1,919 research outputs found

    Exploring the potential climate change impact on urban growth in London by a cellular automata-based Markov chain model

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    This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Urbanization has become a global trend under the combined influence of population growth, socioeconomic development, and globalization. Even though recent urban planning in London has been more deliberate, the relationships between climate change and urban growth in the context of economic geography are still somewhat unclear. This study relies on rainfall prediction with the aid of the Statistical DownScaling Model (SDSM), which provides the statistical foundation for future flooding potential within the urban space of London while considering major socioeconomic policies related to land use management. These SDSM findings, along with current land use policies, were included as other factors or constraints in a cellular automata-based Markov Chain model to simulate and predict land use changes in London for 2030 and 2050. Two scenarios with the inclusion and exclusion of flood impact factor, respectively, were applied to evaluate the impact of climate change on urban growth. Findings indicated: (1) mean monthly projected precipitation derived by SDSM is expected to increase for the year 2030 in London, which will affect the flooding potential and hence the area of open space; (2) urban and open space are expected to increase > 16 and 20km 2 (in percentage of 1.51 and 1.92 compared to 2012) in 2030 and 2050, respectively, while agriculture is expected to decrease significantly due to urbanization and climate change; (3) the inclusion of potential flood impact induced from the future precipitation variability drives the development toward more open space and less urban area.The research is supported by the Global Innovation Initiative (British Council Grant No. Gll206), funded by the British Council and the Department for Business, Innovation and Skills

    Spectral weight transfer in a disorder-broadened Landau level

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    In the absence of disorder, the degeneracy of a Landau level (LL) is N=BA/Ď•0N=BA/\phi_0, where BB is the magnetic field, AA is the area of the sample and Ď•0=h/e\phi_0=h/e is the magnetic flux quantum. With disorder, localized states appear at the top and bottom of the broadened LL, while states in the center of the LL (the critical region) remain delocalized. This well-known phenomenology is sufficient to explain most aspects of the Integer Quantum Hall Effect (IQHE) [1]. One unnoticed issue is where the new states appear as the magnetic field is increased. Here we demonstrate that they appear predominantly inside the critical region. This leads to a certain ``spectral ordering'' of the localized states that explains the stripes observed in measurements of the local inverse compressibility [2-3], of two-terminal conductance [4], and of Hall and longitudinal resistances [5] without invoking interactions as done in previous work [6-8].Comment: 5 pages 3 figure

    Nr2e3 is a Genetic Modifier That Rescues Retinal Degeneration and Promotes Homeostasis in Multiple Models of Retinitis Pigmentosa

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    Recent advances in viral vector engineering, as well as an increased understanding of the cellular and molecular mechanism of retinal diseases, have led to the development of novel gene therapy approaches. Furthermore, ease of accessibility and ocular immune privilege makes the retina an ideal target for gene therapies. In this study, the nuclear hormone receptor gene Nr2e3 was evaluated for efficacy as broad-spectrum therapy to attenuate early to intermediate stages of retinal degeneration in five unique mouse models of retinitis pigmentosa (RP). RP is a group of heterogenic inherited retinal diseases associated with over 150 gene mutations, affecting over 1.5 million individuals worldwide. RP varies in age of onset, severity, and rate of progression. In addition, ~40% of RP patients cannot be genetically diagnosed, confounding the ability to develop personalized RP therapies. Remarkably, Nr2e3 administered therapy resulted in reduced retinal degeneration as observed by increase in photoreceptor cells, improved electroretinogram, and a dramatic molecular reset of key transcription factors and associated gene networks. These therapeutic effects improved retinal homeostasis in diseased tissue. Results of this study provide evidence that Nr2e3 can serve as a broad-spectrum therapy to treat multiple forms of RP

    High-sensitivity diamond magnetometer with nanoscale resolution

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    We present a novel approach to the detection of weak magnetic fields that takes advantage of recently developed techniques for the coherent control of solid-state electron spin quantum bits. Specifically, we investigate a magnetic sensor based on Nitrogen-Vacancy centers in room-temperature diamond. We discuss two important applications of this technique: a nanoscale magnetometer that could potentially detect precession of single nuclear spins and an optical magnetic field imager combining spatial resolution ranging from micrometers to millimeters with a sensitivity approaching few femtotesla/Hz1/2^{1/2}.Comment: 29 pages, 4 figure

