnitude of reward prediction error expressed in the striatum is modulated by the administration of drugs enhancing (3,4-dihydroxy-L-phenylalanine; L-DOPA) or reducing (haloperidol) dopaminergic function. Accordingly, subjects treated with L-DOPA have a greater propensity to choose the most rewarding action relative to subjects treated with haloperidol. Furthermore, incorporating the magnitude of the prediction errors into a standard action-value learning algorithm accurately reproduced subjects' behavioural choices under the different drug conditions. We conclude that dopamine-dependent modulation of striatal activity can account for how the human brain uses reward prediction errors to improve future decisions.

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The dependence of the Raman spectrum on the excitation energy has been investigated for ABA-and ABC- stacked few-layer graphene in order to establish the fingerprint of the stacking order and the number of layers, which affect the transport and optical properties of few-layer graphene. Five different excitation sources with energies of 1.96, 2.33, 2.41, 2.54 and 2.81â €...eV were used. The position and the line shape of the Raman 2D, G*, N, M, and other combination modes show dependence on the excitation energy as well as the stacking order and the thickness. One can unambiguously determine the stacking order and the thickness by comparing the 2D band spectra measured with 2 different excitation energies or by carefully comparing weaker combination Raman modes such as N, M, or LOLA modes. The criteria for unambiguous determination of the stacking order and the number of layers up to 5 layers are established.