874 research outputs found

    Theory of Coherent Time-dependent Transport in One-dimensional Multiband Semiconductor Superlattices

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    We present an analytical study of one-dimensional semiconductor superlattices in external electric fields, which may be time-dependent. A number of general results for the (quasi)energies and eigenstates are derived. An equation of motion for the density matrix is obtained for a two-band model, and the properties of the solutions are analyzed. An expression for the current is obtained. Finally, Zener-tunneling in a two-band tight-binding model is considered. The present work gives the background and an extension of the theoretical framework underlying our recent Letter [J. Rotvig {\it et al.}, Phys. Rev. Lett. {\bf 74}, 1831 (1995)], where a set of numerical simulations were presented.Comment: 15 pages, Revtex 3.0, uses epsf, 2 ps figures attache

    Efficient CRISPR/Cas9 genome editing in a salmonid fish cell line using a lentivirus delivery system

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    The present study was funded by were funded by the Biotechnology and Biological Sciences Research Council (BB/R008612/1, BB/S004343/1 to RH and RG; grant BB/R008973/1 to SM and CD) and the Institute Strategic Programme Grants (BBS/E/D/20002172, BBS/E/D/30002275 and BBS/E/D/10002070, to RH and RG). The funders had no roles in the study design, data collection and analysis, decision to publish or preparation of the manuscript.Peer reviewedPublisher PD

    Haemodynamics and flow modification stents for peripheral arterial disease:a review

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    Endovascular stents are widely used for the treatment of peripheral arterial disease (PAD). However, the development of in-stent restenosis and downstream PAD progression remain a challenge. Stent revascularisation of PAD causes arterial trauma and introduces abnormal haemodynamics, which initiate complicated biological processes detrimental to the arterial wall. The interaction between stent struts and arterial cells in contact, and the blood flow field created in a stented region, are highly affected by stent design. Spiral flow is known as a normal physiologic characteristic of arterial circulation and is believed to prevent the development of flow disturbances. This secondary flow motion is lost in atheromatous disease and its re-introduction after endovascular treatment of PAD has been suggested as a method to induce stabilised and coherent haemodynamics. Stent designs able to generate spiral flow may support endothelial function and therefore increase patency rates. This review is focused on secondary flow phenomena in arteries and the development of flow modification stent technologies for the treatment of PAD

    The 2018 GaN Power Electronics Roadmap

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    Gallium nitride (GaN) is a compound semiconductor that has tremendous potential to facilitate economic growth in a semiconductor industry that is silicon-based and currently faced with diminishing returns of performance versus cost of investment. At a material level, its high electric field strength and electron mobility have already shown tremendous potential for high frequency communications and photonic applications. Advances in growth on commercially viable large area substrates are now at the point where power conversion applications of GaN are at the cusp of commercialisation. The future for building on the work described here in ways driven by specific challenges emerging from entirely new markets and applications is very exciting. This collection of GaN technology developments is therefore not itself a road map but a valuable collection of global state-of-the-art GaN research that will inform the next phase of the technology as market driven requirements evolve. First generation production devices are igniting large new markets and applications that can only be achieved using the advantages of higher speed, low specific resistivity and low saturation switching transistors. Major investments are being made by industrial companies in a wide variety of markets exploring the use of the technology in new circuit topologies, packaging solutions and system architectures that are required to achieve and optimise the system advantages offered by GaN transistors. It is this momentum that will drive priorities for the next stages of device research gathered here