    Attenuation Imaging with Pulse-Echo Ultrasound based on an Acoustic Reflector

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    Ultrasound attenuation is caused by absorption and scattering in tissue and is thus a function of tissue composition, hence its imaging offers great potential for screening and differential diagnosis. In this paper we propose a novel method that allows to reconstruct spatial attenuation distribution in tissue based on computed tomography, using reflections from a passive acoustic reflector. This requires a standard ultrasound transducer operating in pulse-echo mode, thus it can be implemented on conventional ultrasound systems with minor modifications. We use calibration with water measurements in order to normalize measurements for quantitative imaging of attenuation. In contrast to earlier techniques, we herein show that attenuation reconstructions are possible without any geometric prior on the inclusion location or shape. We present a quantitative evaluation of reconstructions based on simulations, gelatin phantoms, and ex-vivo bovine skeletal muscle tissue, achieving contrast-to-noise ratio of up to 2.3 for an inclusion in ex-vivo tissue.Comment: Accepted at MICCAI 2019 (International Conference on Medical Image Computing and Computer Assisted Intervention

    Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy

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    Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies

    Quantification of lentiviral vector copy numbers in individual hematopoietic colony-forming cells shows vector dose-dependent effects on the frequency and level of transduction

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    Lentiviral vectors are effective tools for gene transfer and integrate variable numbers of proviral DNA copies in variable proportions of cells. The levels of transduction of a cellular population may therefore depend upon experimental parameters affecting the frequency and/or the distribution of vector integration events in this population. Such analysis would require measuring vector copy numbers (VCN) in individual cells. To evaluate the transduction of hematopoietic progenitor cells at the single-cell level, we measured VCN in individual colony-forming cell (CFC) units, using an adapted quantitative PCR (Q-PCR) method. The feasibility, reproducibility and sensitivity of this approach were tested with characterized cell lines carrying known numbers of vector integration. The method was validated by correlating data in CFC with gene expression or with calculated values, and was found to slightly underestimate VCN. In spite of this, such Q-PCR on CFC was useful to compare transduction levels with different infection protocols and different vectors. Increasing the vector concentration and re-iterating the infection were two different strategies that improved transduction by increasing the frequency of transduced progenitor cells. Repeated infection also augmented the number of integrated copies and the magnitude of this effect seemed to depend on the vector preparation. Thus, the distribution of VCN in hematopoietic colonies may depend upon experimental conditions including features of vectors. This should be carefully evaluated in the context of ex vivo hematopoietic gene therapy studies

    A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus

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    Generally, the second messenger bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-diGMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be—at least partially—functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus

    Effect of gallium doping on the characteristic properties of polycrystalline cadmium telluride thin film

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    Ga-doped CdTe polycrystalline thin films were successfully electrodeposited on glass/fluorine doped tin oxide (FTO) substrates from aqueous electrolytes containing cadmium nitrate (Cd(NO3)2⸱4H2O) and tellurium oxide (TeO2). The effects of different Ga-doping concentrations on the CdTe:Ga coupled with different post-growth treatments were studied by analysing the structural, optical, morphological and electronic properties of the deposited layers using X-ray diffraction (XRD), ultraviolet-visible spectrophotometry, scanning electron microscopy, photoelectrochemical cell measurement and direct-current conductivity test respectively. XRD results show diminishing (111)C CdTe peak above 20 ppm Ga-doping and appearance of (301)M GaTe diffraction above 50 ppm Ga-doping indicating the formation of two phases; CdTe and GaTe . Although, reductions in the absorption edge slopes were observed above 20 ppm Ga-doping for the as-deposited CdTe:Ga layer, no obvious influence on the energy gap of CdTe films with Ga-doping were detected. Morphologically, reductions in grain size were observed at 50 ppm Ga-doping and above with high pinhole density within the layer. For the as-deposited CdTe:Ga layers, conduction type change from n- to p- were observed at 50 ppm, while the n-type conductivity were retained after post-growth treatment. Highest conductivity was observed at 20 ppm Ga-doping of CdTe. These results are systematically reported in this pape
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