    Dissecting Molecular Differences between Wnt Coreceptors LRP5 and LRP6

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    Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6) serve as Wnt co-receptors for the canonical β-catenin pathway. While LRP6 is essential for embryogenesis, both LRP5 and LRP6 play critical roles for skeletal remodeling, osteoporosis pathogenesis and cancer formation, making LRP5 and LRP6 key therapeutic targets for cancer and disease treatment. LRP5 and LRP6 each contain in the cytoplasmic domain five conserved PPPSPxS motifs that are pivotal for signaling and serve collectively as phosphorylation-dependent docking sites for the scaffolding protein Axin. However existing data suggest that LRP6 is more effective than LRP5 in transducing the Wnt signal. To understand the molecular basis that accounts for the different signaling activity of LRP5 and LRP6, we generated a series of chimeric receptors via swapping LRP5 and LRP6 cytoplasmic domains, LRP5C and LRP6C, and studied their Wnt signaling activity using biochemical and functional assays. We demonstrate that LRP6C exhibits strong signaling activity while LRP5C is much less active in cells. Recombinant LRP5C and LRP6C upon in vitro phosphorylation exhibit similar Axin-binding capability, suggesting that LRP5 and LRP6 differ in vivo at a step prior to Axin-binding, likely at receiving phosphorylation. We identified between the two most carboxyl PPPSPxS motifs an intervening “gap4” region that appears to account for much of the difference between LRP5C and LRP6C, and showed that alterations in this region are sufficient to enhance LRP5 PPPSPxS phosphorylation and signaling to levels comparable to LRP6 in cells. In addition we provide evidence that binding of phosphorylated LRP5 or LRP6 to Axin is likely direct and does not require the GSK3 kinase as a bridging intermediate as has been proposed. Our studies therefore uncover a new and important molecular tuning mechanism for differential regulation of LRP5 and LRP6 phosphorylation and signaling activity

    First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

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    Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

    Spatial Proximity and Similarity of the Epigenetic State of Genome Domains

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    Recent studies demonstrate that the organization of the chromatin within the nuclear space might play a crucial role in the regulation of gene expression. The ongoing progress in determination of the 3D structure of the nuclear chromatin allows one to study correlations between spatial proximity of genome domains and their epigenetic state. We combined the data on three-dimensional architecture of the whole human genome with results of high-throughput studies of the chromatin functional state and observed that fragments of different chromosomes that are spatially close tend to have similar patterns of histone modifications, methylation state, DNAse sensitivity, expression level, and chromatin states in general. Moreover, clustering of genome regions by spatial proximity produced compact clusters characterized by the high level of histone modifications and DNAse sensitivity and low methylation level, and loose clusters with the opposite characteristics. We also associated the spatial proximity data with previously detected chimeric transcripts and the results of RNA-seq experiments and observed that the frequency of formation of chimeric transcripts from fragments of two different chromosomes is higher among spatially proximal genome domains. A fair fraction of these chimeric transcripts seems to arise post-transcriptionally via trans-splicing

    Comparative Analyses of SUV420H1 Isoforms and SUV420H2 Reveal Differences in Their Cellular Localization and Effects on Myogenic Differentiation

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    Methylation of histone H4 on lysine 20 plays critical roles in chromatin structure and function via mono- (H4K20me1), di- (H4K20me2), and trimethyl (H4K20me3) derivatives. In previous analyses of histone methylation dynamics in mid-gestation mouse embryos, we documented marked changes in H4K20 methylation during cell differentiation. These changes were particularly robust during myogenesis, both in vivo and in cell culture, where we observed a transition from H4K20me1 to H4K20me3. To assess the significance of this change, we used a gain-of-function strategy involving the lysine methyltransferases SUV420H1 and SUV420H2, which catalyze H4K20me2 and H4K20me3. At the same time, we characterized a second isoform of SUV420H1 (designated SUV420H1_i2) and compared the activity of all three SUV420H proteins with regard to localization and H4K20 methylation.Immunofluorescence revealed that exogenous SUV420H1_i2 was distributed throughout the cell, while a substantial portion of SUV420H1_i1 and SUV420H2 displayed the expected association with constitutive heterochromatin. Moreover, SUV420H1_i2 distribution was unaffected by co-expression of heterochromatin protein-1α, which increased the targeting of SUV420H1_i1 and SUV420H2 to regions of pericentromeric heterochromatin. Consistent with their distributions, SUV420H1_i2 caused an increase in H4K20me3 levels throughout the nucleus, whereas SUV420H1_i1 and SUV420H2 facilitated an increase in pericentric H4K20me3. Striking differences continued when the SUV420H proteins were tested in the C2C12 myogenic model system. Specifically, although SUV420H1_i2 induced precocious appearance of the differentiation marker Myogenin in the presence of mitogens, only SUV420H2 maintained a Myogenin-enriched population over the course of differentiation. Paradoxically, SUV420H1_i1 could not be expressed in C2C12 cells, which suggests it is under post-transcriptional or post-translational control.These data indicate that SUV420H proteins differ substantially in their localization and activity. Importantly, SUV420H2 can induce a transition from H4K20me1 to H4K20me3 in regions of constitutive heterochromatin that is sufficient to enhance myogenic differentiation, suggesting it can act an as epigenetic ‘switch’ in this process
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